Stroke

A routine scan used to evaluate some acute stroke patients can also detect SARS-CoV-2 infection in the upper lungs, a new study shows.

“As part of the stroke evaluation workup process, we were able to diagnose COVID-19 at the same time at no extra cost or additional workload,” lead author Charles Esenwa, MD, commented to Medscape Medical News. “This is an objective way to screen for COVID-19 in the acute stroke setting,” he added.

Esenwa is an assistant professor and a stroke neurologist at the Montefiore Medical Center/Albert Einstein College of Medicine in New York City.

He explained that, during the COVID-19 surge earlier this year, assessment of patients with severe acute stroke using computed tomography angiogram (CTA) scans – used to evaluate suitability for endovascular stroke therapy – also showed findings in the upper lung consistent with viral infection in some patients.

“We then assumed that these patients had COVID-19 and took extra precautions to keep them isolated and to protect staff involved in their care. It also allowed us to triage these patients more quickly than waiting for the COVID-19 swab test and arrange the most appropriate care for them,” Esenwa said.

The researchers have now gone back and analyzed their data on acute stroke patients who underwent CTA at their institution during the COVID-19 surge. They found that the changes identified in the lungs were highly specific for diagnosing SARS-CoV-2 infection.

The study was published online on Oct. 29 in Stroke.

“Stroke patients are normally screened for COVID-19 on hospitalization, but the swab test result can take several hours or longer to come back, and it is very useful for us to know if a patient could be infected,” Esenwa noted.

“When we do a CTA, we look at the blood vessels supplying the brain, but the scan also covers the top of the lung, as it starts at the aortic arch. We don’t normally look closely at that area, but we started to notice signs of active lung infection which could have been COVID-19,” he said. “For this paper, we went back to assess how accurate this approach actually was vs. the COVID-19 PCR test.”

The researchers report on 57 patients who presented to three Montefiore Health System hospitals in the Bronx, in New York City, with acute ischemic stroke and who underwent CTA of the head and neck in March and April 2020, the peak of the COVID-19 outbreak there. The patients also underwent PCR testing for COVID-19.

Results showed that 30 patients had a positive COVID-19 test result and that 27 had a negative result. Lung findings highly or very highly suspicious for COVID-19 pneumonia were identified during the CTA scan in 20 (67%) of the COVID-19–positive patients and in two (7%) of the COVID-19–negative patients.

These findings, when used in isolation, yielded a sensitivity of 0.67 and a specificity of 0.93. They had a positive predictive value of 0.19, a negative predictive value of 0.99, and accuracy of 0.92 for the diagnosis of COVID-19.

When apical lung assessment was combined with self-reported clinical symptoms of cough or dyspnea, sensitivity for the diagnosis of COVID-19 for patients presenting to the hospital for acute ischemic stroke increased to 0.83.

“We wondered whether looking at the whole lung would have found better results, but other studies which have done this actually found similar numbers to ours, so we think actually just looking at the top of the lungs, which can be seen in a stroke CTA, may be sufficient,” Esenwa said.

He emphasized the importance of establishing whether an acute stroke patient has COVID-19. “If we had a high suspicion of COVID-19 infection, we would take more precautions during any procedures, such as thrombectomy, and make sure to keep the patient isolated afterwards. It doesn’t necessarily affect the treatment given for stroke, but it affects the safety of the patients and everyone caring for them,” he commented.

Esenwa explained that intubation – which is sometime necessary during thrombectomy – can expose everyone in the room to aerosolized droplets. “So we would take much higher safety precautions if we thought the patient was COVID-19 positive,” he said.

“Early COVID-19 diagnosis also means patients can be given supportive treatment more quickly, admitted to ICU if appropriate, and we can all keep a close eye on pulmonary issues. So having that information is important in many ways,” he added.

Esenwa advises that any medical center that evaluates acute stroke patients for thrombectomy and is experiencing a COVID-19 surge can use this technique as a screening method for COVID-19.

He pointed out that the Montefiore Health System had a very high rate of COVID-19. That part of New York City was one of the worst hit areas of the world, and the CTA approach for identifying COVID-19 has been validated only in areas with such a high local incidence of COVID. If used in an area of lower prevalence, the accuracy would likely be less.

“We don’t know if this approach would work as well at times of low COVID-19 infection, where any lung findings would be more likely to be caused by other conditions, such as pneumonia due to other causes or congestive heart failure. So there would be more false positives,” Esenwa said.

“But when COVID-19 prevalence is high, the lung findings are much more likely to be a sign of COVID-19 infection. As COVID-19 numbers are now rising for a second time, it is likely to become a useful strategy again.”

The study was approved by the Albert Einstein College of Medicine/Montefiore Medical Center Institutional Review Board and had no external funding. Esenwa has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

A routine scan used to evaluate some acute stroke patients can also detect SARS-CoV-2 infection in the upper lungs, a new study shows.

“As part of the stroke evaluation workup process, we were able to diagnose COVID-19 at the same time at no extra cost or additional workload,” lead author Charles Esenwa, MD, commented to Medscape Medical News. “This is an objective way to screen for COVID-19 in the acute stroke setting,” he added.

Esenwa is an assistant professor and a stroke neurologist at the Montefiore Medical Center/Albert Einstein College of Medicine in New York City.

He explained that, during the COVID-19 surge earlier this year, assessment of patients with severe acute stroke using computed tomography angiogram (CTA) scans – used to evaluate suitability for endovascular stroke therapy – also showed findings in the upper lung consistent with viral infection in some patients.

“We then assumed that these patients had COVID-19 and took extra precautions to keep them isolated and to protect staff involved in their care. It also allowed us to triage these patients more quickly than waiting for the COVID-19 swab test and arrange the most appropriate care for them,” Esenwa said.

The researchers have now gone back and analyzed their data on acute stroke patients who underwent CTA at their institution during the COVID-19 surge. They found that the changes identified in the lungs were highly specific for diagnosing SARS-CoV-2 infection.

The study was published online on Oct. 29 in Stroke.

“Stroke patients are normally screened for COVID-19 on hospitalization, but the swab test result can take several hours or longer to come back, and it is very useful for us to know if a patient could be infected,” Esenwa noted.

“When we do a CTA, we look at the blood vessels supplying the brain, but the scan also covers the top of the lung, as it starts at the aortic arch. We don’t normally look closely at that area, but we started to notice signs of active lung infection which could have been COVID-19,” he said. “For this paper, we went back to assess how accurate this approach actually was vs. the COVID-19 PCR test.”

The researchers report on 57 patients who presented to three Montefiore Health System hospitals in the Bronx, in New York City, with acute ischemic stroke and who underwent CTA of the head and neck in March and April 2020, the peak of the COVID-19 outbreak there. The patients also underwent PCR testing for COVID-19.

Results showed that 30 patients had a positive COVID-19 test result and that 27 had a negative result. Lung findings highly or very highly suspicious for COVID-19 pneumonia were identified during the CTA scan in 20 (67%) of the COVID-19–positive patients and in two (7%) of the COVID-19–negative patients.

These findings, when used in isolation, yielded a sensitivity of 0.67 and a specificity of 0.93. They had a positive predictive value of 0.19, a negative predictive value of 0.99, and accuracy of 0.92 for the diagnosis of COVID-19.

When apical lung assessment was combined with self-reported clinical symptoms of cough or dyspnea, sensitivity for the diagnosis of COVID-19 for patients presenting to the hospital for acute ischemic stroke increased to 0.83.

“We wondered whether looking at the whole lung would have found better results, but other studies which have done this actually found similar numbers to ours, so we think actually just looking at the top of the lungs, which can be seen in a stroke CTA, may be sufficient,” Esenwa said.

He emphasized the importance of establishing whether an acute stroke patient has COVID-19. “If we had a high suspicion of COVID-19 infection, we would take more precautions during any procedures, such as thrombectomy, and make sure to keep the patient isolated afterwards. It doesn’t necessarily affect the treatment given for stroke, but it affects the safety of the patients and everyone caring for them,” he commented.

Esenwa explained that intubation – which is sometime necessary during thrombectomy – can expose everyone in the room to aerosolized droplets. “So we would take much higher safety precautions if we thought the patient was COVID-19 positive,” he said.

“Early COVID-19 diagnosis also means patients can be given supportive treatment more quickly, admitted to ICU if appropriate, and we can all keep a close eye on pulmonary issues. So having that information is important in many ways,” he added.

Esenwa advises that any medical center that evaluates acute stroke patients for thrombectomy and is experiencing a COVID-19 surge can use this technique as a screening method for COVID-19.

He pointed out that the Montefiore Health System had a very high rate of COVID-19. That part of New York City was one of the worst hit areas of the world, and the CTA approach for identifying COVID-19 has been validated only in areas with such a high local incidence of COVID. If used in an area of lower prevalence, the accuracy would likely be less.

“We don’t know if this approach would work as well at times of low COVID-19 infection, where any lung findings would be more likely to be caused by other conditions, such as pneumonia due to other causes or congestive heart failure. So there would be more false positives,” Esenwa said.

“But when COVID-19 prevalence is high, the lung findings are much more likely to be a sign of COVID-19 infection. As COVID-19 numbers are now rising for a second time, it is likely to become a useful strategy again.”

The study was approved by the Albert Einstein College of Medicine/Montefiore Medical Center Institutional Review Board and had no external funding. Esenwa has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

A routine scan used to evaluate some acute stroke patients can also detect SARS-CoV-2 infection in the upper lungs, a new study shows.

“As part of the stroke evaluation workup process, we were able to diagnose COVID-19 at the same time at no extra cost or additional workload,” lead author Charles Esenwa, MD, commented to Medscape Medical News. “This is an objective way to screen for COVID-19 in the acute stroke setting,” he added.

Esenwa is an assistant professor and a stroke neurologist at the Montefiore Medical Center/Albert Einstein College of Medicine in New York City.

He explained that, during the COVID-19 surge earlier this year, assessment of patients with severe acute stroke using computed tomography angiogram (CTA) scans – used to evaluate suitability for endovascular stroke therapy – also showed findings in the upper lung consistent with viral infection in some patients.

“We then assumed that these patients had COVID-19 and took extra precautions to keep them isolated and to protect staff involved in their care. It also allowed us to triage these patients more quickly than waiting for the COVID-19 swab test and arrange the most appropriate care for them,” Esenwa said.

The researchers have now gone back and analyzed their data on acute stroke patients who underwent CTA at their institution during the COVID-19 surge. They found that the changes identified in the lungs were highly specific for diagnosing SARS-CoV-2 infection.

The study was published online on Oct. 29 in Stroke.

“Stroke patients are normally screened for COVID-19 on hospitalization, but the swab test result can take several hours or longer to come back, and it is very useful for us to know if a patient could be infected,” Esenwa noted.

“When we do a CTA, we look at the blood vessels supplying the brain, but the scan also covers the top of the lung, as it starts at the aortic arch. We don’t normally look closely at that area, but we started to notice signs of active lung infection which could have been COVID-19,” he said. “For this paper, we went back to assess how accurate this approach actually was vs. the COVID-19 PCR test.”

The researchers report on 57 patients who presented to three Montefiore Health System hospitals in the Bronx, in New York City, with acute ischemic stroke and who underwent CTA of the head and neck in March and April 2020, the peak of the COVID-19 outbreak there. The patients also underwent PCR testing for COVID-19.

Results showed that 30 patients had a positive COVID-19 test result and that 27 had a negative result. Lung findings highly or very highly suspicious for COVID-19 pneumonia were identified during the CTA scan in 20 (67%) of the COVID-19–positive patients and in two (7%) of the COVID-19–negative patients.

These findings, when used in isolation, yielded a sensitivity of 0.67 and a specificity of 0.93. They had a positive predictive value of 0.19, a negative predictive value of 0.99, and accuracy of 0.92 for the diagnosis of COVID-19.

When apical lung assessment was combined with self-reported clinical symptoms of cough or dyspnea, sensitivity for the diagnosis of COVID-19 for patients presenting to the hospital for acute ischemic stroke increased to 0.83.

“We wondered whether looking at the whole lung would have found better results, but other studies which have done this actually found similar numbers to ours, so we think actually just looking at the top of the lungs, which can be seen in a stroke CTA, may be sufficient,” Esenwa said.

He emphasized the importance of establishing whether an acute stroke patient has COVID-19. “If we had a high suspicion of COVID-19 infection, we would take more precautions during any procedures, such as thrombectomy, and make sure to keep the patient isolated afterwards. It doesn’t necessarily affect the treatment given for stroke, but it affects the safety of the patients and everyone caring for them,” he commented.

Esenwa explained that intubation – which is sometime necessary during thrombectomy – can expose everyone in the room to aerosolized droplets. “So we would take much higher safety precautions if we thought the patient was COVID-19 positive,” he said.

“Early COVID-19 diagnosis also means patients can be given supportive treatment more quickly, admitted to ICU if appropriate, and we can all keep a close eye on pulmonary issues. So having that information is important in many ways,” he added.

Esenwa advises that any medical center that evaluates acute stroke patients for thrombectomy and is experiencing a COVID-19 surge can use this technique as a screening method for COVID-19.

He pointed out that the Montefiore Health System had a very high rate of COVID-19. That part of New York City was one of the worst hit areas of the world, and the CTA approach for identifying COVID-19 has been validated only in areas with such a high local incidence of COVID. If used in an area of lower prevalence, the accuracy would likely be less.

“We don’t know if this approach would work as well at times of low COVID-19 infection, where any lung findings would be more likely to be caused by other conditions, such as pneumonia due to other causes or congestive heart failure. So there would be more false positives,” Esenwa said.

“But when COVID-19 prevalence is high, the lung findings are much more likely to be a sign of COVID-19 infection. As COVID-19 numbers are now rising for a second time, it is likely to become a useful strategy again.”

The study was approved by the Albert Einstein College of Medicine/Montefiore Medical Center Institutional Review Board and had no external funding. Esenwa has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

For patients with diabetic kidney disease, finerenone, an agent from a new class of selective, nonsteroidal mineralocorticoid receptor antagonists, led to significant reductions in combined adverse renal outcomes and in combined adverse cardiovascular outcomes in the pivotal FIDELIO-DKD trial.

And the safety results showed a good level of tolerability. The rate of hyperkalemia was higher with finerenone than with placebo, but the rate of drug discontinuations for elevated potassium was lower than that seen with spironolactone, a steroidal mineralocorticoid receptor antagonist (MRA).

“An ideal drug would cause no hyperkalemia, but the absolute risk we saw is a fraction of what we see with spironolactone in this vulnerable patient population,” said Rajiv Agarwal, MD, from Indiana in Indianapolis, during a press briefing.

After a median follow-up of 2.6 years, finerenone was associated with a 3.4% absolute reduction in the rate of combined adverse renal events, the study’s primary end point, which comprised kidney failure, renal death, and a drop in estimated glomerular filtration rate (eGFR) of at least 40% from baseline. This produced a significant relative risk reduction of 18%, with a number needed to treat of 32 to prevent one of these events, Dr. Agarwal reported at Kidney Week 2020. Findings from the FIDELIO-DKD trial were published simultaneously in the New England Journal of Medicine.

Finerenone was also associated with an absolute 2.4% reduction in the rate of combined adverse cardiovascular events, the study’s “key secondary end point,” which included cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure. This translated into a significant relative risk reduction of 14% and a number needed to treat of 42 to prevent one of these events.

FIDELIO-DKD assessed 5,734 patients with type 2 diabetes and chronic kidney disease from more than 1,000 sites in 48 countries, including the United States, from 2015 to 2018. In the study cohort, average age was slightly more than 65 years, average baseline systolic blood pressure was 138 mm Hg, average duration of diabetes was nearly 17 years, average baseline glycated hemoglobin (A1c) was 7.7%, and fewer than 5% of patients were Black, 25% were Asian, and about 63% were White.
 

A suggestion of less severe hyperkalemia

Finerenone was well tolerated by the participants, and the findings suggest that it caused less clinically meaningful hyperkalemia than spironolactone, the most established and widely used MRA.

Like all MRA drugs, finerenone led to an increase in serum potassium in all patient subgroups – in this case 0.2 mmol/L – unlike placebo, said Dr. Agarwal.

The overall incidence of hyperkalemia was 16% in the 2,827 evaluable patients in the finerenone group and 8% in the 2,831 evaluable patients in the placebo group. Fewer than 10% of patients in the trial received a potassium-binding agent.

The rate of hyperkalemia leading to treatment discontinuation was higher in the finerenone group than in the placebo group (2.3% vs. 0.9%).

That 2.3% rate is 10 times lower than the 23.0% rate of hyperkalemia-related treatment discontinuation in patients who received spironolactone and no potassium-binding agent, said Dr. Agarwal, citing a previous study he was involved with.

He hypothesized that finerenone might cause less clinically meaningful hyperkalemia because it creates no active metabolites that linger in the body, whereas spironolactone produces active metabolites with a half life of about 1 week.

“The risk for hyperkalemia is clearly increased with finerenone compared with placebo, and in the absence of head-to-head studies, it’s hard to know how it compares with spironolactone or eplerenone [Inspra],” the other agents in the MRA class, said Mikhail N. Kosiborod, MD, from the University of Missouri–Kansas City.

“The rates of hyperkalemia observed in FIDELIO-DKD were overall comparable to what we would expect from eplerenone. But the rate of serious hyperkalemia was quite low with finerenone, which is reassuring,” Dr. Kosiborod said in an interview.

And the adverse-effect profile showed that finerenone “is as safe as you could expect from an MRA,” said Janani Rangaswami, MD, from the Einstein Medical Center in Philadelphia.

The rate of hyperkalemia should be interpreted in the context of the high risk the enrolled patients faced, given that they all had moderate to severe diabetic kidney disease with albuminuria and, in some cases, eGFR rates as low as 25 mL/min per 1.73m², she explained. In addition, all patients were on maximally tolerated treatment with either an angiotensin-converting–enzyme inhibitor or an angiotensin receptor blocker to inhibit the renin angiotensin system (RAS).

“Considering this background, it’s a very acceptable adverse-event profile,” Dr. Rangaswami said in an interview.
 

Renal drugs that could work together

More than 99% of patients in FIDELIO-DKD were on an RAS inhibitor, but fewer than 5% were on a sodium glucose cotransporter 2 (SGLT2) inhibitor at baseline, and fewer than 10% started on this drug class during the course of the study.

Despite that, both Dr. Kosiborod and Dr. Rangaswami are enthusiastic about the prospect of using the three drugs in combination to maximize renal and cardiovascular benefits in FIDELIO-DKD–type patients. Recent results from the CREDENCE study of canagliflozin (Invokana) and from the DAPA-CKD study of dapagluflozin (Farxiga) have established SGLT2 inhibitors – at least those two – as key agents for patients with chronic kidney disease.

Dual treatment with an RAS inhibitor and an SGLT2 inhibitor is “clearly established” for patients with diabetic kidney disease, said Dr. Agarwal.

“After CREDENCE, DAPA-CKD, and now FIDELIO-DKD, we need to seriously consider triple therapy as the future of treatment for diabetic kidney disease to prevent both cardiovascular and kidney complications,” said Dr. Kosiborod. The approach will mimic the multidrug therapy that’s now standard for patients with heart failure with reduced ejection fraction (HFrEF). But he cautioned that this triple combination needs further testing.

“Triple therapy will be the standard of care” for patients with diabetic kidney disease, Dr. Rangaswami agreed, but she cautioned that she would not currently expand the target population for finerenone to patients without type 2 diabetes or to patients without the level of albuminuria required for entry into FIDELIO-DKD: at least 30 mg/g of creatinine per day. And patients with HFrEF were excluded from FIDELIO-DKD, so that limitation on finerenone use should remain for the time being, she added.

Dr. Rangaswami said she is optimistic about the potential efficacy of finerenone added to an SGLT2 inhibitor because of the likelihood that the two drug classes work in different but complementary ways. SGLT2 inhibitors seem to exert their renal protective effects largely through hemodynamic effects, whereas it is likely that finerenone exerts its effects largely as an anti-inflammatory and antifibrotic agent, she speculated. The FIDELIO-DKD results appear to rule out any major effect of finerenone on blood pressure lowering because average systolic pressure fell by only about 2 mm Hg in the treatment group.

“The benefits of finerenone for cardiorenal outcomes are substantial and clinically meaningful,” Dr. Kosiborod said. “We cannot assume that other MRAs, such as spironolactone, provide similar benefits,” he cautioned, but the results are “very good news for patients with type 2 diabetes and chronic kidney disease. We now have another effective intervention with a different mechanism of action.”

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone (BAY 94-8862). Dr. Agarwal has been a consultant to and has received honoraria from Bayer and from several other companies. Dr. Kosiborod has been a consultant to Bayer and to AstraZeneca, Boehringer Ingelheim, Jansse, Merck, and Vifor and has received research funding from AstraZeneca and Boehringer Ingelheim. Dr. Rangaswami has disclosed no relevant financial relationships.
 

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

For patients with diabetic kidney disease, finerenone, an agent from a new class of selective, nonsteroidal mineralocorticoid receptor antagonists, led to significant reductions in combined adverse renal outcomes and in combined adverse cardiovascular outcomes in the pivotal FIDELIO-DKD trial.

And the safety results showed a good level of tolerability. The rate of hyperkalemia was higher with finerenone than with placebo, but the rate of drug discontinuations for elevated potassium was lower than that seen with spironolactone, a steroidal mineralocorticoid receptor antagonist (MRA).

“An ideal drug would cause no hyperkalemia, but the absolute risk we saw is a fraction of what we see with spironolactone in this vulnerable patient population,” said Rajiv Agarwal, MD, from Indiana in Indianapolis, during a press briefing.

After a median follow-up of 2.6 years, finerenone was associated with a 3.4% absolute reduction in the rate of combined adverse renal events, the study’s primary end point, which comprised kidney failure, renal death, and a drop in estimated glomerular filtration rate (eGFR) of at least 40% from baseline. This produced a significant relative risk reduction of 18%, with a number needed to treat of 32 to prevent one of these events, Dr. Agarwal reported at Kidney Week 2020. Findings from the FIDELIO-DKD trial were published simultaneously in the New England Journal of Medicine.

Finerenone was also associated with an absolute 2.4% reduction in the rate of combined adverse cardiovascular events, the study’s “key secondary end point,” which included cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure. This translated into a significant relative risk reduction of 14% and a number needed to treat of 42 to prevent one of these events.

FIDELIO-DKD assessed 5,734 patients with type 2 diabetes and chronic kidney disease from more than 1,000 sites in 48 countries, including the United States, from 2015 to 2018. In the study cohort, average age was slightly more than 65 years, average baseline systolic blood pressure was 138 mm Hg, average duration of diabetes was nearly 17 years, average baseline glycated hemoglobin (A1c) was 7.7%, and fewer than 5% of patients were Black, 25% were Asian, and about 63% were White.
 

A suggestion of less severe hyperkalemia

Finerenone was well tolerated by the participants, and the findings suggest that it caused less clinically meaningful hyperkalemia than spironolactone, the most established and widely used MRA.

Like all MRA drugs, finerenone led to an increase in serum potassium in all patient subgroups – in this case 0.2 mmol/L – unlike placebo, said Dr. Agarwal.

The overall incidence of hyperkalemia was 16% in the 2,827 evaluable patients in the finerenone group and 8% in the 2,831 evaluable patients in the placebo group. Fewer than 10% of patients in the trial received a potassium-binding agent.

The rate of hyperkalemia leading to treatment discontinuation was higher in the finerenone group than in the placebo group (2.3% vs. 0.9%).

That 2.3% rate is 10 times lower than the 23.0% rate of hyperkalemia-related treatment discontinuation in patients who received spironolactone and no potassium-binding agent, said Dr. Agarwal, citing a previous study he was involved with.

He hypothesized that finerenone might cause less clinically meaningful hyperkalemia because it creates no active metabolites that linger in the body, whereas spironolactone produces active metabolites with a half life of about 1 week.

“The risk for hyperkalemia is clearly increased with finerenone compared with placebo, and in the absence of head-to-head studies, it’s hard to know how it compares with spironolactone or eplerenone [Inspra],” the other agents in the MRA class, said Mikhail N. Kosiborod, MD, from the University of Missouri–Kansas City.

“The rates of hyperkalemia observed in FIDELIO-DKD were overall comparable to what we would expect from eplerenone. But the rate of serious hyperkalemia was quite low with finerenone, which is reassuring,” Dr. Kosiborod said in an interview.

And the adverse-effect profile showed that finerenone “is as safe as you could expect from an MRA,” said Janani Rangaswami, MD, from the Einstein Medical Center in Philadelphia.

The rate of hyperkalemia should be interpreted in the context of the high risk the enrolled patients faced, given that they all had moderate to severe diabetic kidney disease with albuminuria and, in some cases, eGFR rates as low as 25 mL/min per 1.73m², she explained. In addition, all patients were on maximally tolerated treatment with either an angiotensin-converting–enzyme inhibitor or an angiotensin receptor blocker to inhibit the renin angiotensin system (RAS).

“Considering this background, it’s a very acceptable adverse-event profile,” Dr. Rangaswami said in an interview.
 

Renal drugs that could work together

More than 99% of patients in FIDELIO-DKD were on an RAS inhibitor, but fewer than 5% were on a sodium glucose cotransporter 2 (SGLT2) inhibitor at baseline, and fewer than 10% started on this drug class during the course of the study.

Despite that, both Dr. Kosiborod and Dr. Rangaswami are enthusiastic about the prospect of using the three drugs in combination to maximize renal and cardiovascular benefits in FIDELIO-DKD–type patients. Recent results from the CREDENCE study of canagliflozin (Invokana) and from the DAPA-CKD study of dapagluflozin (Farxiga) have established SGLT2 inhibitors – at least those two – as key agents for patients with chronic kidney disease.

Dual treatment with an RAS inhibitor and an SGLT2 inhibitor is “clearly established” for patients with diabetic kidney disease, said Dr. Agarwal.

“After CREDENCE, DAPA-CKD, and now FIDELIO-DKD, we need to seriously consider triple therapy as the future of treatment for diabetic kidney disease to prevent both cardiovascular and kidney complications,” said Dr. Kosiborod. The approach will mimic the multidrug therapy that’s now standard for patients with heart failure with reduced ejection fraction (HFrEF). But he cautioned that this triple combination needs further testing.

“Triple therapy will be the standard of care” for patients with diabetic kidney disease, Dr. Rangaswami agreed, but she cautioned that she would not currently expand the target population for finerenone to patients without type 2 diabetes or to patients without the level of albuminuria required for entry into FIDELIO-DKD: at least 30 mg/g of creatinine per day. And patients with HFrEF were excluded from FIDELIO-DKD, so that limitation on finerenone use should remain for the time being, she added.

Dr. Rangaswami said she is optimistic about the potential efficacy of finerenone added to an SGLT2 inhibitor because of the likelihood that the two drug classes work in different but complementary ways. SGLT2 inhibitors seem to exert their renal protective effects largely through hemodynamic effects, whereas it is likely that finerenone exerts its effects largely as an anti-inflammatory and antifibrotic agent, she speculated. The FIDELIO-DKD results appear to rule out any major effect of finerenone on blood pressure lowering because average systolic pressure fell by only about 2 mm Hg in the treatment group.

“The benefits of finerenone for cardiorenal outcomes are substantial and clinically meaningful,” Dr. Kosiborod said. “We cannot assume that other MRAs, such as spironolactone, provide similar benefits,” he cautioned, but the results are “very good news for patients with type 2 diabetes and chronic kidney disease. We now have another effective intervention with a different mechanism of action.”

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone (BAY 94-8862). Dr. Agarwal has been a consultant to and has received honoraria from Bayer and from several other companies. Dr. Kosiborod has been a consultant to Bayer and to AstraZeneca, Boehringer Ingelheim, Jansse, Merck, and Vifor and has received research funding from AstraZeneca and Boehringer Ingelheim. Dr. Rangaswami has disclosed no relevant financial relationships.
 

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

For patients with diabetic kidney disease, finerenone, an agent from a new class of selective, nonsteroidal mineralocorticoid receptor antagonists, led to significant reductions in combined adverse renal outcomes and in combined adverse cardiovascular outcomes in the pivotal FIDELIO-DKD trial.

And the safety results showed a good level of tolerability. The rate of hyperkalemia was higher with finerenone than with placebo, but the rate of drug discontinuations for elevated potassium was lower than that seen with spironolactone, a steroidal mineralocorticoid receptor antagonist (MRA).

“An ideal drug would cause no hyperkalemia, but the absolute risk we saw is a fraction of what we see with spironolactone in this vulnerable patient population,” said Rajiv Agarwal, MD, from Indiana in Indianapolis, during a press briefing.

After a median follow-up of 2.6 years, finerenone was associated with a 3.4% absolute reduction in the rate of combined adverse renal events, the study’s primary end point, which comprised kidney failure, renal death, and a drop in estimated glomerular filtration rate (eGFR) of at least 40% from baseline. This produced a significant relative risk reduction of 18%, with a number needed to treat of 32 to prevent one of these events, Dr. Agarwal reported at Kidney Week 2020. Findings from the FIDELIO-DKD trial were published simultaneously in the New England Journal of Medicine.

Finerenone was also associated with an absolute 2.4% reduction in the rate of combined adverse cardiovascular events, the study’s “key secondary end point,” which included cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure. This translated into a significant relative risk reduction of 14% and a number needed to treat of 42 to prevent one of these events.

FIDELIO-DKD assessed 5,734 patients with type 2 diabetes and chronic kidney disease from more than 1,000 sites in 48 countries, including the United States, from 2015 to 2018. In the study cohort, average age was slightly more than 65 years, average baseline systolic blood pressure was 138 mm Hg, average duration of diabetes was nearly 17 years, average baseline glycated hemoglobin (A1c) was 7.7%, and fewer than 5% of patients were Black, 25% were Asian, and about 63% were White.
 

A suggestion of less severe hyperkalemia

Finerenone was well tolerated by the participants, and the findings suggest that it caused less clinically meaningful hyperkalemia than spironolactone, the most established and widely used MRA.

Like all MRA drugs, finerenone led to an increase in serum potassium in all patient subgroups – in this case 0.2 mmol/L – unlike placebo, said Dr. Agarwal.

The overall incidence of hyperkalemia was 16% in the 2,827 evaluable patients in the finerenone group and 8% in the 2,831 evaluable patients in the placebo group. Fewer than 10% of patients in the trial received a potassium-binding agent.

The rate of hyperkalemia leading to treatment discontinuation was higher in the finerenone group than in the placebo group (2.3% vs. 0.9%).

That 2.3% rate is 10 times lower than the 23.0% rate of hyperkalemia-related treatment discontinuation in patients who received spironolactone and no potassium-binding agent, said Dr. Agarwal, citing a previous study he was involved with.

He hypothesized that finerenone might cause less clinically meaningful hyperkalemia because it creates no active metabolites that linger in the body, whereas spironolactone produces active metabolites with a half life of about 1 week.

“The risk for hyperkalemia is clearly increased with finerenone compared with placebo, and in the absence of head-to-head studies, it’s hard to know how it compares with spironolactone or eplerenone [Inspra],” the other agents in the MRA class, said Mikhail N. Kosiborod, MD, from the University of Missouri–Kansas City.

“The rates of hyperkalemia observed in FIDELIO-DKD were overall comparable to what we would expect from eplerenone. But the rate of serious hyperkalemia was quite low with finerenone, which is reassuring,” Dr. Kosiborod said in an interview.

And the adverse-effect profile showed that finerenone “is as safe as you could expect from an MRA,” said Janani Rangaswami, MD, from the Einstein Medical Center in Philadelphia.

The rate of hyperkalemia should be interpreted in the context of the high risk the enrolled patients faced, given that they all had moderate to severe diabetic kidney disease with albuminuria and, in some cases, eGFR rates as low as 25 mL/min per 1.73m², she explained. In addition, all patients were on maximally tolerated treatment with either an angiotensin-converting–enzyme inhibitor or an angiotensin receptor blocker to inhibit the renin angiotensin system (RAS).

“Considering this background, it’s a very acceptable adverse-event profile,” Dr. Rangaswami said in an interview.
 

Renal drugs that could work together

More than 99% of patients in FIDELIO-DKD were on an RAS inhibitor, but fewer than 5% were on a sodium glucose cotransporter 2 (SGLT2) inhibitor at baseline, and fewer than 10% started on this drug class during the course of the study.

Despite that, both Dr. Kosiborod and Dr. Rangaswami are enthusiastic about the prospect of using the three drugs in combination to maximize renal and cardiovascular benefits in FIDELIO-DKD–type patients. Recent results from the CREDENCE study of canagliflozin (Invokana) and from the DAPA-CKD study of dapagluflozin (Farxiga) have established SGLT2 inhibitors – at least those two – as key agents for patients with chronic kidney disease.

Dual treatment with an RAS inhibitor and an SGLT2 inhibitor is “clearly established” for patients with diabetic kidney disease, said Dr. Agarwal.

“After CREDENCE, DAPA-CKD, and now FIDELIO-DKD, we need to seriously consider triple therapy as the future of treatment for diabetic kidney disease to prevent both cardiovascular and kidney complications,” said Dr. Kosiborod. The approach will mimic the multidrug therapy that’s now standard for patients with heart failure with reduced ejection fraction (HFrEF). But he cautioned that this triple combination needs further testing.

“Triple therapy will be the standard of care” for patients with diabetic kidney disease, Dr. Rangaswami agreed, but she cautioned that she would not currently expand the target population for finerenone to patients without type 2 diabetes or to patients without the level of albuminuria required for entry into FIDELIO-DKD: at least 30 mg/g of creatinine per day. And patients with HFrEF were excluded from FIDELIO-DKD, so that limitation on finerenone use should remain for the time being, she added.

Dr. Rangaswami said she is optimistic about the potential efficacy of finerenone added to an SGLT2 inhibitor because of the likelihood that the two drug classes work in different but complementary ways. SGLT2 inhibitors seem to exert their renal protective effects largely through hemodynamic effects, whereas it is likely that finerenone exerts its effects largely as an anti-inflammatory and antifibrotic agent, she speculated. The FIDELIO-DKD results appear to rule out any major effect of finerenone on blood pressure lowering because average systolic pressure fell by only about 2 mm Hg in the treatment group.

“The benefits of finerenone for cardiorenal outcomes are substantial and clinically meaningful,” Dr. Kosiborod said. “We cannot assume that other MRAs, such as spironolactone, provide similar benefits,” he cautioned, but the results are “very good news for patients with type 2 diabetes and chronic kidney disease. We now have another effective intervention with a different mechanism of action.”

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone (BAY 94-8862). Dr. Agarwal has been a consultant to and has received honoraria from Bayer and from several other companies. Dr. Kosiborod has been a consultant to Bayer and to AstraZeneca, Boehringer Ingelheim, Jansse, Merck, and Vifor and has received research funding from AstraZeneca and Boehringer Ingelheim. Dr. Rangaswami has disclosed no relevant financial relationships.
 

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

I have been in practice for 31 years, so many of my patients are now in their 80s and 90s. Practices age with us, and I have been seeing many of these patients for 25-30 years. I have three rules I try to encourage my elderly patients follow, and I wanted to share them with you.

Absolutely, positively make sure you move!

Our older patients often have many reasons not to move, including pain from arthritis, deconditioning, muscle weakness, fatigue, and depression. “Keeping moving” is probably the most important thing a patient can do for their health.

Holme and Anderssen studied a large cohort of men for cardiovascular risk in 1972 and again in 2000. The surviving men were followed over an additional 12 years.¹ They found that 30 minutes of physical activity 6 days a week was associated with a 40% reduction in mortality. Sedentary men had a reduced life expectancy of about 5 years, compared with men who were moderately to vigorously physically active.

Stewart etal. studied the benefit of physical activity in people with stable coronary disease.² They concluded that, in patients with stable coronary heart disease, more physical activity was associated with lower mortality, and the largest benefit occurred in the sedentary patient groups and the highest cardiac risk groups.

Saint-Maurice et al. studied the effects of total daily step count and step intensity on mortality risk.³ They found that the risk of all-cause mortality decreases as the total number of daily steps increases, but that the speed of those steps did not make a difference. This is very encouraging data for our elderly patients. Moving is the secret, even if it may not be moving at a fast pace!
 

Never, ever get on a ladder!

This one should be part of every geriatric’s assessment and every Medicare wellness exam. I first experienced the horror of what can happen when elderly people climb when a 96-year-old healthy patient of mine fell off his roof and died. I never thought to tell him climbing on the roof was an awful idea.

Akland et al. looked at the epidemiology and outcomes of ladder-related falls that required ICU admission.⁴ Hospital mortality was 26%, and almost all of the mortalities occurred in older males in domestic falls, who died as a result of traumatic brain injury. Fewer than half of the survivors were living independently 1 year after the fall.

Valmuur et al. studied ladder related falls in Australia.⁵ They found that rates of ladder related falls requiring hospitalization rose from about 20/100,000 for men ages 15-29 years to 78/100,000 for men aged over 60 years. Of those who died from fall-related injury, 82% were over the age of 60, with more than 70% dying from head injuries.

Schaffarczyk et al. looked at the impact of nonoccupational falls from ladders in men aged over 50 years.⁶ The mean age of the patients in the study was 64 years (range, 50-85), with 27% suffering severe trauma. There was a striking impact on long-term function occurring in over half the study patients. The authors did interviews with patients in follow-up long after the falls and found that most never thought of themselves at risk for a fall, and after the experience of a bad fall, would never consider going on a ladder again. I think it is important for health care professionals to discuss the dangers of ladder use with our older patients, pointing out the higher risk of falling and the potential for the fall to be a life-changing or life-ending event.
 

Let them eat!

Many patients have a reduced appetite as they age. We work hard with our patients to choose a healthy diet throughout their lives, to help ward off obesity, treat hypertension, prevent or control diabetes, or provide heart health. Many patients just stop being interested in food, reduce intake, and may lose weight and muscle mass. When my patients pass the age of 85, I change my focus to encouraging them to eat for calories, socialization, and joy. I think the marginal benefits of more restrictive diets are small, compared with the benefits of helping your patients enjoy eating again. I ask patients what their very favorite foods are and encourage them to have them.

Pearl

Keep your patients eating and moving, except not onto a ladder!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Holme I, Anderssen SA. Increases in physical activity is as important as smoking cessation for reduction in total mortality in elderly men: 12 years of follow-up of the Oslo II study. Br J Sports Med. 2015; 49:743-8.

2. Stewart RAH et al. Physical activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol. 2017 Oct 3;70(14):1689-1700..

3. Saint-Maurice PF et al. Association of daily step count and step intensity with mortality among U.S. adults. JAMA 2020;323:1151-60.

4. Ackland HM et al. Danger at every rung: Epidemiology and outcomes of ICU-admitted ladder-related trauma. Injury. 2016;47:1109-117.

5. Vallmuur K et al. Falls from ladders in Australia: comparing occupational and nonoccupational injuries across age groups. Aust N Z J Public Health. 2016 Dec;40(6):559-63.

6. Schaffarczyk K et al. Nonoccupational falls from ladders in men 50 years and over: Contributing factors and impact. Injury. 2020 Aug;51(8):1798-1804.

I have been in practice for 31 years, so many of my patients are now in their 80s and 90s. Practices age with us, and I have been seeing many of these patients for 25-30 years. I have three rules I try to encourage my elderly patients follow, and I wanted to share them with you.

Absolutely, positively make sure you move!

Our older patients often have many reasons not to move, including pain from arthritis, deconditioning, muscle weakness, fatigue, and depression. “Keeping moving” is probably the most important thing a patient can do for their health.

Holme and Anderssen studied a large cohort of men for cardiovascular risk in 1972 and again in 2000. The surviving men were followed over an additional 12 years.¹ They found that 30 minutes of physical activity 6 days a week was associated with a 40% reduction in mortality. Sedentary men had a reduced life expectancy of about 5 years, compared with men who were moderately to vigorously physically active.

Stewart etal. studied the benefit of physical activity in people with stable coronary disease.² They concluded that, in patients with stable coronary heart disease, more physical activity was associated with lower mortality, and the largest benefit occurred in the sedentary patient groups and the highest cardiac risk groups.

Saint-Maurice et al. studied the effects of total daily step count and step intensity on mortality risk.³ They found that the risk of all-cause mortality decreases as the total number of daily steps increases, but that the speed of those steps did not make a difference. This is very encouraging data for our elderly patients. Moving is the secret, even if it may not be moving at a fast pace!
 

Never, ever get on a ladder!

This one should be part of every geriatric’s assessment and every Medicare wellness exam. I first experienced the horror of what can happen when elderly people climb when a 96-year-old healthy patient of mine fell off his roof and died. I never thought to tell him climbing on the roof was an awful idea.

Akland et al. looked at the epidemiology and outcomes of ladder-related falls that required ICU admission.⁴ Hospital mortality was 26%, and almost all of the mortalities occurred in older males in domestic falls, who died as a result of traumatic brain injury. Fewer than half of the survivors were living independently 1 year after the fall.

Valmuur et al. studied ladder related falls in Australia.⁵ They found that rates of ladder related falls requiring hospitalization rose from about 20/100,000 for men ages 15-29 years to 78/100,000 for men aged over 60 years. Of those who died from fall-related injury, 82% were over the age of 60, with more than 70% dying from head injuries.

Schaffarczyk et al. looked at the impact of nonoccupational falls from ladders in men aged over 50 years.⁶ The mean age of the patients in the study was 64 years (range, 50-85), with 27% suffering severe trauma. There was a striking impact on long-term function occurring in over half the study patients. The authors did interviews with patients in follow-up long after the falls and found that most never thought of themselves at risk for a fall, and after the experience of a bad fall, would never consider going on a ladder again. I think it is important for health care professionals to discuss the dangers of ladder use with our older patients, pointing out the higher risk of falling and the potential for the fall to be a life-changing or life-ending event.
 

Let them eat!

Many patients have a reduced appetite as they age. We work hard with our patients to choose a healthy diet throughout their lives, to help ward off obesity, treat hypertension, prevent or control diabetes, or provide heart health. Many patients just stop being interested in food, reduce intake, and may lose weight and muscle mass. When my patients pass the age of 85, I change my focus to encouraging them to eat for calories, socialization, and joy. I think the marginal benefits of more restrictive diets are small, compared with the benefits of helping your patients enjoy eating again. I ask patients what their very favorite foods are and encourage them to have them.

Pearl

Keep your patients eating and moving, except not onto a ladder!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Holme I, Anderssen SA. Increases in physical activity is as important as smoking cessation for reduction in total mortality in elderly men: 12 years of follow-up of the Oslo II study. Br J Sports Med. 2015; 49:743-8.

2. Stewart RAH et al. Physical activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol. 2017 Oct 3;70(14):1689-1700..

3. Saint-Maurice PF et al. Association of daily step count and step intensity with mortality among U.S. adults. JAMA 2020;323:1151-60.

4. Ackland HM et al. Danger at every rung: Epidemiology and outcomes of ICU-admitted ladder-related trauma. Injury. 2016;47:1109-117.

5. Vallmuur K et al. Falls from ladders in Australia: comparing occupational and nonoccupational injuries across age groups. Aust N Z J Public Health. 2016 Dec;40(6):559-63.

6. Schaffarczyk K et al. Nonoccupational falls from ladders in men 50 years and over: Contributing factors and impact. Injury. 2020 Aug;51(8):1798-1804.

I have been in practice for 31 years, so many of my patients are now in their 80s and 90s. Practices age with us, and I have been seeing many of these patients for 25-30 years. I have three rules I try to encourage my elderly patients follow, and I wanted to share them with you.

Absolutely, positively make sure you move!

Our older patients often have many reasons not to move, including pain from arthritis, deconditioning, muscle weakness, fatigue, and depression. “Keeping moving” is probably the most important thing a patient can do for their health.

Holme and Anderssen studied a large cohort of men for cardiovascular risk in 1972 and again in 2000. The surviving men were followed over an additional 12 years.¹ They found that 30 minutes of physical activity 6 days a week was associated with a 40% reduction in mortality. Sedentary men had a reduced life expectancy of about 5 years, compared with men who were moderately to vigorously physically active.

Stewart etal. studied the benefit of physical activity in people with stable coronary disease.² They concluded that, in patients with stable coronary heart disease, more physical activity was associated with lower mortality, and the largest benefit occurred in the sedentary patient groups and the highest cardiac risk groups.

Saint-Maurice et al. studied the effects of total daily step count and step intensity on mortality risk.³ They found that the risk of all-cause mortality decreases as the total number of daily steps increases, but that the speed of those steps did not make a difference. This is very encouraging data for our elderly patients. Moving is the secret, even if it may not be moving at a fast pace!
 

Never, ever get on a ladder!

This one should be part of every geriatric’s assessment and every Medicare wellness exam. I first experienced the horror of what can happen when elderly people climb when a 96-year-old healthy patient of mine fell off his roof and died. I never thought to tell him climbing on the roof was an awful idea.

Akland et al. looked at the epidemiology and outcomes of ladder-related falls that required ICU admission.⁴ Hospital mortality was 26%, and almost all of the mortalities occurred in older males in domestic falls, who died as a result of traumatic brain injury. Fewer than half of the survivors were living independently 1 year after the fall.

Valmuur et al. studied ladder related falls in Australia.⁵ They found that rates of ladder related falls requiring hospitalization rose from about 20/100,000 for men ages 15-29 years to 78/100,000 for men aged over 60 years. Of those who died from fall-related injury, 82% were over the age of 60, with more than 70% dying from head injuries.

Schaffarczyk et al. looked at the impact of nonoccupational falls from ladders in men aged over 50 years.⁶ The mean age of the patients in the study was 64 years (range, 50-85), with 27% suffering severe trauma. There was a striking impact on long-term function occurring in over half the study patients. The authors did interviews with patients in follow-up long after the falls and found that most never thought of themselves at risk for a fall, and after the experience of a bad fall, would never consider going on a ladder again. I think it is important for health care professionals to discuss the dangers of ladder use with our older patients, pointing out the higher risk of falling and the potential for the fall to be a life-changing or life-ending event.
 

Let them eat!

Many patients have a reduced appetite as they age. We work hard with our patients to choose a healthy diet throughout their lives, to help ward off obesity, treat hypertension, prevent or control diabetes, or provide heart health. Many patients just stop being interested in food, reduce intake, and may lose weight and muscle mass. When my patients pass the age of 85, I change my focus to encouraging them to eat for calories, socialization, and joy. I think the marginal benefits of more restrictive diets are small, compared with the benefits of helping your patients enjoy eating again. I ask patients what their very favorite foods are and encourage them to have them.

Pearl

Keep your patients eating and moving, except not onto a ladder!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Holme I, Anderssen SA. Increases in physical activity is as important as smoking cessation for reduction in total mortality in elderly men: 12 years of follow-up of the Oslo II study. Br J Sports Med. 2015; 49:743-8.

2. Stewart RAH et al. Physical activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol. 2017 Oct 3;70(14):1689-1700..

3. Saint-Maurice PF et al. Association of daily step count and step intensity with mortality among U.S. adults. JAMA 2020;323:1151-60.

4. Ackland HM et al. Danger at every rung: Epidemiology and outcomes of ICU-admitted ladder-related trauma. Injury. 2016;47:1109-117.

5. Vallmuur K et al. Falls from ladders in Australia: comparing occupational and nonoccupational injuries across age groups. Aust N Z J Public Health. 2016 Dec;40(6):559-63.

6. Schaffarczyk K et al. Nonoccupational falls from ladders in men 50 years and over: Contributing factors and impact. Injury. 2020 Aug;51(8):1798-1804.

The risk for death goes up for patients with atrial fibrillation (AFib) who are put on direct oral anticoagulants (DOAC) at dosages other than those approved for stroke prevention, whether higher or lower than doses specified in the labeling, suggests a large registry study.

A quarter of more than 10,000 patients in the registry took the drugs at such nonrecommended higher or lower dosages. Overwhelmingly it was the latter, perhaps reflecting caution on the part of some practitioners looking to minimize the risk of bleeding complications.

The risk of major bleeding indeed dropped sharply for those taking DOACs at lower-than-recommended levels, but at the cost of a 25% jump in all-cause mortality over 2 years, report investigators from their analysis of patients in the GARFIELD-AF registry published Sept. 14 in the Journal of the American College of Cardiology.

Risks of major bleeding and of stroke or systemic embolism didn’t climb significantly for patients either under- or overdosed.

In general, “physicians are worried about giving too much anticoagulant, and they tend to favor erring on the low-dose side,” lead author A. John Camm, MD, St. George’s University of London, said in an interview. That’s how it was when an oral anticoagulation meant a vitamin K antagonist (VKA) and underdosing was frequent; and it remains an issue in the DOAC era. “It’s not just a little problem. It’s a very big problem.”

Today, clinicians may prescribe DOACs similar to how they prescribed VKAs, by cautiously choosing a lower dosage for selected patients based on their risk profile, Dr. Camm observed. But in contrast to the VKAs, the DOACs “were studied with different dose-reduction strategies, and their labeling requires them to be prescribed according to different parameters.”

They variously base dosage reductions on age, body weight, renal function, or drug-drug interactions, for example, but some clinicians “tend to think that all of those factors should be applied in every instance, with every drug,” he said.

“So I think there’s some confusion and a lot of caution that physicians use with anticoagulants, and they often forget that the purpose of the anticoagulant is to prevent strokes and adverse outcomes such as mortality,” Dr. Camm said. “But by reducing the dose, they expose their patients to these other major cardiovascular events.”

Numerically, the excess mortality among underdosed patients appeared to be driven by death from heart failure or myocardial infarction. There was little or no contribution from sudden death, fatal strokes, or noncardiovascular death.

The findings “remind clinicians to dose DOACs properly and that there are consequences of dosing errors,” observes Gerald V. Naccarelli, MD, of Penn State University and the Milton S. Hershey Medical Center, Hershey, in an accompanying editorial.

Based on the major clinical trials that established the drugs as mainstream stroke-preventive therapy in AFib, as well as extensive regulatory review, each DOAC’s label-recommended dosing “is a guidance of the truth to achieve the highest efficacy and most safety in our patients,” Dr. Naccarelli wrote. “As clinicians are risk adverse, underdosing might result in lower major bleeding rates, and physicians are blamed for bleeding but not necessarily for allowing embolic strokes to occur. These data raise the issue that underdosing is associated with worse patient outcomes.”

The GARFIELD-AF analysis covered 10,426 adults with nonvalvular AFib in 35 countries who initiated a DOAC from 2013 to 2016. The drugs were prescribed at dosages consistent with recommendations in each respective country’s labeling for stroke prevention in AFib in 72.9% of the cohort. Most full and adjusted dose levels approved by the European Medicines Agency, Food and Drug Administration, and regulators in Japan were the same or similar.

But there were a few exceptions. All dosing criteria across the three regulatory domains were the same for apixaban (Eliquis). But variations included lower dosage options for rivaroxaban (Xarelto) and edoxaban (Savaysa, Lixiana) in Japan, and a uniquely low dabigatran (Pradaxa) dosage option in the United States.

The DOAC used least often was the one most frequently underdosed. More than half of patients prescribed edoxaban were given it at a lower-than-recommended dosage.

The adjusted hazard ratio for all-cause mortality at 2 years for DOAC under- or overdosing, compared with dosing at recommended levels, was 1.24 (95% confidence interval, 1.04-1.48). The difference was driven by underdosing, for which the HR was 1.25 (95% CI, 1.04-1.50). The HR for over-dosing was only 1.19 (95% CI, 0.83-1.71).

Multivariate adjustment accounted for age, sex, and ethnicity; type of AFib; diabetes; hypertension; history of bleeding; prior stroke, transient ischemic attack, or systemic embolism; heart failure; vascular disease; smoking; and heavy alcohol consumption.

The risk of stroke or systemic embolism didn’t go up or down significantly for either overdosed or underdosed patients. Neither group showed an increased risk for major bleeding; however, the HR for major bleeding in underdosed patients fell to 0.50 (95% CI, 0.28-0.88).

Underdosing was more common in some world regions than others. The rate exceeded 30% in all Latin American countries except Argentina, the report stated, and in all Asian countries except Singapore.

Japanese patients have long received oral anticoagulation at lower dosages than are used in the West, Dr. Camm observed. When VKAs were the only choice, for example, international normalized ratio targets were consistently a bit lower in Japan than in, for example, North America or Europe.

“And when [novel] OACs were developed, again, the Japanese took the view that their patients are more vulnerable to bleeding, and therefore a lower dose would be appropriate. In some instances, lower-dose regimens have been specifically studied in the Japanese,” Dr. Camm said. “Having said that, this concept of bleeding being more problematic in Asian patients has expanded well beyond Japan, and therefore in many Asian communities, lower doses of [novel] OACs are chosen.”

Many other factors may contribute to DOAC underdosing, including differences in dosing strategies between primary care practitioners and specialists, or between hospital-based and office-based clinicians, for example.

“It might also be argued that a physician who fails to treat a patient adequately in one arena may also be failing to treat the patient well in other aspects of their care,” Dr. Camm proposed. “Therefore you could have increased mortality due to other cardiovascular causes, or even noncardiovascular events, through absence of good quality care. Our study did not address that specifically. But it might be the case, speculatively.”

The study was supported by a grant from Bayer to the Thrombosis Research Institute, “which sponsors the GARFIELD-AF registry.” Dr. Camm discloses receiving grants and personal fees from Bayer, Boehringer Ingelheim, Pfizer/Bristol-Myers Squibb, and Daiichi Sankyo. Disclosures for the other authors are in the report. Dr. Naccarelli disclosed consulting and participating in research for Janssen and serving as a consultant for Milestone, Sanofi, Omeicos, and Acesion Pharma.

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

The risk for death goes up for patients with atrial fibrillation (AFib) who are put on direct oral anticoagulants (DOAC) at dosages other than those approved for stroke prevention, whether higher or lower than doses specified in the labeling, suggests a large registry study.

A quarter of more than 10,000 patients in the registry took the drugs at such nonrecommended higher or lower dosages. Overwhelmingly it was the latter, perhaps reflecting caution on the part of some practitioners looking to minimize the risk of bleeding complications.

The risk of major bleeding indeed dropped sharply for those taking DOACs at lower-than-recommended levels, but at the cost of a 25% jump in all-cause mortality over 2 years, report investigators from their analysis of patients in the GARFIELD-AF registry published Sept. 14 in the Journal of the American College of Cardiology.

Risks of major bleeding and of stroke or systemic embolism didn’t climb significantly for patients either under- or overdosed.

In general, “physicians are worried about giving too much anticoagulant, and they tend to favor erring on the low-dose side,” lead author A. John Camm, MD, St. George’s University of London, said in an interview. That’s how it was when an oral anticoagulation meant a vitamin K antagonist (VKA) and underdosing was frequent; and it remains an issue in the DOAC era. “It’s not just a little problem. It’s a very big problem.”

Today, clinicians may prescribe DOACs similar to how they prescribed VKAs, by cautiously choosing a lower dosage for selected patients based on their risk profile, Dr. Camm observed. But in contrast to the VKAs, the DOACs “were studied with different dose-reduction strategies, and their labeling requires them to be prescribed according to different parameters.”

They variously base dosage reductions on age, body weight, renal function, or drug-drug interactions, for example, but some clinicians “tend to think that all of those factors should be applied in every instance, with every drug,” he said.

“So I think there’s some confusion and a lot of caution that physicians use with anticoagulants, and they often forget that the purpose of the anticoagulant is to prevent strokes and adverse outcomes such as mortality,” Dr. Camm said. “But by reducing the dose, they expose their patients to these other major cardiovascular events.”

Numerically, the excess mortality among underdosed patients appeared to be driven by death from heart failure or myocardial infarction. There was little or no contribution from sudden death, fatal strokes, or noncardiovascular death.

The findings “remind clinicians to dose DOACs properly and that there are consequences of dosing errors,” observes Gerald V. Naccarelli, MD, of Penn State University and the Milton S. Hershey Medical Center, Hershey, in an accompanying editorial.

Based on the major clinical trials that established the drugs as mainstream stroke-preventive therapy in AFib, as well as extensive regulatory review, each DOAC’s label-recommended dosing “is a guidance of the truth to achieve the highest efficacy and most safety in our patients,” Dr. Naccarelli wrote. “As clinicians are risk adverse, underdosing might result in lower major bleeding rates, and physicians are blamed for bleeding but not necessarily for allowing embolic strokes to occur. These data raise the issue that underdosing is associated with worse patient outcomes.”

The GARFIELD-AF analysis covered 10,426 adults with nonvalvular AFib in 35 countries who initiated a DOAC from 2013 to 2016. The drugs were prescribed at dosages consistent with recommendations in each respective country’s labeling for stroke prevention in AFib in 72.9% of the cohort. Most full and adjusted dose levels approved by the European Medicines Agency, Food and Drug Administration, and regulators in Japan were the same or similar.

But there were a few exceptions. All dosing criteria across the three regulatory domains were the same for apixaban (Eliquis). But variations included lower dosage options for rivaroxaban (Xarelto) and edoxaban (Savaysa, Lixiana) in Japan, and a uniquely low dabigatran (Pradaxa) dosage option in the United States.

The DOAC used least often was the one most frequently underdosed. More than half of patients prescribed edoxaban were given it at a lower-than-recommended dosage.

The adjusted hazard ratio for all-cause mortality at 2 years for DOAC under- or overdosing, compared with dosing at recommended levels, was 1.24 (95% confidence interval, 1.04-1.48). The difference was driven by underdosing, for which the HR was 1.25 (95% CI, 1.04-1.50). The HR for over-dosing was only 1.19 (95% CI, 0.83-1.71).

Multivariate adjustment accounted for age, sex, and ethnicity; type of AFib; diabetes; hypertension; history of bleeding; prior stroke, transient ischemic attack, or systemic embolism; heart failure; vascular disease; smoking; and heavy alcohol consumption.

The risk of stroke or systemic embolism didn’t go up or down significantly for either overdosed or underdosed patients. Neither group showed an increased risk for major bleeding; however, the HR for major bleeding in underdosed patients fell to 0.50 (95% CI, 0.28-0.88).

Underdosing was more common in some world regions than others. The rate exceeded 30% in all Latin American countries except Argentina, the report stated, and in all Asian countries except Singapore.

Japanese patients have long received oral anticoagulation at lower dosages than are used in the West, Dr. Camm observed. When VKAs were the only choice, for example, international normalized ratio targets were consistently a bit lower in Japan than in, for example, North America or Europe.

“And when [novel] OACs were developed, again, the Japanese took the view that their patients are more vulnerable to bleeding, and therefore a lower dose would be appropriate. In some instances, lower-dose regimens have been specifically studied in the Japanese,” Dr. Camm said. “Having said that, this concept of bleeding being more problematic in Asian patients has expanded well beyond Japan, and therefore in many Asian communities, lower doses of [novel] OACs are chosen.”

Many other factors may contribute to DOAC underdosing, including differences in dosing strategies between primary care practitioners and specialists, or between hospital-based and office-based clinicians, for example.

“It might also be argued that a physician who fails to treat a patient adequately in one arena may also be failing to treat the patient well in other aspects of their care,” Dr. Camm proposed. “Therefore you could have increased mortality due to other cardiovascular causes, or even noncardiovascular events, through absence of good quality care. Our study did not address that specifically. But it might be the case, speculatively.”

The study was supported by a grant from Bayer to the Thrombosis Research Institute, “which sponsors the GARFIELD-AF registry.” Dr. Camm discloses receiving grants and personal fees from Bayer, Boehringer Ingelheim, Pfizer/Bristol-Myers Squibb, and Daiichi Sankyo. Disclosures for the other authors are in the report. Dr. Naccarelli disclosed consulting and participating in research for Janssen and serving as a consultant for Milestone, Sanofi, Omeicos, and Acesion Pharma.

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

The risk for death goes up for patients with atrial fibrillation (AFib) who are put on direct oral anticoagulants (DOAC) at dosages other than those approved for stroke prevention, whether higher or lower than doses specified in the labeling, suggests a large registry study.

A quarter of more than 10,000 patients in the registry took the drugs at such nonrecommended higher or lower dosages. Overwhelmingly it was the latter, perhaps reflecting caution on the part of some practitioners looking to minimize the risk of bleeding complications.

The risk of major bleeding indeed dropped sharply for those taking DOACs at lower-than-recommended levels, but at the cost of a 25% jump in all-cause mortality over 2 years, report investigators from their analysis of patients in the GARFIELD-AF registry published Sept. 14 in the Journal of the American College of Cardiology.

Risks of major bleeding and of stroke or systemic embolism didn’t climb significantly for patients either under- or overdosed.

In general, “physicians are worried about giving too much anticoagulant, and they tend to favor erring on the low-dose side,” lead author A. John Camm, MD, St. George’s University of London, said in an interview. That’s how it was when an oral anticoagulation meant a vitamin K antagonist (VKA) and underdosing was frequent; and it remains an issue in the DOAC era. “It’s not just a little problem. It’s a very big problem.”

Today, clinicians may prescribe DOACs similar to how they prescribed VKAs, by cautiously choosing a lower dosage for selected patients based on their risk profile, Dr. Camm observed. But in contrast to the VKAs, the DOACs “were studied with different dose-reduction strategies, and their labeling requires them to be prescribed according to different parameters.”

They variously base dosage reductions on age, body weight, renal function, or drug-drug interactions, for example, but some clinicians “tend to think that all of those factors should be applied in every instance, with every drug,” he said.

“So I think there’s some confusion and a lot of caution that physicians use with anticoagulants, and they often forget that the purpose of the anticoagulant is to prevent strokes and adverse outcomes such as mortality,” Dr. Camm said. “But by reducing the dose, they expose their patients to these other major cardiovascular events.”

Numerically, the excess mortality among underdosed patients appeared to be driven by death from heart failure or myocardial infarction. There was little or no contribution from sudden death, fatal strokes, or noncardiovascular death.

The findings “remind clinicians to dose DOACs properly and that there are consequences of dosing errors,” observes Gerald V. Naccarelli, MD, of Penn State University and the Milton S. Hershey Medical Center, Hershey, in an accompanying editorial.

Based on the major clinical trials that established the drugs as mainstream stroke-preventive therapy in AFib, as well as extensive regulatory review, each DOAC’s label-recommended dosing “is a guidance of the truth to achieve the highest efficacy and most safety in our patients,” Dr. Naccarelli wrote. “As clinicians are risk adverse, underdosing might result in lower major bleeding rates, and physicians are blamed for bleeding but not necessarily for allowing embolic strokes to occur. These data raise the issue that underdosing is associated with worse patient outcomes.”

The GARFIELD-AF analysis covered 10,426 adults with nonvalvular AFib in 35 countries who initiated a DOAC from 2013 to 2016. The drugs were prescribed at dosages consistent with recommendations in each respective country’s labeling for stroke prevention in AFib in 72.9% of the cohort. Most full and adjusted dose levels approved by the European Medicines Agency, Food and Drug Administration, and regulators in Japan were the same or similar.

But there were a few exceptions. All dosing criteria across the three regulatory domains were the same for apixaban (Eliquis). But variations included lower dosage options for rivaroxaban (Xarelto) and edoxaban (Savaysa, Lixiana) in Japan, and a uniquely low dabigatran (Pradaxa) dosage option in the United States.

The DOAC used least often was the one most frequently underdosed. More than half of patients prescribed edoxaban were given it at a lower-than-recommended dosage.

The adjusted hazard ratio for all-cause mortality at 2 years for DOAC under- or overdosing, compared with dosing at recommended levels, was 1.24 (95% confidence interval, 1.04-1.48). The difference was driven by underdosing, for which the HR was 1.25 (95% CI, 1.04-1.50). The HR for over-dosing was only 1.19 (95% CI, 0.83-1.71).

Multivariate adjustment accounted for age, sex, and ethnicity; type of AFib; diabetes; hypertension; history of bleeding; prior stroke, transient ischemic attack, or systemic embolism; heart failure; vascular disease; smoking; and heavy alcohol consumption.

The risk of stroke or systemic embolism didn’t go up or down significantly for either overdosed or underdosed patients. Neither group showed an increased risk for major bleeding; however, the HR for major bleeding in underdosed patients fell to 0.50 (95% CI, 0.28-0.88).

Underdosing was more common in some world regions than others. The rate exceeded 30% in all Latin American countries except Argentina, the report stated, and in all Asian countries except Singapore.

Japanese patients have long received oral anticoagulation at lower dosages than are used in the West, Dr. Camm observed. When VKAs were the only choice, for example, international normalized ratio targets were consistently a bit lower in Japan than in, for example, North America or Europe.

“And when [novel] OACs were developed, again, the Japanese took the view that their patients are more vulnerable to bleeding, and therefore a lower dose would be appropriate. In some instances, lower-dose regimens have been specifically studied in the Japanese,” Dr. Camm said. “Having said that, this concept of bleeding being more problematic in Asian patients has expanded well beyond Japan, and therefore in many Asian communities, lower doses of [novel] OACs are chosen.”

Many other factors may contribute to DOAC underdosing, including differences in dosing strategies between primary care practitioners and specialists, or between hospital-based and office-based clinicians, for example.

“It might also be argued that a physician who fails to treat a patient adequately in one arena may also be failing to treat the patient well in other aspects of their care,” Dr. Camm proposed. “Therefore you could have increased mortality due to other cardiovascular causes, or even noncardiovascular events, through absence of good quality care. Our study did not address that specifically. But it might be the case, speculatively.”

The study was supported by a grant from Bayer to the Thrombosis Research Institute, “which sponsors the GARFIELD-AF registry.” Dr. Camm discloses receiving grants and personal fees from Bayer, Boehringer Ingelheim, Pfizer/Bristol-Myers Squibb, and Daiichi Sankyo. Disclosures for the other authors are in the report. Dr. Naccarelli disclosed consulting and participating in research for Janssen and serving as a consultant for Milestone, Sanofi, Omeicos, and Acesion Pharma.

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

Current guidelines recommend a 5-minute rest period before a blood pressure screening measurement, but that might not be necessary for all patients.

In a prospective crossover study, average differences in blood pressure measurements obtained after 0 or 2 minutes of rest were not significantly different than readings obtained after the recommended 5 minutes of rest in adults with systolic blood pressure below 140 mm Hg.

“The average differences in BP by rest period were small, and BPs obtained after shorter rest periods were noninferior to those obtained after 5 minutes when SBP is below 140,” Tammy M. Brady, MD, PhD, Johns Hopkins University, Baltimore, said in an interview.

“This suggests shorter rest times, even 0 minutes, may be reasonable for screening when the initial SBP is below 140,” said Brady.

She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension..
 

A challenging recommendation

The 5-minute rest period is “challenging” to implement in busy clinical settings, Dr. Brady said. The researchers therefore set out to determine the effect of no rest and the effect of a shorter rest period (2 minutes) on blood pressure screening.

They recruited 113 adults (mean age, 55; 64% women, 74% Black) with SBP that ranged from below 115 mm Hg to above 145 mm Hg and with diastolic BP that ranged from below 75 mm Hg to above 105 mm Hg. About one-quarter (28%) had SBP in the stage 2 hypertension range (at least 140 mm Hg).

They obtained four sets of automated BP measurements after 5, 2, or 0 minutes of rest. All participants had their BP measured after a second 5-minute rest period as their last measurement to estimate repeatability.

Overall, there was no significant difference in the average BP obtained at any of the rest periods.

After the first and second 5-minute rest period, BPs were 127.5/74.7 mm Hg and 127.0/75.6 mm Hg, respectively. After 2 and 0 minutes of rest, BPs were 126.8/73.7 mm Hg and 126.5/74.0 mm Hg.

When looking just at adults with SBP below 140 mm Hg, there was no more than an average difference of ±2 mm Hg between BPs obtained at the 5-minute resting periods, compared with the shorter resting periods.

However, in those with SBP below 140 mm Hg, BP values were significantly different (defined as more than ±2 mm Hg) with shorter rest periods, “suggesting that shorter rest periods were in fact inferior to resting for 5 minutes in these patients,” Dr. Brady said.
 

More efficient, economic

“Economics play a significant role in blood pressure screenings, as clinics not as well-funded may find it especially challenging to implement a uniform, 5-minute rest period before testing, which could ultimately reduce the number of patients able to be screened,” Dr. Brady added in a conference statement.

“While our study sample was small, a reasonable approach based on these findings would be to measure blood pressure after minimal to no rest, and then repeat the measurements after 5 minutes only if a patient is found to have elevated blood pressure,” she said.

Weighing in on the results, Karen A. Griffin, MD, who chairs the AHA council on hypertension, said that “reducing the rest period to screen an individual for hypertension may result in faster throughput in the clinic and confer a cost savings.”

“At the present time, in order to maintain the clinic flow, some clinics use a single, often times ‘nonrested’ BP measurement as a screen, reserving the 5-minute rest automated-office BP measurement for patients found to have an elevated screening BP,” noted Dr. Griffin, professor of medicine, Loyola University Medical Center, Maywood, Ill.

“Nevertheless, even if limiting the use of automated-office BP to those who fail the initial screening BP, a cost savings would still be realized by reducing the currently recommended 5-minute rest to 2 minutes and have the most impact in very busy, less well-funded clinics,” said Dr. Griffin.

She cautioned, however, that further studies in a larger population will be needed before making a change to current clinical practice guidelines.

The study had no specific funding. Dr. Brady and Dr. Griffin have no relevant disclosures.

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

Current guidelines recommend a 5-minute rest period before a blood pressure screening measurement, but that might not be necessary for all patients.

In a prospective crossover study, average differences in blood pressure measurements obtained after 0 or 2 minutes of rest were not significantly different than readings obtained after the recommended 5 minutes of rest in adults with systolic blood pressure below 140 mm Hg.

“The average differences in BP by rest period were small, and BPs obtained after shorter rest periods were noninferior to those obtained after 5 minutes when SBP is below 140,” Tammy M. Brady, MD, PhD, Johns Hopkins University, Baltimore, said in an interview.

“This suggests shorter rest times, even 0 minutes, may be reasonable for screening when the initial SBP is below 140,” said Brady.

She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension..
 

A challenging recommendation

The 5-minute rest period is “challenging” to implement in busy clinical settings, Dr. Brady said. The researchers therefore set out to determine the effect of no rest and the effect of a shorter rest period (2 minutes) on blood pressure screening.

They recruited 113 adults (mean age, 55; 64% women, 74% Black) with SBP that ranged from below 115 mm Hg to above 145 mm Hg and with diastolic BP that ranged from below 75 mm Hg to above 105 mm Hg. About one-quarter (28%) had SBP in the stage 2 hypertension range (at least 140 mm Hg).

They obtained four sets of automated BP measurements after 5, 2, or 0 minutes of rest. All participants had their BP measured after a second 5-minute rest period as their last measurement to estimate repeatability.

Overall, there was no significant difference in the average BP obtained at any of the rest periods.

After the first and second 5-minute rest period, BPs were 127.5/74.7 mm Hg and 127.0/75.6 mm Hg, respectively. After 2 and 0 minutes of rest, BPs were 126.8/73.7 mm Hg and 126.5/74.0 mm Hg.

When looking just at adults with SBP below 140 mm Hg, there was no more than an average difference of ±2 mm Hg between BPs obtained at the 5-minute resting periods, compared with the shorter resting periods.

However, in those with SBP below 140 mm Hg, BP values were significantly different (defined as more than ±2 mm Hg) with shorter rest periods, “suggesting that shorter rest periods were in fact inferior to resting for 5 minutes in these patients,” Dr. Brady said.
 

More efficient, economic

“Economics play a significant role in blood pressure screenings, as clinics not as well-funded may find it especially challenging to implement a uniform, 5-minute rest period before testing, which could ultimately reduce the number of patients able to be screened,” Dr. Brady added in a conference statement.

“While our study sample was small, a reasonable approach based on these findings would be to measure blood pressure after minimal to no rest, and then repeat the measurements after 5 minutes only if a patient is found to have elevated blood pressure,” she said.

Weighing in on the results, Karen A. Griffin, MD, who chairs the AHA council on hypertension, said that “reducing the rest period to screen an individual for hypertension may result in faster throughput in the clinic and confer a cost savings.”

“At the present time, in order to maintain the clinic flow, some clinics use a single, often times ‘nonrested’ BP measurement as a screen, reserving the 5-minute rest automated-office BP measurement for patients found to have an elevated screening BP,” noted Dr. Griffin, professor of medicine, Loyola University Medical Center, Maywood, Ill.

“Nevertheless, even if limiting the use of automated-office BP to those who fail the initial screening BP, a cost savings would still be realized by reducing the currently recommended 5-minute rest to 2 minutes and have the most impact in very busy, less well-funded clinics,” said Dr. Griffin.

She cautioned, however, that further studies in a larger population will be needed before making a change to current clinical practice guidelines.

The study had no specific funding. Dr. Brady and Dr. Griffin have no relevant disclosures.

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

Current guidelines recommend a 5-minute rest period before a blood pressure screening measurement, but that might not be necessary for all patients.

In a prospective crossover study, average differences in blood pressure measurements obtained after 0 or 2 minutes of rest were not significantly different than readings obtained after the recommended 5 minutes of rest in adults with systolic blood pressure below 140 mm Hg.

“The average differences in BP by rest period were small, and BPs obtained after shorter rest periods were noninferior to those obtained after 5 minutes when SBP is below 140,” Tammy M. Brady, MD, PhD, Johns Hopkins University, Baltimore, said in an interview.

“This suggests shorter rest times, even 0 minutes, may be reasonable for screening when the initial SBP is below 140,” said Brady.

She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension..
 

A challenging recommendation

The 5-minute rest period is “challenging” to implement in busy clinical settings, Dr. Brady said. The researchers therefore set out to determine the effect of no rest and the effect of a shorter rest period (2 minutes) on blood pressure screening.

They recruited 113 adults (mean age, 55; 64% women, 74% Black) with SBP that ranged from below 115 mm Hg to above 145 mm Hg and with diastolic BP that ranged from below 75 mm Hg to above 105 mm Hg. About one-quarter (28%) had SBP in the stage 2 hypertension range (at least 140 mm Hg).

They obtained four sets of automated BP measurements after 5, 2, or 0 minutes of rest. All participants had their BP measured after a second 5-minute rest period as their last measurement to estimate repeatability.

Overall, there was no significant difference in the average BP obtained at any of the rest periods.

After the first and second 5-minute rest period, BPs were 127.5/74.7 mm Hg and 127.0/75.6 mm Hg, respectively. After 2 and 0 minutes of rest, BPs were 126.8/73.7 mm Hg and 126.5/74.0 mm Hg.

When looking just at adults with SBP below 140 mm Hg, there was no more than an average difference of ±2 mm Hg between BPs obtained at the 5-minute resting periods, compared with the shorter resting periods.

However, in those with SBP below 140 mm Hg, BP values were significantly different (defined as more than ±2 mm Hg) with shorter rest periods, “suggesting that shorter rest periods were in fact inferior to resting for 5 minutes in these patients,” Dr. Brady said.
 

More efficient, economic

“Economics play a significant role in blood pressure screenings, as clinics not as well-funded may find it especially challenging to implement a uniform, 5-minute rest period before testing, which could ultimately reduce the number of patients able to be screened,” Dr. Brady added in a conference statement.

“While our study sample was small, a reasonable approach based on these findings would be to measure blood pressure after minimal to no rest, and then repeat the measurements after 5 minutes only if a patient is found to have elevated blood pressure,” she said.

Weighing in on the results, Karen A. Griffin, MD, who chairs the AHA council on hypertension, said that “reducing the rest period to screen an individual for hypertension may result in faster throughput in the clinic and confer a cost savings.”

“At the present time, in order to maintain the clinic flow, some clinics use a single, often times ‘nonrested’ BP measurement as a screen, reserving the 5-minute rest automated-office BP measurement for patients found to have an elevated screening BP,” noted Dr. Griffin, professor of medicine, Loyola University Medical Center, Maywood, Ill.

“Nevertheless, even if limiting the use of automated-office BP to those who fail the initial screening BP, a cost savings would still be realized by reducing the currently recommended 5-minute rest to 2 minutes and have the most impact in very busy, less well-funded clinics,” said Dr. Griffin.

She cautioned, however, that further studies in a larger population will be needed before making a change to current clinical practice guidelines.

The study had no specific funding. Dr. Brady and Dr. Griffin have no relevant disclosures.

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

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

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

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

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

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

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

The earlier the anti-inflammatory drug colchicine is initiated after a myocardial infarction (MI) the greater the benefit, a new COLCOT analysis suggests.

The parent trial was conducted in patients with a recent MI because of the intense inflammation present at that time, and added colchicine 0.5 mg daily to standard care within 30 days following MI.

As previously reported, colchicine significantly reduced the risk of the primary end point – a composite of cardiovascular (CV) death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring revascularization – by 23% compared with placebo.

This new analysis shows the risk was reduced by 48% in patients receiving colchicine within 3 days of an MI (4.3% vs. 8.3%; adjusted hazard ratio, 0.52; 95% confidence interval, 0.32-0.84, P = .007).

Risk of a secondary efficacy end point – CV death, resuscitated cardiac arrest, MI, or stroke – was reduced by 45% over an average follow up of 22.7 months (3.3% vs 6.1%; adjusted HR, 0.55; 95% CI, 0.32-0.95, P = .031).

“We believe that our results support an early, in-hospital initiation of adjunctive colchicine for post-MI prevention,” Nadia Bouabdallaoui, MD, Montreal Heart Institute, Quebec, Canada, said during an online session devoted to colchicine at the European Society of Cardiology Congress 2020.

Session moderator Massimo Imazio, MD, professor of cardiology at the University of Turin, Italy, said the improved outcomes suggest that earlier treatment is better – a finding that parallels his own experience using colchicine in patients with pericarditis.

“This substudy is very important because this is probably also the year in cardiovascular applications [that] early use of the drug could improve outcomes,” he said.

Positive data have been accumulating for colchicine from COLCOT, LoDoCo, and, most recently, the LoDoCo2 trial, even as another anti-inflammatory drug, methotrexate, flamed out as secondary prevention in the CIRT trial.

The new COLCOT substudy included 4,661 of the 4,745 original patients and examined treatment initiation using three strata: within 0-3 days (n = 1,193), 4-7 days (n = 720), and 8-30 days (n = 2,748). Patients who received treatment within 3 days were slightly younger, more likely to be smokers, and to have a shorter time from MI to randomization (2.1 days vs 5.1 days vs. 20.8 days, respectively).

In the subset receiving treatment within 3 days, those assigned to colchicine had the same number of cardiac deaths as those given placebo (2 vs. 2) but fewer resuscitated cardiac arrests (1 vs. 3), MIs (17 vs. 29), strokes (1 vs. 5), and urgent hospitalizations for angina requiring revascularization (6 vs. 17).

“A larger trial might have allowed for a better assessment of individual endpoints and subgroups,” observed Bouabdallaoui.

Although there is growing support for colchicine, experts caution that the drug many not be for everyone. In COLCOT, 1 in 10 patients were unable to tolerate the drug, largely because of gastrointestinal (GI) issues.
 

Pharmacogenomics substudy

A second COLCOT substudy aimed to identify genetic markers predictive of colchicine response and to gain insights into the mechanisms behind this response. It included 767 patients treated with colchicine and another 755 treated with placebo – or about one-third the patients in the original trial.

A genome-wide association study did not find a significant association for the primary CV endpoint, although a prespecified subgroup analysis in men identified an interesting region on chromosome 9 (variant: rs10811106), which just missed reaching genomewide significance, said Marie-Pierre Dubé, PhD, director of the Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre at the Montreal Heart Institute.

In addition, the genomewide analysis found two significant regions for GI events: one on chromosome 6 (variant: rs6916345) and one on chromosome 10 (variant: rs74795203).

For each of the identified regions, the researchers then tested the effect of the allele in the placebo group and the interaction between the genetic variant and treatment with colchicine. For the chromosome 9 region in males, there was no effect in the placebo group and a significant interaction in the colchicine group.

For the significant GI event findings, there was a small effect for the chromosome 6 region in the placebo group and a very significant interaction with colchicine, Dubé said. Similarly, there was no effect for the chromosome 10 region in the placebo group and a significant interaction with colchicine.

Additional analyses in stratified patient populations showed that males with the protective allele (CC) for the chromosome 9 region represented 83% of the population. The primary CV endpoint occurred in 3.2% of these men treated with colchicine and 6.3% treated with placebo (HR, 0.46; 95% CI, 0.24 - 0.86).

For the gastrointestinal events, 25% of patients carried the risk allele (AA) for the chromosome 6 region and 36.9% of these had GI events when treated with colchicine versus 18.6% when treated with placebo (HR, 2.42; 95% CI, 1.57-3.72).

Similarly, 13% of individuals carried one or two copies of the risk allele (AG+GG) for the chromosome 10 region and the risk of GI events in these was nearly four times higher with colchicine (47.1% vs. 18.9%; HR, 3.98; 95% CI 2.24-7.07).

Functional genomic analyses of the identified regions were also performed and showed that the chromosome 9 locus overlaps with the SAXO1 gene, a stabilizer of axonemal microtubules 1.

“The leading variant at this locus (rs10811106 C allele) correlated with the expression of the HAUS6 gene, which is involved in microtubule generation from existing microtubules, and may interact with the effect of colchicine, which is known to inhibit microtubule formation,” observed Dubé. 

Also, the chromosome 6 locus associated with gastrointestinal events was colocalizing with the Crohn’s disease locus, adding further support for this region.

“The results support potential personalized approaches to inflammation reduction for cardiovascular prevention,” Dubé said.

This is a post hoc subgroup analysis, however, and replication is necessary, ideally in prospective randomized trials, she noted.

The substudy is important because it provides further insights into the link between colchicine and microtubule polymerization, affecting the activation of the inflammasome, session moderator Imazio said.

“Second, it is important because pharmacogenomics can help us to better understand the optimal responder to colchicine and colchicine resistance,” he said. “So it can be useful for personalized medicine, leading to the proper use of the drug for the proper patient.”

COLCOT was supported by the government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Bouabdallaoui has disclosed no relevant financial relationships. Dubé reported grants from the government of Quebec; personal fees from DalCor and GlaxoSmithKline; research support from AstraZeneca, Pfizer, Servier, Sanofi; and minor equity interest in DalCor. Dubé is also coauthor of patents on pharmacogenomics-guided CETP inhibition, and pharmacogenomics markers of response to colchicine.  

This article first appeared on Medscape.com.

The earlier the anti-inflammatory drug colchicine is initiated after a myocardial infarction (MI) the greater the benefit, a new COLCOT analysis suggests.

The parent trial was conducted in patients with a recent MI because of the intense inflammation present at that time, and added colchicine 0.5 mg daily to standard care within 30 days following MI.

As previously reported, colchicine significantly reduced the risk of the primary end point – a composite of cardiovascular (CV) death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring revascularization – by 23% compared with placebo.

This new analysis shows the risk was reduced by 48% in patients receiving colchicine within 3 days of an MI (4.3% vs. 8.3%; adjusted hazard ratio, 0.52; 95% confidence interval, 0.32-0.84, P = .007).

Risk of a secondary efficacy end point – CV death, resuscitated cardiac arrest, MI, or stroke – was reduced by 45% over an average follow up of 22.7 months (3.3% vs 6.1%; adjusted HR, 0.55; 95% CI, 0.32-0.95, P = .031).

“We believe that our results support an early, in-hospital initiation of adjunctive colchicine for post-MI prevention,” Nadia Bouabdallaoui, MD, Montreal Heart Institute, Quebec, Canada, said during an online session devoted to colchicine at the European Society of Cardiology Congress 2020.

Session moderator Massimo Imazio, MD, professor of cardiology at the University of Turin, Italy, said the improved outcomes suggest that earlier treatment is better – a finding that parallels his own experience using colchicine in patients with pericarditis.

“This substudy is very important because this is probably also the year in cardiovascular applications [that] early use of the drug could improve outcomes,” he said.

Positive data have been accumulating for colchicine from COLCOT, LoDoCo, and, most recently, the LoDoCo2 trial, even as another anti-inflammatory drug, methotrexate, flamed out as secondary prevention in the CIRT trial.

The new COLCOT substudy included 4,661 of the 4,745 original patients and examined treatment initiation using three strata: within 0-3 days (n = 1,193), 4-7 days (n = 720), and 8-30 days (n = 2,748). Patients who received treatment within 3 days were slightly younger, more likely to be smokers, and to have a shorter time from MI to randomization (2.1 days vs 5.1 days vs. 20.8 days, respectively).

In the subset receiving treatment within 3 days, those assigned to colchicine had the same number of cardiac deaths as those given placebo (2 vs. 2) but fewer resuscitated cardiac arrests (1 vs. 3), MIs (17 vs. 29), strokes (1 vs. 5), and urgent hospitalizations for angina requiring revascularization (6 vs. 17).

“A larger trial might have allowed for a better assessment of individual endpoints and subgroups,” observed Bouabdallaoui.

Although there is growing support for colchicine, experts caution that the drug many not be for everyone. In COLCOT, 1 in 10 patients were unable to tolerate the drug, largely because of gastrointestinal (GI) issues.
 

Pharmacogenomics substudy

A second COLCOT substudy aimed to identify genetic markers predictive of colchicine response and to gain insights into the mechanisms behind this response. It included 767 patients treated with colchicine and another 755 treated with placebo – or about one-third the patients in the original trial.

A genome-wide association study did not find a significant association for the primary CV endpoint, although a prespecified subgroup analysis in men identified an interesting region on chromosome 9 (variant: rs10811106), which just missed reaching genomewide significance, said Marie-Pierre Dubé, PhD, director of the Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre at the Montreal Heart Institute.

In addition, the genomewide analysis found two significant regions for GI events: one on chromosome 6 (variant: rs6916345) and one on chromosome 10 (variant: rs74795203).

For each of the identified regions, the researchers then tested the effect of the allele in the placebo group and the interaction between the genetic variant and treatment with colchicine. For the chromosome 9 region in males, there was no effect in the placebo group and a significant interaction in the colchicine group.

For the significant GI event findings, there was a small effect for the chromosome 6 region in the placebo group and a very significant interaction with colchicine, Dubé said. Similarly, there was no effect for the chromosome 10 region in the placebo group and a significant interaction with colchicine.

Additional analyses in stratified patient populations showed that males with the protective allele (CC) for the chromosome 9 region represented 83% of the population. The primary CV endpoint occurred in 3.2% of these men treated with colchicine and 6.3% treated with placebo (HR, 0.46; 95% CI, 0.24 - 0.86).

For the gastrointestinal events, 25% of patients carried the risk allele (AA) for the chromosome 6 region and 36.9% of these had GI events when treated with colchicine versus 18.6% when treated with placebo (HR, 2.42; 95% CI, 1.57-3.72).

Similarly, 13% of individuals carried one or two copies of the risk allele (AG+GG) for the chromosome 10 region and the risk of GI events in these was nearly four times higher with colchicine (47.1% vs. 18.9%; HR, 3.98; 95% CI 2.24-7.07).

Functional genomic analyses of the identified regions were also performed and showed that the chromosome 9 locus overlaps with the SAXO1 gene, a stabilizer of axonemal microtubules 1.

“The leading variant at this locus (rs10811106 C allele) correlated with the expression of the HAUS6 gene, which is involved in microtubule generation from existing microtubules, and may interact with the effect of colchicine, which is known to inhibit microtubule formation,” observed Dubé. 

Also, the chromosome 6 locus associated with gastrointestinal events was colocalizing with the Crohn’s disease locus, adding further support for this region.

“The results support potential personalized approaches to inflammation reduction for cardiovascular prevention,” Dubé said.

This is a post hoc subgroup analysis, however, and replication is necessary, ideally in prospective randomized trials, she noted.

The substudy is important because it provides further insights into the link between colchicine and microtubule polymerization, affecting the activation of the inflammasome, session moderator Imazio said.

“Second, it is important because pharmacogenomics can help us to better understand the optimal responder to colchicine and colchicine resistance,” he said. “So it can be useful for personalized medicine, leading to the proper use of the drug for the proper patient.”

COLCOT was supported by the government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Bouabdallaoui has disclosed no relevant financial relationships. Dubé reported grants from the government of Quebec; personal fees from DalCor and GlaxoSmithKline; research support from AstraZeneca, Pfizer, Servier, Sanofi; and minor equity interest in DalCor. Dubé is also coauthor of patents on pharmacogenomics-guided CETP inhibition, and pharmacogenomics markers of response to colchicine.  

This article first appeared on Medscape.com.

The earlier the anti-inflammatory drug colchicine is initiated after a myocardial infarction (MI) the greater the benefit, a new COLCOT analysis suggests.

The parent trial was conducted in patients with a recent MI because of the intense inflammation present at that time, and added colchicine 0.5 mg daily to standard care within 30 days following MI.

As previously reported, colchicine significantly reduced the risk of the primary end point – a composite of cardiovascular (CV) death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring revascularization – by 23% compared with placebo.

This new analysis shows the risk was reduced by 48% in patients receiving colchicine within 3 days of an MI (4.3% vs. 8.3%; adjusted hazard ratio, 0.52; 95% confidence interval, 0.32-0.84, P = .007).

Risk of a secondary efficacy end point – CV death, resuscitated cardiac arrest, MI, or stroke – was reduced by 45% over an average follow up of 22.7 months (3.3% vs 6.1%; adjusted HR, 0.55; 95% CI, 0.32-0.95, P = .031).

“We believe that our results support an early, in-hospital initiation of adjunctive colchicine for post-MI prevention,” Nadia Bouabdallaoui, MD, Montreal Heart Institute, Quebec, Canada, said during an online session devoted to colchicine at the European Society of Cardiology Congress 2020.

Session moderator Massimo Imazio, MD, professor of cardiology at the University of Turin, Italy, said the improved outcomes suggest that earlier treatment is better – a finding that parallels his own experience using colchicine in patients with pericarditis.

“This substudy is very important because this is probably also the year in cardiovascular applications [that] early use of the drug could improve outcomes,” he said.

Positive data have been accumulating for colchicine from COLCOT, LoDoCo, and, most recently, the LoDoCo2 trial, even as another anti-inflammatory drug, methotrexate, flamed out as secondary prevention in the CIRT trial.

The new COLCOT substudy included 4,661 of the 4,745 original patients and examined treatment initiation using three strata: within 0-3 days (n = 1,193), 4-7 days (n = 720), and 8-30 days (n = 2,748). Patients who received treatment within 3 days were slightly younger, more likely to be smokers, and to have a shorter time from MI to randomization (2.1 days vs 5.1 days vs. 20.8 days, respectively).

In the subset receiving treatment within 3 days, those assigned to colchicine had the same number of cardiac deaths as those given placebo (2 vs. 2) but fewer resuscitated cardiac arrests (1 vs. 3), MIs (17 vs. 29), strokes (1 vs. 5), and urgent hospitalizations for angina requiring revascularization (6 vs. 17).

“A larger trial might have allowed for a better assessment of individual endpoints and subgroups,” observed Bouabdallaoui.

Although there is growing support for colchicine, experts caution that the drug many not be for everyone. In COLCOT, 1 in 10 patients were unable to tolerate the drug, largely because of gastrointestinal (GI) issues.
 

Pharmacogenomics substudy

A second COLCOT substudy aimed to identify genetic markers predictive of colchicine response and to gain insights into the mechanisms behind this response. It included 767 patients treated with colchicine and another 755 treated with placebo – or about one-third the patients in the original trial.

A genome-wide association study did not find a significant association for the primary CV endpoint, although a prespecified subgroup analysis in men identified an interesting region on chromosome 9 (variant: rs10811106), which just missed reaching genomewide significance, said Marie-Pierre Dubé, PhD, director of the Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre at the Montreal Heart Institute.

In addition, the genomewide analysis found two significant regions for GI events: one on chromosome 6 (variant: rs6916345) and one on chromosome 10 (variant: rs74795203).

For each of the identified regions, the researchers then tested the effect of the allele in the placebo group and the interaction between the genetic variant and treatment with colchicine. For the chromosome 9 region in males, there was no effect in the placebo group and a significant interaction in the colchicine group.

For the significant GI event findings, there was a small effect for the chromosome 6 region in the placebo group and a very significant interaction with colchicine, Dubé said. Similarly, there was no effect for the chromosome 10 region in the placebo group and a significant interaction with colchicine.

Additional analyses in stratified patient populations showed that males with the protective allele (CC) for the chromosome 9 region represented 83% of the population. The primary CV endpoint occurred in 3.2% of these men treated with colchicine and 6.3% treated with placebo (HR, 0.46; 95% CI, 0.24 - 0.86).

For the gastrointestinal events, 25% of patients carried the risk allele (AA) for the chromosome 6 region and 36.9% of these had GI events when treated with colchicine versus 18.6% when treated with placebo (HR, 2.42; 95% CI, 1.57-3.72).

Similarly, 13% of individuals carried one or two copies of the risk allele (AG+GG) for the chromosome 10 region and the risk of GI events in these was nearly four times higher with colchicine (47.1% vs. 18.9%; HR, 3.98; 95% CI 2.24-7.07).

Functional genomic analyses of the identified regions were also performed and showed that the chromosome 9 locus overlaps with the SAXO1 gene, a stabilizer of axonemal microtubules 1.

“The leading variant at this locus (rs10811106 C allele) correlated with the expression of the HAUS6 gene, which is involved in microtubule generation from existing microtubules, and may interact with the effect of colchicine, which is known to inhibit microtubule formation,” observed Dubé. 

Also, the chromosome 6 locus associated with gastrointestinal events was colocalizing with the Crohn’s disease locus, adding further support for this region.

“The results support potential personalized approaches to inflammation reduction for cardiovascular prevention,” Dubé said.

This is a post hoc subgroup analysis, however, and replication is necessary, ideally in prospective randomized trials, she noted.

The substudy is important because it provides further insights into the link between colchicine and microtubule polymerization, affecting the activation of the inflammasome, session moderator Imazio said.

“Second, it is important because pharmacogenomics can help us to better understand the optimal responder to colchicine and colchicine resistance,” he said. “So it can be useful for personalized medicine, leading to the proper use of the drug for the proper patient.”

COLCOT was supported by the government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Bouabdallaoui has disclosed no relevant financial relationships. Dubé reported grants from the government of Quebec; personal fees from DalCor and GlaxoSmithKline; research support from AstraZeneca, Pfizer, Servier, Sanofi; and minor equity interest in DalCor. Dubé is also coauthor of patents on pharmacogenomics-guided CETP inhibition, and pharmacogenomics markers of response to colchicine.  

This article first appeared on Medscape.com.

In contrast to findings of previous research, low levels of von Willebrand Factor (VWF) and blood group O were not associated with a first-ever intracerebral hemorrhage (ICH), according to a study published in Thrombosis Research.

The researchers compared 176 cases of ICH with 349 age- and sex-matched controls. The mean patient age was 57 years, and 50% were women. The median time from baseline blood sampling to the first ICH was 5.6 years, according to the study reported by Kristina Johansson of Umeå (Sweden) University and her colleagues.
 

Complicated picture

The level of VWF differed significantly among blood groups: In individuals with blood group O, the mean VWF level was 1.29 kIU/L; for blood group A, it was 1.52 kIU/L; for blood group AB, 1.59 kIU/L; and in blood group B, 1.76 kIU/L. However, there was no difference in VWF concentration between cases and controls.

The researchers found no association between blood group O and the risk of ICH, a finding previously seen in other studies. They did, however, find that, in the limited number of patients with blood group B there was an association with a lower risk of ICH, compared with blood group A (odds ratio, 0.47; 95% confidence interval, 0.23-0.95).

“To our knowledge this is the largest prospective study investigating the association between VWF, ABO blood group and ICH. We found no association between VWF or blood group O and risk of future ICH,” the researchers concluded.

The study was funded by public institutions in Sweden. The authors declared that they had no conflicts.
 

[email protected]

SOURCE: Johansson K et al. Thromb Res. 2020 Jul 5;195:77-80.

In contrast to findings of previous research, low levels of von Willebrand Factor (VWF) and blood group O were not associated with a first-ever intracerebral hemorrhage (ICH), according to a study published in Thrombosis Research.

The researchers compared 176 cases of ICH with 349 age- and sex-matched controls. The mean patient age was 57 years, and 50% were women. The median time from baseline blood sampling to the first ICH was 5.6 years, according to the study reported by Kristina Johansson of Umeå (Sweden) University and her colleagues.
 

Complicated picture

The level of VWF differed significantly among blood groups: In individuals with blood group O, the mean VWF level was 1.29 kIU/L; for blood group A, it was 1.52 kIU/L; for blood group AB, 1.59 kIU/L; and in blood group B, 1.76 kIU/L. However, there was no difference in VWF concentration between cases and controls.

The researchers found no association between blood group O and the risk of ICH, a finding previously seen in other studies. They did, however, find that, in the limited number of patients with blood group B there was an association with a lower risk of ICH, compared with blood group A (odds ratio, 0.47; 95% confidence interval, 0.23-0.95).

“To our knowledge this is the largest prospective study investigating the association between VWF, ABO blood group and ICH. We found no association between VWF or blood group O and risk of future ICH,” the researchers concluded.

The study was funded by public institutions in Sweden. The authors declared that they had no conflicts.
 

[email protected]

SOURCE: Johansson K et al. Thromb Res. 2020 Jul 5;195:77-80.

In contrast to findings of previous research, low levels of von Willebrand Factor (VWF) and blood group O were not associated with a first-ever intracerebral hemorrhage (ICH), according to a study published in Thrombosis Research.

The researchers compared 176 cases of ICH with 349 age- and sex-matched controls. The mean patient age was 57 years, and 50% were women. The median time from baseline blood sampling to the first ICH was 5.6 years, according to the study reported by Kristina Johansson of Umeå (Sweden) University and her colleagues.
 

Complicated picture

The level of VWF differed significantly among blood groups: In individuals with blood group O, the mean VWF level was 1.29 kIU/L; for blood group A, it was 1.52 kIU/L; for blood group AB, 1.59 kIU/L; and in blood group B, 1.76 kIU/L. However, there was no difference in VWF concentration between cases and controls.

The researchers found no association between blood group O and the risk of ICH, a finding previously seen in other studies. They did, however, find that, in the limited number of patients with blood group B there was an association with a lower risk of ICH, compared with blood group A (odds ratio, 0.47; 95% confidence interval, 0.23-0.95).

“To our knowledge this is the largest prospective study investigating the association between VWF, ABO blood group and ICH. We found no association between VWF or blood group O and risk of future ICH,” the researchers concluded.

The study was funded by public institutions in Sweden. The authors declared that they had no conflicts.
 

[email protected]

SOURCE: Johansson K et al. Thromb Res. 2020 Jul 5;195:77-80.

SSRIs effectively treat depression following intracerebral hemorrhage (ICH) but also increase risk for recurrent hemorrhagic stroke, particularly in patients at high risk for repeat ICH, new research indicates.

“Clinicians must exercise judgment when weighing the use of SSRIs for ICH survivors in the high risk category – especially those with multiple ICH events,” study investigator Alessandro Biffi, MD, director, Aging and Brain Health Research (ABHR) Group, Departments of Neurology and Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

The study was published online August 31 in JAMA Neurology.
 

Risks and benefits

Depression is common following stroke. SSRIs are generally considered first-line treatment for post-stroke depression but are associated with increased risk for first ICH, most likely owing to their antithrombotic effects. Less is known about SSRI use and recurrent ICH risk.

To investigate, Biffi and colleagues followed 1,279 adults (mean age, 71.3 years) for a median of 53.2 months (4.5 years) following primary ICH; 602 were women, 1049 were White, 89 Black, 77 Hispanic, and 64 were other race/ethnicity.

During follow-up, 128 adults suffered recurrent ICH (annual rate, 4.2%) and 766 (60%) were diagnosed with depression.

In multivariable analyses, SSRIs were associated with an increased likelihood of post-ICH depression remission (subhazard ratio, 1.53; 95% CI, 1.12-2.09; P = .009).

However, SSRI use was also an independent risk factor for recurrent ICH (SHR, 1.31; 95% CI, 1.08-1.59; P = .006).

High SSRI dose was associated with higher ICH recurrence risk (SHR, 1.61; 95% CI, 1.15-2.25), with a larger effect size (comparison P = .02) than low SSRI dose (SHR, 1.25; 95% CI, 1.01-1.55), but there was no difference in depression remission comparing low vs. high SSRI dose.

Among individuals at high risk for recurrent ICH, SSRI use was associated with further increased risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22 - 2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes).

These higher-risk subgroups included carriers of the APOE e2/e4 alleles, patients with lobar ICH, patients with prior ICH, and minority participants.

“Our analyses identified patients for whom the risks are higher, and therefore additional thought is warranted. This approach may in the future lead to personalized/precision medicine approaches to determining whether these patients should receive SSRIs or not,” said Biffi.
 

Experts weigh in

Commenting on the research for Medscape Medical News, Daniel G. Hackam, MD, division of clinical pharmacology, Western University, London, Ont., said the study is “an important contribution to the literature, as there are to date no data on the risk of ICH in prior ICH survivors in relation to SSRI exposure.”

“The bottom line is that I would be very cautious about initiating SSRIs in patients with a history of ICH,” said Hackam, who was not involved with the study.

“There are other nonserotonergic antidepressants that could be used instead, which do not inhibit platelet function. There was still a risk even in the lower-risk ICH survivors. ICH is a highly recurrent disease. We already avoid antiplatelets, anticoagulants, and high dose statins in these patients. I would add SSRI’s to that list, based on this study,” said Hackam.

Also weighing in, Amytis Towfighi, MD, associate professor of neurology, University of Southern California, Los Angeles, said this study addresses a “common clinical dilemma: how to manage depression among individuals with ICH, given the high risk of recurrent ICH among ICH survivors and potential for SSRIs to increase that risk. This scenario is common, and a source of debate for practicing clinicians.”

“The authors conducted an elegant study,” said Towfighi, by considering sociodemographic, historical, imaging, and genetic factors.

“One must interpret this study with caution as it is a single-center cohort study. However, it provides the most rigorous information to date regarding the associations between SSRI use and recurrent ICH,” she told Medscape Medical News.

The study was supported by the National Institutes of Health. Biffi, Hackam, and Towfighi have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

SSRIs effectively treat depression following intracerebral hemorrhage (ICH) but also increase risk for recurrent hemorrhagic stroke, particularly in patients at high risk for repeat ICH, new research indicates.

“Clinicians must exercise judgment when weighing the use of SSRIs for ICH survivors in the high risk category – especially those with multiple ICH events,” study investigator Alessandro Biffi, MD, director, Aging and Brain Health Research (ABHR) Group, Departments of Neurology and Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

The study was published online August 31 in JAMA Neurology.
 

Risks and benefits

Depression is common following stroke. SSRIs are generally considered first-line treatment for post-stroke depression but are associated with increased risk for first ICH, most likely owing to their antithrombotic effects. Less is known about SSRI use and recurrent ICH risk.

To investigate, Biffi and colleagues followed 1,279 adults (mean age, 71.3 years) for a median of 53.2 months (4.5 years) following primary ICH; 602 were women, 1049 were White, 89 Black, 77 Hispanic, and 64 were other race/ethnicity.

During follow-up, 128 adults suffered recurrent ICH (annual rate, 4.2%) and 766 (60%) were diagnosed with depression.

In multivariable analyses, SSRIs were associated with an increased likelihood of post-ICH depression remission (subhazard ratio, 1.53; 95% CI, 1.12-2.09; P = .009).

However, SSRI use was also an independent risk factor for recurrent ICH (SHR, 1.31; 95% CI, 1.08-1.59; P = .006).

High SSRI dose was associated with higher ICH recurrence risk (SHR, 1.61; 95% CI, 1.15-2.25), with a larger effect size (comparison P = .02) than low SSRI dose (SHR, 1.25; 95% CI, 1.01-1.55), but there was no difference in depression remission comparing low vs. high SSRI dose.

Among individuals at high risk for recurrent ICH, SSRI use was associated with further increased risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22 - 2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes).

These higher-risk subgroups included carriers of the APOE e2/e4 alleles, patients with lobar ICH, patients with prior ICH, and minority participants.

“Our analyses identified patients for whom the risks are higher, and therefore additional thought is warranted. This approach may in the future lead to personalized/precision medicine approaches to determining whether these patients should receive SSRIs or not,” said Biffi.
 

Experts weigh in

Commenting on the research for Medscape Medical News, Daniel G. Hackam, MD, division of clinical pharmacology, Western University, London, Ont., said the study is “an important contribution to the literature, as there are to date no data on the risk of ICH in prior ICH survivors in relation to SSRI exposure.”

“The bottom line is that I would be very cautious about initiating SSRIs in patients with a history of ICH,” said Hackam, who was not involved with the study.

“There are other nonserotonergic antidepressants that could be used instead, which do not inhibit platelet function. There was still a risk even in the lower-risk ICH survivors. ICH is a highly recurrent disease. We already avoid antiplatelets, anticoagulants, and high dose statins in these patients. I would add SSRI’s to that list, based on this study,” said Hackam.

Also weighing in, Amytis Towfighi, MD, associate professor of neurology, University of Southern California, Los Angeles, said this study addresses a “common clinical dilemma: how to manage depression among individuals with ICH, given the high risk of recurrent ICH among ICH survivors and potential for SSRIs to increase that risk. This scenario is common, and a source of debate for practicing clinicians.”

“The authors conducted an elegant study,” said Towfighi, by considering sociodemographic, historical, imaging, and genetic factors.

“One must interpret this study with caution as it is a single-center cohort study. However, it provides the most rigorous information to date regarding the associations between SSRI use and recurrent ICH,” she told Medscape Medical News.

The study was supported by the National Institutes of Health. Biffi, Hackam, and Towfighi have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

SSRIs effectively treat depression following intracerebral hemorrhage (ICH) but also increase risk for recurrent hemorrhagic stroke, particularly in patients at high risk for repeat ICH, new research indicates.

“Clinicians must exercise judgment when weighing the use of SSRIs for ICH survivors in the high risk category – especially those with multiple ICH events,” study investigator Alessandro Biffi, MD, director, Aging and Brain Health Research (ABHR) Group, Departments of Neurology and Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

The study was published online August 31 in JAMA Neurology.
 

Risks and benefits

Depression is common following stroke. SSRIs are generally considered first-line treatment for post-stroke depression but are associated with increased risk for first ICH, most likely owing to their antithrombotic effects. Less is known about SSRI use and recurrent ICH risk.

To investigate, Biffi and colleagues followed 1,279 adults (mean age, 71.3 years) for a median of 53.2 months (4.5 years) following primary ICH; 602 were women, 1049 were White, 89 Black, 77 Hispanic, and 64 were other race/ethnicity.

During follow-up, 128 adults suffered recurrent ICH (annual rate, 4.2%) and 766 (60%) were diagnosed with depression.

In multivariable analyses, SSRIs were associated with an increased likelihood of post-ICH depression remission (subhazard ratio, 1.53; 95% CI, 1.12-2.09; P = .009).

However, SSRI use was also an independent risk factor for recurrent ICH (SHR, 1.31; 95% CI, 1.08-1.59; P = .006).

High SSRI dose was associated with higher ICH recurrence risk (SHR, 1.61; 95% CI, 1.15-2.25), with a larger effect size (comparison P = .02) than low SSRI dose (SHR, 1.25; 95% CI, 1.01-1.55), but there was no difference in depression remission comparing low vs. high SSRI dose.

Among individuals at high risk for recurrent ICH, SSRI use was associated with further increased risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22 - 2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes).

These higher-risk subgroups included carriers of the APOE e2/e4 alleles, patients with lobar ICH, patients with prior ICH, and minority participants.

“Our analyses identified patients for whom the risks are higher, and therefore additional thought is warranted. This approach may in the future lead to personalized/precision medicine approaches to determining whether these patients should receive SSRIs or not,” said Biffi.
 

Experts weigh in

Commenting on the research for Medscape Medical News, Daniel G. Hackam, MD, division of clinical pharmacology, Western University, London, Ont., said the study is “an important contribution to the literature, as there are to date no data on the risk of ICH in prior ICH survivors in relation to SSRI exposure.”

“The bottom line is that I would be very cautious about initiating SSRIs in patients with a history of ICH,” said Hackam, who was not involved with the study.

“There are other nonserotonergic antidepressants that could be used instead, which do not inhibit platelet function. There was still a risk even in the lower-risk ICH survivors. ICH is a highly recurrent disease. We already avoid antiplatelets, anticoagulants, and high dose statins in these patients. I would add SSRI’s to that list, based on this study,” said Hackam.

Also weighing in, Amytis Towfighi, MD, associate professor of neurology, University of Southern California, Los Angeles, said this study addresses a “common clinical dilemma: how to manage depression among individuals with ICH, given the high risk of recurrent ICH among ICH survivors and potential for SSRIs to increase that risk. This scenario is common, and a source of debate for practicing clinicians.”

“The authors conducted an elegant study,” said Towfighi, by considering sociodemographic, historical, imaging, and genetic factors.

“One must interpret this study with caution as it is a single-center cohort study. However, it provides the most rigorous information to date regarding the associations between SSRI use and recurrent ICH,” she told Medscape Medical News.

The study was supported by the National Institutes of Health. Biffi, Hackam, and Towfighi have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

An ultralow dose of direct oral anticoagulant (DOAC) may safely cut the risk for stroke in very elderly patients with atrial fibrillation (AFib) whose bleeding risk is considered too high for standard dosages, suggests a randomized trial conducted in Japan.

Many of the study’s 984 mostly octogenarian patients were objectively frail with poor renal function, low body weight, a history of serious bleeding, or other conditions that made them poor candidates for regular-dose oral anticoagulation. Yet those who took the factor Xa inhibitor edoxaban (Savaysa) at the off-label dosage of 15 mg once daily showed a two-thirds drop in risk for stroke or systemic embolism (P < .001), compared with patients who received placebo. There were no fatal bleeds and virtually no intracranial hemorrhages.

For such high-risk patients with nonvalvular AFib who otherwise would not be given an OAC, edoxaban 15 mg “can be an acceptable treatment option in decreasing the risk of devastating stroke”; however, “it may increase the risk of gastrointestinal bleeding, so care should be given in every patient,” said Ken Okumura, MD, PhD. Indeed, the rate of gastrointestinal bleeding tripled among the patients who received edoxaban, compared with those given placebo, at about 2.3% per year versus 0.8% per year.

Although their 87% increased risk for major bleeding did not reach significance, it hit close, with a P value of .09 in the trial, called Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF).

Dr. Okumura, of Saiseikai Kumamoto (Japan) Hospital, presented the study August 30 during the virtual annual congress of the European Society of Cardiology. He is lead author of an article describing the study, which was simultaneously published in the New England Journal of Medicine.

Many patients with AFib suffer strokes if they are not given oral anticoagulation because of “fear of major bleeding caused by standard OAC therapy,” Dr. Okumura noted. Others are inappropriately administered antiplatelets or anticoagulants at conventional dosages. “There is no standard of practice in Japan for patients like those in the present trial,” Dr. Okumura said. “However, I believe the present study opens a new possible path of thromboprophylaxis in such high-risk patients.”

Even with its relatively few bleeding events, ELDERCARE-AF “does suggest that the risk of the worst types of bleeds is not that high,” said Daniel E. Singer, MD, of Massachusetts General Hospital, Boston. “Gastrointestinal bleeding is annoying, and it will probably stop people from taking their edoxaban, but for the most part it doesn’t kill people.”

Moreover, he added, the trial suggests that low-dose edoxaban, in exchange for a steep reduction in thromboembolic risk, “doesn’t add to your risk of intracranial hemorrhage!”

ELDERCARE-AF may give practitioners “yet another reason to rethink” whether a low-dose DOAC such as edoxaban 15 mg/day may well be a good approach for such patients with AFib who are not receiving standard-dose OAC because of a perceived high risk for serious bleeding, said Dr. Singer, who was not involved in the study.

The trial randomly and evenly assigned 984 patients with AF in Japan to take either edoxaban 15 mg/day or placebo. The patients, who were at least 80 years old and had a CHADS2 score of 2 or higher, were judged inappropriate candidates for OAC at dosages approved for stroke prevention.

The mean age of the patients was 86.6, more than a decade older than patients “in the previous landmark clinical trials of direct oral anticoagulants,” and were 5-10 years older than the general AFib population, reported Dr. Okumura and colleagues.

Their mean weight was 52 kg, and mean creatinine clearance was 36.3 mL/min; 41% were classified as frail according to validated assessment tools.

Of the 303 patients who did not complete the trial, 158 voluntarily withdrew for various reasons. The withdrawal rate was similar in the two treatment arms. Outcomes were analyzed by intention to treat, the report noted.

The annualized rate of stroke or systemic embolism, the primary efficacy endpoint, was 2.3% for those who received edoxaban and 6.7% for the control group. Corresponding rates for the primary safety endpoint, major bleeding as determined by International Society on Thrombosis and Hemostasis criteria, were 3.3% and 1.8%, respectively.

“The question is, can the Food and Drug Administration act on this information? I doubt it can. What will be needed is to reproduce the study in a U.S. population to see if it holds,” Dr. Singer proposed.

“Edoxaban isn’t used much in the U.S. This could heighten interest. And who knows, there may be a gold rush,” he said, if the strategy were to pan out for the other DOACs, rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa).

ELDERCARE-AF was funded by Daiichi Sankyo, from which Dr. Okumura reported receiving grants and personal fees; he also disclosed personal fees from Daiichi Sankyo, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Johnson & Johnson, and Bayer.

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

An ultralow dose of direct oral anticoagulant (DOAC) may safely cut the risk for stroke in very elderly patients with atrial fibrillation (AFib) whose bleeding risk is considered too high for standard dosages, suggests a randomized trial conducted in Japan.

Many of the study’s 984 mostly octogenarian patients were objectively frail with poor renal function, low body weight, a history of serious bleeding, or other conditions that made them poor candidates for regular-dose oral anticoagulation. Yet those who took the factor Xa inhibitor edoxaban (Savaysa) at the off-label dosage of 15 mg once daily showed a two-thirds drop in risk for stroke or systemic embolism (P < .001), compared with patients who received placebo. There were no fatal bleeds and virtually no intracranial hemorrhages.

For such high-risk patients with nonvalvular AFib who otherwise would not be given an OAC, edoxaban 15 mg “can be an acceptable treatment option in decreasing the risk of devastating stroke”; however, “it may increase the risk of gastrointestinal bleeding, so care should be given in every patient,” said Ken Okumura, MD, PhD. Indeed, the rate of gastrointestinal bleeding tripled among the patients who received edoxaban, compared with those given placebo, at about 2.3% per year versus 0.8% per year.

Although their 87% increased risk for major bleeding did not reach significance, it hit close, with a P value of .09 in the trial, called Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF).

Dr. Okumura, of Saiseikai Kumamoto (Japan) Hospital, presented the study August 30 during the virtual annual congress of the European Society of Cardiology. He is lead author of an article describing the study, which was simultaneously published in the New England Journal of Medicine.

Many patients with AFib suffer strokes if they are not given oral anticoagulation because of “fear of major bleeding caused by standard OAC therapy,” Dr. Okumura noted. Others are inappropriately administered antiplatelets or anticoagulants at conventional dosages. “There is no standard of practice in Japan for patients like those in the present trial,” Dr. Okumura said. “However, I believe the present study opens a new possible path of thromboprophylaxis in such high-risk patients.”

Even with its relatively few bleeding events, ELDERCARE-AF “does suggest that the risk of the worst types of bleeds is not that high,” said Daniel E. Singer, MD, of Massachusetts General Hospital, Boston. “Gastrointestinal bleeding is annoying, and it will probably stop people from taking their edoxaban, but for the most part it doesn’t kill people.”

Moreover, he added, the trial suggests that low-dose edoxaban, in exchange for a steep reduction in thromboembolic risk, “doesn’t add to your risk of intracranial hemorrhage!”

ELDERCARE-AF may give practitioners “yet another reason to rethink” whether a low-dose DOAC such as edoxaban 15 mg/day may well be a good approach for such patients with AFib who are not receiving standard-dose OAC because of a perceived high risk for serious bleeding, said Dr. Singer, who was not involved in the study.

The trial randomly and evenly assigned 984 patients with AF in Japan to take either edoxaban 15 mg/day or placebo. The patients, who were at least 80 years old and had a CHADS2 score of 2 or higher, were judged inappropriate candidates for OAC at dosages approved for stroke prevention.

The mean age of the patients was 86.6, more than a decade older than patients “in the previous landmark clinical trials of direct oral anticoagulants,” and were 5-10 years older than the general AFib population, reported Dr. Okumura and colleagues.

Their mean weight was 52 kg, and mean creatinine clearance was 36.3 mL/min; 41% were classified as frail according to validated assessment tools.

Of the 303 patients who did not complete the trial, 158 voluntarily withdrew for various reasons. The withdrawal rate was similar in the two treatment arms. Outcomes were analyzed by intention to treat, the report noted.

The annualized rate of stroke or systemic embolism, the primary efficacy endpoint, was 2.3% for those who received edoxaban and 6.7% for the control group. Corresponding rates for the primary safety endpoint, major bleeding as determined by International Society on Thrombosis and Hemostasis criteria, were 3.3% and 1.8%, respectively.

“The question is, can the Food and Drug Administration act on this information? I doubt it can. What will be needed is to reproduce the study in a U.S. population to see if it holds,” Dr. Singer proposed.

“Edoxaban isn’t used much in the U.S. This could heighten interest. And who knows, there may be a gold rush,” he said, if the strategy were to pan out for the other DOACs, rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa).

ELDERCARE-AF was funded by Daiichi Sankyo, from which Dr. Okumura reported receiving grants and personal fees; he also disclosed personal fees from Daiichi Sankyo, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Johnson & Johnson, and Bayer.

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

An ultralow dose of direct oral anticoagulant (DOAC) may safely cut the risk for stroke in very elderly patients with atrial fibrillation (AFib) whose bleeding risk is considered too high for standard dosages, suggests a randomized trial conducted in Japan.

Many of the study’s 984 mostly octogenarian patients were objectively frail with poor renal function, low body weight, a history of serious bleeding, or other conditions that made them poor candidates for regular-dose oral anticoagulation. Yet those who took the factor Xa inhibitor edoxaban (Savaysa) at the off-label dosage of 15 mg once daily showed a two-thirds drop in risk for stroke or systemic embolism (P < .001), compared with patients who received placebo. There were no fatal bleeds and virtually no intracranial hemorrhages.

For such high-risk patients with nonvalvular AFib who otherwise would not be given an OAC, edoxaban 15 mg “can be an acceptable treatment option in decreasing the risk of devastating stroke”; however, “it may increase the risk of gastrointestinal bleeding, so care should be given in every patient,” said Ken Okumura, MD, PhD. Indeed, the rate of gastrointestinal bleeding tripled among the patients who received edoxaban, compared with those given placebo, at about 2.3% per year versus 0.8% per year.

Although their 87% increased risk for major bleeding did not reach significance, it hit close, with a P value of .09 in the trial, called Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF).

Dr. Okumura, of Saiseikai Kumamoto (Japan) Hospital, presented the study August 30 during the virtual annual congress of the European Society of Cardiology. He is lead author of an article describing the study, which was simultaneously published in the New England Journal of Medicine.

Many patients with AFib suffer strokes if they are not given oral anticoagulation because of “fear of major bleeding caused by standard OAC therapy,” Dr. Okumura noted. Others are inappropriately administered antiplatelets or anticoagulants at conventional dosages. “There is no standard of practice in Japan for patients like those in the present trial,” Dr. Okumura said. “However, I believe the present study opens a new possible path of thromboprophylaxis in such high-risk patients.”

Even with its relatively few bleeding events, ELDERCARE-AF “does suggest that the risk of the worst types of bleeds is not that high,” said Daniel E. Singer, MD, of Massachusetts General Hospital, Boston. “Gastrointestinal bleeding is annoying, and it will probably stop people from taking their edoxaban, but for the most part it doesn’t kill people.”

Moreover, he added, the trial suggests that low-dose edoxaban, in exchange for a steep reduction in thromboembolic risk, “doesn’t add to your risk of intracranial hemorrhage!”

ELDERCARE-AF may give practitioners “yet another reason to rethink” whether a low-dose DOAC such as edoxaban 15 mg/day may well be a good approach for such patients with AFib who are not receiving standard-dose OAC because of a perceived high risk for serious bleeding, said Dr. Singer, who was not involved in the study.

The trial randomly and evenly assigned 984 patients with AF in Japan to take either edoxaban 15 mg/day or placebo. The patients, who were at least 80 years old and had a CHADS2 score of 2 or higher, were judged inappropriate candidates for OAC at dosages approved for stroke prevention.

The mean age of the patients was 86.6, more than a decade older than patients “in the previous landmark clinical trials of direct oral anticoagulants,” and were 5-10 years older than the general AFib population, reported Dr. Okumura and colleagues.

Their mean weight was 52 kg, and mean creatinine clearance was 36.3 mL/min; 41% were classified as frail according to validated assessment tools.

Of the 303 patients who did not complete the trial, 158 voluntarily withdrew for various reasons. The withdrawal rate was similar in the two treatment arms. Outcomes were analyzed by intention to treat, the report noted.

The annualized rate of stroke or systemic embolism, the primary efficacy endpoint, was 2.3% for those who received edoxaban and 6.7% for the control group. Corresponding rates for the primary safety endpoint, major bleeding as determined by International Society on Thrombosis and Hemostasis criteria, were 3.3% and 1.8%, respectively.

“The question is, can the Food and Drug Administration act on this information? I doubt it can. What will be needed is to reproduce the study in a U.S. population to see if it holds,” Dr. Singer proposed.

“Edoxaban isn’t used much in the U.S. This could heighten interest. And who knows, there may be a gold rush,” he said, if the strategy were to pan out for the other DOACs, rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa).

ELDERCARE-AF was funded by Daiichi Sankyo, from which Dr. Okumura reported receiving grants and personal fees; he also disclosed personal fees from Daiichi Sankyo, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Johnson & Johnson, and Bayer.

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