Richard Mark Kirkner

The time has come to rethink the conventional primary endpoints investigators use in coronary revascularization trials – a composite of major adverse cardiovascular events (MACE), death or MI, and other endpoints – and shift toward greater emphasis on quality of life, two clinical trial investigators say.

Gregg Stone, MD, and Mario Gaudino, MD, MSCE, PhD, made their case in the Journal of the American College of Cardiology, writing: “The classic academic exercise of comparing revascularization modalities in an elusive search for a clear ‘winner’ has failed.” Dr. Stone was the principal investigator of the landmark EXCEL trial and an investigator for the ISCHEMIA trial, the latter of which Dr. Gaudino was also an investigator. Both trials evaluated percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) as treatments for coronary artery disease.

In an interview, Dr. Stone, a cardiologist at the Icahn School of Medicine at Mount Sinai, New York, said: “We’re proposing a new endpoint called a composite endpoint measured in a hierarchical fashion of death or quality of life [QOL].” Dr. Gaudino is a cardiac surgeon at Weill Cornell Medicine, New York.
 

Quality of life as a validation tool

As a measure of revascularization after PCI or CABG, Dr. Stone said, QOL is ready for prime time. “Over the last 20 years there’s been a very rich literature of science developed linking certain quality of life instruments to improved outcomes, in particularly health but also heart failure.”

Those instruments include the Seattle Angina Questionnaire, the Minnesota Living with Heart Failure Questionnaire and the Kansas City Cardiomyopathy questionnaire. “All of these are sufficiently validated that the [Food and Drug Administration] considers them ‘validated tools’ for use in clinical trials.” Dr. Stone also noted that substudies of three landmark trials comparing PCI and CABG – EXCEL, SYNTAX, and FREEDOM – used those instruments to evaluate QOL as an endpoint alongside “hard” outcomes such as death, MI or stroke. “So quality of life already is being used and it is already widely accepted. What we’re saying is, when you think about the information you need for medical studies, we believe it’s time to elevate that from secondary supportive information to primary.”

He and Dr. Gaudino are putting their money where their mouths are. They’ve applied for a grant through the Patient-Centered Outcomes Research Institute to use QOL as an outcomes measure in a trial of revascularization strategies in women and minority patients.
 

Shortcomings with traditional endpoints

Dr. Stone explained some of the shortcomings with the traditional endpoints revascularization studies have used. “Everybody agrees that mortality or survival is the most important endpoint, but studies can never be large enough to be powered for that. So we always end up combining them with myocardial infarction, stroke, and often with repeat revascularization” into one MACE endpoint.

But those four types of events are “very, very different,” Dr. Stone said. The severity of MIs and strokes can range from minor, almost inconsequential events to major, debilitating events. “Some strokes resolve in a few days but we count them all the same.”

He ticked off a list of the other outcomes the traditional endpoints don’t account for: atrial fibrillation, kidney dysfunction, musculoskeletal disorders, depression, cognitive changes, and vascular complications. They all can all have a significant impact on a patient’s QOL, Dr. Stone said.

“We’ve now entered an era that is much more patient centered,” Dr. Stone said. “My goal as a physician is to try to impart my knowledge of the evidence that’s out there so that the patient can make the decision that gives them the best chance of meeting their life goals and objectives. When you ask patients what they want, they all want to live longer and they want to live better.”

Mass General

MACE as a composite endpoint has its shortcomings, but using QOL can also be fraught with problems, said Suzanne Baron, MD, director of interventional cardiology research at Massachusetts General Hospital, Boston.

With regards to MACE, she echoed some of Dr. Stone’s concerns. “Patients and clinicians likely would not consider a repeat stenting procedure to be the same as having a stroke, and so weighting these two outcomes equally within a composite endpoint can potentially result in a skewed trial conclusion.”

One potential issue with QOL as an endpoint is that it can vary from day to day. “If quality of life is only measured at a few time points, such as annually, it is possible that those measurements may only reflect a small portion of the patient’s overall quality of life,” she said. “Accordingly, I think that it will be important to incorporate frequent assessments of a patient’s quality of life if these measures will be used as a primary endpoint in cardiac revascularization trials.”

And, in a cost-conscious health care system, quantity (length) of life tends to carry more weight than QOL, she said. “So it will be important that a trial using quality-of-life improvement as a primary endpoint mandates that the degree of improvement be large enough to ensure that the treatment remains high-value from a health economics standpoint.”

Dr. Stone disclosed financial relationships with numerous pharmaceutical companies. Dr. Baron reported financial relationships with Abiomed, Acarix, Boston Scientific, Medtronic, Zoll Medical, Biotronik, Edwards Lifesciences, and Janssen.
 

The time has come to rethink the conventional primary endpoints investigators use in coronary revascularization trials – a composite of major adverse cardiovascular events (MACE), death or MI, and other endpoints – and shift toward greater emphasis on quality of life, two clinical trial investigators say.

Gregg Stone, MD, and Mario Gaudino, MD, MSCE, PhD, made their case in the Journal of the American College of Cardiology, writing: “The classic academic exercise of comparing revascularization modalities in an elusive search for a clear ‘winner’ has failed.” Dr. Stone was the principal investigator of the landmark EXCEL trial and an investigator for the ISCHEMIA trial, the latter of which Dr. Gaudino was also an investigator. Both trials evaluated percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) as treatments for coronary artery disease.

In an interview, Dr. Stone, a cardiologist at the Icahn School of Medicine at Mount Sinai, New York, said: “We’re proposing a new endpoint called a composite endpoint measured in a hierarchical fashion of death or quality of life [QOL].” Dr. Gaudino is a cardiac surgeon at Weill Cornell Medicine, New York.
 

Quality of life as a validation tool

As a measure of revascularization after PCI or CABG, Dr. Stone said, QOL is ready for prime time. “Over the last 20 years there’s been a very rich literature of science developed linking certain quality of life instruments to improved outcomes, in particularly health but also heart failure.”

Those instruments include the Seattle Angina Questionnaire, the Minnesota Living with Heart Failure Questionnaire and the Kansas City Cardiomyopathy questionnaire. “All of these are sufficiently validated that the [Food and Drug Administration] considers them ‘validated tools’ for use in clinical trials.” Dr. Stone also noted that substudies of three landmark trials comparing PCI and CABG – EXCEL, SYNTAX, and FREEDOM – used those instruments to evaluate QOL as an endpoint alongside “hard” outcomes such as death, MI or stroke. “So quality of life already is being used and it is already widely accepted. What we’re saying is, when you think about the information you need for medical studies, we believe it’s time to elevate that from secondary supportive information to primary.”

He and Dr. Gaudino are putting their money where their mouths are. They’ve applied for a grant through the Patient-Centered Outcomes Research Institute to use QOL as an outcomes measure in a trial of revascularization strategies in women and minority patients.
 

Shortcomings with traditional endpoints

Dr. Stone explained some of the shortcomings with the traditional endpoints revascularization studies have used. “Everybody agrees that mortality or survival is the most important endpoint, but studies can never be large enough to be powered for that. So we always end up combining them with myocardial infarction, stroke, and often with repeat revascularization” into one MACE endpoint.

But those four types of events are “very, very different,” Dr. Stone said. The severity of MIs and strokes can range from minor, almost inconsequential events to major, debilitating events. “Some strokes resolve in a few days but we count them all the same.”

He ticked off a list of the other outcomes the traditional endpoints don’t account for: atrial fibrillation, kidney dysfunction, musculoskeletal disorders, depression, cognitive changes, and vascular complications. They all can all have a significant impact on a patient’s QOL, Dr. Stone said.

“We’ve now entered an era that is much more patient centered,” Dr. Stone said. “My goal as a physician is to try to impart my knowledge of the evidence that’s out there so that the patient can make the decision that gives them the best chance of meeting their life goals and objectives. When you ask patients what they want, they all want to live longer and they want to live better.”

Mass General

MACE as a composite endpoint has its shortcomings, but using QOL can also be fraught with problems, said Suzanne Baron, MD, director of interventional cardiology research at Massachusetts General Hospital, Boston.

With regards to MACE, she echoed some of Dr. Stone’s concerns. “Patients and clinicians likely would not consider a repeat stenting procedure to be the same as having a stroke, and so weighting these two outcomes equally within a composite endpoint can potentially result in a skewed trial conclusion.”

One potential issue with QOL as an endpoint is that it can vary from day to day. “If quality of life is only measured at a few time points, such as annually, it is possible that those measurements may only reflect a small portion of the patient’s overall quality of life,” she said. “Accordingly, I think that it will be important to incorporate frequent assessments of a patient’s quality of life if these measures will be used as a primary endpoint in cardiac revascularization trials.”

And, in a cost-conscious health care system, quantity (length) of life tends to carry more weight than QOL, she said. “So it will be important that a trial using quality-of-life improvement as a primary endpoint mandates that the degree of improvement be large enough to ensure that the treatment remains high-value from a health economics standpoint.”

Dr. Stone disclosed financial relationships with numerous pharmaceutical companies. Dr. Baron reported financial relationships with Abiomed, Acarix, Boston Scientific, Medtronic, Zoll Medical, Biotronik, Edwards Lifesciences, and Janssen.
 

The time has come to rethink the conventional primary endpoints investigators use in coronary revascularization trials – a composite of major adverse cardiovascular events (MACE), death or MI, and other endpoints – and shift toward greater emphasis on quality of life, two clinical trial investigators say.

Gregg Stone, MD, and Mario Gaudino, MD, MSCE, PhD, made their case in the Journal of the American College of Cardiology, writing: “The classic academic exercise of comparing revascularization modalities in an elusive search for a clear ‘winner’ has failed.” Dr. Stone was the principal investigator of the landmark EXCEL trial and an investigator for the ISCHEMIA trial, the latter of which Dr. Gaudino was also an investigator. Both trials evaluated percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) as treatments for coronary artery disease.

In an interview, Dr. Stone, a cardiologist at the Icahn School of Medicine at Mount Sinai, New York, said: “We’re proposing a new endpoint called a composite endpoint measured in a hierarchical fashion of death or quality of life [QOL].” Dr. Gaudino is a cardiac surgeon at Weill Cornell Medicine, New York.
 

Quality of life as a validation tool

As a measure of revascularization after PCI or CABG, Dr. Stone said, QOL is ready for prime time. “Over the last 20 years there’s been a very rich literature of science developed linking certain quality of life instruments to improved outcomes, in particularly health but also heart failure.”

Those instruments include the Seattle Angina Questionnaire, the Minnesota Living with Heart Failure Questionnaire and the Kansas City Cardiomyopathy questionnaire. “All of these are sufficiently validated that the [Food and Drug Administration] considers them ‘validated tools’ for use in clinical trials.” Dr. Stone also noted that substudies of three landmark trials comparing PCI and CABG – EXCEL, SYNTAX, and FREEDOM – used those instruments to evaluate QOL as an endpoint alongside “hard” outcomes such as death, MI or stroke. “So quality of life already is being used and it is already widely accepted. What we’re saying is, when you think about the information you need for medical studies, we believe it’s time to elevate that from secondary supportive information to primary.”

He and Dr. Gaudino are putting their money where their mouths are. They’ve applied for a grant through the Patient-Centered Outcomes Research Institute to use QOL as an outcomes measure in a trial of revascularization strategies in women and minority patients.
 

Shortcomings with traditional endpoints

Dr. Stone explained some of the shortcomings with the traditional endpoints revascularization studies have used. “Everybody agrees that mortality or survival is the most important endpoint, but studies can never be large enough to be powered for that. So we always end up combining them with myocardial infarction, stroke, and often with repeat revascularization” into one MACE endpoint.

But those four types of events are “very, very different,” Dr. Stone said. The severity of MIs and strokes can range from minor, almost inconsequential events to major, debilitating events. “Some strokes resolve in a few days but we count them all the same.”

He ticked off a list of the other outcomes the traditional endpoints don’t account for: atrial fibrillation, kidney dysfunction, musculoskeletal disorders, depression, cognitive changes, and vascular complications. They all can all have a significant impact on a patient’s QOL, Dr. Stone said.

“We’ve now entered an era that is much more patient centered,” Dr. Stone said. “My goal as a physician is to try to impart my knowledge of the evidence that’s out there so that the patient can make the decision that gives them the best chance of meeting their life goals and objectives. When you ask patients what they want, they all want to live longer and they want to live better.”

Mass General

MACE as a composite endpoint has its shortcomings, but using QOL can also be fraught with problems, said Suzanne Baron, MD, director of interventional cardiology research at Massachusetts General Hospital, Boston.

With regards to MACE, she echoed some of Dr. Stone’s concerns. “Patients and clinicians likely would not consider a repeat stenting procedure to be the same as having a stroke, and so weighting these two outcomes equally within a composite endpoint can potentially result in a skewed trial conclusion.”

One potential issue with QOL as an endpoint is that it can vary from day to day. “If quality of life is only measured at a few time points, such as annually, it is possible that those measurements may only reflect a small portion of the patient’s overall quality of life,” she said. “Accordingly, I think that it will be important to incorporate frequent assessments of a patient’s quality of life if these measures will be used as a primary endpoint in cardiac revascularization trials.”

And, in a cost-conscious health care system, quantity (length) of life tends to carry more weight than QOL, she said. “So it will be important that a trial using quality-of-life improvement as a primary endpoint mandates that the degree of improvement be large enough to ensure that the treatment remains high-value from a health economics standpoint.”

Dr. Stone disclosed financial relationships with numerous pharmaceutical companies. Dr. Baron reported financial relationships with Abiomed, Acarix, Boston Scientific, Medtronic, Zoll Medical, Biotronik, Edwards Lifesciences, and Janssen.
 

The largest multicenter randomized trial to date of CT angiography before left atrial appendage closure (LAAC) to treat atrial fibrillation has added to the evidence that the imaging technique on top of transesophageal echocardiography achieves a higher degree of short- and long-term success than TEE alone.

The results are from a subanalysis of the Swiss-Apero trial, a randomized comparative trial of the Watchman and Amulet devices for LAAC, which published results in Circulation.

“Our observational data support to use of CT for LAAC procedure planning,” senior investigator Lorenz Räber, MD, PhD, said in an interview. “This is not very surprising given the high variability of the LAA anatomy and the associated complexity of the procedure.” Dr. Räber is director of the catheterization laboratory at Inselspital, Bern (Switzerland) University Hospital.

The study, published online in JACC: Cardiovascular Interventions, included 219 LAAC procedures in which the operators performed coronary CT angiography (CTTA) beforehand. When the investigators designed the study, LAAC procedures were typically planned using TEE alone, and so participating operators were blinded to preprocedural CCTA imaging. Soon after the study launch, European cardiology societies issued a consensus statement that included CCTA as an option for procedure planning. So the Swiss-Apero investigators changed the subanalysis protocol to unblind the operators – that is, they were permitted to plan LAAC procedures with CCTA imaging in addition to TEE. In this subanalysis, most patients had implantation with blinding to CCTA (57.9% vs. 41.2%).
 

Study results

The subanalysis determined that operator unblinding to preprocedural CCTA resulted in better success with LAAC, both in the short term, at 93.5% vs. 81.1% (P = .009; adjusted odds ratio, 2.76; 95% confidence interval, 1.05-7.29; P = .40) and the long term, at 83.7% vs. 72.4% (P = .050; aOR, 2.12; 95% CI, 1.03-4.35; P = .041).

Dr. Räber noted that this is only the third study to date that examined the potential impact of preprocedural CCTA plus TEE. One was a small study of 24 consecutive LAAC procedures with the Watchman device that compared TEE alone and CCTA plus TEE, finding better outcomes in the group that had both imaging modalities . A larger, single-center cohort study of 485 LAAC Watchman procedures found that CCTA resulted in faster operation times and higher successful device implantation rates, but no significant difference in procedural complications.

Dr. Räber explained why his group’s subanalysis may have found a clinical benefit with CCTA on top of TEE. “Our study was much larger, as compared to the randomized clinical trial, and there was no selection bias as in the second study mentioned before, as operators did not have the option to decide whether or not to assess the CCTA prior to the procedure,” he said. “Finally, in the previous studies there was no random allocation of device type” – that is, Amulet versus Watchman.

One study limitation Dr. Räber noted was that significantly more patients in the blinded group were discharged with dual-antiplatelet therapy. “The lower rate of procedure complications observed in unblinded procedures was mostly driven by a lower number of major bleedings and in particular of pericardial tamponade,” he said. “We cannot therefore exclude that the higher percentage of patients under dual-antiplatelet therapy in the CCTA-blinded group might have favored this difference.”

However, he noted the investigators corrected their analysis to account for differences between the groups. “Importantly, the numerical excess in major procedural bleeding was observed within both the single-antiplatelet therapy and dual-antiplatelet therapy subgroups of the TEE-only group.”

In an accompanying editorial, coauthors Brian O’Neill, MD, and Dee Dee Wang, MD, both with the Center for Structural Heard Disease at Henry Ford Hospital in Detroit, noted that the Swiss-Apero subanalysis “reinforced” the benefit of CCTA before LAAC.  

“This study demonstrated, for the first time, improved short- and long-term procedural success using CT in addition to TEE for left atrial appendage occlusion,” Dr. O’Neill said in an interview. “This particular study may serve as a guide to an adequately powered randomized trial of CT versus TEE in left atrial appendage occlusion.” Future LAAC trials should incorporate preprocedural CCTA.

Dr. O’Neill noted that, as a subanalysis of a randomized trial, the “results are hypothesis generating.” However, he added, “the results are in line with several previous studies of CT versus TEE in left atrial appendage occlusion.”

Dr Räber disclosed financial relationships with Abbott Vascular, Boston Scientific, Biotronik, Infraredx, Heartflow, Sanofi, Regeneron, Amgen, AstraZeneca, CSL Behring, Canon, Occlutech, and Vifor. Dr. O’Neill disclosed financial relationships with Edwards Lifesciences, Medtronic, and Abbott Vascular.

The largest multicenter randomized trial to date of CT angiography before left atrial appendage closure (LAAC) to treat atrial fibrillation has added to the evidence that the imaging technique on top of transesophageal echocardiography achieves a higher degree of short- and long-term success than TEE alone.

The results are from a subanalysis of the Swiss-Apero trial, a randomized comparative trial of the Watchman and Amulet devices for LAAC, which published results in Circulation.

“Our observational data support to use of CT for LAAC procedure planning,” senior investigator Lorenz Räber, MD, PhD, said in an interview. “This is not very surprising given the high variability of the LAA anatomy and the associated complexity of the procedure.” Dr. Räber is director of the catheterization laboratory at Inselspital, Bern (Switzerland) University Hospital.

The study, published online in JACC: Cardiovascular Interventions, included 219 LAAC procedures in which the operators performed coronary CT angiography (CTTA) beforehand. When the investigators designed the study, LAAC procedures were typically planned using TEE alone, and so participating operators were blinded to preprocedural CCTA imaging. Soon after the study launch, European cardiology societies issued a consensus statement that included CCTA as an option for procedure planning. So the Swiss-Apero investigators changed the subanalysis protocol to unblind the operators – that is, they were permitted to plan LAAC procedures with CCTA imaging in addition to TEE. In this subanalysis, most patients had implantation with blinding to CCTA (57.9% vs. 41.2%).
 

Study results

The subanalysis determined that operator unblinding to preprocedural CCTA resulted in better success with LAAC, both in the short term, at 93.5% vs. 81.1% (P = .009; adjusted odds ratio, 2.76; 95% confidence interval, 1.05-7.29; P = .40) and the long term, at 83.7% vs. 72.4% (P = .050; aOR, 2.12; 95% CI, 1.03-4.35; P = .041).

Dr. Räber noted that this is only the third study to date that examined the potential impact of preprocedural CCTA plus TEE. One was a small study of 24 consecutive LAAC procedures with the Watchman device that compared TEE alone and CCTA plus TEE, finding better outcomes in the group that had both imaging modalities . A larger, single-center cohort study of 485 LAAC Watchman procedures found that CCTA resulted in faster operation times and higher successful device implantation rates, but no significant difference in procedural complications.

Dr. Räber explained why his group’s subanalysis may have found a clinical benefit with CCTA on top of TEE. “Our study was much larger, as compared to the randomized clinical trial, and there was no selection bias as in the second study mentioned before, as operators did not have the option to decide whether or not to assess the CCTA prior to the procedure,” he said. “Finally, in the previous studies there was no random allocation of device type” – that is, Amulet versus Watchman.

One study limitation Dr. Räber noted was that significantly more patients in the blinded group were discharged with dual-antiplatelet therapy. “The lower rate of procedure complications observed in unblinded procedures was mostly driven by a lower number of major bleedings and in particular of pericardial tamponade,” he said. “We cannot therefore exclude that the higher percentage of patients under dual-antiplatelet therapy in the CCTA-blinded group might have favored this difference.”

However, he noted the investigators corrected their analysis to account for differences between the groups. “Importantly, the numerical excess in major procedural bleeding was observed within both the single-antiplatelet therapy and dual-antiplatelet therapy subgroups of the TEE-only group.”

In an accompanying editorial, coauthors Brian O’Neill, MD, and Dee Dee Wang, MD, both with the Center for Structural Heard Disease at Henry Ford Hospital in Detroit, noted that the Swiss-Apero subanalysis “reinforced” the benefit of CCTA before LAAC.  

“This study demonstrated, for the first time, improved short- and long-term procedural success using CT in addition to TEE for left atrial appendage occlusion,” Dr. O’Neill said in an interview. “This particular study may serve as a guide to an adequately powered randomized trial of CT versus TEE in left atrial appendage occlusion.” Future LAAC trials should incorporate preprocedural CCTA.

Dr. O’Neill noted that, as a subanalysis of a randomized trial, the “results are hypothesis generating.” However, he added, “the results are in line with several previous studies of CT versus TEE in left atrial appendage occlusion.”

Dr Räber disclosed financial relationships with Abbott Vascular, Boston Scientific, Biotronik, Infraredx, Heartflow, Sanofi, Regeneron, Amgen, AstraZeneca, CSL Behring, Canon, Occlutech, and Vifor. Dr. O’Neill disclosed financial relationships with Edwards Lifesciences, Medtronic, and Abbott Vascular.

The largest multicenter randomized trial to date of CT angiography before left atrial appendage closure (LAAC) to treat atrial fibrillation has added to the evidence that the imaging technique on top of transesophageal echocardiography achieves a higher degree of short- and long-term success than TEE alone.

The results are from a subanalysis of the Swiss-Apero trial, a randomized comparative trial of the Watchman and Amulet devices for LAAC, which published results in Circulation.

“Our observational data support to use of CT for LAAC procedure planning,” senior investigator Lorenz Räber, MD, PhD, said in an interview. “This is not very surprising given the high variability of the LAA anatomy and the associated complexity of the procedure.” Dr. Räber is director of the catheterization laboratory at Inselspital, Bern (Switzerland) University Hospital.

The study, published online in JACC: Cardiovascular Interventions, included 219 LAAC procedures in which the operators performed coronary CT angiography (CTTA) beforehand. When the investigators designed the study, LAAC procedures were typically planned using TEE alone, and so participating operators were blinded to preprocedural CCTA imaging. Soon after the study launch, European cardiology societies issued a consensus statement that included CCTA as an option for procedure planning. So the Swiss-Apero investigators changed the subanalysis protocol to unblind the operators – that is, they were permitted to plan LAAC procedures with CCTA imaging in addition to TEE. In this subanalysis, most patients had implantation with blinding to CCTA (57.9% vs. 41.2%).
 

Study results

The subanalysis determined that operator unblinding to preprocedural CCTA resulted in better success with LAAC, both in the short term, at 93.5% vs. 81.1% (P = .009; adjusted odds ratio, 2.76; 95% confidence interval, 1.05-7.29; P = .40) and the long term, at 83.7% vs. 72.4% (P = .050; aOR, 2.12; 95% CI, 1.03-4.35; P = .041).

Dr. Räber noted that this is only the third study to date that examined the potential impact of preprocedural CCTA plus TEE. One was a small study of 24 consecutive LAAC procedures with the Watchman device that compared TEE alone and CCTA plus TEE, finding better outcomes in the group that had both imaging modalities . A larger, single-center cohort study of 485 LAAC Watchman procedures found that CCTA resulted in faster operation times and higher successful device implantation rates, but no significant difference in procedural complications.

Dr. Räber explained why his group’s subanalysis may have found a clinical benefit with CCTA on top of TEE. “Our study was much larger, as compared to the randomized clinical trial, and there was no selection bias as in the second study mentioned before, as operators did not have the option to decide whether or not to assess the CCTA prior to the procedure,” he said. “Finally, in the previous studies there was no random allocation of device type” – that is, Amulet versus Watchman.

One study limitation Dr. Räber noted was that significantly more patients in the blinded group were discharged with dual-antiplatelet therapy. “The lower rate of procedure complications observed in unblinded procedures was mostly driven by a lower number of major bleedings and in particular of pericardial tamponade,” he said. “We cannot therefore exclude that the higher percentage of patients under dual-antiplatelet therapy in the CCTA-blinded group might have favored this difference.”

However, he noted the investigators corrected their analysis to account for differences between the groups. “Importantly, the numerical excess in major procedural bleeding was observed within both the single-antiplatelet therapy and dual-antiplatelet therapy subgroups of the TEE-only group.”

In an accompanying editorial, coauthors Brian O’Neill, MD, and Dee Dee Wang, MD, both with the Center for Structural Heard Disease at Henry Ford Hospital in Detroit, noted that the Swiss-Apero subanalysis “reinforced” the benefit of CCTA before LAAC.  

“This study demonstrated, for the first time, improved short- and long-term procedural success using CT in addition to TEE for left atrial appendage occlusion,” Dr. O’Neill said in an interview. “This particular study may serve as a guide to an adequately powered randomized trial of CT versus TEE in left atrial appendage occlusion.” Future LAAC trials should incorporate preprocedural CCTA.

Dr. O’Neill noted that, as a subanalysis of a randomized trial, the “results are hypothesis generating.” However, he added, “the results are in line with several previous studies of CT versus TEE in left atrial appendage occlusion.”

Dr Räber disclosed financial relationships with Abbott Vascular, Boston Scientific, Biotronik, Infraredx, Heartflow, Sanofi, Regeneron, Amgen, AstraZeneca, CSL Behring, Canon, Occlutech, and Vifor. Dr. O’Neill disclosed financial relationships with Edwards Lifesciences, Medtronic, and Abbott Vascular.

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

An updated consensus statement on transcatheter left atrial appendage closure (LAAC) has put a newfound focus on patient selection for the procedure, specifically recommending that the procedure is appropriate for patients with nonvalvular atrial fibrillation who have risk for thromboembolism, aren’t well suited for direct oral anticoagulants (DOACs) and have a good chance of living for at least another year.

The statement, published online in the Journal of the Society for Cardiovascular Angiography & Interventions, also makes recommendations for how much experience operators should have, how many procedures they should perform to keep their skills up, and when and how to use imaging and prescribe DOACs, among other suggestions.

The statement represents the first updated guidance for LAAC since 2015. “Since then this field has really expanded and evolved,” writing group chair Jacqueline Saw, MD, said in an interview. “For instance, the indications are more matured and specific, and the procedural technical steps have matured. Imaging has also advanced, there’s more understanding about postprocedural care and there are also new devices that have been approved.”

Dr. Saw, an interventional cardiologist at Vancouver General Hospital and St. Paul’s Hospital, and a professor at the University of British Columbia in Vancouver, called the statement “a piece that puts everything together.”

“This document really summarizes the whole practice for doing transcatheter procedures,” she added, “so it’s all-in-one document in terms of recommendation of who we do the procedure for, how we should do it, how we should image and guide the procedure, and what complications to look out for and how to manage patients post procedure, be it with antithrombotic therapy and/or device surveillance.”

 13 recommendations

In all, the statement carries 13 recommendations for LAAC. The Society for Cardiovascular Angiography & Interventions and the Heart Rhythm Society commissioned the writing group. The American College of Cardiology and Society of Cardiovascular Computed Tomography have endorsed the statement. The following are among the recommendations:

• Transcatheter LAAC is appropriate for patients with nonvalvular atrial fibrillation with high thromboembolic risk but for whom long-term oral anticoagulation may be contraindicated and who have at least 1 year’s life expectancy.
• Operators should have performed at least 50 prior left-sided ablations or structural procedures and at least 25 transseptal punctures (TSPs). Interventional-imaging physicians should have experience in guiding 25 or more TSPs before supporting LAAC procedures independently.
• To maintain skills, operators should do 25 or more TSPs and at least 12 LAACs over each 2-year period.
• On-site cardiovascular surgery backup should be available for new programs and for operators early in their learning curve.
• Baseline imaging with transesophageal echocardiography (TEE) or cardiac computed tomography should be performed before LAAC.
• Intraprocedural imaging guidance with TEE or intracardiac echocardiography.
• Follow labeling of each specific LAAC device for technical aspects of the procedure.
• Familiarity with avoiding, recognizing, and managing LAAC complications.
• Predischarge 2-dimensional TEE to rule out pericardial effusion and device embolization.
• Anticoagulation for device-related thrombus.
• Make all efforts to minimize peridevice leaks during implantation because their clinical impact and management isn’t well understood.
• Antithrombotic therapy with warfarin, DOAC, or dual-antiplatelet therapy after LAAC based on the studied regimen and instructions for each specific device, tailored to the bleeding risks for each patient.
• TEE or cardiac computed tomography at 45-90 days after LAAC for device surveillance to assess for peridevice leak and device-related thrombus.

The statement also includes precautionary recommendations. It advises against using routine closure of LAAC-associated iatrogenic atrial septal defects and states that combined procedures with LAAC, such as structural interventions and pulmonary vein isolation, should be avoided because randomized controlled trial data are pending.

“These recommendations are based upon data from updated publications and randomized trial data as well as large registries, including the National Cardiovascular Data Registry, so I think this is a very practical statement that puts all these pieces together for any budding interventionalist doing this procedure and even experienced operations,” Dr. Saw said.

Authors of an accompanying editorial agreed that the “rigorous standards” set out in the statement will help maintain “a high level of procedural safety in the setting of rapid expansion.”

The editorialists, Faisal M. Merchant, MD, of Emory University, Atlanta, and Mohamad Alkhouli, MD, professor of medicine at Mayo Clinic School of Medicine, Rochester, Minn., point out that the incidence of pericardial effusion has decreased from more than 5% in the pivotal Watchman trials to less than 1.5% in the most recent report from the National Cardiovascular Data Registry, which shows that more than 100,000 procedures have been performed in the United States.

But most important as the field moves forward, they stress, is patient selection. The recommendation of limiting patients to those with a life expectancy of 1 year “is a tacit recognition of the fact that the benefits of LAAC take time to accrue, and many older and frail patients are unlikely to derive meaningful benefit.”

Dr. Merchant and Dr. Alkhouli also note that there remains a conundrum in patient selection that remains from the original LAAC trials, which enrolled patients who were eligible for anticoagulation. “Somewhat paradoxically, after its approval, LAAC is mostly prescribed to patients who are not felt to be good anticoagulation candidates.” This leaves physicians “in the precarious position of extrapolating data to patients who were excluded from the original clinical trials.”

Therefore, the consensus statement “is right to put patient selection front and center in its recommendations, but as the field of LAAC comes of age, better evidence to support patient selection will be the real sign of maturity.”

Dr. Saw said she envisions another update over the next 2 years or so as ongoing clinical trials comparing DOAC and LAAC, namely the CHAMPION-AF and OPTION trials, report results.

Dr. Saw and Dr. Merchant, reported no conflicts of interest. Dr. Alkhouli has financial ties to Boston Scientific, Abbott, and Philips.

An updated consensus statement on transcatheter left atrial appendage closure (LAAC) has put a newfound focus on patient selection for the procedure, specifically recommending that the procedure is appropriate for patients with nonvalvular atrial fibrillation who have risk for thromboembolism, aren’t well suited for direct oral anticoagulants (DOACs) and have a good chance of living for at least another year.

The statement, published online in the Journal of the Society for Cardiovascular Angiography & Interventions, also makes recommendations for how much experience operators should have, how many procedures they should perform to keep their skills up, and when and how to use imaging and prescribe DOACs, among other suggestions.

The statement represents the first updated guidance for LAAC since 2015. “Since then this field has really expanded and evolved,” writing group chair Jacqueline Saw, MD, said in an interview. “For instance, the indications are more matured and specific, and the procedural technical steps have matured. Imaging has also advanced, there’s more understanding about postprocedural care and there are also new devices that have been approved.”

Dr. Saw, an interventional cardiologist at Vancouver General Hospital and St. Paul’s Hospital, and a professor at the University of British Columbia in Vancouver, called the statement “a piece that puts everything together.”

“This document really summarizes the whole practice for doing transcatheter procedures,” she added, “so it’s all-in-one document in terms of recommendation of who we do the procedure for, how we should do it, how we should image and guide the procedure, and what complications to look out for and how to manage patients post procedure, be it with antithrombotic therapy and/or device surveillance.”

 13 recommendations

In all, the statement carries 13 recommendations for LAAC. The Society for Cardiovascular Angiography & Interventions and the Heart Rhythm Society commissioned the writing group. The American College of Cardiology and Society of Cardiovascular Computed Tomography have endorsed the statement. The following are among the recommendations:

• Transcatheter LAAC is appropriate for patients with nonvalvular atrial fibrillation with high thromboembolic risk but for whom long-term oral anticoagulation may be contraindicated and who have at least 1 year’s life expectancy.
• Operators should have performed at least 50 prior left-sided ablations or structural procedures and at least 25 transseptal punctures (TSPs). Interventional-imaging physicians should have experience in guiding 25 or more TSPs before supporting LAAC procedures independently.
• To maintain skills, operators should do 25 or more TSPs and at least 12 LAACs over each 2-year period.
• On-site cardiovascular surgery backup should be available for new programs and for operators early in their learning curve.
• Baseline imaging with transesophageal echocardiography (TEE) or cardiac computed tomography should be performed before LAAC.
• Intraprocedural imaging guidance with TEE or intracardiac echocardiography.
• Follow labeling of each specific LAAC device for technical aspects of the procedure.
• Familiarity with avoiding, recognizing, and managing LAAC complications.
• Predischarge 2-dimensional TEE to rule out pericardial effusion and device embolization.
• Anticoagulation for device-related thrombus.
• Make all efforts to minimize peridevice leaks during implantation because their clinical impact and management isn’t well understood.
• Antithrombotic therapy with warfarin, DOAC, or dual-antiplatelet therapy after LAAC based on the studied regimen and instructions for each specific device, tailored to the bleeding risks for each patient.
• TEE or cardiac computed tomography at 45-90 days after LAAC for device surveillance to assess for peridevice leak and device-related thrombus.

The statement also includes precautionary recommendations. It advises against using routine closure of LAAC-associated iatrogenic atrial septal defects and states that combined procedures with LAAC, such as structural interventions and pulmonary vein isolation, should be avoided because randomized controlled trial data are pending.

“These recommendations are based upon data from updated publications and randomized trial data as well as large registries, including the National Cardiovascular Data Registry, so I think this is a very practical statement that puts all these pieces together for any budding interventionalist doing this procedure and even experienced operations,” Dr. Saw said.

Authors of an accompanying editorial agreed that the “rigorous standards” set out in the statement will help maintain “a high level of procedural safety in the setting of rapid expansion.”

The editorialists, Faisal M. Merchant, MD, of Emory University, Atlanta, and Mohamad Alkhouli, MD, professor of medicine at Mayo Clinic School of Medicine, Rochester, Minn., point out that the incidence of pericardial effusion has decreased from more than 5% in the pivotal Watchman trials to less than 1.5% in the most recent report from the National Cardiovascular Data Registry, which shows that more than 100,000 procedures have been performed in the United States.

But most important as the field moves forward, they stress, is patient selection. The recommendation of limiting patients to those with a life expectancy of 1 year “is a tacit recognition of the fact that the benefits of LAAC take time to accrue, and many older and frail patients are unlikely to derive meaningful benefit.”

Dr. Merchant and Dr. Alkhouli also note that there remains a conundrum in patient selection that remains from the original LAAC trials, which enrolled patients who were eligible for anticoagulation. “Somewhat paradoxically, after its approval, LAAC is mostly prescribed to patients who are not felt to be good anticoagulation candidates.” This leaves physicians “in the precarious position of extrapolating data to patients who were excluded from the original clinical trials.”

Therefore, the consensus statement “is right to put patient selection front and center in its recommendations, but as the field of LAAC comes of age, better evidence to support patient selection will be the real sign of maturity.”

Dr. Saw said she envisions another update over the next 2 years or so as ongoing clinical trials comparing DOAC and LAAC, namely the CHAMPION-AF and OPTION trials, report results.

Dr. Saw and Dr. Merchant, reported no conflicts of interest. Dr. Alkhouli has financial ties to Boston Scientific, Abbott, and Philips.

An updated consensus statement on transcatheter left atrial appendage closure (LAAC) has put a newfound focus on patient selection for the procedure, specifically recommending that the procedure is appropriate for patients with nonvalvular atrial fibrillation who have risk for thromboembolism, aren’t well suited for direct oral anticoagulants (DOACs) and have a good chance of living for at least another year.

The statement, published online in the Journal of the Society for Cardiovascular Angiography & Interventions, also makes recommendations for how much experience operators should have, how many procedures they should perform to keep their skills up, and when and how to use imaging and prescribe DOACs, among other suggestions.

The statement represents the first updated guidance for LAAC since 2015. “Since then this field has really expanded and evolved,” writing group chair Jacqueline Saw, MD, said in an interview. “For instance, the indications are more matured and specific, and the procedural technical steps have matured. Imaging has also advanced, there’s more understanding about postprocedural care and there are also new devices that have been approved.”

Dr. Saw, an interventional cardiologist at Vancouver General Hospital and St. Paul’s Hospital, and a professor at the University of British Columbia in Vancouver, called the statement “a piece that puts everything together.”

“This document really summarizes the whole practice for doing transcatheter procedures,” she added, “so it’s all-in-one document in terms of recommendation of who we do the procedure for, how we should do it, how we should image and guide the procedure, and what complications to look out for and how to manage patients post procedure, be it with antithrombotic therapy and/or device surveillance.”

 13 recommendations

In all, the statement carries 13 recommendations for LAAC. The Society for Cardiovascular Angiography & Interventions and the Heart Rhythm Society commissioned the writing group. The American College of Cardiology and Society of Cardiovascular Computed Tomography have endorsed the statement. The following are among the recommendations:

• Transcatheter LAAC is appropriate for patients with nonvalvular atrial fibrillation with high thromboembolic risk but for whom long-term oral anticoagulation may be contraindicated and who have at least 1 year’s life expectancy.
• Operators should have performed at least 50 prior left-sided ablations or structural procedures and at least 25 transseptal punctures (TSPs). Interventional-imaging physicians should have experience in guiding 25 or more TSPs before supporting LAAC procedures independently.
• To maintain skills, operators should do 25 or more TSPs and at least 12 LAACs over each 2-year period.
• On-site cardiovascular surgery backup should be available for new programs and for operators early in their learning curve.
• Baseline imaging with transesophageal echocardiography (TEE) or cardiac computed tomography should be performed before LAAC.
• Intraprocedural imaging guidance with TEE or intracardiac echocardiography.
• Follow labeling of each specific LAAC device for technical aspects of the procedure.
• Familiarity with avoiding, recognizing, and managing LAAC complications.
• Predischarge 2-dimensional TEE to rule out pericardial effusion and device embolization.
• Anticoagulation for device-related thrombus.
• Make all efforts to minimize peridevice leaks during implantation because their clinical impact and management isn’t well understood.
• Antithrombotic therapy with warfarin, DOAC, or dual-antiplatelet therapy after LAAC based on the studied regimen and instructions for each specific device, tailored to the bleeding risks for each patient.
• TEE or cardiac computed tomography at 45-90 days after LAAC for device surveillance to assess for peridevice leak and device-related thrombus.

The statement also includes precautionary recommendations. It advises against using routine closure of LAAC-associated iatrogenic atrial septal defects and states that combined procedures with LAAC, such as structural interventions and pulmonary vein isolation, should be avoided because randomized controlled trial data are pending.

“These recommendations are based upon data from updated publications and randomized trial data as well as large registries, including the National Cardiovascular Data Registry, so I think this is a very practical statement that puts all these pieces together for any budding interventionalist doing this procedure and even experienced operations,” Dr. Saw said.

Authors of an accompanying editorial agreed that the “rigorous standards” set out in the statement will help maintain “a high level of procedural safety in the setting of rapid expansion.”

The editorialists, Faisal M. Merchant, MD, of Emory University, Atlanta, and Mohamad Alkhouli, MD, professor of medicine at Mayo Clinic School of Medicine, Rochester, Minn., point out that the incidence of pericardial effusion has decreased from more than 5% in the pivotal Watchman trials to less than 1.5% in the most recent report from the National Cardiovascular Data Registry, which shows that more than 100,000 procedures have been performed in the United States.

But most important as the field moves forward, they stress, is patient selection. The recommendation of limiting patients to those with a life expectancy of 1 year “is a tacit recognition of the fact that the benefits of LAAC take time to accrue, and many older and frail patients are unlikely to derive meaningful benefit.”

Dr. Merchant and Dr. Alkhouli also note that there remains a conundrum in patient selection that remains from the original LAAC trials, which enrolled patients who were eligible for anticoagulation. “Somewhat paradoxically, after its approval, LAAC is mostly prescribed to patients who are not felt to be good anticoagulation candidates.” This leaves physicians “in the precarious position of extrapolating data to patients who were excluded from the original clinical trials.”

Therefore, the consensus statement “is right to put patient selection front and center in its recommendations, but as the field of LAAC comes of age, better evidence to support patient selection will be the real sign of maturity.”

Dr. Saw said she envisions another update over the next 2 years or so as ongoing clinical trials comparing DOAC and LAAC, namely the CHAMPION-AF and OPTION trials, report results.

Dr. Saw and Dr. Merchant, reported no conflicts of interest. Dr. Alkhouli has financial ties to Boston Scientific, Abbott, and Philips.

Disparities in statin use in minority populations persist regardless of insurance status and 10-year atherosclerotic cardiovascular disease risk.

Those are among the findings of a study that sampled a national population database and has provided robust data and granular details on those disparities.

The researchers reported in JAMA Cardiology that the overall prevalence of statin use was 25.5%, and that it varied significantly between defined ethnic groups: 20% for Blacks, 15.4% for Hispanics, and 27.9% for Whites (P < .001). Statin use rates by Asian participants, at 25.5%, didn’t differ significantly from use by Whites.

University of Utah Intermountain Health

“We know that there are racial and ethnic disparities in the use of guideline-indicated statins after having established heart disease, but it was unknown if these disparities existed in the use of guideline-indicated statins for prevention of heart disease in those who just have risk factors,” lead author Joshua Jacobs, PharmD, a clinical pharmacist of cardiovascular medicine at University of Utah Intermountain Healthcare, said in written comments. “Additionally, race is included in the guideline-recommended risk factor calculation in an effort to reduce these disparities.”

Dr. Jacobs and colleagues evaluated statins for use in primary prevention, building upon previous single-center or diabetes-only cohort studies. What makes their study different from previous studies evaluating disparities in statin use is its use of temporal trends or current 10-year predicted ASCVD risk categorization, he said.

Using data from the National Health and Nutrition Examination Survey (NHANES), the researchers performed a serial, cross-sectional analysis of 3,417 participants that they said represented 39.4 million U.S. adults after applying sampling weights for age, gender, and race and ethnicity. In the weighted sample, 62.2% were men. In terms of self-reported race and ethnicity, 4.2% were of Asian descent, 12.7% were Black, 10.1% were Hispanic, and 73% were White.

Study participants completed a standardized questionnaire given by trained interviewers and also went to mobile examination centers where physical, anthropomorphic, and laboratory measurements, including height, weight, LDL cholesterol, and fasting blood glucose were collected. Pill bottle review also verified participants’ self-reported medication use.

The study noted that for primary prevention of atherosclerotic cardiovascular disease (ASCVD), the 2018 American College of Cardiology/American Heart Association Guideline recommends statins for, among other patient factors, elevated 10-year predicted ASCVD risk. The study divided ASCVD risk strata into three groups – 5% to less than 7.5%, 7.5% to less than 20%, and more than 20% – based on the 2018 ACC/AHA guideline and used pooled cohort equation to calculate 10-year ASCVD risk, which the guideline endorses.

Gaps persist despite ASCVD risk

The analysis found no statistically significant difference within each ASCVD risk strata between the White and Asian groups. But although statin use increased proportionately across each higher risk group, the gap widened noticeably in the highest risk group (more than 20% 10-year risk) between Whites, used as the reference at 37.6%, and Blacks (23.8%; prevalence ratio, .90; 95% confidence interval, .82-.98) and Hispanics (23.9%; PR, .90; 95% CI, .81-.99).

The study also evaluated a number of social determinants of health factors. Health insurance and access to routine health care were significantly associated with greater statin use in Black, Hispanic, and White participants; marital status and food insecurity were not. However, even when variables such as education, household income, and health insurance were applied, statin use was still significantly higher in Whites than in Blacks and Hispanics. For those with health insurance, statin use was 28.6% (95% CI, 25-32), 21.1% (95% CI, 17.3-25.4) and 19.9% (95% CI, 15.9-24.5), respectively.

The study noted that the pooled cohort equation-guided approach to statins for primary prevention, which the 2018 ACC/AHA guideline endorsed, should promote greater use of statins among Black patients. “Equitable use of statin therapy for prevention of heart disease is needed for Black and Hispanic adults,” Dr. Jacobs said. “Improvements in access to care, such as having a routine primary care clinician and health insurance, may decrease these health disparities.”

UT Southwestern Medical Center

A goal of the study was to identify if disparities in statin use held up across different risk groups, senior author Ambarish Pandey, MD, said in an interview. Use of the NHANES data makes this study unique among analyses of statin use disparities, he said.

“A lot of the work that has been done previously has focused on secondary prevention among patients who have atherosclerotic cardiovascular disease or have focused on single-center or hospital-based cohorts and have not really focused on a national representative cohort like NHANES,” said Dr. Pandey, of the UT Southwestern Medical Center, Dallas.

The next step is to do community-based participatory research focusing on different implementation strategies to increase the uptake of preventive statin use among Black and Hispanic communities, Dr. Jacobs said.

Dr. Jacobs has no relevant relationships to disclose. Dr. Pandey disclosed relationships with Gilead Sciences, Applied Therapeutics, Myovista, Tricog Health, Eli Lilly, Cytokinetics, Rivus, Roche Diagnostics, Pieces Technologies, Palomarin, Emmi Solutions, and Axon.

Disparities in statin use in minority populations persist regardless of insurance status and 10-year atherosclerotic cardiovascular disease risk.

Those are among the findings of a study that sampled a national population database and has provided robust data and granular details on those disparities.

The researchers reported in JAMA Cardiology that the overall prevalence of statin use was 25.5%, and that it varied significantly between defined ethnic groups: 20% for Blacks, 15.4% for Hispanics, and 27.9% for Whites (P < .001). Statin use rates by Asian participants, at 25.5%, didn’t differ significantly from use by Whites.

University of Utah Intermountain Health

“We know that there are racial and ethnic disparities in the use of guideline-indicated statins after having established heart disease, but it was unknown if these disparities existed in the use of guideline-indicated statins for prevention of heart disease in those who just have risk factors,” lead author Joshua Jacobs, PharmD, a clinical pharmacist of cardiovascular medicine at University of Utah Intermountain Healthcare, said in written comments. “Additionally, race is included in the guideline-recommended risk factor calculation in an effort to reduce these disparities.”

Dr. Jacobs and colleagues evaluated statins for use in primary prevention, building upon previous single-center or diabetes-only cohort studies. What makes their study different from previous studies evaluating disparities in statin use is its use of temporal trends or current 10-year predicted ASCVD risk categorization, he said.

Using data from the National Health and Nutrition Examination Survey (NHANES), the researchers performed a serial, cross-sectional analysis of 3,417 participants that they said represented 39.4 million U.S. adults after applying sampling weights for age, gender, and race and ethnicity. In the weighted sample, 62.2% were men. In terms of self-reported race and ethnicity, 4.2% were of Asian descent, 12.7% were Black, 10.1% were Hispanic, and 73% were White.

Study participants completed a standardized questionnaire given by trained interviewers and also went to mobile examination centers where physical, anthropomorphic, and laboratory measurements, including height, weight, LDL cholesterol, and fasting blood glucose were collected. Pill bottle review also verified participants’ self-reported medication use.

The study noted that for primary prevention of atherosclerotic cardiovascular disease (ASCVD), the 2018 American College of Cardiology/American Heart Association Guideline recommends statins for, among other patient factors, elevated 10-year predicted ASCVD risk. The study divided ASCVD risk strata into three groups – 5% to less than 7.5%, 7.5% to less than 20%, and more than 20% – based on the 2018 ACC/AHA guideline and used pooled cohort equation to calculate 10-year ASCVD risk, which the guideline endorses.

Gaps persist despite ASCVD risk

The analysis found no statistically significant difference within each ASCVD risk strata between the White and Asian groups. But although statin use increased proportionately across each higher risk group, the gap widened noticeably in the highest risk group (more than 20% 10-year risk) between Whites, used as the reference at 37.6%, and Blacks (23.8%; prevalence ratio, .90; 95% confidence interval, .82-.98) and Hispanics (23.9%; PR, .90; 95% CI, .81-.99).

The study also evaluated a number of social determinants of health factors. Health insurance and access to routine health care were significantly associated with greater statin use in Black, Hispanic, and White participants; marital status and food insecurity were not. However, even when variables such as education, household income, and health insurance were applied, statin use was still significantly higher in Whites than in Blacks and Hispanics. For those with health insurance, statin use was 28.6% (95% CI, 25-32), 21.1% (95% CI, 17.3-25.4) and 19.9% (95% CI, 15.9-24.5), respectively.

The study noted that the pooled cohort equation-guided approach to statins for primary prevention, which the 2018 ACC/AHA guideline endorsed, should promote greater use of statins among Black patients. “Equitable use of statin therapy for prevention of heart disease is needed for Black and Hispanic adults,” Dr. Jacobs said. “Improvements in access to care, such as having a routine primary care clinician and health insurance, may decrease these health disparities.”

UT Southwestern Medical Center

A goal of the study was to identify if disparities in statin use held up across different risk groups, senior author Ambarish Pandey, MD, said in an interview. Use of the NHANES data makes this study unique among analyses of statin use disparities, he said.

“A lot of the work that has been done previously has focused on secondary prevention among patients who have atherosclerotic cardiovascular disease or have focused on single-center or hospital-based cohorts and have not really focused on a national representative cohort like NHANES,” said Dr. Pandey, of the UT Southwestern Medical Center, Dallas.

The next step is to do community-based participatory research focusing on different implementation strategies to increase the uptake of preventive statin use among Black and Hispanic communities, Dr. Jacobs said.

Dr. Jacobs has no relevant relationships to disclose. Dr. Pandey disclosed relationships with Gilead Sciences, Applied Therapeutics, Myovista, Tricog Health, Eli Lilly, Cytokinetics, Rivus, Roche Diagnostics, Pieces Technologies, Palomarin, Emmi Solutions, and Axon.

Disparities in statin use in minority populations persist regardless of insurance status and 10-year atherosclerotic cardiovascular disease risk.

Those are among the findings of a study that sampled a national population database and has provided robust data and granular details on those disparities.

The researchers reported in JAMA Cardiology that the overall prevalence of statin use was 25.5%, and that it varied significantly between defined ethnic groups: 20% for Blacks, 15.4% for Hispanics, and 27.9% for Whites (P < .001). Statin use rates by Asian participants, at 25.5%, didn’t differ significantly from use by Whites.

University of Utah Intermountain Health

“We know that there are racial and ethnic disparities in the use of guideline-indicated statins after having established heart disease, but it was unknown if these disparities existed in the use of guideline-indicated statins for prevention of heart disease in those who just have risk factors,” lead author Joshua Jacobs, PharmD, a clinical pharmacist of cardiovascular medicine at University of Utah Intermountain Healthcare, said in written comments. “Additionally, race is included in the guideline-recommended risk factor calculation in an effort to reduce these disparities.”

Dr. Jacobs and colleagues evaluated statins for use in primary prevention, building upon previous single-center or diabetes-only cohort studies. What makes their study different from previous studies evaluating disparities in statin use is its use of temporal trends or current 10-year predicted ASCVD risk categorization, he said.

Using data from the National Health and Nutrition Examination Survey (NHANES), the researchers performed a serial, cross-sectional analysis of 3,417 participants that they said represented 39.4 million U.S. adults after applying sampling weights for age, gender, and race and ethnicity. In the weighted sample, 62.2% were men. In terms of self-reported race and ethnicity, 4.2% were of Asian descent, 12.7% were Black, 10.1% were Hispanic, and 73% were White.

Study participants completed a standardized questionnaire given by trained interviewers and also went to mobile examination centers where physical, anthropomorphic, and laboratory measurements, including height, weight, LDL cholesterol, and fasting blood glucose were collected. Pill bottle review also verified participants’ self-reported medication use.

The study noted that for primary prevention of atherosclerotic cardiovascular disease (ASCVD), the 2018 American College of Cardiology/American Heart Association Guideline recommends statins for, among other patient factors, elevated 10-year predicted ASCVD risk. The study divided ASCVD risk strata into three groups – 5% to less than 7.5%, 7.5% to less than 20%, and more than 20% – based on the 2018 ACC/AHA guideline and used pooled cohort equation to calculate 10-year ASCVD risk, which the guideline endorses.

Gaps persist despite ASCVD risk

The analysis found no statistically significant difference within each ASCVD risk strata between the White and Asian groups. But although statin use increased proportionately across each higher risk group, the gap widened noticeably in the highest risk group (more than 20% 10-year risk) between Whites, used as the reference at 37.6%, and Blacks (23.8%; prevalence ratio, .90; 95% confidence interval, .82-.98) and Hispanics (23.9%; PR, .90; 95% CI, .81-.99).

The study also evaluated a number of social determinants of health factors. Health insurance and access to routine health care were significantly associated with greater statin use in Black, Hispanic, and White participants; marital status and food insecurity were not. However, even when variables such as education, household income, and health insurance were applied, statin use was still significantly higher in Whites than in Blacks and Hispanics. For those with health insurance, statin use was 28.6% (95% CI, 25-32), 21.1% (95% CI, 17.3-25.4) and 19.9% (95% CI, 15.9-24.5), respectively.

The study noted that the pooled cohort equation-guided approach to statins for primary prevention, which the 2018 ACC/AHA guideline endorsed, should promote greater use of statins among Black patients. “Equitable use of statin therapy for prevention of heart disease is needed for Black and Hispanic adults,” Dr. Jacobs said. “Improvements in access to care, such as having a routine primary care clinician and health insurance, may decrease these health disparities.”

UT Southwestern Medical Center

A goal of the study was to identify if disparities in statin use held up across different risk groups, senior author Ambarish Pandey, MD, said in an interview. Use of the NHANES data makes this study unique among analyses of statin use disparities, he said.

“A lot of the work that has been done previously has focused on secondary prevention among patients who have atherosclerotic cardiovascular disease or have focused on single-center or hospital-based cohorts and have not really focused on a national representative cohort like NHANES,” said Dr. Pandey, of the UT Southwestern Medical Center, Dallas.

The next step is to do community-based participatory research focusing on different implementation strategies to increase the uptake of preventive statin use among Black and Hispanic communities, Dr. Jacobs said.

Dr. Jacobs has no relevant relationships to disclose. Dr. Pandey disclosed relationships with Gilead Sciences, Applied Therapeutics, Myovista, Tricog Health, Eli Lilly, Cytokinetics, Rivus, Roche Diagnostics, Pieces Technologies, Palomarin, Emmi Solutions, and Axon.

In 2012, a small group of specialists, consisting of a critical care pulmonologist, cardiologist, cardiac surgeon, and vascular specialist, at Massachusetts General Hospital, Boston, met to Monday morning quarterback an acute pulmonary embolism case that didn’t go as well as they’d hoped. They came up with a concept known as the pulmonary embolism response team – PERT for short – an idea that soon took hold in other centers and served as the vanguard to other innovative approaches to managing critical care patients with PE, which is the third-leading cause of cardiovascular death in the United States (Intern Emerg Med. 2023. doi: 10.1007/s11739-022-03180-w).

Leisa Thompson/Michigan Medicine

Three years later the PERT Consortium came together, which today has 102 members, according to the organization’s website (www.pertconsortium.org), and members in South America, Europe, Asia, and Australia. Since then, PE strategies have evolved to target mental health issues recovering patients have, improve follow-up after discharge, and even investigate artificial intelligence and apps to expedite diagnosis and treatment. The PERT Consortium, meanwhile, is in the process of creating the PE Centers of Excellence program to certify centers that meet certain requirements.

Harvard Medical School

“Part of the reason we recognized that a discussion across specialties was important was because there weren’t the large clinical trials that could tell us exactly what to do for any given case,” said Christopher Kabrhel, MD, MPH, director of the Center for Vascular Emergencies at Mass General and a professor at Harvard Medical School in Boston, who assembled that formative meeting. “Without a clear basis in data, it was really important to have all the different specialists weigh in and give their perspective and talk about what was the best approach for the patient’s care.”
 

Filling data gaps

Some of those data gaps persist today, Dr. Kabrhel said. “It’s precisely that lack of head-to-head data that existed in 2012, and to a great extent still exists today, that led us to create this system.” The American Heart Association just this January issued a scientific statement on surgical management and mechanical circulatory support in high-risk PE (Circulation. 2023;147:e628­­-47).

But the intervening research has been uneven. The Pulmonary Embolism Thrombolysis (PEITHO) trial in 2014 evaluated systemic thrombolysis and anticoagulation alone (N Engl J Med. 2014;370:1402-11), but head-to-head studies of catheter-directed thrombolysis (CDT), which was just emerging in 2012, and either systemic thrombolysis or anticoagulation have been lacking, Dr. Kabrhel said. The Hi-PEITHO trial in high-risk PE patients is evaluating ultrasound-guided CDT plus anticoagulation vs. anticoagulation alone (Am Heart J. 2022:251:43-54), but it isn’t complete.

“The therapeutic landscape for PE is evolving incredibly rapidly,” he said. “When we first started PERT we were just starting to see CDT. Since then, we’ve seen several new thrombolytic catheters come onto the market, but there’s also been a proliferation of suction embolectomy catheters and we’ve seen a potentially larger role for surgery and the use of ECMO [extracorporeal membrane oxygenation] or cardiac bypass to bridge patients to definitive therapy. With the rapid evolution and the seemingly daily addition of new therapeutic options, I think the need for PERT is only increasing.”

A recent study out of the University of Michigan reported that the PERT there led to a decrease in the use of advanced therapies given to acute PE patients without reducing mortality or extending hospital stays (Thromb Res. 2023;221:73-8). A study in Spain reported that patients with high-risk and intermediate high-risk PE who had PERT-coordinated care had half the 12-month mortality rate of non-PERT counterparts, 9% vs. 22.2% (P = .02) (Med Clin [Barc]. 2023;S0025-7753(23)00017-9). And a 2021 study at University Hospitals in Cleveland reported that PERT-managed PE patients had a 60% lower rate of adverse outcomes at 90 days than non–PERT-managed patients (J Invasive Cardiol. 2021;33:E173-E180).

Michigan Medicine

Nelish Ardeshna, MD, MA, the lead author of the Michigan study, said the PERT there was formed in 2017. Besides the multispecialty team that can be summoned to a teleconference on short notice, the protocol includes having at least one noninvasive specialist, such as a cardiologist or hospitalist, and one interventionalist, such as a radiologist, always on call. The PERT gets activated through the paging system after a hospital or emergency department physician identifies a suspected or established high-risk PE.

“High-risk PE patients can present in all settings, including the emergency department, ICU, surgical floor, or medical floor,” said Dr. Ardeshna, an internal medicine resident. “Management for these patients is equally varied from anticoagulation to systemic thrombolytics. Not all providers may be familiar with current guidelines to select the optimal therapy for high-risk pulmonary embolism patients. PERT aims to bridge that gap by providing a multidisciplinary discussion with PE specialists that can help identify the correct therapeutic options for optimal outcomes.”

Cleveland Clinic

At Cleveland Clinic, where the PERT has been in place since 2012, the PERT can consist of six to eight different specialties and involve up to 15 providers on a conference call, said Leben Tefera, MD, a vascular specialist and head of the PERT team there.

“Each patient will come in and have certain comorbidities,” Dr. Tefera said. “The unfortunate thing about a majority of the PEs that we see, in particular ones [in patients] that are very sick and require inpatient treatment, is that they don’t really fit into a box; you can’t come up with one kind of generic care routine or care path that treats the majority of patients with PE.”
 

Evolving to follow-up care

As the PERT protocol led to better inpatient outcomes, the teams became more aware that discharged PE patients were struggling with mental health and other quality-of-life issues – symptoms that have been understudied, according to a protocol Dr. Tefera coauthored for a prospective observational study of psychological distress symptoms in PE survivors. By contrast, the protocol noted, these symptoms have been studied extensively in myocardial infarction and stroke patients (Res Pract Thromb Hemost. 2023. doi: 10.1016/j.rpth.2023.10045). Other studies have found that 35%-50% of patients reported mental health symptoms 3 months after PE (Chest. 2021;159:2428-38; Qual Life Res. 2019;28:2111-24).

“A lot of physicians have known it for quite some time, but it wasn’t really until the last couple of years that physicians started saying psychological stress is something that we need to quantify and that we need to actually treat, that we actually need to address,” Dr. Tefera said. That led Dr. Tefera and his Cleveland Clinic PERT colleagues to set up a follow-up clinic for PE patients.

At their follow-up visits, patients complete validated questionnaires about anxiety, depression, fear of recurrence, PE-specific quality of life, and posttraumatic stress disorder. “If they flag as positive, we give them a referral to an in-house psychologist,” he said. “One thing I can report is that patients absolutely, positively love this, because it’s something that they are all experiencing that a lot of physicians just aren’t addressing.”
 

Artificial intelligence emerges

At the University of Pittsburgh Medical Center, the PERT has started evaluating artificial intelligence to aid in PE diagnosis. Belinda Rivera-Lebron, MD, director of the acute and chronic embolism program at Pitt, explained that the AI protocol hasn’t been adopted yet, but the concept is to have a platform that’s compatible with the hospital system’s electronic medical record.

University of Pittsburgh

She described how AI would work once the PERT is activated. “Once the patient goes through the CT scanner, within 60 seconds of that scan being completed, the scan gets uploaded into the cloud and the app or the platform is able to tell you whether there is PE present or absent, and whether there is right ventricle dilation on that scan. This is even before you probably even think about opening up the computer to look at the scan, and even before radiology opens up the scan to read,” she said. “It’s so fast.”

The idea is to send the scans rapidly to the PERT. “It will send you a text, a notification on your phone that will tell you Mr. Smith is PE positive,” Dr. Rivera-Lebron said. “Then you open it and you are able to scroll through the CT scan in your phone. So, it’s really remarkable.”
 

Clinical trials worth watching

Meanwhile, a number of clinical trials have started to enroll patients, or will soon, that Dr. Rivera-Lebron said are worth paying attention to.

PEITHO-3 is a randomized, placebo-controlled trial with long-term follow-up comparing the efficacy of a reduced-dose alteplase regimen or standard heparin anticoagulation in patients with intermediate to high-risk PE (Thromb Haemost. 2022;122:867-66).

PEERLESS is a prospective randomized trial comparing mechanical thrombectomy and CDT (ClinicalTrials.gov identifier NCT05111613).

PE-Thrombus Removal with Catheter-directed Therapy (PE-TRACT) is an open-label Phase 3 trial comparing anticoagulation and CDT that’s not yet recruiting (ClinicalTrials.gov identifier NCT05591118).

FlowTriever for Acute Massive Pulmonary Embolism (FLAME) is a prospective cohort study evaluating a clot-retrieving device in high-risk PE patients (ClinicalTrials.gov identifier NCT04795167).

When completed and published, these trials could provide PERTs more evidence for their decision-making.

Dr. Ardeshna and Dr. Tefera have no relevant relationships to disclose. Dr. Rivera-Lebron disclosed relationships with INARI Catheter and Johnson & Johnson. Dr. Kabrhel disclosed relationships with Bristol Myers Squibb and Pfizer.

In 2012, a small group of specialists, consisting of a critical care pulmonologist, cardiologist, cardiac surgeon, and vascular specialist, at Massachusetts General Hospital, Boston, met to Monday morning quarterback an acute pulmonary embolism case that didn’t go as well as they’d hoped. They came up with a concept known as the pulmonary embolism response team – PERT for short – an idea that soon took hold in other centers and served as the vanguard to other innovative approaches to managing critical care patients with PE, which is the third-leading cause of cardiovascular death in the United States (Intern Emerg Med. 2023. doi: 10.1007/s11739-022-03180-w).

Leisa Thompson/Michigan Medicine

Three years later the PERT Consortium came together, which today has 102 members, according to the organization’s website (www.pertconsortium.org), and members in South America, Europe, Asia, and Australia. Since then, PE strategies have evolved to target mental health issues recovering patients have, improve follow-up after discharge, and even investigate artificial intelligence and apps to expedite diagnosis and treatment. The PERT Consortium, meanwhile, is in the process of creating the PE Centers of Excellence program to certify centers that meet certain requirements.

Harvard Medical School

“Part of the reason we recognized that a discussion across specialties was important was because there weren’t the large clinical trials that could tell us exactly what to do for any given case,” said Christopher Kabrhel, MD, MPH, director of the Center for Vascular Emergencies at Mass General and a professor at Harvard Medical School in Boston, who assembled that formative meeting. “Without a clear basis in data, it was really important to have all the different specialists weigh in and give their perspective and talk about what was the best approach for the patient’s care.”
 

Filling data gaps

Some of those data gaps persist today, Dr. Kabrhel said. “It’s precisely that lack of head-to-head data that existed in 2012, and to a great extent still exists today, that led us to create this system.” The American Heart Association just this January issued a scientific statement on surgical management and mechanical circulatory support in high-risk PE (Circulation. 2023;147:e628­­-47).

But the intervening research has been uneven. The Pulmonary Embolism Thrombolysis (PEITHO) trial in 2014 evaluated systemic thrombolysis and anticoagulation alone (N Engl J Med. 2014;370:1402-11), but head-to-head studies of catheter-directed thrombolysis (CDT), which was just emerging in 2012, and either systemic thrombolysis or anticoagulation have been lacking, Dr. Kabrhel said. The Hi-PEITHO trial in high-risk PE patients is evaluating ultrasound-guided CDT plus anticoagulation vs. anticoagulation alone (Am Heart J. 2022:251:43-54), but it isn’t complete.

“The therapeutic landscape for PE is evolving incredibly rapidly,” he said. “When we first started PERT we were just starting to see CDT. Since then, we’ve seen several new thrombolytic catheters come onto the market, but there’s also been a proliferation of suction embolectomy catheters and we’ve seen a potentially larger role for surgery and the use of ECMO [extracorporeal membrane oxygenation] or cardiac bypass to bridge patients to definitive therapy. With the rapid evolution and the seemingly daily addition of new therapeutic options, I think the need for PERT is only increasing.”

A recent study out of the University of Michigan reported that the PERT there led to a decrease in the use of advanced therapies given to acute PE patients without reducing mortality or extending hospital stays (Thromb Res. 2023;221:73-8). A study in Spain reported that patients with high-risk and intermediate high-risk PE who had PERT-coordinated care had half the 12-month mortality rate of non-PERT counterparts, 9% vs. 22.2% (P = .02) (Med Clin [Barc]. 2023;S0025-7753(23)00017-9). And a 2021 study at University Hospitals in Cleveland reported that PERT-managed PE patients had a 60% lower rate of adverse outcomes at 90 days than non–PERT-managed patients (J Invasive Cardiol. 2021;33:E173-E180).

Michigan Medicine

Nelish Ardeshna, MD, MA, the lead author of the Michigan study, said the PERT there was formed in 2017. Besides the multispecialty team that can be summoned to a teleconference on short notice, the protocol includes having at least one noninvasive specialist, such as a cardiologist or hospitalist, and one interventionalist, such as a radiologist, always on call. The PERT gets activated through the paging system after a hospital or emergency department physician identifies a suspected or established high-risk PE.

“High-risk PE patients can present in all settings, including the emergency department, ICU, surgical floor, or medical floor,” said Dr. Ardeshna, an internal medicine resident. “Management for these patients is equally varied from anticoagulation to systemic thrombolytics. Not all providers may be familiar with current guidelines to select the optimal therapy for high-risk pulmonary embolism patients. PERT aims to bridge that gap by providing a multidisciplinary discussion with PE specialists that can help identify the correct therapeutic options for optimal outcomes.”

Cleveland Clinic

At Cleveland Clinic, where the PERT has been in place since 2012, the PERT can consist of six to eight different specialties and involve up to 15 providers on a conference call, said Leben Tefera, MD, a vascular specialist and head of the PERT team there.

“Each patient will come in and have certain comorbidities,” Dr. Tefera said. “The unfortunate thing about a majority of the PEs that we see, in particular ones [in patients] that are very sick and require inpatient treatment, is that they don’t really fit into a box; you can’t come up with one kind of generic care routine or care path that treats the majority of patients with PE.”
 

Evolving to follow-up care

As the PERT protocol led to better inpatient outcomes, the teams became more aware that discharged PE patients were struggling with mental health and other quality-of-life issues – symptoms that have been understudied, according to a protocol Dr. Tefera coauthored for a prospective observational study of psychological distress symptoms in PE survivors. By contrast, the protocol noted, these symptoms have been studied extensively in myocardial infarction and stroke patients (Res Pract Thromb Hemost. 2023. doi: 10.1016/j.rpth.2023.10045). Other studies have found that 35%-50% of patients reported mental health symptoms 3 months after PE (Chest. 2021;159:2428-38; Qual Life Res. 2019;28:2111-24).

“A lot of physicians have known it for quite some time, but it wasn’t really until the last couple of years that physicians started saying psychological stress is something that we need to quantify and that we need to actually treat, that we actually need to address,” Dr. Tefera said. That led Dr. Tefera and his Cleveland Clinic PERT colleagues to set up a follow-up clinic for PE patients.

At their follow-up visits, patients complete validated questionnaires about anxiety, depression, fear of recurrence, PE-specific quality of life, and posttraumatic stress disorder. “If they flag as positive, we give them a referral to an in-house psychologist,” he said. “One thing I can report is that patients absolutely, positively love this, because it’s something that they are all experiencing that a lot of physicians just aren’t addressing.”
 

Artificial intelligence emerges

At the University of Pittsburgh Medical Center, the PERT has started evaluating artificial intelligence to aid in PE diagnosis. Belinda Rivera-Lebron, MD, director of the acute and chronic embolism program at Pitt, explained that the AI protocol hasn’t been adopted yet, but the concept is to have a platform that’s compatible with the hospital system’s electronic medical record.

University of Pittsburgh

She described how AI would work once the PERT is activated. “Once the patient goes through the CT scanner, within 60 seconds of that scan being completed, the scan gets uploaded into the cloud and the app or the platform is able to tell you whether there is PE present or absent, and whether there is right ventricle dilation on that scan. This is even before you probably even think about opening up the computer to look at the scan, and even before radiology opens up the scan to read,” she said. “It’s so fast.”

The idea is to send the scans rapidly to the PERT. “It will send you a text, a notification on your phone that will tell you Mr. Smith is PE positive,” Dr. Rivera-Lebron said. “Then you open it and you are able to scroll through the CT scan in your phone. So, it’s really remarkable.”
 

Clinical trials worth watching

Meanwhile, a number of clinical trials have started to enroll patients, or will soon, that Dr. Rivera-Lebron said are worth paying attention to.

PEITHO-3 is a randomized, placebo-controlled trial with long-term follow-up comparing the efficacy of a reduced-dose alteplase regimen or standard heparin anticoagulation in patients with intermediate to high-risk PE (Thromb Haemost. 2022;122:867-66).

PEERLESS is a prospective randomized trial comparing mechanical thrombectomy and CDT (ClinicalTrials.gov identifier NCT05111613).

PE-Thrombus Removal with Catheter-directed Therapy (PE-TRACT) is an open-label Phase 3 trial comparing anticoagulation and CDT that’s not yet recruiting (ClinicalTrials.gov identifier NCT05591118).

FlowTriever for Acute Massive Pulmonary Embolism (FLAME) is a prospective cohort study evaluating a clot-retrieving device in high-risk PE patients (ClinicalTrials.gov identifier NCT04795167).

When completed and published, these trials could provide PERTs more evidence for their decision-making.

Dr. Ardeshna and Dr. Tefera have no relevant relationships to disclose. Dr. Rivera-Lebron disclosed relationships with INARI Catheter and Johnson & Johnson. Dr. Kabrhel disclosed relationships with Bristol Myers Squibb and Pfizer.

In 2012, a small group of specialists, consisting of a critical care pulmonologist, cardiologist, cardiac surgeon, and vascular specialist, at Massachusetts General Hospital, Boston, met to Monday morning quarterback an acute pulmonary embolism case that didn’t go as well as they’d hoped. They came up with a concept known as the pulmonary embolism response team – PERT for short – an idea that soon took hold in other centers and served as the vanguard to other innovative approaches to managing critical care patients with PE, which is the third-leading cause of cardiovascular death in the United States (Intern Emerg Med. 2023. doi: 10.1007/s11739-022-03180-w).

Leisa Thompson/Michigan Medicine

Three years later the PERT Consortium came together, which today has 102 members, according to the organization’s website (www.pertconsortium.org), and members in South America, Europe, Asia, and Australia. Since then, PE strategies have evolved to target mental health issues recovering patients have, improve follow-up after discharge, and even investigate artificial intelligence and apps to expedite diagnosis and treatment. The PERT Consortium, meanwhile, is in the process of creating the PE Centers of Excellence program to certify centers that meet certain requirements.

Harvard Medical School

“Part of the reason we recognized that a discussion across specialties was important was because there weren’t the large clinical trials that could tell us exactly what to do for any given case,” said Christopher Kabrhel, MD, MPH, director of the Center for Vascular Emergencies at Mass General and a professor at Harvard Medical School in Boston, who assembled that formative meeting. “Without a clear basis in data, it was really important to have all the different specialists weigh in and give their perspective and talk about what was the best approach for the patient’s care.”
 

Filling data gaps

Some of those data gaps persist today, Dr. Kabrhel said. “It’s precisely that lack of head-to-head data that existed in 2012, and to a great extent still exists today, that led us to create this system.” The American Heart Association just this January issued a scientific statement on surgical management and mechanical circulatory support in high-risk PE (Circulation. 2023;147:e628­­-47).

But the intervening research has been uneven. The Pulmonary Embolism Thrombolysis (PEITHO) trial in 2014 evaluated systemic thrombolysis and anticoagulation alone (N Engl J Med. 2014;370:1402-11), but head-to-head studies of catheter-directed thrombolysis (CDT), which was just emerging in 2012, and either systemic thrombolysis or anticoagulation have been lacking, Dr. Kabrhel said. The Hi-PEITHO trial in high-risk PE patients is evaluating ultrasound-guided CDT plus anticoagulation vs. anticoagulation alone (Am Heart J. 2022:251:43-54), but it isn’t complete.

“The therapeutic landscape for PE is evolving incredibly rapidly,” he said. “When we first started PERT we were just starting to see CDT. Since then, we’ve seen several new thrombolytic catheters come onto the market, but there’s also been a proliferation of suction embolectomy catheters and we’ve seen a potentially larger role for surgery and the use of ECMO [extracorporeal membrane oxygenation] or cardiac bypass to bridge patients to definitive therapy. With the rapid evolution and the seemingly daily addition of new therapeutic options, I think the need for PERT is only increasing.”

A recent study out of the University of Michigan reported that the PERT there led to a decrease in the use of advanced therapies given to acute PE patients without reducing mortality or extending hospital stays (Thromb Res. 2023;221:73-8). A study in Spain reported that patients with high-risk and intermediate high-risk PE who had PERT-coordinated care had half the 12-month mortality rate of non-PERT counterparts, 9% vs. 22.2% (P = .02) (Med Clin [Barc]. 2023;S0025-7753(23)00017-9). And a 2021 study at University Hospitals in Cleveland reported that PERT-managed PE patients had a 60% lower rate of adverse outcomes at 90 days than non–PERT-managed patients (J Invasive Cardiol. 2021;33:E173-E180).

Michigan Medicine

Nelish Ardeshna, MD, MA, the lead author of the Michigan study, said the PERT there was formed in 2017. Besides the multispecialty team that can be summoned to a teleconference on short notice, the protocol includes having at least one noninvasive specialist, such as a cardiologist or hospitalist, and one interventionalist, such as a radiologist, always on call. The PERT gets activated through the paging system after a hospital or emergency department physician identifies a suspected or established high-risk PE.

“High-risk PE patients can present in all settings, including the emergency department, ICU, surgical floor, or medical floor,” said Dr. Ardeshna, an internal medicine resident. “Management for these patients is equally varied from anticoagulation to systemic thrombolytics. Not all providers may be familiar with current guidelines to select the optimal therapy for high-risk pulmonary embolism patients. PERT aims to bridge that gap by providing a multidisciplinary discussion with PE specialists that can help identify the correct therapeutic options for optimal outcomes.”

Cleveland Clinic

At Cleveland Clinic, where the PERT has been in place since 2012, the PERT can consist of six to eight different specialties and involve up to 15 providers on a conference call, said Leben Tefera, MD, a vascular specialist and head of the PERT team there.

“Each patient will come in and have certain comorbidities,” Dr. Tefera said. “The unfortunate thing about a majority of the PEs that we see, in particular ones [in patients] that are very sick and require inpatient treatment, is that they don’t really fit into a box; you can’t come up with one kind of generic care routine or care path that treats the majority of patients with PE.”
 

Evolving to follow-up care

As the PERT protocol led to better inpatient outcomes, the teams became more aware that discharged PE patients were struggling with mental health and other quality-of-life issues – symptoms that have been understudied, according to a protocol Dr. Tefera coauthored for a prospective observational study of psychological distress symptoms in PE survivors. By contrast, the protocol noted, these symptoms have been studied extensively in myocardial infarction and stroke patients (Res Pract Thromb Hemost. 2023. doi: 10.1016/j.rpth.2023.10045). Other studies have found that 35%-50% of patients reported mental health symptoms 3 months after PE (Chest. 2021;159:2428-38; Qual Life Res. 2019;28:2111-24).

“A lot of physicians have known it for quite some time, but it wasn’t really until the last couple of years that physicians started saying psychological stress is something that we need to quantify and that we need to actually treat, that we actually need to address,” Dr. Tefera said. That led Dr. Tefera and his Cleveland Clinic PERT colleagues to set up a follow-up clinic for PE patients.

At their follow-up visits, patients complete validated questionnaires about anxiety, depression, fear of recurrence, PE-specific quality of life, and posttraumatic stress disorder. “If they flag as positive, we give them a referral to an in-house psychologist,” he said. “One thing I can report is that patients absolutely, positively love this, because it’s something that they are all experiencing that a lot of physicians just aren’t addressing.”
 

Artificial intelligence emerges

At the University of Pittsburgh Medical Center, the PERT has started evaluating artificial intelligence to aid in PE diagnosis. Belinda Rivera-Lebron, MD, director of the acute and chronic embolism program at Pitt, explained that the AI protocol hasn’t been adopted yet, but the concept is to have a platform that’s compatible with the hospital system’s electronic medical record.

University of Pittsburgh

She described how AI would work once the PERT is activated. “Once the patient goes through the CT scanner, within 60 seconds of that scan being completed, the scan gets uploaded into the cloud and the app or the platform is able to tell you whether there is PE present or absent, and whether there is right ventricle dilation on that scan. This is even before you probably even think about opening up the computer to look at the scan, and even before radiology opens up the scan to read,” she said. “It’s so fast.”

The idea is to send the scans rapidly to the PERT. “It will send you a text, a notification on your phone that will tell you Mr. Smith is PE positive,” Dr. Rivera-Lebron said. “Then you open it and you are able to scroll through the CT scan in your phone. So, it’s really remarkable.”
 

Clinical trials worth watching

Meanwhile, a number of clinical trials have started to enroll patients, or will soon, that Dr. Rivera-Lebron said are worth paying attention to.

PEITHO-3 is a randomized, placebo-controlled trial with long-term follow-up comparing the efficacy of a reduced-dose alteplase regimen or standard heparin anticoagulation in patients with intermediate to high-risk PE (Thromb Haemost. 2022;122:867-66).

PEERLESS is a prospective randomized trial comparing mechanical thrombectomy and CDT (ClinicalTrials.gov identifier NCT05111613).

PE-Thrombus Removal with Catheter-directed Therapy (PE-TRACT) is an open-label Phase 3 trial comparing anticoagulation and CDT that’s not yet recruiting (ClinicalTrials.gov identifier NCT05591118).

FlowTriever for Acute Massive Pulmonary Embolism (FLAME) is a prospective cohort study evaluating a clot-retrieving device in high-risk PE patients (ClinicalTrials.gov identifier NCT04795167).

When completed and published, these trials could provide PERTs more evidence for their decision-making.

Dr. Ardeshna and Dr. Tefera have no relevant relationships to disclose. Dr. Rivera-Lebron disclosed relationships with INARI Catheter and Johnson & Johnson. Dr. Kabrhel disclosed relationships with Bristol Myers Squibb and Pfizer.

A secondary analysis of a large landmark clinical trial of how the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin effects cardiovascular risk has identified two biomarkers that can help better determine which patients with type 2 diabetes (T2D) and cardiovascular disease risk would derive the most benefit from the drug.

Brigham and Women’s Hospital

The researchers found that N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) levels helped identify a subset of T2D patients at higher risk of major adverse cardiovascular events who would benefit most from dapagliflozin.

“We’ve shown previously that these two biomarkers are very robust risk indicators for cardiovascular death and heart failure events,” senior study author David A. Morrow, MD, of Harvard University, Boston, said in an interview. “In this study, we now show that the two biomarkers also yield important prognostic information for MACE [major adverse cardiovascular events].”

Although NT-proBNP is typically measured to diagnose heart failure, and hsTnT to diagnose acute MI, Dr. Morrow pointed out that this analysis demonstrated the potential for using the two tests to evaluate risks in T2D patients.
 

Study results

The secondary analysis included 14,565 patients in the DECLARE-TIMI 58 trial. The patients had T2D and multiple risk factors for atherosclerotic cardiovascular disease (about 60%) or established ASCVD (about 40%). All patients had available blood samples and the data were collected from May 2013 to September 2018. The primary outcome was MACE, a composite of MI, ischemic stroke, and cardiovascular death. The results were reported online in JAMA Cardiology.

The analysis found that higher baseline concentrations of NT-proBNP increased MACE risks by 62% (95% confidence interval, 1.49-1.76) and hsTnT elevated those risks by 59% (95% CI, 1.46-1.74).

Among placebo patients, when divided into risk quartiles, those in the highest quartile had significantly higher risk with both elevated NT-proBNP and hsTnT, compared with those with low concentrations. For example, patients with established ASCVD had a 22.9% risk vs. 9.5% with elevated NT-proBNP (P < .001) and a 24.2% vs. 7.2% risk with elevated hsTnT (P < .001). The gap was similar for patients with multiple risk factors.

Dr. Morrow noted that the main DECLARE-TIMI 58 trial showed that dapagliflozin reduced the rates of cardiovascular death or hospitalization for heart failure in patients with T2D, when compared to placebo, but didn’t reach statistical significance for MACE (N Engl J Med. 2019;380:347-57).

“We have previously shown that among patients with T2D who have high risk indicators, such as prior MI or long-standing diabetes, dapagliflozin also appeared to reduce MACE,” Dr. Morrow said. “In this study, we find that these two widely available biomarkers also identify a high-risk group who may have even more potential benefits from treatment with an SGLT2i.”

Dr. Morrow noted that the study design – a nested prospective biomarker study within a randomized, double-blind, placebo-controlled clinical trial – “is a particular strength.”
 

Results clarify which patients will benefit

This secondary analysis of DECLARE-TIMI 58 brings more clarity to the types of T2D patients who will get the most cardiovascular benefits from dapagliflozin, said Matthew J. Budoff, MD, professor of medicine at University of California, Los Angeles, and Endowed Chair of Preventive Cardiology at the Lundquist Institute in Torrance, Calif.

Lundquist Institute

“The big picture is, we’ve known for some time from epidemiologic studies that these biomarkers, when they’re elevated, mean that the patient is at higher risk of having a cardiovascular event,” he said, “but I think what it helps us with is in knowing in whom to use dapagliflozin for prevention of ASCVD. The effect in the DECLARE-TIMI 58 trial was quite modest, but if you can subgroup it, in these high-risk people there’s a more profound effect. It helps in risk stratification because the absolute benefit is larger.”

The specific biomarkers, NT-proBNP and hsTnT, “haven’t been explored very much in clinical trials,” Dr. Budoff said, “so I do think that it’s nice that in a randomized trial it plays out the way we might expect.”

He added that “for many clinicians this is novel, because I don’t think they were aware of the biomarker data, so I think that this does add some clinical benefit in that context.” The findings also strengthen the case to get T2D patients with higher ASCVD risk onto SGLT2 inhibitors if they’re not already, he said.

Dr. Morrow disclosed relationships with AstraZeneca, Roche Diagnostics, Abbott Laboratories, Anthos Therapeutics, ARCA Biopharma, Merck, Novartis, Pfizer, Regeneron, Siemens, and InCarda outside the reported work.

Dr. Budoff has no relevant disclosures.

A secondary analysis of a large landmark clinical trial of how the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin effects cardiovascular risk has identified two biomarkers that can help better determine which patients with type 2 diabetes (T2D) and cardiovascular disease risk would derive the most benefit from the drug.

Brigham and Women’s Hospital

The researchers found that N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) levels helped identify a subset of T2D patients at higher risk of major adverse cardiovascular events who would benefit most from dapagliflozin.

“We’ve shown previously that these two biomarkers are very robust risk indicators for cardiovascular death and heart failure events,” senior study author David A. Morrow, MD, of Harvard University, Boston, said in an interview. “In this study, we now show that the two biomarkers also yield important prognostic information for MACE [major adverse cardiovascular events].”

Although NT-proBNP is typically measured to diagnose heart failure, and hsTnT to diagnose acute MI, Dr. Morrow pointed out that this analysis demonstrated the potential for using the two tests to evaluate risks in T2D patients.
 

Study results

The secondary analysis included 14,565 patients in the DECLARE-TIMI 58 trial. The patients had T2D and multiple risk factors for atherosclerotic cardiovascular disease (about 60%) or established ASCVD (about 40%). All patients had available blood samples and the data were collected from May 2013 to September 2018. The primary outcome was MACE, a composite of MI, ischemic stroke, and cardiovascular death. The results were reported online in JAMA Cardiology.

The analysis found that higher baseline concentrations of NT-proBNP increased MACE risks by 62% (95% confidence interval, 1.49-1.76) and hsTnT elevated those risks by 59% (95% CI, 1.46-1.74).

Among placebo patients, when divided into risk quartiles, those in the highest quartile had significantly higher risk with both elevated NT-proBNP and hsTnT, compared with those with low concentrations. For example, patients with established ASCVD had a 22.9% risk vs. 9.5% with elevated NT-proBNP (P < .001) and a 24.2% vs. 7.2% risk with elevated hsTnT (P < .001). The gap was similar for patients with multiple risk factors.

Dr. Morrow noted that the main DECLARE-TIMI 58 trial showed that dapagliflozin reduced the rates of cardiovascular death or hospitalization for heart failure in patients with T2D, when compared to placebo, but didn’t reach statistical significance for MACE (N Engl J Med. 2019;380:347-57).

“We have previously shown that among patients with T2D who have high risk indicators, such as prior MI or long-standing diabetes, dapagliflozin also appeared to reduce MACE,” Dr. Morrow said. “In this study, we find that these two widely available biomarkers also identify a high-risk group who may have even more potential benefits from treatment with an SGLT2i.”

Dr. Morrow noted that the study design – a nested prospective biomarker study within a randomized, double-blind, placebo-controlled clinical trial – “is a particular strength.”
 

Results clarify which patients will benefit

This secondary analysis of DECLARE-TIMI 58 brings more clarity to the types of T2D patients who will get the most cardiovascular benefits from dapagliflozin, said Matthew J. Budoff, MD, professor of medicine at University of California, Los Angeles, and Endowed Chair of Preventive Cardiology at the Lundquist Institute in Torrance, Calif.

Lundquist Institute

“The big picture is, we’ve known for some time from epidemiologic studies that these biomarkers, when they’re elevated, mean that the patient is at higher risk of having a cardiovascular event,” he said, “but I think what it helps us with is in knowing in whom to use dapagliflozin for prevention of ASCVD. The effect in the DECLARE-TIMI 58 trial was quite modest, but if you can subgroup it, in these high-risk people there’s a more profound effect. It helps in risk stratification because the absolute benefit is larger.”

The specific biomarkers, NT-proBNP and hsTnT, “haven’t been explored very much in clinical trials,” Dr. Budoff said, “so I do think that it’s nice that in a randomized trial it plays out the way we might expect.”

He added that “for many clinicians this is novel, because I don’t think they were aware of the biomarker data, so I think that this does add some clinical benefit in that context.” The findings also strengthen the case to get T2D patients with higher ASCVD risk onto SGLT2 inhibitors if they’re not already, he said.

Dr. Morrow disclosed relationships with AstraZeneca, Roche Diagnostics, Abbott Laboratories, Anthos Therapeutics, ARCA Biopharma, Merck, Novartis, Pfizer, Regeneron, Siemens, and InCarda outside the reported work.

Dr. Budoff has no relevant disclosures.

A secondary analysis of a large landmark clinical trial of how the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin effects cardiovascular risk has identified two biomarkers that can help better determine which patients with type 2 diabetes (T2D) and cardiovascular disease risk would derive the most benefit from the drug.

Brigham and Women’s Hospital

The researchers found that N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) levels helped identify a subset of T2D patients at higher risk of major adverse cardiovascular events who would benefit most from dapagliflozin.

“We’ve shown previously that these two biomarkers are very robust risk indicators for cardiovascular death and heart failure events,” senior study author David A. Morrow, MD, of Harvard University, Boston, said in an interview. “In this study, we now show that the two biomarkers also yield important prognostic information for MACE [major adverse cardiovascular events].”

Although NT-proBNP is typically measured to diagnose heart failure, and hsTnT to diagnose acute MI, Dr. Morrow pointed out that this analysis demonstrated the potential for using the two tests to evaluate risks in T2D patients.
 

Study results

The secondary analysis included 14,565 patients in the DECLARE-TIMI 58 trial. The patients had T2D and multiple risk factors for atherosclerotic cardiovascular disease (about 60%) or established ASCVD (about 40%). All patients had available blood samples and the data were collected from May 2013 to September 2018. The primary outcome was MACE, a composite of MI, ischemic stroke, and cardiovascular death. The results were reported online in JAMA Cardiology.

The analysis found that higher baseline concentrations of NT-proBNP increased MACE risks by 62% (95% confidence interval, 1.49-1.76) and hsTnT elevated those risks by 59% (95% CI, 1.46-1.74).

Among placebo patients, when divided into risk quartiles, those in the highest quartile had significantly higher risk with both elevated NT-proBNP and hsTnT, compared with those with low concentrations. For example, patients with established ASCVD had a 22.9% risk vs. 9.5% with elevated NT-proBNP (P < .001) and a 24.2% vs. 7.2% risk with elevated hsTnT (P < .001). The gap was similar for patients with multiple risk factors.

Dr. Morrow noted that the main DECLARE-TIMI 58 trial showed that dapagliflozin reduced the rates of cardiovascular death or hospitalization for heart failure in patients with T2D, when compared to placebo, but didn’t reach statistical significance for MACE (N Engl J Med. 2019;380:347-57).

“We have previously shown that among patients with T2D who have high risk indicators, such as prior MI or long-standing diabetes, dapagliflozin also appeared to reduce MACE,” Dr. Morrow said. “In this study, we find that these two widely available biomarkers also identify a high-risk group who may have even more potential benefits from treatment with an SGLT2i.”

Dr. Morrow noted that the study design – a nested prospective biomarker study within a randomized, double-blind, placebo-controlled clinical trial – “is a particular strength.”
 

Results clarify which patients will benefit

This secondary analysis of DECLARE-TIMI 58 brings more clarity to the types of T2D patients who will get the most cardiovascular benefits from dapagliflozin, said Matthew J. Budoff, MD, professor of medicine at University of California, Los Angeles, and Endowed Chair of Preventive Cardiology at the Lundquist Institute in Torrance, Calif.

Lundquist Institute

“The big picture is, we’ve known for some time from epidemiologic studies that these biomarkers, when they’re elevated, mean that the patient is at higher risk of having a cardiovascular event,” he said, “but I think what it helps us with is in knowing in whom to use dapagliflozin for prevention of ASCVD. The effect in the DECLARE-TIMI 58 trial was quite modest, but if you can subgroup it, in these high-risk people there’s a more profound effect. It helps in risk stratification because the absolute benefit is larger.”

The specific biomarkers, NT-proBNP and hsTnT, “haven’t been explored very much in clinical trials,” Dr. Budoff said, “so I do think that it’s nice that in a randomized trial it plays out the way we might expect.”

He added that “for many clinicians this is novel, because I don’t think they were aware of the biomarker data, so I think that this does add some clinical benefit in that context.” The findings also strengthen the case to get T2D patients with higher ASCVD risk onto SGLT2 inhibitors if they’re not already, he said.

Dr. Morrow disclosed relationships with AstraZeneca, Roche Diagnostics, Abbott Laboratories, Anthos Therapeutics, ARCA Biopharma, Merck, Novartis, Pfizer, Regeneron, Siemens, and InCarda outside the reported work.

Dr. Budoff has no relevant disclosures.

A new meta-analysis has added evidence questioning the utility and efficacy of prophylactic low-dose aspirin for preventing cardiovascular events in people who don’t have atherosclerotic cardiovascular disease (ASCVD), whether or not they’re also taking statins, and finds that at every level of ASCVD risk the aspirin carries a risk of major bleeding that exceeds its potentially protective benefits.

In a study published online in JACC: Advances, the researchers, led by Safi U. Khan, MD, MS, analyzed data from 16 trials with 171,215 individuals, with a median age of 64 years. Of the population analyzed, 35% were taking statins.

“This study focused on patients without ASCVD who are taking aspirin with or without statin therapy to prevent ASCVD events,” Dr. Khan, a cardiovascular disease fellow at Houston Methodist DeBakey Heart and Vascular Institute, told this news organization. “We noted that the absolute risk of major bleeding in this patient population exceeds the absolute reduction in MI by aspirin across different ASCVD risk categories. Furthermore, concomitant statin therapy use further diminishes aspirin’s cardiovascular effects without influencing bleeding risk.”

Across the 16 studies, people taking aspirin had a relative risk reduction of 15% for MI vs. controls (RR .85; 95% confidence interval [CI], .77 to .95; P < .001). However, they had a 48% greater risk of major bleeding (RR, 1.48; 95% CI, 1.31-1.66; P < .001).

The meta-analysis also found that aspirin, either as monotherapy or with a statin, carried a slight to significant benefit depending on the estimated risk of developing ASCVD. The risk of major bleeding exceeded the benefit across all three risk-stratified groups. The greatest benefit, and greatest risk, was in the groups with high to very-high ASCVD risk groups, defined as a 20%-30% and 30% or greater ASCVD risk, respectively: 20-37 fewer MIs per 10,000 with monotherapy and 27-49 fewer with statin, but 78-98 more major bleeding events with monotherapy and 74-95 more with statin.

And aspirin, either as monotherapy or with statin, didn’t reduce the risk of other key endpoints: stroke, all-cause mortality, or cardiovascular mortality. While aspirin was associated with a lower risk of nonfatal MI (RR, .82; 95% CI, .72 to .94; P ≤. 001), it  wasn’t associated with reducing the risk of nonfatal stroke. Aspirin patients had a significantly 32% greater risk of intracranial hemorrhage (RR, 1.32; 95% CI, 1.12-1.55; P ≤ .001) and 51% increased risk of gastrointestinal bleeding (RR, 1.51; 95% CI, 1.33-1.72; P ≤ .001).

“We used randomized data from all key primary prevention of aspirin trials and estimated the absolute effects of aspirin therapy with or without concomitant statin across different baseline risks of the patients,” Dr. Khan said. “This approach allowed us to identify aspirin therapy’s risk-benefit equilibrium, which is tilted towards more harm than benefit.”

He acknowledged study limitations included using study-level rather than patient-level meta-analysis, and the inability to calculate effects in younger populations at high absolute risk.  

The investigators acknowledged the controversy surrounding aspirin use to prevent ASCVD, noting the three major guidelines: the 2019 American College of Cardiology/American Heart Association and the 2021 European Society of Cardiology guidelines for aspirin only among asymptomatic individuals with high risk of ASCVD events, low bleeding risk, and age 70 years and younger; and the United States Preventive Services Task Force guidelines, updated in 2022, recommending individualized low-dose aspirin only among adults ages 40-59 years with 10-year ASCVD risk of 10% or greater and a low bleeding risk.

The findings are not a clarion call to halt aspirin therapy, Dr. Khan said. “This research focuses only on patients who do not have ASCVD,” he said. “Patients who do have ASCVD should continue with aspirin and statin therapy. However, we noted that aspirin has a limited role for patients who do not have ASCVD beyond lifestyle modifications, smoking cessation, exercise, and preventive statin therapy. Therefore, they should only consider using aspirin if their physicians suggest that the risk of having a cardiovascular event exceeds their bleeding risk. Otherwise, they should discuss with their physicians about omitting aspirin.”

The study confirms the move away from low-dose aspirin to prevent ASCVD, said Tahmid Rahman, MD, cardiologist and associate director of the Center for Advanced Lipid Management at Stony Brook (N.Y.) Heart Institute. “The study really continues to add to essentially what we already know,” he said. “There was a big push that aspirin, initially before the major statin trials, was the way to go to prevent heart disease, but with later studies, and especially now with newer antiplatelet therapies and longer duration of medication for people with both secondary prevention and primary prevention, we are getting away from routine aspirin, especially in primary prevention.”

A new meta-analysis has added evidence questioning the utility and efficacy of prophylactic low-dose aspirin for preventing cardiovascular events in people who don’t have atherosclerotic cardiovascular disease (ASCVD), whether or not they’re also taking statins, and finds that at every level of ASCVD risk the aspirin carries a risk of major bleeding that exceeds its potentially protective benefits.

In a study published online in JACC: Advances, the researchers, led by Safi U. Khan, MD, MS, analyzed data from 16 trials with 171,215 individuals, with a median age of 64 years. Of the population analyzed, 35% were taking statins.

“This study focused on patients without ASCVD who are taking aspirin with or without statin therapy to prevent ASCVD events,” Dr. Khan, a cardiovascular disease fellow at Houston Methodist DeBakey Heart and Vascular Institute, told this news organization. “We noted that the absolute risk of major bleeding in this patient population exceeds the absolute reduction in MI by aspirin across different ASCVD risk categories. Furthermore, concomitant statin therapy use further diminishes aspirin’s cardiovascular effects without influencing bleeding risk.”

Across the 16 studies, people taking aspirin had a relative risk reduction of 15% for MI vs. controls (RR .85; 95% confidence interval [CI], .77 to .95; P < .001). However, they had a 48% greater risk of major bleeding (RR, 1.48; 95% CI, 1.31-1.66; P < .001).

The meta-analysis also found that aspirin, either as monotherapy or with a statin, carried a slight to significant benefit depending on the estimated risk of developing ASCVD. The risk of major bleeding exceeded the benefit across all three risk-stratified groups. The greatest benefit, and greatest risk, was in the groups with high to very-high ASCVD risk groups, defined as a 20%-30% and 30% or greater ASCVD risk, respectively: 20-37 fewer MIs per 10,000 with monotherapy and 27-49 fewer with statin, but 78-98 more major bleeding events with monotherapy and 74-95 more with statin.

And aspirin, either as monotherapy or with statin, didn’t reduce the risk of other key endpoints: stroke, all-cause mortality, or cardiovascular mortality. While aspirin was associated with a lower risk of nonfatal MI (RR, .82; 95% CI, .72 to .94; P ≤. 001), it  wasn’t associated with reducing the risk of nonfatal stroke. Aspirin patients had a significantly 32% greater risk of intracranial hemorrhage (RR, 1.32; 95% CI, 1.12-1.55; P ≤ .001) and 51% increased risk of gastrointestinal bleeding (RR, 1.51; 95% CI, 1.33-1.72; P ≤ .001).

“We used randomized data from all key primary prevention of aspirin trials and estimated the absolute effects of aspirin therapy with or without concomitant statin across different baseline risks of the patients,” Dr. Khan said. “This approach allowed us to identify aspirin therapy’s risk-benefit equilibrium, which is tilted towards more harm than benefit.”

He acknowledged study limitations included using study-level rather than patient-level meta-analysis, and the inability to calculate effects in younger populations at high absolute risk.  

The investigators acknowledged the controversy surrounding aspirin use to prevent ASCVD, noting the three major guidelines: the 2019 American College of Cardiology/American Heart Association and the 2021 European Society of Cardiology guidelines for aspirin only among asymptomatic individuals with high risk of ASCVD events, low bleeding risk, and age 70 years and younger; and the United States Preventive Services Task Force guidelines, updated in 2022, recommending individualized low-dose aspirin only among adults ages 40-59 years with 10-year ASCVD risk of 10% or greater and a low bleeding risk.

The findings are not a clarion call to halt aspirin therapy, Dr. Khan said. “This research focuses only on patients who do not have ASCVD,” he said. “Patients who do have ASCVD should continue with aspirin and statin therapy. However, we noted that aspirin has a limited role for patients who do not have ASCVD beyond lifestyle modifications, smoking cessation, exercise, and preventive statin therapy. Therefore, they should only consider using aspirin if their physicians suggest that the risk of having a cardiovascular event exceeds their bleeding risk. Otherwise, they should discuss with their physicians about omitting aspirin.”

The study confirms the move away from low-dose aspirin to prevent ASCVD, said Tahmid Rahman, MD, cardiologist and associate director of the Center for Advanced Lipid Management at Stony Brook (N.Y.) Heart Institute. “The study really continues to add to essentially what we already know,” he said. “There was a big push that aspirin, initially before the major statin trials, was the way to go to prevent heart disease, but with later studies, and especially now with newer antiplatelet therapies and longer duration of medication for people with both secondary prevention and primary prevention, we are getting away from routine aspirin, especially in primary prevention.”

A new meta-analysis has added evidence questioning the utility and efficacy of prophylactic low-dose aspirin for preventing cardiovascular events in people who don’t have atherosclerotic cardiovascular disease (ASCVD), whether or not they’re also taking statins, and finds that at every level of ASCVD risk the aspirin carries a risk of major bleeding that exceeds its potentially protective benefits.

In a study published online in JACC: Advances, the researchers, led by Safi U. Khan, MD, MS, analyzed data from 16 trials with 171,215 individuals, with a median age of 64 years. Of the population analyzed, 35% were taking statins.

“This study focused on patients without ASCVD who are taking aspirin with or without statin therapy to prevent ASCVD events,” Dr. Khan, a cardiovascular disease fellow at Houston Methodist DeBakey Heart and Vascular Institute, told this news organization. “We noted that the absolute risk of major bleeding in this patient population exceeds the absolute reduction in MI by aspirin across different ASCVD risk categories. Furthermore, concomitant statin therapy use further diminishes aspirin’s cardiovascular effects without influencing bleeding risk.”

Across the 16 studies, people taking aspirin had a relative risk reduction of 15% for MI vs. controls (RR .85; 95% confidence interval [CI], .77 to .95; P < .001). However, they had a 48% greater risk of major bleeding (RR, 1.48; 95% CI, 1.31-1.66; P < .001).

The meta-analysis also found that aspirin, either as monotherapy or with a statin, carried a slight to significant benefit depending on the estimated risk of developing ASCVD. The risk of major bleeding exceeded the benefit across all three risk-stratified groups. The greatest benefit, and greatest risk, was in the groups with high to very-high ASCVD risk groups, defined as a 20%-30% and 30% or greater ASCVD risk, respectively: 20-37 fewer MIs per 10,000 with monotherapy and 27-49 fewer with statin, but 78-98 more major bleeding events with monotherapy and 74-95 more with statin.

And aspirin, either as monotherapy or with statin, didn’t reduce the risk of other key endpoints: stroke, all-cause mortality, or cardiovascular mortality. While aspirin was associated with a lower risk of nonfatal MI (RR, .82; 95% CI, .72 to .94; P ≤. 001), it  wasn’t associated with reducing the risk of nonfatal stroke. Aspirin patients had a significantly 32% greater risk of intracranial hemorrhage (RR, 1.32; 95% CI, 1.12-1.55; P ≤ .001) and 51% increased risk of gastrointestinal bleeding (RR, 1.51; 95% CI, 1.33-1.72; P ≤ .001).

“We used randomized data from all key primary prevention of aspirin trials and estimated the absolute effects of aspirin therapy with or without concomitant statin across different baseline risks of the patients,” Dr. Khan said. “This approach allowed us to identify aspirin therapy’s risk-benefit equilibrium, which is tilted towards more harm than benefit.”

He acknowledged study limitations included using study-level rather than patient-level meta-analysis, and the inability to calculate effects in younger populations at high absolute risk.  

The investigators acknowledged the controversy surrounding aspirin use to prevent ASCVD, noting the three major guidelines: the 2019 American College of Cardiology/American Heart Association and the 2021 European Society of Cardiology guidelines for aspirin only among asymptomatic individuals with high risk of ASCVD events, low bleeding risk, and age 70 years and younger; and the United States Preventive Services Task Force guidelines, updated in 2022, recommending individualized low-dose aspirin only among adults ages 40-59 years with 10-year ASCVD risk of 10% or greater and a low bleeding risk.

The findings are not a clarion call to halt aspirin therapy, Dr. Khan said. “This research focuses only on patients who do not have ASCVD,” he said. “Patients who do have ASCVD should continue with aspirin and statin therapy. However, we noted that aspirin has a limited role for patients who do not have ASCVD beyond lifestyle modifications, smoking cessation, exercise, and preventive statin therapy. Therefore, they should only consider using aspirin if their physicians suggest that the risk of having a cardiovascular event exceeds their bleeding risk. Otherwise, they should discuss with their physicians about omitting aspirin.”

The study confirms the move away from low-dose aspirin to prevent ASCVD, said Tahmid Rahman, MD, cardiologist and associate director of the Center for Advanced Lipid Management at Stony Brook (N.Y.) Heart Institute. “The study really continues to add to essentially what we already know,” he said. “There was a big push that aspirin, initially before the major statin trials, was the way to go to prevent heart disease, but with later studies, and especially now with newer antiplatelet therapies and longer duration of medication for people with both secondary prevention and primary prevention, we are getting away from routine aspirin, especially in primary prevention.”

The Society for Cardiovascular Angiography and Interventions has issued an updated expert consensus statement to provide clearer guidance on what percutaneous coronary angioplasty cases can be done in outpatient settings such as ambulatory surgery centers (ASCs) and office-based laboratories and which are best left to more traditional settings, such as hospitals with full cardiac support.

PCI has evolved quickly since SCAI issued its last update almost 9 years ago. The updated statement, published online in the Journal of the Society for Cardiovascular Angiography and Interventions, notes that the proportion of same-day PCI discharges has increased from 4.5% in 2009 to 28.6% in 2017.

The statement also notes that the Medicare facility fee for outpatient PCI in an ASC is about 40% less than the hospital fee: $6,111 versus $10,258 for the facility fee for 2022. The Centers for Medicare & Medicaid Services in 2020 extended coverage for PCIs in ASCs.
 

Rationale for update

Writing group chair Cindy Grines, MD, explained the rationale for updating the statement now. “The 2014 SCAI statement was very conservative, recommending only the simplest of cases be done without surgical backup,” Dr. Grines, chief scientific officer at Northside Hospital Cardiovascular Institute in Atlanta, said in an interview.

The statement drew on 12 global studies from 2015 to 2022 that evaluated more than 8 million PCIs at facilities with and without surgery on site. Dr. Grines noted those studies reported complication rates as low as 0.1% in PCI procedures in centers without surgical backup.

She also noted that the writing committee also received input that “by restricting the use of certain devices such as atherectomy, some patients who needed it as a bailout could be harmed.”

Another factor in prompting the statement update, Dr. Grines said: “Many hospitals have consolidated into heath systems, and these systems consolidated bypass surgery into one center. Therefore, centers with high volume, experienced operators, and excellent outcomes were now left with no surgery on site. It didn’t make sense to withdraw complex PCI from these centers who haven’t sent a patient for emergency bypass in several years.”
 

Statement guidance

The centerpiece of the update is an algorithm that covers the range of settings for PCI, from having a surgeon on site to ACS or office-based lab.

For example, indications for on-site surgical capability are PCI of the last remaining patent vessel or retrograde approach to epicardial chronic total occlusion (CTO), and when the patient is a candidate for surgery.

Indications for PCI in a hospital without on-site surgery but with percutaneous ventricular assist device or extracorporeal membrane oxygenation, calcium modification devices and high PCI volume are patients with decreased left ventricular ejection fraction, unprotected left main artery, CTO, or degenerated vein grafts.

For patients at high risk for transfusion, acute kidney injury or vascular complications, or who have high baseline respiratory risk, a hospital without on-site surgery but with respiratory care, blood bank, and vascular surgery services is indicated.

And for patients with none of the aforementioned characteristics or risks, ASC, office-based lab, or any hospital facility is acceptable.

The statement also provides guidance for operator experience. Those with less than 3 years’ experience, considered to have limited exposure to atherectomy devices and limited ST-segmented elevation MI (STEMI)/shock experience, should avoid doing PCIs in an ASC and performing atherectomy cases on their own, and have a colleague review case selection and assist in higher-risk cases. Experienced (3-10 years’ experience) and very experienced (more than 10 years’) should be able to perform in any setting and be competent with, if not highly experienced with, atherectomy and STEMI/shock.

Dr. Grines acknowledged the writing group didn’t want to set a specific operator volume requirement. “However, we recognize that lifetime operator experience is particularly important in more complex cases such as CTO, atherectomy, bifurcation stenoses, etc.,” she said. “In addition, performing these cases at a larger institution that has other operators that may assist in the event of a complication is very important. Specifically, we did not believe that recent fellow graduates with less than 3 years in practice or low-volume operators should attempt higher-risk cases in a no-SOS [surgeon-on-site] setting or perform cases in ASC or office-based labs where no colleagues are there to assist in case of a complication.”

In an interview, Gregory J. Dehmer, MD, professor of medicine at Virginia Tech University, Roanoke, reprised the theme of his accompanying editorial. “Things are evolving again, as Bob Dylan would say, ‘The Times They Are A-Changin’, so it’s very timely that the society in collaboration with other professional societies updated what are guidelines and rules of road if you’re going to do PCI in ASCs or office based laboratories,” said Dr. Dehmer, who chaired the writing committees of the 2007 and 2014 SCAI expert statements on PCI.

Having this statement is important for centers that don’t have on-site surgical backup, he said. “You couldn’t sustain a PCI operation at a rural hospital on just acute MIs alone. The key thing is that all of this built upon numerous studies both in the U.S. and abroad that showed the safety of doing elective cases – not only STEMIs, but elective PCI – at facilities without on-site surgery.”

CMS pushed the envelope when it decided to reimburse PCIs done in ASCs, Dr. Dehmer said. “That was not based on a lot of data. It was kind of a leap of faith. It’s logical that this should work, but in order for it to work and be safe for pats you have to follow the rules. That’s where SCAI stepped in at this point and said this is a whole new environment and we need to set some ground rules for physicians of who and who should not be having these procures in an office-based lab or an ambulatory surgery center.”

Dr. Grines and Dr. Dehmer have no relevant disclosures.
 

The Society for Cardiovascular Angiography and Interventions has issued an updated expert consensus statement to provide clearer guidance on what percutaneous coronary angioplasty cases can be done in outpatient settings such as ambulatory surgery centers (ASCs) and office-based laboratories and which are best left to more traditional settings, such as hospitals with full cardiac support.

PCI has evolved quickly since SCAI issued its last update almost 9 years ago. The updated statement, published online in the Journal of the Society for Cardiovascular Angiography and Interventions, notes that the proportion of same-day PCI discharges has increased from 4.5% in 2009 to 28.6% in 2017.

The statement also notes that the Medicare facility fee for outpatient PCI in an ASC is about 40% less than the hospital fee: $6,111 versus $10,258 for the facility fee for 2022. The Centers for Medicare & Medicaid Services in 2020 extended coverage for PCIs in ASCs.
 

Rationale for update

Writing group chair Cindy Grines, MD, explained the rationale for updating the statement now. “The 2014 SCAI statement was very conservative, recommending only the simplest of cases be done without surgical backup,” Dr. Grines, chief scientific officer at Northside Hospital Cardiovascular Institute in Atlanta, said in an interview.

The statement drew on 12 global studies from 2015 to 2022 that evaluated more than 8 million PCIs at facilities with and without surgery on site. Dr. Grines noted those studies reported complication rates as low as 0.1% in PCI procedures in centers without surgical backup.

She also noted that the writing committee also received input that “by restricting the use of certain devices such as atherectomy, some patients who needed it as a bailout could be harmed.”

Another factor in prompting the statement update, Dr. Grines said: “Many hospitals have consolidated into heath systems, and these systems consolidated bypass surgery into one center. Therefore, centers with high volume, experienced operators, and excellent outcomes were now left with no surgery on site. It didn’t make sense to withdraw complex PCI from these centers who haven’t sent a patient for emergency bypass in several years.”
 

Statement guidance

The centerpiece of the update is an algorithm that covers the range of settings for PCI, from having a surgeon on site to ACS or office-based lab.

For example, indications for on-site surgical capability are PCI of the last remaining patent vessel or retrograde approach to epicardial chronic total occlusion (CTO), and when the patient is a candidate for surgery.

Indications for PCI in a hospital without on-site surgery but with percutaneous ventricular assist device or extracorporeal membrane oxygenation, calcium modification devices and high PCI volume are patients with decreased left ventricular ejection fraction, unprotected left main artery, CTO, or degenerated vein grafts.

For patients at high risk for transfusion, acute kidney injury or vascular complications, or who have high baseline respiratory risk, a hospital without on-site surgery but with respiratory care, blood bank, and vascular surgery services is indicated.

And for patients with none of the aforementioned characteristics or risks, ASC, office-based lab, or any hospital facility is acceptable.

The statement also provides guidance for operator experience. Those with less than 3 years’ experience, considered to have limited exposure to atherectomy devices and limited ST-segmented elevation MI (STEMI)/shock experience, should avoid doing PCIs in an ASC and performing atherectomy cases on their own, and have a colleague review case selection and assist in higher-risk cases. Experienced (3-10 years’ experience) and very experienced (more than 10 years’) should be able to perform in any setting and be competent with, if not highly experienced with, atherectomy and STEMI/shock.

Dr. Grines acknowledged the writing group didn’t want to set a specific operator volume requirement. “However, we recognize that lifetime operator experience is particularly important in more complex cases such as CTO, atherectomy, bifurcation stenoses, etc.,” she said. “In addition, performing these cases at a larger institution that has other operators that may assist in the event of a complication is very important. Specifically, we did not believe that recent fellow graduates with less than 3 years in practice or low-volume operators should attempt higher-risk cases in a no-SOS [surgeon-on-site] setting or perform cases in ASC or office-based labs where no colleagues are there to assist in case of a complication.”

In an interview, Gregory J. Dehmer, MD, professor of medicine at Virginia Tech University, Roanoke, reprised the theme of his accompanying editorial. “Things are evolving again, as Bob Dylan would say, ‘The Times They Are A-Changin’, so it’s very timely that the society in collaboration with other professional societies updated what are guidelines and rules of road if you’re going to do PCI in ASCs or office based laboratories,” said Dr. Dehmer, who chaired the writing committees of the 2007 and 2014 SCAI expert statements on PCI.

Having this statement is important for centers that don’t have on-site surgical backup, he said. “You couldn’t sustain a PCI operation at a rural hospital on just acute MIs alone. The key thing is that all of this built upon numerous studies both in the U.S. and abroad that showed the safety of doing elective cases – not only STEMIs, but elective PCI – at facilities without on-site surgery.”

CMS pushed the envelope when it decided to reimburse PCIs done in ASCs, Dr. Dehmer said. “That was not based on a lot of data. It was kind of a leap of faith. It’s logical that this should work, but in order for it to work and be safe for pats you have to follow the rules. That’s where SCAI stepped in at this point and said this is a whole new environment and we need to set some ground rules for physicians of who and who should not be having these procures in an office-based lab or an ambulatory surgery center.”

Dr. Grines and Dr. Dehmer have no relevant disclosures.
 

The Society for Cardiovascular Angiography and Interventions has issued an updated expert consensus statement to provide clearer guidance on what percutaneous coronary angioplasty cases can be done in outpatient settings such as ambulatory surgery centers (ASCs) and office-based laboratories and which are best left to more traditional settings, such as hospitals with full cardiac support.

PCI has evolved quickly since SCAI issued its last update almost 9 years ago. The updated statement, published online in the Journal of the Society for Cardiovascular Angiography and Interventions, notes that the proportion of same-day PCI discharges has increased from 4.5% in 2009 to 28.6% in 2017.

The statement also notes that the Medicare facility fee for outpatient PCI in an ASC is about 40% less than the hospital fee: $6,111 versus $10,258 for the facility fee for 2022. The Centers for Medicare & Medicaid Services in 2020 extended coverage for PCIs in ASCs.
 

Rationale for update

Writing group chair Cindy Grines, MD, explained the rationale for updating the statement now. “The 2014 SCAI statement was very conservative, recommending only the simplest of cases be done without surgical backup,” Dr. Grines, chief scientific officer at Northside Hospital Cardiovascular Institute in Atlanta, said in an interview.

The statement drew on 12 global studies from 2015 to 2022 that evaluated more than 8 million PCIs at facilities with and without surgery on site. Dr. Grines noted those studies reported complication rates as low as 0.1% in PCI procedures in centers without surgical backup.

She also noted that the writing committee also received input that “by restricting the use of certain devices such as atherectomy, some patients who needed it as a bailout could be harmed.”

Another factor in prompting the statement update, Dr. Grines said: “Many hospitals have consolidated into heath systems, and these systems consolidated bypass surgery into one center. Therefore, centers with high volume, experienced operators, and excellent outcomes were now left with no surgery on site. It didn’t make sense to withdraw complex PCI from these centers who haven’t sent a patient for emergency bypass in several years.”
 

Statement guidance

The centerpiece of the update is an algorithm that covers the range of settings for PCI, from having a surgeon on site to ACS or office-based lab.

For example, indications for on-site surgical capability are PCI of the last remaining patent vessel or retrograde approach to epicardial chronic total occlusion (CTO), and when the patient is a candidate for surgery.

Indications for PCI in a hospital without on-site surgery but with percutaneous ventricular assist device or extracorporeal membrane oxygenation, calcium modification devices and high PCI volume are patients with decreased left ventricular ejection fraction, unprotected left main artery, CTO, or degenerated vein grafts.

For patients at high risk for transfusion, acute kidney injury or vascular complications, or who have high baseline respiratory risk, a hospital without on-site surgery but with respiratory care, blood bank, and vascular surgery services is indicated.

And for patients with none of the aforementioned characteristics or risks, ASC, office-based lab, or any hospital facility is acceptable.

The statement also provides guidance for operator experience. Those with less than 3 years’ experience, considered to have limited exposure to atherectomy devices and limited ST-segmented elevation MI (STEMI)/shock experience, should avoid doing PCIs in an ASC and performing atherectomy cases on their own, and have a colleague review case selection and assist in higher-risk cases. Experienced (3-10 years’ experience) and very experienced (more than 10 years’) should be able to perform in any setting and be competent with, if not highly experienced with, atherectomy and STEMI/shock.

Dr. Grines acknowledged the writing group didn’t want to set a specific operator volume requirement. “However, we recognize that lifetime operator experience is particularly important in more complex cases such as CTO, atherectomy, bifurcation stenoses, etc.,” she said. “In addition, performing these cases at a larger institution that has other operators that may assist in the event of a complication is very important. Specifically, we did not believe that recent fellow graduates with less than 3 years in practice or low-volume operators should attempt higher-risk cases in a no-SOS [surgeon-on-site] setting or perform cases in ASC or office-based labs where no colleagues are there to assist in case of a complication.”

In an interview, Gregory J. Dehmer, MD, professor of medicine at Virginia Tech University, Roanoke, reprised the theme of his accompanying editorial. “Things are evolving again, as Bob Dylan would say, ‘The Times They Are A-Changin’, so it’s very timely that the society in collaboration with other professional societies updated what are guidelines and rules of road if you’re going to do PCI in ASCs or office based laboratories,” said Dr. Dehmer, who chaired the writing committees of the 2007 and 2014 SCAI expert statements on PCI.

Having this statement is important for centers that don’t have on-site surgical backup, he said. “You couldn’t sustain a PCI operation at a rural hospital on just acute MIs alone. The key thing is that all of this built upon numerous studies both in the U.S. and abroad that showed the safety of doing elective cases – not only STEMIs, but elective PCI – at facilities without on-site surgery.”

CMS pushed the envelope when it decided to reimburse PCIs done in ASCs, Dr. Dehmer said. “That was not based on a lot of data. It was kind of a leap of faith. It’s logical that this should work, but in order for it to work and be safe for pats you have to follow the rules. That’s where SCAI stepped in at this point and said this is a whole new environment and we need to set some ground rules for physicians of who and who should not be having these procures in an office-based lab or an ambulatory surgery center.”

Dr. Grines and Dr. Dehmer have no relevant disclosures.
 

People with diabetes who adhere to a healthy diet, exercise regularly, and follow other healthy lifestyle practices have a significantly lower risk of microvascular complications from the disease, such as diabetic neuropathy, retinopathy, and nephropathy, as well as foot disorders, than counterparts with diabetes who don’t, a prospective cohort study of more than 7,000 patients with type 2 diabetes has found.

“We believe this is one of the first large-scale analyses among diabetes patients that specifically examined an overall healthy lifestyle in relation to the risk of developing microvascular complications,” senior study author Qi Sun, MD, ScD, said in an interview. “The results are not surprising that the healthy lifestyle is associated with lower risk of developing these complications and the enhanced adherence to the healthy lifestyle is associated with lower risk as well. And these findings bear lots of public health significance as they suggest the important role of living a healthy lifestyle in the prevention of diabetes complications, on top of the clinical treatment.”

Dr. Sun is an associate professor of nutrition and epidemiology at the Harvard T.H. Chan School of Public Health, Boston.

The study stated that the findings “lend support” for the American Diabetes Association guidelines for healthy lifestyle practices in people with diabetes.

The study used a cohort from two large prospective cohort studies, the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), comprising 4,982 women and 2,095 men who were diagnosed with type 2 diabetes during follow-up. They had no cardiovascular disease or cancer at the time of their diabetes diagnosis. Both NHS and HPFS used validated questionnaires to gather information on diet, lifestyle, medical history, and newly diagnosed diseases every 2-4 years. The latter study included NHS and HPFS participants who also completed supplementary questionnaires about their diabetes.

The latest study took into account five modifiable lifestyle-related factors: diet, body weight, smoking status, alcohol, and physical activity. For diet, both large studies used the 2010 Alternate Healthy Eating Index to assess diet quality; those in the upper 40th percentile of the study population were defined as healthy diet. Healthy body weight was defined at a body mass index of 18.5-25 kg/m².

Among the latter study cohort, 2,878 incident cases of diabetic microvascular complications were documented during follow-up. Patients who adhered to a healthy lifestyle before their diabetes diagnosis, defined as having four or more low-risk lifestyle factors, had a 27% lower relative risk of developing any microvascular complication than counterparts with no low-risk lifestyle factors (relative risk, 0.73; 95% confidence interval, 0.35-1; P = .006).

The study found similar outcomes for those who adopted a healthy lifestyle after their diabetes diagnosis, with a 32% reduction in relative risk compared with those who didn’t adopt any healthy lifestyle practices (RR, 0.68; 95% CI, 0.55-0.83; P < .001).

Dr. Sun noted what was noteworthy about his group’s cohort study. “The unique design is truly the prospective follow-up over time so that we could examine the lifestyle at diabetes diagnosis as well as changes in lifestyle before and after diabetes in relation to the future risk of developing the complications,” he said.

A randomized trial would be a more rigorous way to evaluate the impact of a healthy lifestyle, he added, “although it’s much more expensive than a cohort study like what we did with this investigation.”

As for future research, Dr. Sun said, “It will be interesting to understand mechanisms underlying these observations. It’s also critical to understand why certain diabetes patients may not benefit from a healthy lifestyle, since some of them, even when living a healthy lifestyle, still develop the complications.”

This trial shows in a new light the benefits of healthy lifestyle practices on microvascular complications of type 2 diabetes, Paul S. Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., and a professor at the University of Miami, said in a comment. “These benefits have always been surmised and demonstrated in a limited way in previous trials, but not subject to the level of analysis seen in this prospective cohort trial.”

He called the study design “excellent,” adding, “ ‘Validated’ self-reported questionnaires were used widely, although minimal detail is provided about the validation process.” One limitation, he noted, was “the homogeneity of the participants; all were health professionals.”

The study “affirms” and “quantitates” the benefits of a healthy lifestyle in type 2 diabetes. “The issue is not unawareness but rather application,” Dr. Jellinger said. “Modifying long-held lifestyle habits is a real challenge. Perhaps by ‘quantitating’ the benefit, as shown in this trial and hopefully additional studies, impetus will be provided to refocus on this approach, which is too often simply given lip service.”

The National Institutes of Health provided funding for the study. Dr. Sun has no relevant disclosures. Dr. Jellinger disclosed relationships with Amgen and Esperion.
 

People with diabetes who adhere to a healthy diet, exercise regularly, and follow other healthy lifestyle practices have a significantly lower risk of microvascular complications from the disease, such as diabetic neuropathy, retinopathy, and nephropathy, as well as foot disorders, than counterparts with diabetes who don’t, a prospective cohort study of more than 7,000 patients with type 2 diabetes has found.

“We believe this is one of the first large-scale analyses among diabetes patients that specifically examined an overall healthy lifestyle in relation to the risk of developing microvascular complications,” senior study author Qi Sun, MD, ScD, said in an interview. “The results are not surprising that the healthy lifestyle is associated with lower risk of developing these complications and the enhanced adherence to the healthy lifestyle is associated with lower risk as well. And these findings bear lots of public health significance as they suggest the important role of living a healthy lifestyle in the prevention of diabetes complications, on top of the clinical treatment.”

Dr. Sun is an associate professor of nutrition and epidemiology at the Harvard T.H. Chan School of Public Health, Boston.

The study stated that the findings “lend support” for the American Diabetes Association guidelines for healthy lifestyle practices in people with diabetes.

The study used a cohort from two large prospective cohort studies, the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), comprising 4,982 women and 2,095 men who were diagnosed with type 2 diabetes during follow-up. They had no cardiovascular disease or cancer at the time of their diabetes diagnosis. Both NHS and HPFS used validated questionnaires to gather information on diet, lifestyle, medical history, and newly diagnosed diseases every 2-4 years. The latter study included NHS and HPFS participants who also completed supplementary questionnaires about their diabetes.

The latest study took into account five modifiable lifestyle-related factors: diet, body weight, smoking status, alcohol, and physical activity. For diet, both large studies used the 2010 Alternate Healthy Eating Index to assess diet quality; those in the upper 40th percentile of the study population were defined as healthy diet. Healthy body weight was defined at a body mass index of 18.5-25 kg/m².

Among the latter study cohort, 2,878 incident cases of diabetic microvascular complications were documented during follow-up. Patients who adhered to a healthy lifestyle before their diabetes diagnosis, defined as having four or more low-risk lifestyle factors, had a 27% lower relative risk of developing any microvascular complication than counterparts with no low-risk lifestyle factors (relative risk, 0.73; 95% confidence interval, 0.35-1; P = .006).

The study found similar outcomes for those who adopted a healthy lifestyle after their diabetes diagnosis, with a 32% reduction in relative risk compared with those who didn’t adopt any healthy lifestyle practices (RR, 0.68; 95% CI, 0.55-0.83; P < .001).

Dr. Sun noted what was noteworthy about his group’s cohort study. “The unique design is truly the prospective follow-up over time so that we could examine the lifestyle at diabetes diagnosis as well as changes in lifestyle before and after diabetes in relation to the future risk of developing the complications,” he said.

A randomized trial would be a more rigorous way to evaluate the impact of a healthy lifestyle, he added, “although it’s much more expensive than a cohort study like what we did with this investigation.”

As for future research, Dr. Sun said, “It will be interesting to understand mechanisms underlying these observations. It’s also critical to understand why certain diabetes patients may not benefit from a healthy lifestyle, since some of them, even when living a healthy lifestyle, still develop the complications.”

This trial shows in a new light the benefits of healthy lifestyle practices on microvascular complications of type 2 diabetes, Paul S. Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., and a professor at the University of Miami, said in a comment. “These benefits have always been surmised and demonstrated in a limited way in previous trials, but not subject to the level of analysis seen in this prospective cohort trial.”

He called the study design “excellent,” adding, “ ‘Validated’ self-reported questionnaires were used widely, although minimal detail is provided about the validation process.” One limitation, he noted, was “the homogeneity of the participants; all were health professionals.”

The study “affirms” and “quantitates” the benefits of a healthy lifestyle in type 2 diabetes. “The issue is not unawareness but rather application,” Dr. Jellinger said. “Modifying long-held lifestyle habits is a real challenge. Perhaps by ‘quantitating’ the benefit, as shown in this trial and hopefully additional studies, impetus will be provided to refocus on this approach, which is too often simply given lip service.”

The National Institutes of Health provided funding for the study. Dr. Sun has no relevant disclosures. Dr. Jellinger disclosed relationships with Amgen and Esperion.
 

People with diabetes who adhere to a healthy diet, exercise regularly, and follow other healthy lifestyle practices have a significantly lower risk of microvascular complications from the disease, such as diabetic neuropathy, retinopathy, and nephropathy, as well as foot disorders, than counterparts with diabetes who don’t, a prospective cohort study of more than 7,000 patients with type 2 diabetes has found.

“We believe this is one of the first large-scale analyses among diabetes patients that specifically examined an overall healthy lifestyle in relation to the risk of developing microvascular complications,” senior study author Qi Sun, MD, ScD, said in an interview. “The results are not surprising that the healthy lifestyle is associated with lower risk of developing these complications and the enhanced adherence to the healthy lifestyle is associated with lower risk as well. And these findings bear lots of public health significance as they suggest the important role of living a healthy lifestyle in the prevention of diabetes complications, on top of the clinical treatment.”

Dr. Sun is an associate professor of nutrition and epidemiology at the Harvard T.H. Chan School of Public Health, Boston.

The study stated that the findings “lend support” for the American Diabetes Association guidelines for healthy lifestyle practices in people with diabetes.

The study used a cohort from two large prospective cohort studies, the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), comprising 4,982 women and 2,095 men who were diagnosed with type 2 diabetes during follow-up. They had no cardiovascular disease or cancer at the time of their diabetes diagnosis. Both NHS and HPFS used validated questionnaires to gather information on diet, lifestyle, medical history, and newly diagnosed diseases every 2-4 years. The latter study included NHS and HPFS participants who also completed supplementary questionnaires about their diabetes.

The latest study took into account five modifiable lifestyle-related factors: diet, body weight, smoking status, alcohol, and physical activity. For diet, both large studies used the 2010 Alternate Healthy Eating Index to assess diet quality; those in the upper 40th percentile of the study population were defined as healthy diet. Healthy body weight was defined at a body mass index of 18.5-25 kg/m².

Among the latter study cohort, 2,878 incident cases of diabetic microvascular complications were documented during follow-up. Patients who adhered to a healthy lifestyle before their diabetes diagnosis, defined as having four or more low-risk lifestyle factors, had a 27% lower relative risk of developing any microvascular complication than counterparts with no low-risk lifestyle factors (relative risk, 0.73; 95% confidence interval, 0.35-1; P = .006).

The study found similar outcomes for those who adopted a healthy lifestyle after their diabetes diagnosis, with a 32% reduction in relative risk compared with those who didn’t adopt any healthy lifestyle practices (RR, 0.68; 95% CI, 0.55-0.83; P < .001).

Dr. Sun noted what was noteworthy about his group’s cohort study. “The unique design is truly the prospective follow-up over time so that we could examine the lifestyle at diabetes diagnosis as well as changes in lifestyle before and after diabetes in relation to the future risk of developing the complications,” he said.

A randomized trial would be a more rigorous way to evaluate the impact of a healthy lifestyle, he added, “although it’s much more expensive than a cohort study like what we did with this investigation.”

As for future research, Dr. Sun said, “It will be interesting to understand mechanisms underlying these observations. It’s also critical to understand why certain diabetes patients may not benefit from a healthy lifestyle, since some of them, even when living a healthy lifestyle, still develop the complications.”

This trial shows in a new light the benefits of healthy lifestyle practices on microvascular complications of type 2 diabetes, Paul S. Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., and a professor at the University of Miami, said in a comment. “These benefits have always been surmised and demonstrated in a limited way in previous trials, but not subject to the level of analysis seen in this prospective cohort trial.”

He called the study design “excellent,” adding, “ ‘Validated’ self-reported questionnaires were used widely, although minimal detail is provided about the validation process.” One limitation, he noted, was “the homogeneity of the participants; all were health professionals.”

The study “affirms” and “quantitates” the benefits of a healthy lifestyle in type 2 diabetes. “The issue is not unawareness but rather application,” Dr. Jellinger said. “Modifying long-held lifestyle habits is a real challenge. Perhaps by ‘quantitating’ the benefit, as shown in this trial and hopefully additional studies, impetus will be provided to refocus on this approach, which is too often simply given lip service.”

The National Institutes of Health provided funding for the study. Dr. Sun has no relevant disclosures. Dr. Jellinger disclosed relationships with Amgen and Esperion.