MDedge Cardiology

“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.

Regardless of your opinion on BMI (body mass index), this conversation highlighted that the medical community needs to discuss the limitations of BMI and decide its future.

As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
 

BMI: From observational measurement to clinical use

Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.

The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.

Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.

In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.

By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
 

BMI as a tool to diagnose obesity

We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.

Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.

Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.

This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.

Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
 

Is it time to phase out BMI?

The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:

• Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
• Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
• Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.

The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.

Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.

Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.

A version of this article first appeared on Medscape.com.

“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.

Regardless of your opinion on BMI (body mass index), this conversation highlighted that the medical community needs to discuss the limitations of BMI and decide its future.

As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
 

BMI: From observational measurement to clinical use

Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.

The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.

Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.

In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.

By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
 

BMI as a tool to diagnose obesity

We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.

Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.

Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.

This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.

Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
 

Is it time to phase out BMI?

The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:

• Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
• Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
• Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.

The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.

Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.

Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.

A version of this article first appeared on Medscape.com.

“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.

Regardless of your opinion on BMI (body mass index), this conversation highlighted that the medical community needs to discuss the limitations of BMI and decide its future.

As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
 

BMI: From observational measurement to clinical use

Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.

The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.

Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.

In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.

By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
 

BMI as a tool to diagnose obesity

We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.

Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.

Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.

This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.

Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
 

Is it time to phase out BMI?

The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:

• Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
• Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
• Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.

The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.

Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.

Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.

A version of this article first appeared on Medscape.com.

New research shows that “polypills” can prevent a combination of cardiovascular events and cardiovascular deaths among patients who have recently experienced a myocardial infarction.

But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.

How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?

Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.

As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
 

A matter of adherence?

In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.

Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).

Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)

The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).

“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.

“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.

Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.

In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.

Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.

One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.

Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.

Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.

When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”

“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
 

Can the results be replicated?

Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”

“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.

Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.

Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.

To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”

“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.

In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.

“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”

Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.

But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.

“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”

For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.

Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.

Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.

Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.

Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.

“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.

That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.

The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.” 

The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.

A version of this article first appeared on Medscape.com.

New research shows that “polypills” can prevent a combination of cardiovascular events and cardiovascular deaths among patients who have recently experienced a myocardial infarction.

But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.

How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?

Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.

As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
 

A matter of adherence?

In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.

Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).

Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)

The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).

“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.

“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.

Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.

In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.

Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.

One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.

Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.

Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.

When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”

“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
 

Can the results be replicated?

Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”

“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.

Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.

Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.

To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”

“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.

In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.

“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”

Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.

But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.

“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”

For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.

Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.

Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.

Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.

Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.

“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.

That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.

The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.” 

The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.

A version of this article first appeared on Medscape.com.

New research shows that “polypills” can prevent a combination of cardiovascular events and cardiovascular deaths among patients who have recently experienced a myocardial infarction.

But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.

How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?

Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.

As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
 

A matter of adherence?

In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.

Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).

Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)

The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).

“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.

“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.

Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.

In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.

Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.

One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.

Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.

Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.

When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”

“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
 

Can the results be replicated?

Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”

“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.

Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.

Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.

To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”

“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.

In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.

“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”

Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.

But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.

“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”

For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.

Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.

Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.

Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.

Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.

“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.

That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.

The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.” 

The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.

A version of this article first appeared on Medscape.com.

Intake of salt is a biological necessity, inextricably woven into physiologic systems. However, excessive salt intake is associated with high blood pressure. Hypertension is linked to increased cardiovascular morbidity and mortality, and it is estimated that excessive salt intake causes approximately 5 million deaths per year worldwide. Reducing salt intake lowers blood pressure, but processed foods contain “hidden” salt, which makes dietary control of salt difficult. This problem is compounded by growing inequalities in food systems, which present another hurdle to sustaining individual dietary control of salt intake.

Krisana Antharith / EyeEm / Getty Images

Of the 87 risk factors included in the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, high systolic blood pressure was identified as the leading risk factor for disease burden at the global level and for its effect on human health. A range of strategies, including primary care management and reduction in sodium intake, are known to reduce the burden of this critical risk factor. Two questions remain unanswered: “What is the relationship between mortality and adding salt to foods?” and “How much does a reduction in salt intake influence people’s health?”
 

Cardiovascular disease and death

Because dietary sodium intake has been identified as a risk factor for cardiovascular disease and premature death, high sodium intake can be expected to curtail life span. A study tested this hypothesis by analyzing the relationship between sodium intake and life expectancy and survival in 181 countries. Sodium intake correlated positively with life expectancy and inversely with all-cause mortality worldwide and in high-income countries, which argues against dietary sodium intake curtailing life span or a being risk factor for premature death. These results help fuel a scientific debate about sodium intake, life expectancy, and mortality. The debate requires interpreting composite data of positive linear, J-shaped, or inverse linear correlations, which underscores the uncertainty regarding this issue.

In a prospective study of 501,379 participants from the UK Biobank, researchers found that higher frequency of adding salt to foods was significantly associated with a higher risk of premature mortality and lower life expectancy independently of diet, lifestyle, socioeconomic level, and preexisting diseases. They found that the positive association appeared to be attenuated with increasing intake of high-potassium foods (vegetables and fruits).

In addition, the researchers made the following observations:

• For cause-specific premature mortality, they found that higher frequency of adding salt to foods was significantly associated with a higher risk of cardiovascular disease mortality and cancer mortality (P-trend < .001 and P-trend < .001, respectively).
• Always adding salt to foods was associated with the lower life expectancy at the age of 50 years by 1.50 (95% confidence interval, 0.72-2.30) and 2.28 (95% CI, 1.66-2.90) years for women and men, respectively, compared with participants who never or rarely added salt to foods.

The researchers noted that adding salt to foods (usually at the table) is common and is directly related to an individual’s long-term preference for salty foods and habitual salt intake. Indeed, in the Western diet, adding salt at the table accounts for 6%-20% of total salt intake. In addition, commonly used table salt contains 97%-99% sodium chloride, minimizing the potential confounding effects of other dietary factors, including potassium. Therefore, adding salt to foods provides a way to evaluate the association between habitual sodium intake and mortality – something that is relevant, given that it has been estimated that in 2010, a total of 1.65 million deaths from cardiovascular causes were attributable to consumption of more than 2.0 g of sodium per day.
 

Salt sensitivity

Current evidence supports a recommendation for moderate sodium intake in the general population (3-5 g/day). Persons with hypertension should consume salt at the lower end of that range. Some dietary guidelines recommend consuming less than 2,300 mg dietary sodium per day for persons aged 14 years or older and less for persons aged 2-13 years. Although low sodium intake (< 2.0 g/day) has been achieved in short-term clinical trials, sustained low sodium intake has not been achieved in any of the longer-term clinical trials (duration > 6 months).

The controversy continues as to the relationship between low sodium intake and blood pressure or cardiovascular diseases. Most studies show that both in individuals with hypertension and those without, blood pressure is reduced by consuming less sodium. However, it is not necessarily lowered by reducing sodium intake (< 3-5 g/day). With a sodium-rich diet, most normotensive individuals experienced a minimal change in mean arterial pressure; for many individuals with hypertension, the values increased by about 4 mm Hg. In addition, among individuals with hypertension who are “salt sensitive,” arterial pressure can increase by > 10 mm Hg in response to high sodium intake.
 

The effect of potassium

Replacing some of the sodium chloride in regular salt with potassium chloride may mitigate some of salt’s harmful cardiovascular effects. Indeed, salt substitutes that have reduced sodium levels and increased potassium levels have been shown to lower blood pressure.

In one trial, researchers enrolled over 20,000 persons from 600 villages in rural China and compared the use of regular salt (100% sodium chloride) with the use of a salt substitute (75% sodium chloride and 25% potassium chloride by mass).

The participants were at high risk for stroke, cardiovascular events, and death. The mean duration of follow-up was 4.74 years. The results were surprising. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1,000 person-years; rate ratio, 0.86; 95% CI, 0.77-0.96; P = .006), as were the rates of major cardiovascular events and death from any cause. The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt.

Although there is an ongoing debate about the extent of salt’s effects on the cardiovascular system, there is no doubt that in most places in the world, people are consuming more salt than the body needs.

A lot depends upon the kind of diet consumed by a particular population. Processed food is rarely used in rural areas, such as those involved in the above-mentioned trial, with dietary sodium chloride being added while preparing food at home. This is a determining factor with regard to cardiovascular outcomes, but it cannot be generalized to other social-environmental settings.

In much of the world, commercial food preservation introduces a lot of sodium chloride into the diet, and most salt intake could not be fully attributed to the use of salt substitutes. Indeed, by comparing the sodium content of cereal-based products currently sold on the Italian market with the respective benchmarks proposed by the World Health Organization, researchers found that for most items, the sodium content is much higher than the benchmarks, especially with flatbreads, leavened breads, and crackers/savory biscuits. This shows that there is work to be done to achieve the World Health Organization/United Nations objective of a 30% global reduction in sodium intake by 2025.

This article was translated from Univadis Italy. A version of this article first appeared on Medscape.com.

Intake of salt is a biological necessity, inextricably woven into physiologic systems. However, excessive salt intake is associated with high blood pressure. Hypertension is linked to increased cardiovascular morbidity and mortality, and it is estimated that excessive salt intake causes approximately 5 million deaths per year worldwide. Reducing salt intake lowers blood pressure, but processed foods contain “hidden” salt, which makes dietary control of salt difficult. This problem is compounded by growing inequalities in food systems, which present another hurdle to sustaining individual dietary control of salt intake.

Krisana Antharith / EyeEm / Getty Images

Of the 87 risk factors included in the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, high systolic blood pressure was identified as the leading risk factor for disease burden at the global level and for its effect on human health. A range of strategies, including primary care management and reduction in sodium intake, are known to reduce the burden of this critical risk factor. Two questions remain unanswered: “What is the relationship between mortality and adding salt to foods?” and “How much does a reduction in salt intake influence people’s health?”
 

Cardiovascular disease and death

Because dietary sodium intake has been identified as a risk factor for cardiovascular disease and premature death, high sodium intake can be expected to curtail life span. A study tested this hypothesis by analyzing the relationship between sodium intake and life expectancy and survival in 181 countries. Sodium intake correlated positively with life expectancy and inversely with all-cause mortality worldwide and in high-income countries, which argues against dietary sodium intake curtailing life span or a being risk factor for premature death. These results help fuel a scientific debate about sodium intake, life expectancy, and mortality. The debate requires interpreting composite data of positive linear, J-shaped, or inverse linear correlations, which underscores the uncertainty regarding this issue.

In a prospective study of 501,379 participants from the UK Biobank, researchers found that higher frequency of adding salt to foods was significantly associated with a higher risk of premature mortality and lower life expectancy independently of diet, lifestyle, socioeconomic level, and preexisting diseases. They found that the positive association appeared to be attenuated with increasing intake of high-potassium foods (vegetables and fruits).

In addition, the researchers made the following observations:

• For cause-specific premature mortality, they found that higher frequency of adding salt to foods was significantly associated with a higher risk of cardiovascular disease mortality and cancer mortality (P-trend < .001 and P-trend < .001, respectively).
• Always adding salt to foods was associated with the lower life expectancy at the age of 50 years by 1.50 (95% confidence interval, 0.72-2.30) and 2.28 (95% CI, 1.66-2.90) years for women and men, respectively, compared with participants who never or rarely added salt to foods.

The researchers noted that adding salt to foods (usually at the table) is common and is directly related to an individual’s long-term preference for salty foods and habitual salt intake. Indeed, in the Western diet, adding salt at the table accounts for 6%-20% of total salt intake. In addition, commonly used table salt contains 97%-99% sodium chloride, minimizing the potential confounding effects of other dietary factors, including potassium. Therefore, adding salt to foods provides a way to evaluate the association between habitual sodium intake and mortality – something that is relevant, given that it has been estimated that in 2010, a total of 1.65 million deaths from cardiovascular causes were attributable to consumption of more than 2.0 g of sodium per day.
 

Salt sensitivity

Current evidence supports a recommendation for moderate sodium intake in the general population (3-5 g/day). Persons with hypertension should consume salt at the lower end of that range. Some dietary guidelines recommend consuming less than 2,300 mg dietary sodium per day for persons aged 14 years or older and less for persons aged 2-13 years. Although low sodium intake (< 2.0 g/day) has been achieved in short-term clinical trials, sustained low sodium intake has not been achieved in any of the longer-term clinical trials (duration > 6 months).

The controversy continues as to the relationship between low sodium intake and blood pressure or cardiovascular diseases. Most studies show that both in individuals with hypertension and those without, blood pressure is reduced by consuming less sodium. However, it is not necessarily lowered by reducing sodium intake (< 3-5 g/day). With a sodium-rich diet, most normotensive individuals experienced a minimal change in mean arterial pressure; for many individuals with hypertension, the values increased by about 4 mm Hg. In addition, among individuals with hypertension who are “salt sensitive,” arterial pressure can increase by > 10 mm Hg in response to high sodium intake.
 

The effect of potassium

Replacing some of the sodium chloride in regular salt with potassium chloride may mitigate some of salt’s harmful cardiovascular effects. Indeed, salt substitutes that have reduced sodium levels and increased potassium levels have been shown to lower blood pressure.

In one trial, researchers enrolled over 20,000 persons from 600 villages in rural China and compared the use of regular salt (100% sodium chloride) with the use of a salt substitute (75% sodium chloride and 25% potassium chloride by mass).

The participants were at high risk for stroke, cardiovascular events, and death. The mean duration of follow-up was 4.74 years. The results were surprising. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1,000 person-years; rate ratio, 0.86; 95% CI, 0.77-0.96; P = .006), as were the rates of major cardiovascular events and death from any cause. The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt.

Although there is an ongoing debate about the extent of salt’s effects on the cardiovascular system, there is no doubt that in most places in the world, people are consuming more salt than the body needs.

A lot depends upon the kind of diet consumed by a particular population. Processed food is rarely used in rural areas, such as those involved in the above-mentioned trial, with dietary sodium chloride being added while preparing food at home. This is a determining factor with regard to cardiovascular outcomes, but it cannot be generalized to other social-environmental settings.

In much of the world, commercial food preservation introduces a lot of sodium chloride into the diet, and most salt intake could not be fully attributed to the use of salt substitutes. Indeed, by comparing the sodium content of cereal-based products currently sold on the Italian market with the respective benchmarks proposed by the World Health Organization, researchers found that for most items, the sodium content is much higher than the benchmarks, especially with flatbreads, leavened breads, and crackers/savory biscuits. This shows that there is work to be done to achieve the World Health Organization/United Nations objective of a 30% global reduction in sodium intake by 2025.

This article was translated from Univadis Italy. A version of this article first appeared on Medscape.com.

Intake of salt is a biological necessity, inextricably woven into physiologic systems. However, excessive salt intake is associated with high blood pressure. Hypertension is linked to increased cardiovascular morbidity and mortality, and it is estimated that excessive salt intake causes approximately 5 million deaths per year worldwide. Reducing salt intake lowers blood pressure, but processed foods contain “hidden” salt, which makes dietary control of salt difficult. This problem is compounded by growing inequalities in food systems, which present another hurdle to sustaining individual dietary control of salt intake.

Krisana Antharith / EyeEm / Getty Images

Of the 87 risk factors included in the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, high systolic blood pressure was identified as the leading risk factor for disease burden at the global level and for its effect on human health. A range of strategies, including primary care management and reduction in sodium intake, are known to reduce the burden of this critical risk factor. Two questions remain unanswered: “What is the relationship between mortality and adding salt to foods?” and “How much does a reduction in salt intake influence people’s health?”
 

Cardiovascular disease and death

Because dietary sodium intake has been identified as a risk factor for cardiovascular disease and premature death, high sodium intake can be expected to curtail life span. A study tested this hypothesis by analyzing the relationship between sodium intake and life expectancy and survival in 181 countries. Sodium intake correlated positively with life expectancy and inversely with all-cause mortality worldwide and in high-income countries, which argues against dietary sodium intake curtailing life span or a being risk factor for premature death. These results help fuel a scientific debate about sodium intake, life expectancy, and mortality. The debate requires interpreting composite data of positive linear, J-shaped, or inverse linear correlations, which underscores the uncertainty regarding this issue.

In a prospective study of 501,379 participants from the UK Biobank, researchers found that higher frequency of adding salt to foods was significantly associated with a higher risk of premature mortality and lower life expectancy independently of diet, lifestyle, socioeconomic level, and preexisting diseases. They found that the positive association appeared to be attenuated with increasing intake of high-potassium foods (vegetables and fruits).

In addition, the researchers made the following observations:

• For cause-specific premature mortality, they found that higher frequency of adding salt to foods was significantly associated with a higher risk of cardiovascular disease mortality and cancer mortality (P-trend < .001 and P-trend < .001, respectively).
• Always adding salt to foods was associated with the lower life expectancy at the age of 50 years by 1.50 (95% confidence interval, 0.72-2.30) and 2.28 (95% CI, 1.66-2.90) years for women and men, respectively, compared with participants who never or rarely added salt to foods.

The researchers noted that adding salt to foods (usually at the table) is common and is directly related to an individual’s long-term preference for salty foods and habitual salt intake. Indeed, in the Western diet, adding salt at the table accounts for 6%-20% of total salt intake. In addition, commonly used table salt contains 97%-99% sodium chloride, minimizing the potential confounding effects of other dietary factors, including potassium. Therefore, adding salt to foods provides a way to evaluate the association between habitual sodium intake and mortality – something that is relevant, given that it has been estimated that in 2010, a total of 1.65 million deaths from cardiovascular causes were attributable to consumption of more than 2.0 g of sodium per day.
 

Salt sensitivity

Current evidence supports a recommendation for moderate sodium intake in the general population (3-5 g/day). Persons with hypertension should consume salt at the lower end of that range. Some dietary guidelines recommend consuming less than 2,300 mg dietary sodium per day for persons aged 14 years or older and less for persons aged 2-13 years. Although low sodium intake (< 2.0 g/day) has been achieved in short-term clinical trials, sustained low sodium intake has not been achieved in any of the longer-term clinical trials (duration > 6 months).

The controversy continues as to the relationship between low sodium intake and blood pressure or cardiovascular diseases. Most studies show that both in individuals with hypertension and those without, blood pressure is reduced by consuming less sodium. However, it is not necessarily lowered by reducing sodium intake (< 3-5 g/day). With a sodium-rich diet, most normotensive individuals experienced a minimal change in mean arterial pressure; for many individuals with hypertension, the values increased by about 4 mm Hg. In addition, among individuals with hypertension who are “salt sensitive,” arterial pressure can increase by > 10 mm Hg in response to high sodium intake.
 

The effect of potassium

Replacing some of the sodium chloride in regular salt with potassium chloride may mitigate some of salt’s harmful cardiovascular effects. Indeed, salt substitutes that have reduced sodium levels and increased potassium levels have been shown to lower blood pressure.

In one trial, researchers enrolled over 20,000 persons from 600 villages in rural China and compared the use of regular salt (100% sodium chloride) with the use of a salt substitute (75% sodium chloride and 25% potassium chloride by mass).

The participants were at high risk for stroke, cardiovascular events, and death. The mean duration of follow-up was 4.74 years. The results were surprising. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1,000 person-years; rate ratio, 0.86; 95% CI, 0.77-0.96; P = .006), as were the rates of major cardiovascular events and death from any cause. The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt.

Although there is an ongoing debate about the extent of salt’s effects on the cardiovascular system, there is no doubt that in most places in the world, people are consuming more salt than the body needs.

A lot depends upon the kind of diet consumed by a particular population. Processed food is rarely used in rural areas, such as those involved in the above-mentioned trial, with dietary sodium chloride being added while preparing food at home. This is a determining factor with regard to cardiovascular outcomes, but it cannot be generalized to other social-environmental settings.

In much of the world, commercial food preservation introduces a lot of sodium chloride into the diet, and most salt intake could not be fully attributed to the use of salt substitutes. Indeed, by comparing the sodium content of cereal-based products currently sold on the Italian market with the respective benchmarks proposed by the World Health Organization, researchers found that for most items, the sodium content is much higher than the benchmarks, especially with flatbreads, leavened breads, and crackers/savory biscuits. This shows that there is work to be done to achieve the World Health Organization/United Nations objective of a 30% global reduction in sodium intake by 2025.

This article was translated from Univadis Italy. A version of this article first appeared on Medscape.com.

Comments from the White House this week suggesting a once-a-year COVID-19 shot for most Americans, “just like your annual flu shot,” were met with backlash from many who say COVID and influenza come from different viruses and need different schedules.

Remarks, from “capitulation” to too few data, hit the airwaves and social media.

Some, however, agree with the White House vision and say that asking people to get one shot in the fall instead of periodic pushes for boosters will raise public confidence and buy-in and reduce consumer confusion.  

Health leaders, including Bob Wachter, MD, chair of the department of medicine at the University of California, San Francisco, say they like the framing of the concept – that people who are not high-risk should plan each year for a COVID shot and a flu shot.

“Doesn’t mean we KNOW shot will prevent transmission for a year. DOES mean it’ll likely lower odds of SEVERE case for a year & we need strategy to bump uptake,” Dr. Wachter tweeted this week.

But the numbers of Americans seeking boosters remain low. Only one-third of all eligible people 50 years and older have gotten a second COVID booster, according to the Centers for Disease Control and Prevention. About half of those who got the original two shots got a first booster.

Meanwhile, the United States is still averaging about 70,000 new COVID cases and more than 300 deaths every day.

The suggested change in approach comes as Pfizer/BioNTech and Moderna roll out their new boosters that target Omicron subvariants BA.4 and BA.5 after the CDC recommended their use and the U.S. Food and Drug Administration approved emergency use authorization. 

“As the virus continues to change, we will now be able to update our vaccines annually to target the dominant variant,” President Joe Biden said in a statement promoting the yearly approach.
 

Some say annual shot premature

Other experts say it’s too soon to tell whether an annual approach will work.

“We have no data to support that current vaccines, including the new BA.5 booster, will provide durable protection beyond 4-6 months. It would be good to aspire to this objective, and much longer duration or protection, but that will likely require next generation and nasal vaccines,” said Eric Topol, MD, Medscape’s editor-in-chief and founder and director of the Scripps Research Translational Institute.

A report in Nature Reviews Immunology states, “Mucosal vaccines offer the potential to trigger robust protective immune responses at the predominant sites of pathogen infection” and potentially “can prevent an infection from becoming established in the first place, rather than only curtailing infection and protecting against the development of disease symptoms.”

Dr. Topol tweeted after the White House statements, “[An annual vaccine] has the ring of Covid capitulation.”

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., told this news organization that he cautions against interpreting the White House comments as official policy.

“This is the difficulty of having public health announcements come out of Washington,” he said. “They ought to come out of the CDC.”

He says there is a reasonable analogy between COVID and influenza, but warns, “don’t push the analogy.”

They are both serious respiratory viruses that can cause much illness and death in essentially the same populations, he notes. These are the older, frail people, people who have underlying illnesses or are immunocompromised.

Both viruses also mutate. But there the paths diverge.

“We’ve gotten into a pattern of annually updating the influenza vaccine because it is such a singularly seasonal virus,” Dr. Schaffner said. “Basically it disappears during the summer. We’ve had plenty of COVID during the summers.”

For COVID, he said, “We will need a periodic booster. Could this be annually? That would certainly make it easier.” But it’s too soon to tell, he said.

Dr. Schaffner noted that several manufacturers are working on a combined flu/COVID vaccine.
 

Just a ‘first step’ toward annual shot

The currently updated COVID vaccine may be the first step toward an annual vaccine, but it’s only the first step, Dr. Schaffner said. “We haven’t committed to further steps yet because we’re watching this virus.”

Syra Madad, DHSc, MSc, an infectious disease epidemiologist at Harvard University’s Belfer Center for Science and International Affairs, Cambridge, Mass., and the New York City hospital system, told this news organization that arguments on both sides make sense.

Having a single message once a year can help eliminate the considerable confusion involving people on individual timelines with different levels of immunity and separate campaigns for COVID and flu shots coming at different times of the year.

“Communication around vaccines is very muddled and that shows in our overall vaccination rates, particularly booster rates,” she says. “The overall strategy is hopeful and makes sense if we’re going to progress that way based on data.”

However, she said that the data are just not there yet to show it’s time for an annual vaccine. First, scientists will need to see how long protection lasts with the Omicron-specific vaccine and how well and how long it protects against severe disease and death as well as infection.

COVID is less predictable than influenza and the influenza vaccine has been around for decades, Dr. Madad noted. With influenza, the patterns are more easily anticipated with their “ladder-like pattern,” she said. “COVID-19 is not like that.”

What is hopeful, she said, “is that we’ve been in the Omicron dynasty since November of 2021. I’m hopeful that we’ll stick with that particular variant.”

Dr. Topol, Dr. Schaffner, and Dr. Madad declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Comments from the White House this week suggesting a once-a-year COVID-19 shot for most Americans, “just like your annual flu shot,” were met with backlash from many who say COVID and influenza come from different viruses and need different schedules.

Remarks, from “capitulation” to too few data, hit the airwaves and social media.

Some, however, agree with the White House vision and say that asking people to get one shot in the fall instead of periodic pushes for boosters will raise public confidence and buy-in and reduce consumer confusion.  

Health leaders, including Bob Wachter, MD, chair of the department of medicine at the University of California, San Francisco, say they like the framing of the concept – that people who are not high-risk should plan each year for a COVID shot and a flu shot.

“Doesn’t mean we KNOW shot will prevent transmission for a year. DOES mean it’ll likely lower odds of SEVERE case for a year & we need strategy to bump uptake,” Dr. Wachter tweeted this week.

But the numbers of Americans seeking boosters remain low. Only one-third of all eligible people 50 years and older have gotten a second COVID booster, according to the Centers for Disease Control and Prevention. About half of those who got the original two shots got a first booster.

Meanwhile, the United States is still averaging about 70,000 new COVID cases and more than 300 deaths every day.

The suggested change in approach comes as Pfizer/BioNTech and Moderna roll out their new boosters that target Omicron subvariants BA.4 and BA.5 after the CDC recommended their use and the U.S. Food and Drug Administration approved emergency use authorization. 

“As the virus continues to change, we will now be able to update our vaccines annually to target the dominant variant,” President Joe Biden said in a statement promoting the yearly approach.
 

Some say annual shot premature

Other experts say it’s too soon to tell whether an annual approach will work.

“We have no data to support that current vaccines, including the new BA.5 booster, will provide durable protection beyond 4-6 months. It would be good to aspire to this objective, and much longer duration or protection, but that will likely require next generation and nasal vaccines,” said Eric Topol, MD, Medscape’s editor-in-chief and founder and director of the Scripps Research Translational Institute.

A report in Nature Reviews Immunology states, “Mucosal vaccines offer the potential to trigger robust protective immune responses at the predominant sites of pathogen infection” and potentially “can prevent an infection from becoming established in the first place, rather than only curtailing infection and protecting against the development of disease symptoms.”

Dr. Topol tweeted after the White House statements, “[An annual vaccine] has the ring of Covid capitulation.”

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., told this news organization that he cautions against interpreting the White House comments as official policy.

“This is the difficulty of having public health announcements come out of Washington,” he said. “They ought to come out of the CDC.”

He says there is a reasonable analogy between COVID and influenza, but warns, “don’t push the analogy.”

They are both serious respiratory viruses that can cause much illness and death in essentially the same populations, he notes. These are the older, frail people, people who have underlying illnesses or are immunocompromised.

Both viruses also mutate. But there the paths diverge.

“We’ve gotten into a pattern of annually updating the influenza vaccine because it is such a singularly seasonal virus,” Dr. Schaffner said. “Basically it disappears during the summer. We’ve had plenty of COVID during the summers.”

For COVID, he said, “We will need a periodic booster. Could this be annually? That would certainly make it easier.” But it’s too soon to tell, he said.

Dr. Schaffner noted that several manufacturers are working on a combined flu/COVID vaccine.
 

Just a ‘first step’ toward annual shot

The currently updated COVID vaccine may be the first step toward an annual vaccine, but it’s only the first step, Dr. Schaffner said. “We haven’t committed to further steps yet because we’re watching this virus.”

Syra Madad, DHSc, MSc, an infectious disease epidemiologist at Harvard University’s Belfer Center for Science and International Affairs, Cambridge, Mass., and the New York City hospital system, told this news organization that arguments on both sides make sense.

Having a single message once a year can help eliminate the considerable confusion involving people on individual timelines with different levels of immunity and separate campaigns for COVID and flu shots coming at different times of the year.

“Communication around vaccines is very muddled and that shows in our overall vaccination rates, particularly booster rates,” she says. “The overall strategy is hopeful and makes sense if we’re going to progress that way based on data.”

However, she said that the data are just not there yet to show it’s time for an annual vaccine. First, scientists will need to see how long protection lasts with the Omicron-specific vaccine and how well and how long it protects against severe disease and death as well as infection.

COVID is less predictable than influenza and the influenza vaccine has been around for decades, Dr. Madad noted. With influenza, the patterns are more easily anticipated with their “ladder-like pattern,” she said. “COVID-19 is not like that.”

What is hopeful, she said, “is that we’ve been in the Omicron dynasty since November of 2021. I’m hopeful that we’ll stick with that particular variant.”

Dr. Topol, Dr. Schaffner, and Dr. Madad declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Comments from the White House this week suggesting a once-a-year COVID-19 shot for most Americans, “just like your annual flu shot,” were met with backlash from many who say COVID and influenza come from different viruses and need different schedules.

Remarks, from “capitulation” to too few data, hit the airwaves and social media.

Some, however, agree with the White House vision and say that asking people to get one shot in the fall instead of periodic pushes for boosters will raise public confidence and buy-in and reduce consumer confusion.  

Health leaders, including Bob Wachter, MD, chair of the department of medicine at the University of California, San Francisco, say they like the framing of the concept – that people who are not high-risk should plan each year for a COVID shot and a flu shot.

“Doesn’t mean we KNOW shot will prevent transmission for a year. DOES mean it’ll likely lower odds of SEVERE case for a year & we need strategy to bump uptake,” Dr. Wachter tweeted this week.

But the numbers of Americans seeking boosters remain low. Only one-third of all eligible people 50 years and older have gotten a second COVID booster, according to the Centers for Disease Control and Prevention. About half of those who got the original two shots got a first booster.

Meanwhile, the United States is still averaging about 70,000 new COVID cases and more than 300 deaths every day.

The suggested change in approach comes as Pfizer/BioNTech and Moderna roll out their new boosters that target Omicron subvariants BA.4 and BA.5 after the CDC recommended their use and the U.S. Food and Drug Administration approved emergency use authorization. 

“As the virus continues to change, we will now be able to update our vaccines annually to target the dominant variant,” President Joe Biden said in a statement promoting the yearly approach.
 

Some say annual shot premature

Other experts say it’s too soon to tell whether an annual approach will work.

“We have no data to support that current vaccines, including the new BA.5 booster, will provide durable protection beyond 4-6 months. It would be good to aspire to this objective, and much longer duration or protection, but that will likely require next generation and nasal vaccines,” said Eric Topol, MD, Medscape’s editor-in-chief and founder and director of the Scripps Research Translational Institute.

A report in Nature Reviews Immunology states, “Mucosal vaccines offer the potential to trigger robust protective immune responses at the predominant sites of pathogen infection” and potentially “can prevent an infection from becoming established in the first place, rather than only curtailing infection and protecting against the development of disease symptoms.”

Dr. Topol tweeted after the White House statements, “[An annual vaccine] has the ring of Covid capitulation.”

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., told this news organization that he cautions against interpreting the White House comments as official policy.

“This is the difficulty of having public health announcements come out of Washington,” he said. “They ought to come out of the CDC.”

He says there is a reasonable analogy between COVID and influenza, but warns, “don’t push the analogy.”

They are both serious respiratory viruses that can cause much illness and death in essentially the same populations, he notes. These are the older, frail people, people who have underlying illnesses or are immunocompromised.

Both viruses also mutate. But there the paths diverge.

“We’ve gotten into a pattern of annually updating the influenza vaccine because it is such a singularly seasonal virus,” Dr. Schaffner said. “Basically it disappears during the summer. We’ve had plenty of COVID during the summers.”

For COVID, he said, “We will need a periodic booster. Could this be annually? That would certainly make it easier.” But it’s too soon to tell, he said.

Dr. Schaffner noted that several manufacturers are working on a combined flu/COVID vaccine.
 

Just a ‘first step’ toward annual shot

The currently updated COVID vaccine may be the first step toward an annual vaccine, but it’s only the first step, Dr. Schaffner said. “We haven’t committed to further steps yet because we’re watching this virus.”

Syra Madad, DHSc, MSc, an infectious disease epidemiologist at Harvard University’s Belfer Center for Science and International Affairs, Cambridge, Mass., and the New York City hospital system, told this news organization that arguments on both sides make sense.

Having a single message once a year can help eliminate the considerable confusion involving people on individual timelines with different levels of immunity and separate campaigns for COVID and flu shots coming at different times of the year.

“Communication around vaccines is very muddled and that shows in our overall vaccination rates, particularly booster rates,” she says. “The overall strategy is hopeful and makes sense if we’re going to progress that way based on data.”

However, she said that the data are just not there yet to show it’s time for an annual vaccine. First, scientists will need to see how long protection lasts with the Omicron-specific vaccine and how well and how long it protects against severe disease and death as well as infection.

COVID is less predictable than influenza and the influenza vaccine has been around for decades, Dr. Madad noted. With influenza, the patterns are more easily anticipated with their “ladder-like pattern,” she said. “COVID-19 is not like that.”

What is hopeful, she said, “is that we’ve been in the Omicron dynasty since November of 2021. I’m hopeful that we’ll stick with that particular variant.”

Dr. Topol, Dr. Schaffner, and Dr. Madad declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

During a medical malpractice trial in New Jersey, jurors waited nearly 4 hours for the physician defendant to show up. When he did arrive, the body-building surgeon was sporting two thick gold chains and a diamond pinky ring, and had the top buttons of his shirt open enough to reveal his chest hair.

“This trial was in a very rural, farming community,” recalls medical liability defense attorney Catherine Flynn, of Flynn Watts LLC, based in Parsippany, N.J. “Many of the jurors were wearing flannel shirts and jeans. The doctor’s wife walked in wearing a five-carat diamond ring and other jewelry.”

Ms. Flynn took the couple aside and asked them to remove the jewelry. She explained that the opulent accessories could damage the jury’s view of the physician. The surgeon and his wife, however, refused to remove their jewelry, she said. They didn’t think it was a big deal.

The case against the surgeon involved intraoperative damage to a patient when the physician inadvertently removed a portion of nerve in the area of the procedure. After repair of the nerve, the patient had a positive result. However, the patient alleged the surgeon’s negligence resulted in permanent damage despite the successful repair.

Jurors ultimately found the physician negligent in the case and awarded the plaintiff $1.2 million. Ms. Flynn believes that physician’s flamboyant attire and arrogant nature tainted the jury’s decision.

“In certain counties in New Jersey, his attire would not have been a problem,” she said. “In this rural, farming county, it was a huge problem. You have to know your audience. There are a lot of other things that come into play in a medical malpractice case, but when it comes to damages in a case, you don’t want to be sending the message that supports what somebody’s bias may already be telling them about a doctor.”

The surgeon appealed the verdict, and the case ultimately settled for a lesser amount, according to Ms. Flynn.

An over-the-top wardrobe is just one way that physicians can negatively influence jurors during legal trials. From subtle facial expressions to sudden outbursts to downright rudeness, attorneys have witnessed countless examples of physicians sabotaging their own trials. Legal experts say the cringeworthy experiences are good reminders that jurors are often judging more than just evidence.  

“The minute you enter the courthouse, jurors or potential jurors are sizing you up,” says health law attorney Michael Clark, of Womble Bond Dickinson (US) LLP, based in Houston. “The same phenomenon occurs in a deposition. Awareness of how you are being assessed at all times, and the image that is needed, is important since a negative impression by jurors can have a detrimental effect on a physician’s case.”
 

Juror: We didn’t like the doctor’s shoes

In another case, attorneys warned a physician defendant against dressing in his signature wardrobe during his trial. Against their advice, the doctor showed up daily to his trial in bright pastel, monochromatic suits with matching Gucci-brand shoes, said medical liability defense attorney Meredith C. Lander, of Kaufman Borgeest & Ryan LLP, based in Connecticut. On the witness stand, the doctor was long-winded and wasn’t “terribly likable,” Ms. Lander said.

However, the evidence weighed in the physician’s favor, and there was strong testimony by defense experts. The physician won the case, Ms. Lander said, but after the verdict, the jury foreperson approached the trial attorney and made some disparaging remarks about the defendant.

“The foreperson said the jury didn’t like the doctor or his ‘Gucci suits and shoes,’ but they believed the experts,” Ms. Lander said.

Disruptive behavior can also harm jurors’ perception of physicians, Ms. Flynn adds. During one instance, a surgeon insisted on sitting next to Ms. Flynn, although she generally requests clients sit in the first row so that jurors are not so focused on their reactions during testimony. The surgeon loudly peppered Ms. Flynn with questions as witnesses testified, prompting a reprimand from the judge.

“The judge admonished the doctor several times and said, ‘Doctor, you’re raising your voice. You’ll get a chance to speak with your attorney during the break,’ ” Ms. Flynn recalled. “The doctor refused to stop talking, and the judge told him in front of the jury to go sit in the back of the courtroom. His reaction was, ‘Why do I have to move?! I need to sit here!’ ”

The surgeon eventually moved to the back of the courtroom and a sheriff’s deputy stood next to him. Testimony continued until a note in the form of a paper airplane landed on the table in front of Ms. Flynn. She carefully crumpled the note and tossed it in the wastebasket. Luckily, this drew a laugh from jurors, she said. 

But things got worse when the surgeon testified. Rather than answer the questions, he interrupted and started telling jurors his own version of events.

“The judge finally said, ‘Doctor, if you don’t listen to your attorney and answer her questions, I’m going to make you get off the stand,’ ” Ms. Flynn said. “That was the most unbelievable, egregious self-sabotage trial moment I’ve ever experienced.”

Fortunately, the physician’s legal case was strong, and the experts who testified drove the defense’s side home, Ms. Flynn said. The surgeon won the case.
 

Attorney: Watch what you say in the elevator

Other, more subtle behaviors – while often unintentional – can also be damaging.

Physicians often let their guard down while outside the courtroom and can unknowingly wind up next to a juror in an elevator or standing in a hallway, said Laura Postilion, a partner at Quintairos, Prieto, Wood & Boyer, P.A., based in Chicago.

“For instance, a doctor is in an elevator and feels that some witness on the stand was lying,” Ms. Postilion said. “They might be very upset about it and start ranting about a witness lying, not realizing there is a juror is in the elevator with you.”

Physicians should also be cautious when speaking on the phone to their family or friends during a trial break.

“At the Daley Center in downtown Chicago, there are these long corridors and long line of windows; a lot of people will stand there during breaks. A doctor may be talking to his or her spouse and saying, ‘Yeah, this juror is sleeping!’ Jurors are [often] looking for drama. They’re looking for somebody letting their guard down. Hearing a doctor speak badly about them would certainly give them a reason to dislike the physician.”

Ms. Postilion warns against talking about jurors in or outside of the courtroom. This includes parking structures, she said.

Physicians can take additional steps to save themselves from negative judgment from jurors, attorneys say. Even before the trial starts, Ms. Postilion advises clients to make their social media accounts private. Some curious jurors may look up a physician’s social media accounts to learn more about their personal life, political leanings, or social beliefs, which could prejudice them against the doctor, she said.

Once on the stand, the words and tone used are key. The last thing a physician defendant wants is to come across as arrogant or condescending to jurors, said medical liability defense attorney Michael Moroney, of Flynn Watts LLC.

“For instance, a defendant might say, ‘Well, let me make this simple for you,’ as if they’re talking to a bunch of schoolchildren,” he said. “You don’t know who’s on the jury. That type of language can be offensive.”

Ms. Lander counsels her clients to refrain from using the common phrase, “honestly,” before answering questions on the stand.

“Everything you’re saying on the stand is presumed to be honest,” she said. “When you start an answer with, ‘Honestly…’ out of habit, it really does undercut everything that follows and everything else that’s already been said. It suggests that you were not being honest in your other answers.”
 

Attitude, body language speak volumes

Keep in mind that plaintiffs’ attorneys will try their best to rattle physicians on the stand and get them to appear unlikeable, says Mr. Clark, the Houston-based health law attorney. Physicians who lose their cool and begin arguing with attorneys play into their strategy.

“Plaintiffs’ attorneys have been trained in ways to get under their skin,” he said. “Righteous indignation and annoyance are best left for a rare occasion. Think about how you feel in a social setting when people are bickering in front of you. It’s uncomfortable at best. That’s how a jury feels too.”

Body language is also important, Mr. Clark notes. Physicians should avoid crossed arms, leaning back and rocking, or putting a hand on their mouth while testifying, he said. Many attorneys have practice sessions with their clients and record the interaction so that doctors can watch it and see how they look.

“Know your strengths and weaknesses,” he said. “Get help from your lawyer and perhaps consultants about how to improve these skills. Practice and preparation are important.”

Ms. Postilion goes over courtroom clothing with physician clients before trial. Anything “too flashy, too high-end, or too dumpy” should be avoided, she said. Getting accustomed to the courtroom and practicing in an empty courtroom are good ways to ensure that a physician’s voice is loud enough and projecting far enough in the courtroom, she adds.

“The doctor should try to be the best version of him- or herself to jurors,” she said. “A jury can pick up someone who’s trying to be something they’re not. A good attorney can help the doctor find the best version of themselves and capitalize on it. What is it that you want the jury to know about your care of the patient? Take that overall feeling and make sure it’s clearly expressed to the jury.”

A version of this article first appeared on Medscape.com.

During a medical malpractice trial in New Jersey, jurors waited nearly 4 hours for the physician defendant to show up. When he did arrive, the body-building surgeon was sporting two thick gold chains and a diamond pinky ring, and had the top buttons of his shirt open enough to reveal his chest hair.

“This trial was in a very rural, farming community,” recalls medical liability defense attorney Catherine Flynn, of Flynn Watts LLC, based in Parsippany, N.J. “Many of the jurors were wearing flannel shirts and jeans. The doctor’s wife walked in wearing a five-carat diamond ring and other jewelry.”

Ms. Flynn took the couple aside and asked them to remove the jewelry. She explained that the opulent accessories could damage the jury’s view of the physician. The surgeon and his wife, however, refused to remove their jewelry, she said. They didn’t think it was a big deal.

The case against the surgeon involved intraoperative damage to a patient when the physician inadvertently removed a portion of nerve in the area of the procedure. After repair of the nerve, the patient had a positive result. However, the patient alleged the surgeon’s negligence resulted in permanent damage despite the successful repair.

Jurors ultimately found the physician negligent in the case and awarded the plaintiff $1.2 million. Ms. Flynn believes that physician’s flamboyant attire and arrogant nature tainted the jury’s decision.

“In certain counties in New Jersey, his attire would not have been a problem,” she said. “In this rural, farming county, it was a huge problem. You have to know your audience. There are a lot of other things that come into play in a medical malpractice case, but when it comes to damages in a case, you don’t want to be sending the message that supports what somebody’s bias may already be telling them about a doctor.”

The surgeon appealed the verdict, and the case ultimately settled for a lesser amount, according to Ms. Flynn.

An over-the-top wardrobe is just one way that physicians can negatively influence jurors during legal trials. From subtle facial expressions to sudden outbursts to downright rudeness, attorneys have witnessed countless examples of physicians sabotaging their own trials. Legal experts say the cringeworthy experiences are good reminders that jurors are often judging more than just evidence.  

“The minute you enter the courthouse, jurors or potential jurors are sizing you up,” says health law attorney Michael Clark, of Womble Bond Dickinson (US) LLP, based in Houston. “The same phenomenon occurs in a deposition. Awareness of how you are being assessed at all times, and the image that is needed, is important since a negative impression by jurors can have a detrimental effect on a physician’s case.”
 

Juror: We didn’t like the doctor’s shoes

In another case, attorneys warned a physician defendant against dressing in his signature wardrobe during his trial. Against their advice, the doctor showed up daily to his trial in bright pastel, monochromatic suits with matching Gucci-brand shoes, said medical liability defense attorney Meredith C. Lander, of Kaufman Borgeest & Ryan LLP, based in Connecticut. On the witness stand, the doctor was long-winded and wasn’t “terribly likable,” Ms. Lander said.

However, the evidence weighed in the physician’s favor, and there was strong testimony by defense experts. The physician won the case, Ms. Lander said, but after the verdict, the jury foreperson approached the trial attorney and made some disparaging remarks about the defendant.

“The foreperson said the jury didn’t like the doctor or his ‘Gucci suits and shoes,’ but they believed the experts,” Ms. Lander said.

Disruptive behavior can also harm jurors’ perception of physicians, Ms. Flynn adds. During one instance, a surgeon insisted on sitting next to Ms. Flynn, although she generally requests clients sit in the first row so that jurors are not so focused on their reactions during testimony. The surgeon loudly peppered Ms. Flynn with questions as witnesses testified, prompting a reprimand from the judge.

“The judge admonished the doctor several times and said, ‘Doctor, you’re raising your voice. You’ll get a chance to speak with your attorney during the break,’ ” Ms. Flynn recalled. “The doctor refused to stop talking, and the judge told him in front of the jury to go sit in the back of the courtroom. His reaction was, ‘Why do I have to move?! I need to sit here!’ ”

The surgeon eventually moved to the back of the courtroom and a sheriff’s deputy stood next to him. Testimony continued until a note in the form of a paper airplane landed on the table in front of Ms. Flynn. She carefully crumpled the note and tossed it in the wastebasket. Luckily, this drew a laugh from jurors, she said. 

But things got worse when the surgeon testified. Rather than answer the questions, he interrupted and started telling jurors his own version of events.

“The judge finally said, ‘Doctor, if you don’t listen to your attorney and answer her questions, I’m going to make you get off the stand,’ ” Ms. Flynn said. “That was the most unbelievable, egregious self-sabotage trial moment I’ve ever experienced.”

Fortunately, the physician’s legal case was strong, and the experts who testified drove the defense’s side home, Ms. Flynn said. The surgeon won the case.
 

Attorney: Watch what you say in the elevator

Other, more subtle behaviors – while often unintentional – can also be damaging.

Physicians often let their guard down while outside the courtroom and can unknowingly wind up next to a juror in an elevator or standing in a hallway, said Laura Postilion, a partner at Quintairos, Prieto, Wood & Boyer, P.A., based in Chicago.

“For instance, a doctor is in an elevator and feels that some witness on the stand was lying,” Ms. Postilion said. “They might be very upset about it and start ranting about a witness lying, not realizing there is a juror is in the elevator with you.”

Physicians should also be cautious when speaking on the phone to their family or friends during a trial break.

“At the Daley Center in downtown Chicago, there are these long corridors and long line of windows; a lot of people will stand there during breaks. A doctor may be talking to his or her spouse and saying, ‘Yeah, this juror is sleeping!’ Jurors are [often] looking for drama. They’re looking for somebody letting their guard down. Hearing a doctor speak badly about them would certainly give them a reason to dislike the physician.”

Ms. Postilion warns against talking about jurors in or outside of the courtroom. This includes parking structures, she said.

Physicians can take additional steps to save themselves from negative judgment from jurors, attorneys say. Even before the trial starts, Ms. Postilion advises clients to make their social media accounts private. Some curious jurors may look up a physician’s social media accounts to learn more about their personal life, political leanings, or social beliefs, which could prejudice them against the doctor, she said.

Once on the stand, the words and tone used are key. The last thing a physician defendant wants is to come across as arrogant or condescending to jurors, said medical liability defense attorney Michael Moroney, of Flynn Watts LLC.

“For instance, a defendant might say, ‘Well, let me make this simple for you,’ as if they’re talking to a bunch of schoolchildren,” he said. “You don’t know who’s on the jury. That type of language can be offensive.”

Ms. Lander counsels her clients to refrain from using the common phrase, “honestly,” before answering questions on the stand.

“Everything you’re saying on the stand is presumed to be honest,” she said. “When you start an answer with, ‘Honestly…’ out of habit, it really does undercut everything that follows and everything else that’s already been said. It suggests that you were not being honest in your other answers.”
 

Attitude, body language speak volumes

Keep in mind that plaintiffs’ attorneys will try their best to rattle physicians on the stand and get them to appear unlikeable, says Mr. Clark, the Houston-based health law attorney. Physicians who lose their cool and begin arguing with attorneys play into their strategy.

“Plaintiffs’ attorneys have been trained in ways to get under their skin,” he said. “Righteous indignation and annoyance are best left for a rare occasion. Think about how you feel in a social setting when people are bickering in front of you. It’s uncomfortable at best. That’s how a jury feels too.”

Body language is also important, Mr. Clark notes. Physicians should avoid crossed arms, leaning back and rocking, or putting a hand on their mouth while testifying, he said. Many attorneys have practice sessions with their clients and record the interaction so that doctors can watch it and see how they look.

“Know your strengths and weaknesses,” he said. “Get help from your lawyer and perhaps consultants about how to improve these skills. Practice and preparation are important.”

Ms. Postilion goes over courtroom clothing with physician clients before trial. Anything “too flashy, too high-end, or too dumpy” should be avoided, she said. Getting accustomed to the courtroom and practicing in an empty courtroom are good ways to ensure that a physician’s voice is loud enough and projecting far enough in the courtroom, she adds.

“The doctor should try to be the best version of him- or herself to jurors,” she said. “A jury can pick up someone who’s trying to be something they’re not. A good attorney can help the doctor find the best version of themselves and capitalize on it. What is it that you want the jury to know about your care of the patient? Take that overall feeling and make sure it’s clearly expressed to the jury.”

A version of this article first appeared on Medscape.com.

During a medical malpractice trial in New Jersey, jurors waited nearly 4 hours for the physician defendant to show up. When he did arrive, the body-building surgeon was sporting two thick gold chains and a diamond pinky ring, and had the top buttons of his shirt open enough to reveal his chest hair.

“This trial was in a very rural, farming community,” recalls medical liability defense attorney Catherine Flynn, of Flynn Watts LLC, based in Parsippany, N.J. “Many of the jurors were wearing flannel shirts and jeans. The doctor’s wife walked in wearing a five-carat diamond ring and other jewelry.”

Ms. Flynn took the couple aside and asked them to remove the jewelry. She explained that the opulent accessories could damage the jury’s view of the physician. The surgeon and his wife, however, refused to remove their jewelry, she said. They didn’t think it was a big deal.

The case against the surgeon involved intraoperative damage to a patient when the physician inadvertently removed a portion of nerve in the area of the procedure. After repair of the nerve, the patient had a positive result. However, the patient alleged the surgeon’s negligence resulted in permanent damage despite the successful repair.

Jurors ultimately found the physician negligent in the case and awarded the plaintiff $1.2 million. Ms. Flynn believes that physician’s flamboyant attire and arrogant nature tainted the jury’s decision.

“In certain counties in New Jersey, his attire would not have been a problem,” she said. “In this rural, farming county, it was a huge problem. You have to know your audience. There are a lot of other things that come into play in a medical malpractice case, but when it comes to damages in a case, you don’t want to be sending the message that supports what somebody’s bias may already be telling them about a doctor.”

The surgeon appealed the verdict, and the case ultimately settled for a lesser amount, according to Ms. Flynn.

An over-the-top wardrobe is just one way that physicians can negatively influence jurors during legal trials. From subtle facial expressions to sudden outbursts to downright rudeness, attorneys have witnessed countless examples of physicians sabotaging their own trials. Legal experts say the cringeworthy experiences are good reminders that jurors are often judging more than just evidence.  

“The minute you enter the courthouse, jurors or potential jurors are sizing you up,” says health law attorney Michael Clark, of Womble Bond Dickinson (US) LLP, based in Houston. “The same phenomenon occurs in a deposition. Awareness of how you are being assessed at all times, and the image that is needed, is important since a negative impression by jurors can have a detrimental effect on a physician’s case.”
 

Juror: We didn’t like the doctor’s shoes

In another case, attorneys warned a physician defendant against dressing in his signature wardrobe during his trial. Against their advice, the doctor showed up daily to his trial in bright pastel, monochromatic suits with matching Gucci-brand shoes, said medical liability defense attorney Meredith C. Lander, of Kaufman Borgeest & Ryan LLP, based in Connecticut. On the witness stand, the doctor was long-winded and wasn’t “terribly likable,” Ms. Lander said.

However, the evidence weighed in the physician’s favor, and there was strong testimony by defense experts. The physician won the case, Ms. Lander said, but after the verdict, the jury foreperson approached the trial attorney and made some disparaging remarks about the defendant.

“The foreperson said the jury didn’t like the doctor or his ‘Gucci suits and shoes,’ but they believed the experts,” Ms. Lander said.

Disruptive behavior can also harm jurors’ perception of physicians, Ms. Flynn adds. During one instance, a surgeon insisted on sitting next to Ms. Flynn, although she generally requests clients sit in the first row so that jurors are not so focused on their reactions during testimony. The surgeon loudly peppered Ms. Flynn with questions as witnesses testified, prompting a reprimand from the judge.

“The judge admonished the doctor several times and said, ‘Doctor, you’re raising your voice. You’ll get a chance to speak with your attorney during the break,’ ” Ms. Flynn recalled. “The doctor refused to stop talking, and the judge told him in front of the jury to go sit in the back of the courtroom. His reaction was, ‘Why do I have to move?! I need to sit here!’ ”

The surgeon eventually moved to the back of the courtroom and a sheriff’s deputy stood next to him. Testimony continued until a note in the form of a paper airplane landed on the table in front of Ms. Flynn. She carefully crumpled the note and tossed it in the wastebasket. Luckily, this drew a laugh from jurors, she said. 

But things got worse when the surgeon testified. Rather than answer the questions, he interrupted and started telling jurors his own version of events.

“The judge finally said, ‘Doctor, if you don’t listen to your attorney and answer her questions, I’m going to make you get off the stand,’ ” Ms. Flynn said. “That was the most unbelievable, egregious self-sabotage trial moment I’ve ever experienced.”

Fortunately, the physician’s legal case was strong, and the experts who testified drove the defense’s side home, Ms. Flynn said. The surgeon won the case.
 

Attorney: Watch what you say in the elevator

Other, more subtle behaviors – while often unintentional – can also be damaging.

Physicians often let their guard down while outside the courtroom and can unknowingly wind up next to a juror in an elevator or standing in a hallway, said Laura Postilion, a partner at Quintairos, Prieto, Wood & Boyer, P.A., based in Chicago.

“For instance, a doctor is in an elevator and feels that some witness on the stand was lying,” Ms. Postilion said. “They might be very upset about it and start ranting about a witness lying, not realizing there is a juror is in the elevator with you.”

Physicians should also be cautious when speaking on the phone to their family or friends during a trial break.

“At the Daley Center in downtown Chicago, there are these long corridors and long line of windows; a lot of people will stand there during breaks. A doctor may be talking to his or her spouse and saying, ‘Yeah, this juror is sleeping!’ Jurors are [often] looking for drama. They’re looking for somebody letting their guard down. Hearing a doctor speak badly about them would certainly give them a reason to dislike the physician.”

Ms. Postilion warns against talking about jurors in or outside of the courtroom. This includes parking structures, she said.

Physicians can take additional steps to save themselves from negative judgment from jurors, attorneys say. Even before the trial starts, Ms. Postilion advises clients to make their social media accounts private. Some curious jurors may look up a physician’s social media accounts to learn more about their personal life, political leanings, or social beliefs, which could prejudice them against the doctor, she said.

Once on the stand, the words and tone used are key. The last thing a physician defendant wants is to come across as arrogant or condescending to jurors, said medical liability defense attorney Michael Moroney, of Flynn Watts LLC.

“For instance, a defendant might say, ‘Well, let me make this simple for you,’ as if they’re talking to a bunch of schoolchildren,” he said. “You don’t know who’s on the jury. That type of language can be offensive.”

Ms. Lander counsels her clients to refrain from using the common phrase, “honestly,” before answering questions on the stand.

“Everything you’re saying on the stand is presumed to be honest,” she said. “When you start an answer with, ‘Honestly…’ out of habit, it really does undercut everything that follows and everything else that’s already been said. It suggests that you were not being honest in your other answers.”
 

Attitude, body language speak volumes

Keep in mind that plaintiffs’ attorneys will try their best to rattle physicians on the stand and get them to appear unlikeable, says Mr. Clark, the Houston-based health law attorney. Physicians who lose their cool and begin arguing with attorneys play into their strategy.

“Plaintiffs’ attorneys have been trained in ways to get under their skin,” he said. “Righteous indignation and annoyance are best left for a rare occasion. Think about how you feel in a social setting when people are bickering in front of you. It’s uncomfortable at best. That’s how a jury feels too.”

Body language is also important, Mr. Clark notes. Physicians should avoid crossed arms, leaning back and rocking, or putting a hand on their mouth while testifying, he said. Many attorneys have practice sessions with their clients and record the interaction so that doctors can watch it and see how they look.

“Know your strengths and weaknesses,” he said. “Get help from your lawyer and perhaps consultants about how to improve these skills. Practice and preparation are important.”

Ms. Postilion goes over courtroom clothing with physician clients before trial. Anything “too flashy, too high-end, or too dumpy” should be avoided, she said. Getting accustomed to the courtroom and practicing in an empty courtroom are good ways to ensure that a physician’s voice is loud enough and projecting far enough in the courtroom, she adds.

“The doctor should try to be the best version of him- or herself to jurors,” she said. “A jury can pick up someone who’s trying to be something they’re not. A good attorney can help the doctor find the best version of themselves and capitalize on it. What is it that you want the jury to know about your care of the patient? Take that overall feeling and make sure it’s clearly expressed to the jury.”

A version of this article first appeared on Medscape.com.

BARCELONA – Hospitalized patients in the ICU because of an acute COVID-19 infection had significantly fewer thrombotic events and complications when treated with full-dose anticoagulation, compared with patients who received standard-dose anticoagulation prophylaxis, but full-dose anticoagulation also triggered an excess of moderate and severe bleeding events, randomized trial results show.

The new findings from the COVID-PACT trial in an exclusively U.S.-based cohort of 382 on-treatment patients in the ICU with COVID-19 infection may lead to a change in existing guidelines, which currently recommend standard-dose prophylaxis based on results from prior head-to-head comparisons, such as guidelines posted March 2022 from the American Society of Hematology.

The new findings suggest “full-dose anticoagulation should be considered to prevent thrombotic complications in selected critically ill patients with COVID-19” after weighing an individual patient’s risk for both thrombotic events and bleeding, David D. Berg, MD, said at the annual congress of the European Society of Cardiology. Simultaneous with his report at the congress, the results also appeared online in the journal Circulation.

“What the results tell us is that full-dose anticoagulation in critically ill patients with COVID-19 is highly effective for reducing thrombotic complications,” said Dr. Berg, a cardiologist and critical care physician at Brigham and Women’s Hospital, Boston.

The report’s designated discussant agreed with Dr. Berg’s conclusions.
 

‘Need to replace the guidelines’

“We probably need to replace the guidelines,” said Eduardo Ramacciotti, MD, PhD, MPH, a professor of vascular surgery at Santa Casa School of Medicine, São Paulo. Dr. Ramacciotti praised the study’s design, the endpoints, and the fact that the design excluded patients at high risk for bleeding complications, particularly those with a fibrinogen level below 200 mg/dL (2 g/L).

But other experts questioned the significance of the COVID-PACT results given that the outcomes did not show that full-dose anticoagulation produced incremental improvement in patient survival.

“We should abandon the thought that intensified anticoagulation should be routine, because it did not overall increase the number of patients discharged from the hospital alive,” commented John W. Eikelboom, MBBS, a professor of hematology and thromboembolism at McMaster University, Hamilton, Ont.

“Preventing venous thrombosis is a good thing, but the money is in saving lives and stopping need for ventilation, and we haven’t been successful doing that with an antithrombotic strategy,” said Dr. Eikelboom. “It is useful to prevent venous thrombosis, but we need to look elsewhere to improve the outcomes of [critically ill] patients with COVID-19.”
 

Reducing thromboembolism is a ‘valid goal’

Dr. Berg took a different view. “It’s a valid goal to try to reduce venous thromboembolism complications,” the major benefit seen in his study, he said. “There is clinical significance to reducing thrombotic events in terms of how people feel, their functional status, and their complications. There are a lot of clinically relevant consequences of thrombosis beyond mortality.”

COVID-PACT ran at 34 U.S. centers from August 2020 to March 2022 but stopped short of its enrollment goal of 750 patients because of waning numbers of patients with COVID-19 admitted to ICUs. In addition to randomly assigning patients within 96 hours of their ICU admission to full-dose anticoagulation or to standard-dose antithrombotic prophylaxis, the study included a second, concurrent randomization to the antiplatelet agent clopidogrel (Plavix) or to no antiplatelet drug. Both randomizations used an open-label design.

The results failed to show a discernable effect from adding clopidogrel on both the primary efficacy and primary safety endpoints, adding to accumulated evidence that treatment with an antiplatelet agent, including aspirin, confers no antithrombotic benefit in patients with COVID-19.

The trial’s participants averaged 61 years old, 68% were obese, 59% had hypertension, and 32% had diabetes. The median time after ICU admission when randomized treatment began was 2.1 days, and researchers followed patients for a median of 13 days, including a median time on anticoagulation of 10.6 days.

The trial design allowed clinicians to use either low molecular weight heparin or unfractionated heparin for anticoagulation, and 82% of patients received low molecular weight heparin as their initial treatment. The prespecified design called for an on-treatment analysis because of an anticipated high crossover rate. During the trial, 34% of patients who started on the prophylactic dose switched to full dose, and 17% had the reverse crossover.
 

95% increased win ratio with full dose

The study’s primary efficacy endpoint used a win-ratio analysis that included seven different adverse outcomes that ranged from death from venous or arterial thrombosis to clinically silent deep vein thrombosis. Treatment with full-dose anticoagulation led to a significant 95% increase in win ratio.

Researchers also applied a more conventional time-to-first-event secondary efficacy analysis, which showed that full-dose anticoagulation cut the incidence of an adverse outcome by a significant 44% relative to prophylactic dosing.

The two study groups showed no difference in all-cause death rates. The efficacy advantage of the full-dose regimen was driven by reduced rates of venous thrombotic events, especially a reduction in clinically evident deep vein thrombotic events.

The primary safety endpoint was the rate of fatal or life-threatening bleeding episodes, and while life-threatening bleeds were numerically more common among the full-dose recipients (four events, compared with one event on prophylaxis dosing) the difference was not significant, and no patients died from a bleeding event.
 

More secondary safety bleeds

The safety difference showed up in a secondary measure of bleeding severity, the rate of GUSTO moderate or severe bleeds. These occurred in 15 of the full-dose recipients, compared with 1 patient on the prophylactic dose.

Dr. Berg highlighted that several prior studies have assessed various anticoagulation regimens in critically ill (ICU-admitted and on respiratory or cardiovascular support) patients with COVID-19. For example, two influential reports published in 2021 by the same team of investigators in the New England Journal of Medicine had sharply divergent results.

One multicenter study, which tested full-dose heparin against prophylactic treatment in more than 1,000 critically ill patients, was stopped prematurely because it had not shown a significant difference between the treatment arms. The second study, in more than 2,000 multicenter patients with COVID-19 who did not require critical-level organ support, showed clear superiority of the full-dose heparin regimen.

Notably, both previous studies used a different primary efficacy endpoint than the COVID-PACT study. The earlier reports both measured efficacy in terms of patients being alive and off organ support by 21 days from randomization.
 

Patients to exclude

Although Dr. Berg stressed the clear positive result, he also cautioned that they should not apply to patients excluded from the study: those with severe coagulopathies, those with severe thrombocytopenia, and patients already maintained on dual antiplatelet therapy. He also cautioned against using the full-dose strategy in elderly patients, because in COVID-PACT, those who developed bleeding complications tended to be older.

Dr. Berg also noted that heparin prophylaxis is a well-established intervention for ICU-admitted patients without COVID-19 for the purpose of preventing venous thromboembolisms without evidence that this approach reduces deaths or organ failure.

But he conceded that “the priority of treatment depends on whether it saves lives, so anticoagulation is probably not as high a priority as other effective treatments” that reduce mortality. “Preventing venous thromboembolism has rarely been shown to have a mortality benefit,” Dr. Berg noted.

COVID-PACT received no direct commercial funding. Dr. Berg has been a consultant to AstraZeneca, Mobility Bio, and Youngene Therapeutics, and he participated in a trial sponsored by Kowa. Dr. Ramacciotti has been a consultant to or speaker on behalf of Aspen, Bayer, Daiichi Sankyo, Mylan, Pfizer, and Sanofi, and he has received research support from Bayer, Esperon, Novartis, and Pfizer. Dr. Eikelboom has received honoraria and research support from Bayer.

A version of this article first appeared on Medscape.com.

BARCELONA – Hospitalized patients in the ICU because of an acute COVID-19 infection had significantly fewer thrombotic events and complications when treated with full-dose anticoagulation, compared with patients who received standard-dose anticoagulation prophylaxis, but full-dose anticoagulation also triggered an excess of moderate and severe bleeding events, randomized trial results show.

The new findings from the COVID-PACT trial in an exclusively U.S.-based cohort of 382 on-treatment patients in the ICU with COVID-19 infection may lead to a change in existing guidelines, which currently recommend standard-dose prophylaxis based on results from prior head-to-head comparisons, such as guidelines posted March 2022 from the American Society of Hematology.

The new findings suggest “full-dose anticoagulation should be considered to prevent thrombotic complications in selected critically ill patients with COVID-19” after weighing an individual patient’s risk for both thrombotic events and bleeding, David D. Berg, MD, said at the annual congress of the European Society of Cardiology. Simultaneous with his report at the congress, the results also appeared online in the journal Circulation.

“What the results tell us is that full-dose anticoagulation in critically ill patients with COVID-19 is highly effective for reducing thrombotic complications,” said Dr. Berg, a cardiologist and critical care physician at Brigham and Women’s Hospital, Boston.

The report’s designated discussant agreed with Dr. Berg’s conclusions.
 

‘Need to replace the guidelines’

“We probably need to replace the guidelines,” said Eduardo Ramacciotti, MD, PhD, MPH, a professor of vascular surgery at Santa Casa School of Medicine, São Paulo. Dr. Ramacciotti praised the study’s design, the endpoints, and the fact that the design excluded patients at high risk for bleeding complications, particularly those with a fibrinogen level below 200 mg/dL (2 g/L).

But other experts questioned the significance of the COVID-PACT results given that the outcomes did not show that full-dose anticoagulation produced incremental improvement in patient survival.

“We should abandon the thought that intensified anticoagulation should be routine, because it did not overall increase the number of patients discharged from the hospital alive,” commented John W. Eikelboom, MBBS, a professor of hematology and thromboembolism at McMaster University, Hamilton, Ont.

“Preventing venous thrombosis is a good thing, but the money is in saving lives and stopping need for ventilation, and we haven’t been successful doing that with an antithrombotic strategy,” said Dr. Eikelboom. “It is useful to prevent venous thrombosis, but we need to look elsewhere to improve the outcomes of [critically ill] patients with COVID-19.”
 

Reducing thromboembolism is a ‘valid goal’

Dr. Berg took a different view. “It’s a valid goal to try to reduce venous thromboembolism complications,” the major benefit seen in his study, he said. “There is clinical significance to reducing thrombotic events in terms of how people feel, their functional status, and their complications. There are a lot of clinically relevant consequences of thrombosis beyond mortality.”

COVID-PACT ran at 34 U.S. centers from August 2020 to March 2022 but stopped short of its enrollment goal of 750 patients because of waning numbers of patients with COVID-19 admitted to ICUs. In addition to randomly assigning patients within 96 hours of their ICU admission to full-dose anticoagulation or to standard-dose antithrombotic prophylaxis, the study included a second, concurrent randomization to the antiplatelet agent clopidogrel (Plavix) or to no antiplatelet drug. Both randomizations used an open-label design.

The results failed to show a discernable effect from adding clopidogrel on both the primary efficacy and primary safety endpoints, adding to accumulated evidence that treatment with an antiplatelet agent, including aspirin, confers no antithrombotic benefit in patients with COVID-19.

The trial’s participants averaged 61 years old, 68% were obese, 59% had hypertension, and 32% had diabetes. The median time after ICU admission when randomized treatment began was 2.1 days, and researchers followed patients for a median of 13 days, including a median time on anticoagulation of 10.6 days.

The trial design allowed clinicians to use either low molecular weight heparin or unfractionated heparin for anticoagulation, and 82% of patients received low molecular weight heparin as their initial treatment. The prespecified design called for an on-treatment analysis because of an anticipated high crossover rate. During the trial, 34% of patients who started on the prophylactic dose switched to full dose, and 17% had the reverse crossover.
 

95% increased win ratio with full dose

The study’s primary efficacy endpoint used a win-ratio analysis that included seven different adverse outcomes that ranged from death from venous or arterial thrombosis to clinically silent deep vein thrombosis. Treatment with full-dose anticoagulation led to a significant 95% increase in win ratio.

Researchers also applied a more conventional time-to-first-event secondary efficacy analysis, which showed that full-dose anticoagulation cut the incidence of an adverse outcome by a significant 44% relative to prophylactic dosing.

The two study groups showed no difference in all-cause death rates. The efficacy advantage of the full-dose regimen was driven by reduced rates of venous thrombotic events, especially a reduction in clinically evident deep vein thrombotic events.

The primary safety endpoint was the rate of fatal or life-threatening bleeding episodes, and while life-threatening bleeds were numerically more common among the full-dose recipients (four events, compared with one event on prophylaxis dosing) the difference was not significant, and no patients died from a bleeding event.
 

More secondary safety bleeds

The safety difference showed up in a secondary measure of bleeding severity, the rate of GUSTO moderate or severe bleeds. These occurred in 15 of the full-dose recipients, compared with 1 patient on the prophylactic dose.

Dr. Berg highlighted that several prior studies have assessed various anticoagulation regimens in critically ill (ICU-admitted and on respiratory or cardiovascular support) patients with COVID-19. For example, two influential reports published in 2021 by the same team of investigators in the New England Journal of Medicine had sharply divergent results.

One multicenter study, which tested full-dose heparin against prophylactic treatment in more than 1,000 critically ill patients, was stopped prematurely because it had not shown a significant difference between the treatment arms. The second study, in more than 2,000 multicenter patients with COVID-19 who did not require critical-level organ support, showed clear superiority of the full-dose heparin regimen.

Notably, both previous studies used a different primary efficacy endpoint than the COVID-PACT study. The earlier reports both measured efficacy in terms of patients being alive and off organ support by 21 days from randomization.
 

Patients to exclude

Although Dr. Berg stressed the clear positive result, he also cautioned that they should not apply to patients excluded from the study: those with severe coagulopathies, those with severe thrombocytopenia, and patients already maintained on dual antiplatelet therapy. He also cautioned against using the full-dose strategy in elderly patients, because in COVID-PACT, those who developed bleeding complications tended to be older.

Dr. Berg also noted that heparin prophylaxis is a well-established intervention for ICU-admitted patients without COVID-19 for the purpose of preventing venous thromboembolisms without evidence that this approach reduces deaths or organ failure.

But he conceded that “the priority of treatment depends on whether it saves lives, so anticoagulation is probably not as high a priority as other effective treatments” that reduce mortality. “Preventing venous thromboembolism has rarely been shown to have a mortality benefit,” Dr. Berg noted.

COVID-PACT received no direct commercial funding. Dr. Berg has been a consultant to AstraZeneca, Mobility Bio, and Youngene Therapeutics, and he participated in a trial sponsored by Kowa. Dr. Ramacciotti has been a consultant to or speaker on behalf of Aspen, Bayer, Daiichi Sankyo, Mylan, Pfizer, and Sanofi, and he has received research support from Bayer, Esperon, Novartis, and Pfizer. Dr. Eikelboom has received honoraria and research support from Bayer.

A version of this article first appeared on Medscape.com.

BARCELONA – Hospitalized patients in the ICU because of an acute COVID-19 infection had significantly fewer thrombotic events and complications when treated with full-dose anticoagulation, compared with patients who received standard-dose anticoagulation prophylaxis, but full-dose anticoagulation also triggered an excess of moderate and severe bleeding events, randomized trial results show.

The new findings from the COVID-PACT trial in an exclusively U.S.-based cohort of 382 on-treatment patients in the ICU with COVID-19 infection may lead to a change in existing guidelines, which currently recommend standard-dose prophylaxis based on results from prior head-to-head comparisons, such as guidelines posted March 2022 from the American Society of Hematology.

The new findings suggest “full-dose anticoagulation should be considered to prevent thrombotic complications in selected critically ill patients with COVID-19” after weighing an individual patient’s risk for both thrombotic events and bleeding, David D. Berg, MD, said at the annual congress of the European Society of Cardiology. Simultaneous with his report at the congress, the results also appeared online in the journal Circulation.

“What the results tell us is that full-dose anticoagulation in critically ill patients with COVID-19 is highly effective for reducing thrombotic complications,” said Dr. Berg, a cardiologist and critical care physician at Brigham and Women’s Hospital, Boston.

The report’s designated discussant agreed with Dr. Berg’s conclusions.
 

‘Need to replace the guidelines’

“We probably need to replace the guidelines,” said Eduardo Ramacciotti, MD, PhD, MPH, a professor of vascular surgery at Santa Casa School of Medicine, São Paulo. Dr. Ramacciotti praised the study’s design, the endpoints, and the fact that the design excluded patients at high risk for bleeding complications, particularly those with a fibrinogen level below 200 mg/dL (2 g/L).

But other experts questioned the significance of the COVID-PACT results given that the outcomes did not show that full-dose anticoagulation produced incremental improvement in patient survival.

“We should abandon the thought that intensified anticoagulation should be routine, because it did not overall increase the number of patients discharged from the hospital alive,” commented John W. Eikelboom, MBBS, a professor of hematology and thromboembolism at McMaster University, Hamilton, Ont.

“Preventing venous thrombosis is a good thing, but the money is in saving lives and stopping need for ventilation, and we haven’t been successful doing that with an antithrombotic strategy,” said Dr. Eikelboom. “It is useful to prevent venous thrombosis, but we need to look elsewhere to improve the outcomes of [critically ill] patients with COVID-19.”
 

Reducing thromboembolism is a ‘valid goal’

Dr. Berg took a different view. “It’s a valid goal to try to reduce venous thromboembolism complications,” the major benefit seen in his study, he said. “There is clinical significance to reducing thrombotic events in terms of how people feel, their functional status, and their complications. There are a lot of clinically relevant consequences of thrombosis beyond mortality.”

COVID-PACT ran at 34 U.S. centers from August 2020 to March 2022 but stopped short of its enrollment goal of 750 patients because of waning numbers of patients with COVID-19 admitted to ICUs. In addition to randomly assigning patients within 96 hours of their ICU admission to full-dose anticoagulation or to standard-dose antithrombotic prophylaxis, the study included a second, concurrent randomization to the antiplatelet agent clopidogrel (Plavix) or to no antiplatelet drug. Both randomizations used an open-label design.

The results failed to show a discernable effect from adding clopidogrel on both the primary efficacy and primary safety endpoints, adding to accumulated evidence that treatment with an antiplatelet agent, including aspirin, confers no antithrombotic benefit in patients with COVID-19.

The trial’s participants averaged 61 years old, 68% were obese, 59% had hypertension, and 32% had diabetes. The median time after ICU admission when randomized treatment began was 2.1 days, and researchers followed patients for a median of 13 days, including a median time on anticoagulation of 10.6 days.

The trial design allowed clinicians to use either low molecular weight heparin or unfractionated heparin for anticoagulation, and 82% of patients received low molecular weight heparin as their initial treatment. The prespecified design called for an on-treatment analysis because of an anticipated high crossover rate. During the trial, 34% of patients who started on the prophylactic dose switched to full dose, and 17% had the reverse crossover.
 

95% increased win ratio with full dose

The study’s primary efficacy endpoint used a win-ratio analysis that included seven different adverse outcomes that ranged from death from venous or arterial thrombosis to clinically silent deep vein thrombosis. Treatment with full-dose anticoagulation led to a significant 95% increase in win ratio.

Researchers also applied a more conventional time-to-first-event secondary efficacy analysis, which showed that full-dose anticoagulation cut the incidence of an adverse outcome by a significant 44% relative to prophylactic dosing.

The two study groups showed no difference in all-cause death rates. The efficacy advantage of the full-dose regimen was driven by reduced rates of venous thrombotic events, especially a reduction in clinically evident deep vein thrombotic events.

The primary safety endpoint was the rate of fatal or life-threatening bleeding episodes, and while life-threatening bleeds were numerically more common among the full-dose recipients (four events, compared with one event on prophylaxis dosing) the difference was not significant, and no patients died from a bleeding event.
 

More secondary safety bleeds

The safety difference showed up in a secondary measure of bleeding severity, the rate of GUSTO moderate or severe bleeds. These occurred in 15 of the full-dose recipients, compared with 1 patient on the prophylactic dose.

Dr. Berg highlighted that several prior studies have assessed various anticoagulation regimens in critically ill (ICU-admitted and on respiratory or cardiovascular support) patients with COVID-19. For example, two influential reports published in 2021 by the same team of investigators in the New England Journal of Medicine had sharply divergent results.

One multicenter study, which tested full-dose heparin against prophylactic treatment in more than 1,000 critically ill patients, was stopped prematurely because it had not shown a significant difference between the treatment arms. The second study, in more than 2,000 multicenter patients with COVID-19 who did not require critical-level organ support, showed clear superiority of the full-dose heparin regimen.

Notably, both previous studies used a different primary efficacy endpoint than the COVID-PACT study. The earlier reports both measured efficacy in terms of patients being alive and off organ support by 21 days from randomization.
 

Patients to exclude

Although Dr. Berg stressed the clear positive result, he also cautioned that they should not apply to patients excluded from the study: those with severe coagulopathies, those with severe thrombocytopenia, and patients already maintained on dual antiplatelet therapy. He also cautioned against using the full-dose strategy in elderly patients, because in COVID-PACT, those who developed bleeding complications tended to be older.

Dr. Berg also noted that heparin prophylaxis is a well-established intervention for ICU-admitted patients without COVID-19 for the purpose of preventing venous thromboembolisms without evidence that this approach reduces deaths or organ failure.

But he conceded that “the priority of treatment depends on whether it saves lives, so anticoagulation is probably not as high a priority as other effective treatments” that reduce mortality. “Preventing venous thromboembolism has rarely been shown to have a mortality benefit,” Dr. Berg noted.

COVID-PACT received no direct commercial funding. Dr. Berg has been a consultant to AstraZeneca, Mobility Bio, and Youngene Therapeutics, and he participated in a trial sponsored by Kowa. Dr. Ramacciotti has been a consultant to or speaker on behalf of Aspen, Bayer, Daiichi Sankyo, Mylan, Pfizer, and Sanofi, and he has received research support from Bayer, Esperon, Novartis, and Pfizer. Dr. Eikelboom has received honoraria and research support from Bayer.

A version of this article first appeared on Medscape.com.

Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.

The statement was published in the Journal of Clinical Lipidology.

Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”

“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”

“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).

However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”

There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.

“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”

“That’s better than any drug we’ve got on the market.”

He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.

The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.

Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”

“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.

Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.

Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.

This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.

Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”

The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.

It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”

This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.

This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.

Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.

Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.

However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.

Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.

Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.

In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).

Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”

Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).

In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.

Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”

These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”

Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”

No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.

A version of this article first appeared on Medscape.com.

Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.

The statement was published in the Journal of Clinical Lipidology.

Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”

“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”

“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).

However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”

There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.

“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”

“That’s better than any drug we’ve got on the market.”

He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.

The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.

Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”

“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.

Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.

Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.

This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.

Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”

The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.

It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”

This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.

This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.

Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.

Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.

However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.

Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.

Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.

In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).

Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”

Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).

In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.

Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”

These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”

Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”

No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.

A version of this article first appeared on Medscape.com.

Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.

The statement was published in the Journal of Clinical Lipidology.

Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”

“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”

“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).

However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”

There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.

“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”

“That’s better than any drug we’ve got on the market.”

He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.

The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.

Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”

“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.

Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.

Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.

This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.

Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”

The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.

It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”

This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.

This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.

Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.

Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.

However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.

Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.

Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.

In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).

Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”

Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).

In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.

Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”

These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”

Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”

No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.

A version of this article first appeared on Medscape.com.

A panel of infectious disease experts shared their take recently on the importance of the newly approved bivalent COVID-19 vaccines, why authorization without human data is not for them a cause for alarm, and what they are most optimistic about at this stage of the pandemic.

“I’m very encouraged by this new development,” Kathryn M. Edwards, MD, said during a media briefing sponsored by the Infectious Diseases Society of America (IDSA).

It makes sense to develop a vaccine that targets both the original SARS-CoV-2 strain and Omicron BA.4 and BA.5, she said. “It does seem that if you have a circulating strain BA.4 and BA.5, hitting it with the appropriate vaccine targeted for that is most immunogenic, certainly. We will hopefully see that in terms of effectiveness.”

Changing the vaccines at this point is appropriate, Walter A. Orenstein, MD, said. “One of our challenges is that this virus mutates. Our immune response is focused on an area of the virus that can change and be evaded,” said Dr. Orenstein, professor and associate director of the Emory Vaccine Center at Emory University, Atlanta.

“This is different than measles or polio,” he said. “But for influenza and now with SARS-CoV-2 ... we have to update our vaccines, because the virus changes.”
 

Man versus mouse

Dr. Edwards addressed the controversy over a lack of human data specific to these next-generation Pfizer/BioNTech and Moderna vaccines. “I do not want people to be unhappy or worried that the bivalent vaccine will act in a different way than the ones that we have been administering for the past 2 years.”

The Food and Drug Administration emergency use authorization may have relied primarily on animal studies, she said, but mice given a vaccine specific to BA.4 and BA.5 “have a much more robust immune response,” compared with those given a BA.1 vaccine.

Also, “over and over and over again we have seen with these SARS-CoV-2 vaccines that the mouse responses mirror the human responses,” said Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program at Vanderbilt University, Nashville, Tenn., and an IDSA fellow.

“Human data will be coming very soon to look at the immunogenicity,” she said.
 

A ‘glass half full’ perspective

When asked what they are most optimistic about at this point in the COVID-19 pandemic, Dr. Orenstein said, “I’m really positive in the sense that the vaccines we have are already very effective against severe disease, death, and hospitalization. I feel really good about that. And we have great tools.

“The bottom line for me is, I want to get it myself,” he said regarding the bivalent vaccine.

“There are a lot of things to be happy with,” Dr. Edwards said. “I’m kind of a glass-half-full kind of person.”

Dr. Edwards is confident that the surveillance systems now in place can accurately detect major changes in the virus, including new variants. She is also optimistic about the mRNA technology that allows rapid updates to COVID-19 vaccines.

Furthermore, “I’m happy that we’re beginning to open up – that we can go do different things that we have done in the past and feel much more comfortable,” she said.
 

More motivational messaging needed

Now is also a good time to renew efforts to get people vaccinated.

“We invested a lot into developing these vaccines, but I think we also need to invest in what I call ‘implementation science research,’ ” Dr. Orenstein said, the goal being to convince people to get vaccinated.

He pointed out that it’s vaccinations, not vaccines, that saves lives. “Vaccine doses that remain in the vial are 0% effective.

“When I was director of the United States’ immunization program at the CDC,” Dr. Orenstein said, “my director of communications used to say that you need the right message delivered by the right messenger through the right communications channel.”

Dr. Edwards agreed that listening to people’s concerns and respecting their questions are important. “We also need to make sure that we use the proper messenger, just as Walt said. Maybe the proper messenger isn’t an old gray-haired lady,” she said, referring to herself, “but it’s someone that lives in your community or is your primary care doctor who has taken care of you or your children for many years.”

Research on how to better motivate people to get vaccinated is warranted, Dr. Edwards said, as well as on “how to make sure that this is really a medical issue and not a political issue. That’s been a really big problem.”

A version of this article first appeared on Medscape.com.

A panel of infectious disease experts shared their take recently on the importance of the newly approved bivalent COVID-19 vaccines, why authorization without human data is not for them a cause for alarm, and what they are most optimistic about at this stage of the pandemic.

“I’m very encouraged by this new development,” Kathryn M. Edwards, MD, said during a media briefing sponsored by the Infectious Diseases Society of America (IDSA).

It makes sense to develop a vaccine that targets both the original SARS-CoV-2 strain and Omicron BA.4 and BA.5, she said. “It does seem that if you have a circulating strain BA.4 and BA.5, hitting it with the appropriate vaccine targeted for that is most immunogenic, certainly. We will hopefully see that in terms of effectiveness.”

Changing the vaccines at this point is appropriate, Walter A. Orenstein, MD, said. “One of our challenges is that this virus mutates. Our immune response is focused on an area of the virus that can change and be evaded,” said Dr. Orenstein, professor and associate director of the Emory Vaccine Center at Emory University, Atlanta.

“This is different than measles or polio,” he said. “But for influenza and now with SARS-CoV-2 ... we have to update our vaccines, because the virus changes.”
 

Man versus mouse

Dr. Edwards addressed the controversy over a lack of human data specific to these next-generation Pfizer/BioNTech and Moderna vaccines. “I do not want people to be unhappy or worried that the bivalent vaccine will act in a different way than the ones that we have been administering for the past 2 years.”

The Food and Drug Administration emergency use authorization may have relied primarily on animal studies, she said, but mice given a vaccine specific to BA.4 and BA.5 “have a much more robust immune response,” compared with those given a BA.1 vaccine.

Also, “over and over and over again we have seen with these SARS-CoV-2 vaccines that the mouse responses mirror the human responses,” said Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program at Vanderbilt University, Nashville, Tenn., and an IDSA fellow.

“Human data will be coming very soon to look at the immunogenicity,” she said.
 

A ‘glass half full’ perspective

When asked what they are most optimistic about at this point in the COVID-19 pandemic, Dr. Orenstein said, “I’m really positive in the sense that the vaccines we have are already very effective against severe disease, death, and hospitalization. I feel really good about that. And we have great tools.

“The bottom line for me is, I want to get it myself,” he said regarding the bivalent vaccine.

“There are a lot of things to be happy with,” Dr. Edwards said. “I’m kind of a glass-half-full kind of person.”

Dr. Edwards is confident that the surveillance systems now in place can accurately detect major changes in the virus, including new variants. She is also optimistic about the mRNA technology that allows rapid updates to COVID-19 vaccines.

Furthermore, “I’m happy that we’re beginning to open up – that we can go do different things that we have done in the past and feel much more comfortable,” she said.
 

More motivational messaging needed

Now is also a good time to renew efforts to get people vaccinated.

“We invested a lot into developing these vaccines, but I think we also need to invest in what I call ‘implementation science research,’ ” Dr. Orenstein said, the goal being to convince people to get vaccinated.

He pointed out that it’s vaccinations, not vaccines, that saves lives. “Vaccine doses that remain in the vial are 0% effective.

“When I was director of the United States’ immunization program at the CDC,” Dr. Orenstein said, “my director of communications used to say that you need the right message delivered by the right messenger through the right communications channel.”

Dr. Edwards agreed that listening to people’s concerns and respecting their questions are important. “We also need to make sure that we use the proper messenger, just as Walt said. Maybe the proper messenger isn’t an old gray-haired lady,” she said, referring to herself, “but it’s someone that lives in your community or is your primary care doctor who has taken care of you or your children for many years.”

Research on how to better motivate people to get vaccinated is warranted, Dr. Edwards said, as well as on “how to make sure that this is really a medical issue and not a political issue. That’s been a really big problem.”

A version of this article first appeared on Medscape.com.

A panel of infectious disease experts shared their take recently on the importance of the newly approved bivalent COVID-19 vaccines, why authorization without human data is not for them a cause for alarm, and what they are most optimistic about at this stage of the pandemic.

“I’m very encouraged by this new development,” Kathryn M. Edwards, MD, said during a media briefing sponsored by the Infectious Diseases Society of America (IDSA).

It makes sense to develop a vaccine that targets both the original SARS-CoV-2 strain and Omicron BA.4 and BA.5, she said. “It does seem that if you have a circulating strain BA.4 and BA.5, hitting it with the appropriate vaccine targeted for that is most immunogenic, certainly. We will hopefully see that in terms of effectiveness.”

Changing the vaccines at this point is appropriate, Walter A. Orenstein, MD, said. “One of our challenges is that this virus mutates. Our immune response is focused on an area of the virus that can change and be evaded,” said Dr. Orenstein, professor and associate director of the Emory Vaccine Center at Emory University, Atlanta.

“This is different than measles or polio,” he said. “But for influenza and now with SARS-CoV-2 ... we have to update our vaccines, because the virus changes.”
 

Man versus mouse

Dr. Edwards addressed the controversy over a lack of human data specific to these next-generation Pfizer/BioNTech and Moderna vaccines. “I do not want people to be unhappy or worried that the bivalent vaccine will act in a different way than the ones that we have been administering for the past 2 years.”

The Food and Drug Administration emergency use authorization may have relied primarily on animal studies, she said, but mice given a vaccine specific to BA.4 and BA.5 “have a much more robust immune response,” compared with those given a BA.1 vaccine.

Also, “over and over and over again we have seen with these SARS-CoV-2 vaccines that the mouse responses mirror the human responses,” said Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program at Vanderbilt University, Nashville, Tenn., and an IDSA fellow.

“Human data will be coming very soon to look at the immunogenicity,” she said.
 

A ‘glass half full’ perspective

When asked what they are most optimistic about at this point in the COVID-19 pandemic, Dr. Orenstein said, “I’m really positive in the sense that the vaccines we have are already very effective against severe disease, death, and hospitalization. I feel really good about that. And we have great tools.

“The bottom line for me is, I want to get it myself,” he said regarding the bivalent vaccine.

“There are a lot of things to be happy with,” Dr. Edwards said. “I’m kind of a glass-half-full kind of person.”

Dr. Edwards is confident that the surveillance systems now in place can accurately detect major changes in the virus, including new variants. She is also optimistic about the mRNA technology that allows rapid updates to COVID-19 vaccines.

Furthermore, “I’m happy that we’re beginning to open up – that we can go do different things that we have done in the past and feel much more comfortable,” she said.
 

More motivational messaging needed

Now is also a good time to renew efforts to get people vaccinated.

“We invested a lot into developing these vaccines, but I think we also need to invest in what I call ‘implementation science research,’ ” Dr. Orenstein said, the goal being to convince people to get vaccinated.

He pointed out that it’s vaccinations, not vaccines, that saves lives. “Vaccine doses that remain in the vial are 0% effective.

“When I was director of the United States’ immunization program at the CDC,” Dr. Orenstein said, “my director of communications used to say that you need the right message delivered by the right messenger through the right communications channel.”

Dr. Edwards agreed that listening to people’s concerns and respecting their questions are important. “We also need to make sure that we use the proper messenger, just as Walt said. Maybe the proper messenger isn’t an old gray-haired lady,” she said, referring to herself, “but it’s someone that lives in your community or is your primary care doctor who has taken care of you or your children for many years.”

Research on how to better motivate people to get vaccinated is warranted, Dr. Edwards said, as well as on “how to make sure that this is really a medical issue and not a political issue. That’s been a really big problem.”

A version of this article first appeared on Medscape.com.

A trip to the cath lab for possible revascularization after a positive stress test, compared with a wait-and-see approach backed by optimal medications, did not improve 5-year survival for patients with advanced chronic kidney disease (CKD) in the ISCHEMIA-CKD trial’s extension study, ISCHEMIA-CKD EXTEND.

The long-term results, from the same 777 patients followed for an average of 2.2 years in the main trial, are consistent with the overall findings of no survival advantage with an initially invasive strategy, compared with one that is initially conservative. The finding applies to patients like those in the trial who had moderate to severe ischemia at stress testing and whose CKD put them in an especially high-risk and little-studied coronary artery disease (CAD) category.

Indeed, in a reflection of that high-risk status, 5-year all-cause mortality reached about 40% and cardiovascular (CV) mortality approached 30%, with no significant differences between patients in the invasive- and conservative-strategy groups.

MDedge News/Mitchel L. Zoler

Those numbers arguably put CKD’s effect on CAD survival in about the same league as an ejection fraction (EF) of 35% or less. For context, all-cause mortality over 3-4 years was about 32% in the REVIVED-BCIS2 trial of such patients with ischemic reduced-EF cardiomyopathy, whether or not they were revascularized, observed Sripal Bangalore, MD, MHA.

Yet in ISCHEMIA-CKD EXTEND, “you’re seeing in a group of patients, with largely preserved EF but advanced CKD, a mortality rate close to 40% at 5 years,” said Dr. Bangalore of New York University.

Although the study doesn’t show benefit from the initially invasive approach in CKD patients with stable CAD, for those with acute coronary syndromes (ACS), it seems to suggest that “at least the invasive strategy is safe,” Dr. Bangalore said during a press conference preceding his presentation of the study Aug. 29 at the annual congress of the European Society of Cardiology, held in Barcelona.

REVIVED-BCIS2 was also presented at the ESC sessions on Aug. 27, as reported by this news organization.

ISCHEMIA-CKD EXTEND “is a large trial and a very well-done trial. The results are robust, and they should influence clinical practice,” Deepak L. Bhatt, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center, Boston, said as the invited discussant after Dr. Bangalore’s presentation.

“The main message here, really, is don’t just go looking for ischemia, at least with the modalities used in this trial, in your CKD patients as a routine practice, and then try to stomp out that ischemia with revascularization,” Dr. Bhatt said. “The right thing to do in these high-risk patients is to focus on lifestyle modification and intensive medical therapy.”

A caveat, he said, is that the trial’s results don’t apply to the types of patients excluded from it, including those with recent ACS and those who are highly symptomatic or have an EF of less than 35%.

“Those CKD patients likely benefit from an invasive strategy with anatomically appropriate revascularization,” whether percutaneous coronary intervention (PCI) or coronary bypass surgery, Dr. Bhatt said.

At a median follow-up of 5 years in the extension study, the rates of death from any cause were 40.6% for patients in the invasive-strategy group and 37.4% for those in the conservative-strategy group. That yielded a hazard ratio of 1.12 (95% confidence interval, 0.89-1.41; P = .32) after adjustment for age, sex, diabetes status, EF, dialysis status, and – for patients not on dialysis – baseline estimated glomerular filtration rate.

The rates of CV death were 29% for patients managed invasively and 27% for those initially managed conservatively, for a similarly adjusted HR of 1.04 (95% CI, 0.80-1.37; P = .75).

In subgroup analyses, Dr. Bangalore reported, there were no significant differences in all-cause or CV mortality by diabetes status, by severity of baseline ischemia, or by whether the patient had recently experienced new or more frequent angina at study entry, was on guideline-directed medical therapy at baseline, or was on dialysis.

Among the contributions of ISCHEMIA-CKD and its 5-year extension study, Dr. Bangalore told this news organization, is that the relative safety of revascularization they showed may help to counter “renalism,” that is, the aversion to invasive intervention in patients with advanced CKD in clinical practice.

For example, if a patient with advanced CKD presents with an acute myocardial infarction, “people are hesitant to take them to the cath lab,” Dr. Bangalore said. But “if you follow protocols, if you follow strategies to minimize the risk, you can safely go ahead and do it.”

But in patients with stable CAD, as the ISCHEMIA-CKD studies show, “routinely revascularizing them may not have significant benefits.”

ISCHEMIC-CKD and its extension study were funded by the National Heart, Lung, and Blood Institute. Dr. Bangalore discloses receiving research grants from NHLBI and serving as a consultant for Abbott Vascular, Biotronik, Boston Scientific, Amgen, Pfizer, Merck, and Reata. Dr. Bhatt has disclosed grants and/or personal fees from many companies; personal fees from WebMD and other publications or organizations; and having other relationships with Medscape Cardiology and other publications or organizations.

A version of this article first appeared on Medscape.com.

A trip to the cath lab for possible revascularization after a positive stress test, compared with a wait-and-see approach backed by optimal medications, did not improve 5-year survival for patients with advanced chronic kidney disease (CKD) in the ISCHEMIA-CKD trial’s extension study, ISCHEMIA-CKD EXTEND.

The long-term results, from the same 777 patients followed for an average of 2.2 years in the main trial, are consistent with the overall findings of no survival advantage with an initially invasive strategy, compared with one that is initially conservative. The finding applies to patients like those in the trial who had moderate to severe ischemia at stress testing and whose CKD put them in an especially high-risk and little-studied coronary artery disease (CAD) category.

Indeed, in a reflection of that high-risk status, 5-year all-cause mortality reached about 40% and cardiovascular (CV) mortality approached 30%, with no significant differences between patients in the invasive- and conservative-strategy groups.

MDedge News/Mitchel L. Zoler

Those numbers arguably put CKD’s effect on CAD survival in about the same league as an ejection fraction (EF) of 35% or less. For context, all-cause mortality over 3-4 years was about 32% in the REVIVED-BCIS2 trial of such patients with ischemic reduced-EF cardiomyopathy, whether or not they were revascularized, observed Sripal Bangalore, MD, MHA.

Yet in ISCHEMIA-CKD EXTEND, “you’re seeing in a group of patients, with largely preserved EF but advanced CKD, a mortality rate close to 40% at 5 years,” said Dr. Bangalore of New York University.

Although the study doesn’t show benefit from the initially invasive approach in CKD patients with stable CAD, for those with acute coronary syndromes (ACS), it seems to suggest that “at least the invasive strategy is safe,” Dr. Bangalore said during a press conference preceding his presentation of the study Aug. 29 at the annual congress of the European Society of Cardiology, held in Barcelona.

REVIVED-BCIS2 was also presented at the ESC sessions on Aug. 27, as reported by this news organization.

ISCHEMIA-CKD EXTEND “is a large trial and a very well-done trial. The results are robust, and they should influence clinical practice,” Deepak L. Bhatt, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center, Boston, said as the invited discussant after Dr. Bangalore’s presentation.

“The main message here, really, is don’t just go looking for ischemia, at least with the modalities used in this trial, in your CKD patients as a routine practice, and then try to stomp out that ischemia with revascularization,” Dr. Bhatt said. “The right thing to do in these high-risk patients is to focus on lifestyle modification and intensive medical therapy.”

A caveat, he said, is that the trial’s results don’t apply to the types of patients excluded from it, including those with recent ACS and those who are highly symptomatic or have an EF of less than 35%.

“Those CKD patients likely benefit from an invasive strategy with anatomically appropriate revascularization,” whether percutaneous coronary intervention (PCI) or coronary bypass surgery, Dr. Bhatt said.

At a median follow-up of 5 years in the extension study, the rates of death from any cause were 40.6% for patients in the invasive-strategy group and 37.4% for those in the conservative-strategy group. That yielded a hazard ratio of 1.12 (95% confidence interval, 0.89-1.41; P = .32) after adjustment for age, sex, diabetes status, EF, dialysis status, and – for patients not on dialysis – baseline estimated glomerular filtration rate.

The rates of CV death were 29% for patients managed invasively and 27% for those initially managed conservatively, for a similarly adjusted HR of 1.04 (95% CI, 0.80-1.37; P = .75).

In subgroup analyses, Dr. Bangalore reported, there were no significant differences in all-cause or CV mortality by diabetes status, by severity of baseline ischemia, or by whether the patient had recently experienced new or more frequent angina at study entry, was on guideline-directed medical therapy at baseline, or was on dialysis.

Among the contributions of ISCHEMIA-CKD and its 5-year extension study, Dr. Bangalore told this news organization, is that the relative safety of revascularization they showed may help to counter “renalism,” that is, the aversion to invasive intervention in patients with advanced CKD in clinical practice.

For example, if a patient with advanced CKD presents with an acute myocardial infarction, “people are hesitant to take them to the cath lab,” Dr. Bangalore said. But “if you follow protocols, if you follow strategies to minimize the risk, you can safely go ahead and do it.”

But in patients with stable CAD, as the ISCHEMIA-CKD studies show, “routinely revascularizing them may not have significant benefits.”

ISCHEMIC-CKD and its extension study were funded by the National Heart, Lung, and Blood Institute. Dr. Bangalore discloses receiving research grants from NHLBI and serving as a consultant for Abbott Vascular, Biotronik, Boston Scientific, Amgen, Pfizer, Merck, and Reata. Dr. Bhatt has disclosed grants and/or personal fees from many companies; personal fees from WebMD and other publications or organizations; and having other relationships with Medscape Cardiology and other publications or organizations.

A version of this article first appeared on Medscape.com.

A trip to the cath lab for possible revascularization after a positive stress test, compared with a wait-and-see approach backed by optimal medications, did not improve 5-year survival for patients with advanced chronic kidney disease (CKD) in the ISCHEMIA-CKD trial’s extension study, ISCHEMIA-CKD EXTEND.

The long-term results, from the same 777 patients followed for an average of 2.2 years in the main trial, are consistent with the overall findings of no survival advantage with an initially invasive strategy, compared with one that is initially conservative. The finding applies to patients like those in the trial who had moderate to severe ischemia at stress testing and whose CKD put them in an especially high-risk and little-studied coronary artery disease (CAD) category.

Indeed, in a reflection of that high-risk status, 5-year all-cause mortality reached about 40% and cardiovascular (CV) mortality approached 30%, with no significant differences between patients in the invasive- and conservative-strategy groups.

MDedge News/Mitchel L. Zoler

Those numbers arguably put CKD’s effect on CAD survival in about the same league as an ejection fraction (EF) of 35% or less. For context, all-cause mortality over 3-4 years was about 32% in the REVIVED-BCIS2 trial of such patients with ischemic reduced-EF cardiomyopathy, whether or not they were revascularized, observed Sripal Bangalore, MD, MHA.

Yet in ISCHEMIA-CKD EXTEND, “you’re seeing in a group of patients, with largely preserved EF but advanced CKD, a mortality rate close to 40% at 5 years,” said Dr. Bangalore of New York University.

Although the study doesn’t show benefit from the initially invasive approach in CKD patients with stable CAD, for those with acute coronary syndromes (ACS), it seems to suggest that “at least the invasive strategy is safe,” Dr. Bangalore said during a press conference preceding his presentation of the study Aug. 29 at the annual congress of the European Society of Cardiology, held in Barcelona.

REVIVED-BCIS2 was also presented at the ESC sessions on Aug. 27, as reported by this news organization.

ISCHEMIA-CKD EXTEND “is a large trial and a very well-done trial. The results are robust, and they should influence clinical practice,” Deepak L. Bhatt, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center, Boston, said as the invited discussant after Dr. Bangalore’s presentation.

“The main message here, really, is don’t just go looking for ischemia, at least with the modalities used in this trial, in your CKD patients as a routine practice, and then try to stomp out that ischemia with revascularization,” Dr. Bhatt said. “The right thing to do in these high-risk patients is to focus on lifestyle modification and intensive medical therapy.”

A caveat, he said, is that the trial’s results don’t apply to the types of patients excluded from it, including those with recent ACS and those who are highly symptomatic or have an EF of less than 35%.

“Those CKD patients likely benefit from an invasive strategy with anatomically appropriate revascularization,” whether percutaneous coronary intervention (PCI) or coronary bypass surgery, Dr. Bhatt said.

At a median follow-up of 5 years in the extension study, the rates of death from any cause were 40.6% for patients in the invasive-strategy group and 37.4% for those in the conservative-strategy group. That yielded a hazard ratio of 1.12 (95% confidence interval, 0.89-1.41; P = .32) after adjustment for age, sex, diabetes status, EF, dialysis status, and – for patients not on dialysis – baseline estimated glomerular filtration rate.

The rates of CV death were 29% for patients managed invasively and 27% for those initially managed conservatively, for a similarly adjusted HR of 1.04 (95% CI, 0.80-1.37; P = .75).

In subgroup analyses, Dr. Bangalore reported, there were no significant differences in all-cause or CV mortality by diabetes status, by severity of baseline ischemia, or by whether the patient had recently experienced new or more frequent angina at study entry, was on guideline-directed medical therapy at baseline, or was on dialysis.

Among the contributions of ISCHEMIA-CKD and its 5-year extension study, Dr. Bangalore told this news organization, is that the relative safety of revascularization they showed may help to counter “renalism,” that is, the aversion to invasive intervention in patients with advanced CKD in clinical practice.

For example, if a patient with advanced CKD presents with an acute myocardial infarction, “people are hesitant to take them to the cath lab,” Dr. Bangalore said. But “if you follow protocols, if you follow strategies to minimize the risk, you can safely go ahead and do it.”

But in patients with stable CAD, as the ISCHEMIA-CKD studies show, “routinely revascularizing them may not have significant benefits.”

ISCHEMIC-CKD and its extension study were funded by the National Heart, Lung, and Blood Institute. Dr. Bangalore discloses receiving research grants from NHLBI and serving as a consultant for Abbott Vascular, Biotronik, Boston Scientific, Amgen, Pfizer, Merck, and Reata. Dr. Bhatt has disclosed grants and/or personal fees from many companies; personal fees from WebMD and other publications or organizations; and having other relationships with Medscape Cardiology and other publications or organizations.

A version of this article first appeared on Medscape.com.

The American College of Cardiology/American Heart Association have issued a set of data standards for chest pain and acute myocardial infarction to accompany the 2021 guidelines for evaluation and diagnosis of chest pain.

In October 2021, the AHA/ACC issued a joint clinical practice guideline encouraging clinicians to use standardized risk assessments, clinical pathways, and tools to evaluate and communicate with patients who present with chest pain, as reported by this news organization.

The writing group underscored the need to reach a consensus for the definitions of chest pain. The new document standardizes related data elements for consistent reporting on chest pain syndromes.

“This is an appendix to the guidelines and a planned effort to try to harmonize and bring uniformity to the language applied,” writing committee chair H.V. “Skip” Anderson, MD, with UT Health Science Center, Houston, told this news organization.

“You want heart attack to mean the same thing in Miami Beach as in Western Pennsylvania, as in Oregon and Washington and every place in between,” Dr. Anderson explained. “You want everybody to be using the same language, so that’s what these data standards are meant to do.”

In the document, data elements are grouped into three broad categories: chest pain, myocardial injury, and MI.

“We deliberately followed the plans contained in the new guideline and focused on potentially serious cardiovascular causes of chest pain as might be encountered in emergency departments,” the writing group notes in the document.

The terms “typical” and “atypical” as descriptors of chest pain or anginal syndromes are not used in the new document, in line with the 2021 guidance to abandon these terms.

Instead, the new document divides chest pain syndromes into three categories: “cardiac,” “possible cardiac,” and “noncardiac” – again, in keeping with the chest pain guideline.

The document also includes data elements for risk stratification scoring according to several common risk scoring algorithms and for procedure-related myocardial injury and procedure-related MI.

Each year, chest pain sends more than 7 million adults to the emergency department in the United States. Although noncardiac causes of chest pain make up a large majority of these cases, there are several life-threatening causes of chest pain that must be identified and treated promptly.

Distinguishing between serious and nonserious causes of chest pain is an urgent imperative, the writing group says.

Overall, they say this new clinical lexicon and set of data standards should be “broadly applicable” in various settings, including clinical trials and observational studies, patient care, electronic health records (EHRs), quality and performance improvement initiatives, registries, and public reporting programs.

The 2022 ACC/AHA Key Data Elements and Definitions for Chest Pain and Acute Myocardial Infarction was simultaneously published online in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.

It was developed in collaboration with the American College of Emergency Physicians and the Society for Cardiac Angiography and Interventions and endorsed by the Society for Academic Emergency Medicine.

Dr. Anderson noted that “almost all of the guidelines that come out now, certainly in the last few years, have been followed after a certain interval by a set of data standards applicable to the guidelines.”

“It would be really great if it could actually be attached as an appendix, but the nature of the development of these things is such that there will always be a bit of a time lag between the writing group that develops the guidelines and the work group that develops the data standards; you can’t really have them working in parallel at the same time,” Dr. Anderson said in an interview.

This research had no commercial funding. The authors have no relevant disclosures.

A version of this article first appeared on Medscape.com.

The American College of Cardiology/American Heart Association have issued a set of data standards for chest pain and acute myocardial infarction to accompany the 2021 guidelines for evaluation and diagnosis of chest pain.

In October 2021, the AHA/ACC issued a joint clinical practice guideline encouraging clinicians to use standardized risk assessments, clinical pathways, and tools to evaluate and communicate with patients who present with chest pain, as reported by this news organization.

The writing group underscored the need to reach a consensus for the definitions of chest pain. The new document standardizes related data elements for consistent reporting on chest pain syndromes.

“This is an appendix to the guidelines and a planned effort to try to harmonize and bring uniformity to the language applied,” writing committee chair H.V. “Skip” Anderson, MD, with UT Health Science Center, Houston, told this news organization.

“You want heart attack to mean the same thing in Miami Beach as in Western Pennsylvania, as in Oregon and Washington and every place in between,” Dr. Anderson explained. “You want everybody to be using the same language, so that’s what these data standards are meant to do.”

In the document, data elements are grouped into three broad categories: chest pain, myocardial injury, and MI.

“We deliberately followed the plans contained in the new guideline and focused on potentially serious cardiovascular causes of chest pain as might be encountered in emergency departments,” the writing group notes in the document.

The terms “typical” and “atypical” as descriptors of chest pain or anginal syndromes are not used in the new document, in line with the 2021 guidance to abandon these terms.

Instead, the new document divides chest pain syndromes into three categories: “cardiac,” “possible cardiac,” and “noncardiac” – again, in keeping with the chest pain guideline.

The document also includes data elements for risk stratification scoring according to several common risk scoring algorithms and for procedure-related myocardial injury and procedure-related MI.

Each year, chest pain sends more than 7 million adults to the emergency department in the United States. Although noncardiac causes of chest pain make up a large majority of these cases, there are several life-threatening causes of chest pain that must be identified and treated promptly.

Distinguishing between serious and nonserious causes of chest pain is an urgent imperative, the writing group says.

Overall, they say this new clinical lexicon and set of data standards should be “broadly applicable” in various settings, including clinical trials and observational studies, patient care, electronic health records (EHRs), quality and performance improvement initiatives, registries, and public reporting programs.

The 2022 ACC/AHA Key Data Elements and Definitions for Chest Pain and Acute Myocardial Infarction was simultaneously published online in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.

It was developed in collaboration with the American College of Emergency Physicians and the Society for Cardiac Angiography and Interventions and endorsed by the Society for Academic Emergency Medicine.

Dr. Anderson noted that “almost all of the guidelines that come out now, certainly in the last few years, have been followed after a certain interval by a set of data standards applicable to the guidelines.”

“It would be really great if it could actually be attached as an appendix, but the nature of the development of these things is such that there will always be a bit of a time lag between the writing group that develops the guidelines and the work group that develops the data standards; you can’t really have them working in parallel at the same time,” Dr. Anderson said in an interview.

This research had no commercial funding. The authors have no relevant disclosures.

A version of this article first appeared on Medscape.com.

The American College of Cardiology/American Heart Association have issued a set of data standards for chest pain and acute myocardial infarction to accompany the 2021 guidelines for evaluation and diagnosis of chest pain.

In October 2021, the AHA/ACC issued a joint clinical practice guideline encouraging clinicians to use standardized risk assessments, clinical pathways, and tools to evaluate and communicate with patients who present with chest pain, as reported by this news organization.

The writing group underscored the need to reach a consensus for the definitions of chest pain. The new document standardizes related data elements for consistent reporting on chest pain syndromes.

“This is an appendix to the guidelines and a planned effort to try to harmonize and bring uniformity to the language applied,” writing committee chair H.V. “Skip” Anderson, MD, with UT Health Science Center, Houston, told this news organization.

“You want heart attack to mean the same thing in Miami Beach as in Western Pennsylvania, as in Oregon and Washington and every place in between,” Dr. Anderson explained. “You want everybody to be using the same language, so that’s what these data standards are meant to do.”

In the document, data elements are grouped into three broad categories: chest pain, myocardial injury, and MI.

“We deliberately followed the plans contained in the new guideline and focused on potentially serious cardiovascular causes of chest pain as might be encountered in emergency departments,” the writing group notes in the document.

The terms “typical” and “atypical” as descriptors of chest pain or anginal syndromes are not used in the new document, in line with the 2021 guidance to abandon these terms.

Instead, the new document divides chest pain syndromes into three categories: “cardiac,” “possible cardiac,” and “noncardiac” – again, in keeping with the chest pain guideline.

The document also includes data elements for risk stratification scoring according to several common risk scoring algorithms and for procedure-related myocardial injury and procedure-related MI.

Each year, chest pain sends more than 7 million adults to the emergency department in the United States. Although noncardiac causes of chest pain make up a large majority of these cases, there are several life-threatening causes of chest pain that must be identified and treated promptly.

Distinguishing between serious and nonserious causes of chest pain is an urgent imperative, the writing group says.

Overall, they say this new clinical lexicon and set of data standards should be “broadly applicable” in various settings, including clinical trials and observational studies, patient care, electronic health records (EHRs), quality and performance improvement initiatives, registries, and public reporting programs.

The 2022 ACC/AHA Key Data Elements and Definitions for Chest Pain and Acute Myocardial Infarction was simultaneously published online in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.

It was developed in collaboration with the American College of Emergency Physicians and the Society for Cardiac Angiography and Interventions and endorsed by the Society for Academic Emergency Medicine.

Dr. Anderson noted that “almost all of the guidelines that come out now, certainly in the last few years, have been followed after a certain interval by a set of data standards applicable to the guidelines.”

“It would be really great if it could actually be attached as an appendix, but the nature of the development of these things is such that there will always be a bit of a time lag between the writing group that develops the guidelines and the work group that develops the data standards; you can’t really have them working in parallel at the same time,” Dr. Anderson said in an interview.

This research had no commercial funding. The authors have no relevant disclosures.

A version of this article first appeared on Medscape.com.