Cardiology

CHICAGO – It’s been said that one can observe a lot just by watching. Turning such observation inward, new evidence suggests, might lead to blood pressure (BP) reductions that approach what’s possible from an antihypertensive agent.

Systolic BP fell over 6 months by almost 6 mm Hg, on average, in people with elevated BP who participated in an 8-week mindful awareness program as part of a randomized trial that included a usual-care control group.

The program taught established mindfulness-training techniques aimed at modifying behaviors regarding diet, exercise, and other controllable influences on the success of antihypertensive therapy.

Participants in the program, called Mindfulness-Based Blood Pressure Reduction (MB-BP), also the name of the single-center study, “showed potentially clinically relevant reductions in systolic blood pressure,” said principal investigator Eric B. Loucks, PhD, Brown University, Providence, R.I.

The phase 2 trial has some limitations, he observed, including on generalizability. For example, it entered about 200 mostly White, college-educated adults from one metropolitan area.

But if these findings are replicated in further studies, “preferably by other research groups, in a larger and broader population, and with longer follow-up,” Dr. Loucks said, the MB-BP intervention could become “an appealing approach to help control blood pressure.”

Dr. Loucks made the comments at a press conference prior to his formal presentation of MB-BP Nov. 6 at American Heart Association (AHA) Scientific Sessions 2022, held in Chicago and virtually.

Mindfulness-based interventions for elevated BP have not been widely studied, “so this is exactly what we need: a well-done trial with a control group to show that it actually works,” Amit Khera, MD, not connected with MB-BP, told this news organization.

The trial is “really important for proof of concept, but it had only 200 people. You need a larger one, and you need longer-term data,” agreed Dr. Khera, who directs the preventive cardiology program at the University of Texas Southwestern Medical Center, in Dallas. “Six months is good, but we want to see if it’s durable.”

Rhian M. Touyz, MBBCh, also not part of MB-BP, agreed that the nearly 6 mm Hg mean systolic BP reduction among program participants is clinically relevant. “I think in the context of global risk and reduction of target organ damage and cardiovascular events, it is significant in terms of events at a population level,” Dr. Touyz, McGill University Health Centre, Montreal, told this news organization.

Many patients on antihypertensive therapy that’s falling short resist the addition of another such agent, she observed, and instead might show further BP reduction from mindfulness training. The intervention probably also “would benefit health in general.” Mindfulness-based approaches could therefore be useful additions to treatment protocols for elevated BP, Dr. Touyz said.
 

How the training works

The MB-BP program used validated mindfulness-based stress-management techniques, adapted to address elevated BP, that included “personalized feedback and education about hypertension risk factors, mindful awareness training of participants’ relationships with hypertension risk factors, and support for behavior change,” Dr. Loucks and colleagues reported.

Participants were trained in mindfulness skills that included “self-awareness and emotion regulation,” Dr. Loucks said, which they then could apply to their “relationships with the things that we know influence blood pressure, like physical activity, diet, antihypertensive medication adherence, or alcohol consumption.”

One goal is to promote greater “attention control,” he said, “so that there’s some self-awareness that arises in terms of how we feel the next day, after a lot of alcohol consumption, for example, or lack of physical activity.” The process can provide insights that inspire patients to modify behaviors and risk factors that elevate BP, Dr. Loucks explained.
 

Effects on medication use

Systolic BP responses led some program participants to be managed on fewer or reduced dosages of antihypertensive meds, he told this news organization. Physicians seen outside of the trial could adjust their prescriptions, intensifying or pulling back on meds depending on their assessments of the patient. Any prescription changes would be documented by the researchers at the patient’s next class or trial-clinic visit.

The group that did the training, Dr. Loucks said, was 33% less likely to increase and 30% more likely to decrease their use of BP-lowering medications compared with the control group.

Elevated BP is so common and undertreated that “there is a need for every possible level of intervention, starting from the population level to the individual and everything else in between,” nephrologist Janani Rangaswami, MD, George Washington University, Washington, said at the press conference.

Therefore, “this mindfulness-based approach, in addition to standard of care with pharmacotherapy, is a really welcome addition to the hypertension literature,” said Dr. Rangaswami, who directs her center’s cardiorenal program. The systolic BP reduction seen in the intervention group, she agreed, was “clinically important and meaningful.”
 

Blinded assessments

The trial entered 201 patients with systolic and diastolic BP greater than 120 mm Hg and 80 mm Hg, respectively; 58.7% were women, 81% were White, and 73% were college-educated, Dr. Loucks reported.

The 100 assigned to the “enhanced usual care” control group received educational materials on controlling high BP. They and the 101 who followed the mindfulness-based program were given and trained on a home BP-monitoring device. They were then followed for the primary endpoint of change in systolic BP at 6 months.

Data management and outcomes assessments were conducted by trialists not involved in the training intervention who were blinded to randomization assignment.

In a prespecified unadjusted analysis by intention-to-treat, systolic BP in the intervention group dropped by a mean of 5.9 mm Hg (P < .001) compared with baseline and 4.5 mm Hg (P = .045), compared with the control group.

A post hoc analysis adjusted for sex and baseline BP showed an average 4.3 mm Hg reduction (P = .056) in those following the MB-BP program, compared with controls.

There were no observed significant effects on diastolic BP.

The study offered clues to how engagement in the MB-BP program might promote reductions in systolic BP, Dr. Loucks observed. For example, it may have led to increased activity levels, reduced sodium intake, and other dietary improvements.

Indeed, program participants averaged about 351 minutes less sedentary time (P = .02) and showed a 0.32-point improvement in Dietary Approaches to Stop Hypertension scores (P = .08), compared with the control group, Dr. Loucks reported. Other modifiable risk factors for elevated BP that could have responded to the mindfulness-based training, he proposed, include obesity, alcohol intake, and reaction to stress.

Dr. Loucks reports that he developed the MB-BP training and was a program instructor but did not receive related financial compensation; he had no other disclosures. Dr. Khera, Dr. Touyz, and Dr. Rangaswami had no relevant financial relationships.

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

CHICAGO – It’s been said that one can observe a lot just by watching. Turning such observation inward, new evidence suggests, might lead to blood pressure (BP) reductions that approach what’s possible from an antihypertensive agent.

Systolic BP fell over 6 months by almost 6 mm Hg, on average, in people with elevated BP who participated in an 8-week mindful awareness program as part of a randomized trial that included a usual-care control group.

The program taught established mindfulness-training techniques aimed at modifying behaviors regarding diet, exercise, and other controllable influences on the success of antihypertensive therapy.

Participants in the program, called Mindfulness-Based Blood Pressure Reduction (MB-BP), also the name of the single-center study, “showed potentially clinically relevant reductions in systolic blood pressure,” said principal investigator Eric B. Loucks, PhD, Brown University, Providence, R.I.

The phase 2 trial has some limitations, he observed, including on generalizability. For example, it entered about 200 mostly White, college-educated adults from one metropolitan area.

But if these findings are replicated in further studies, “preferably by other research groups, in a larger and broader population, and with longer follow-up,” Dr. Loucks said, the MB-BP intervention could become “an appealing approach to help control blood pressure.”

Dr. Loucks made the comments at a press conference prior to his formal presentation of MB-BP Nov. 6 at American Heart Association (AHA) Scientific Sessions 2022, held in Chicago and virtually.

Mindfulness-based interventions for elevated BP have not been widely studied, “so this is exactly what we need: a well-done trial with a control group to show that it actually works,” Amit Khera, MD, not connected with MB-BP, told this news organization.

The trial is “really important for proof of concept, but it had only 200 people. You need a larger one, and you need longer-term data,” agreed Dr. Khera, who directs the preventive cardiology program at the University of Texas Southwestern Medical Center, in Dallas. “Six months is good, but we want to see if it’s durable.”

Rhian M. Touyz, MBBCh, also not part of MB-BP, agreed that the nearly 6 mm Hg mean systolic BP reduction among program participants is clinically relevant. “I think in the context of global risk and reduction of target organ damage and cardiovascular events, it is significant in terms of events at a population level,” Dr. Touyz, McGill University Health Centre, Montreal, told this news organization.

Many patients on antihypertensive therapy that’s falling short resist the addition of another such agent, she observed, and instead might show further BP reduction from mindfulness training. The intervention probably also “would benefit health in general.” Mindfulness-based approaches could therefore be useful additions to treatment protocols for elevated BP, Dr. Touyz said.
 

How the training works

The MB-BP program used validated mindfulness-based stress-management techniques, adapted to address elevated BP, that included “personalized feedback and education about hypertension risk factors, mindful awareness training of participants’ relationships with hypertension risk factors, and support for behavior change,” Dr. Loucks and colleagues reported.

Participants were trained in mindfulness skills that included “self-awareness and emotion regulation,” Dr. Loucks said, which they then could apply to their “relationships with the things that we know influence blood pressure, like physical activity, diet, antihypertensive medication adherence, or alcohol consumption.”

One goal is to promote greater “attention control,” he said, “so that there’s some self-awareness that arises in terms of how we feel the next day, after a lot of alcohol consumption, for example, or lack of physical activity.” The process can provide insights that inspire patients to modify behaviors and risk factors that elevate BP, Dr. Loucks explained.
 

Effects on medication use

Systolic BP responses led some program participants to be managed on fewer or reduced dosages of antihypertensive meds, he told this news organization. Physicians seen outside of the trial could adjust their prescriptions, intensifying or pulling back on meds depending on their assessments of the patient. Any prescription changes would be documented by the researchers at the patient’s next class or trial-clinic visit.

The group that did the training, Dr. Loucks said, was 33% less likely to increase and 30% more likely to decrease their use of BP-lowering medications compared with the control group.

Elevated BP is so common and undertreated that “there is a need for every possible level of intervention, starting from the population level to the individual and everything else in between,” nephrologist Janani Rangaswami, MD, George Washington University, Washington, said at the press conference.

Therefore, “this mindfulness-based approach, in addition to standard of care with pharmacotherapy, is a really welcome addition to the hypertension literature,” said Dr. Rangaswami, who directs her center’s cardiorenal program. The systolic BP reduction seen in the intervention group, she agreed, was “clinically important and meaningful.”
 

Blinded assessments

The trial entered 201 patients with systolic and diastolic BP greater than 120 mm Hg and 80 mm Hg, respectively; 58.7% were women, 81% were White, and 73% were college-educated, Dr. Loucks reported.

The 100 assigned to the “enhanced usual care” control group received educational materials on controlling high BP. They and the 101 who followed the mindfulness-based program were given and trained on a home BP-monitoring device. They were then followed for the primary endpoint of change in systolic BP at 6 months.

Data management and outcomes assessments were conducted by trialists not involved in the training intervention who were blinded to randomization assignment.

In a prespecified unadjusted analysis by intention-to-treat, systolic BP in the intervention group dropped by a mean of 5.9 mm Hg (P < .001) compared with baseline and 4.5 mm Hg (P = .045), compared with the control group.

A post hoc analysis adjusted for sex and baseline BP showed an average 4.3 mm Hg reduction (P = .056) in those following the MB-BP program, compared with controls.

There were no observed significant effects on diastolic BP.

The study offered clues to how engagement in the MB-BP program might promote reductions in systolic BP, Dr. Loucks observed. For example, it may have led to increased activity levels, reduced sodium intake, and other dietary improvements.

Indeed, program participants averaged about 351 minutes less sedentary time (P = .02) and showed a 0.32-point improvement in Dietary Approaches to Stop Hypertension scores (P = .08), compared with the control group, Dr. Loucks reported. Other modifiable risk factors for elevated BP that could have responded to the mindfulness-based training, he proposed, include obesity, alcohol intake, and reaction to stress.

Dr. Loucks reports that he developed the MB-BP training and was a program instructor but did not receive related financial compensation; he had no other disclosures. Dr. Khera, Dr. Touyz, and Dr. Rangaswami had no relevant financial relationships.

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

CHICAGO – It’s been said that one can observe a lot just by watching. Turning such observation inward, new evidence suggests, might lead to blood pressure (BP) reductions that approach what’s possible from an antihypertensive agent.

Systolic BP fell over 6 months by almost 6 mm Hg, on average, in people with elevated BP who participated in an 8-week mindful awareness program as part of a randomized trial that included a usual-care control group.

The program taught established mindfulness-training techniques aimed at modifying behaviors regarding diet, exercise, and other controllable influences on the success of antihypertensive therapy.

Participants in the program, called Mindfulness-Based Blood Pressure Reduction (MB-BP), also the name of the single-center study, “showed potentially clinically relevant reductions in systolic blood pressure,” said principal investigator Eric B. Loucks, PhD, Brown University, Providence, R.I.

The phase 2 trial has some limitations, he observed, including on generalizability. For example, it entered about 200 mostly White, college-educated adults from one metropolitan area.

But if these findings are replicated in further studies, “preferably by other research groups, in a larger and broader population, and with longer follow-up,” Dr. Loucks said, the MB-BP intervention could become “an appealing approach to help control blood pressure.”

Dr. Loucks made the comments at a press conference prior to his formal presentation of MB-BP Nov. 6 at American Heart Association (AHA) Scientific Sessions 2022, held in Chicago and virtually.

Mindfulness-based interventions for elevated BP have not been widely studied, “so this is exactly what we need: a well-done trial with a control group to show that it actually works,” Amit Khera, MD, not connected with MB-BP, told this news organization.

The trial is “really important for proof of concept, but it had only 200 people. You need a larger one, and you need longer-term data,” agreed Dr. Khera, who directs the preventive cardiology program at the University of Texas Southwestern Medical Center, in Dallas. “Six months is good, but we want to see if it’s durable.”

Rhian M. Touyz, MBBCh, also not part of MB-BP, agreed that the nearly 6 mm Hg mean systolic BP reduction among program participants is clinically relevant. “I think in the context of global risk and reduction of target organ damage and cardiovascular events, it is significant in terms of events at a population level,” Dr. Touyz, McGill University Health Centre, Montreal, told this news organization.

Many patients on antihypertensive therapy that’s falling short resist the addition of another such agent, she observed, and instead might show further BP reduction from mindfulness training. The intervention probably also “would benefit health in general.” Mindfulness-based approaches could therefore be useful additions to treatment protocols for elevated BP, Dr. Touyz said.
 

How the training works

The MB-BP program used validated mindfulness-based stress-management techniques, adapted to address elevated BP, that included “personalized feedback and education about hypertension risk factors, mindful awareness training of participants’ relationships with hypertension risk factors, and support for behavior change,” Dr. Loucks and colleagues reported.

Participants were trained in mindfulness skills that included “self-awareness and emotion regulation,” Dr. Loucks said, which they then could apply to their “relationships with the things that we know influence blood pressure, like physical activity, diet, antihypertensive medication adherence, or alcohol consumption.”

One goal is to promote greater “attention control,” he said, “so that there’s some self-awareness that arises in terms of how we feel the next day, after a lot of alcohol consumption, for example, or lack of physical activity.” The process can provide insights that inspire patients to modify behaviors and risk factors that elevate BP, Dr. Loucks explained.
 

Effects on medication use

Systolic BP responses led some program participants to be managed on fewer or reduced dosages of antihypertensive meds, he told this news organization. Physicians seen outside of the trial could adjust their prescriptions, intensifying or pulling back on meds depending on their assessments of the patient. Any prescription changes would be documented by the researchers at the patient’s next class or trial-clinic visit.

The group that did the training, Dr. Loucks said, was 33% less likely to increase and 30% more likely to decrease their use of BP-lowering medications compared with the control group.

Elevated BP is so common and undertreated that “there is a need for every possible level of intervention, starting from the population level to the individual and everything else in between,” nephrologist Janani Rangaswami, MD, George Washington University, Washington, said at the press conference.

Therefore, “this mindfulness-based approach, in addition to standard of care with pharmacotherapy, is a really welcome addition to the hypertension literature,” said Dr. Rangaswami, who directs her center’s cardiorenal program. The systolic BP reduction seen in the intervention group, she agreed, was “clinically important and meaningful.”
 

Blinded assessments

The trial entered 201 patients with systolic and diastolic BP greater than 120 mm Hg and 80 mm Hg, respectively; 58.7% were women, 81% were White, and 73% were college-educated, Dr. Loucks reported.

The 100 assigned to the “enhanced usual care” control group received educational materials on controlling high BP. They and the 101 who followed the mindfulness-based program were given and trained on a home BP-monitoring device. They were then followed for the primary endpoint of change in systolic BP at 6 months.

Data management and outcomes assessments were conducted by trialists not involved in the training intervention who were blinded to randomization assignment.

In a prespecified unadjusted analysis by intention-to-treat, systolic BP in the intervention group dropped by a mean of 5.9 mm Hg (P < .001) compared with baseline and 4.5 mm Hg (P = .045), compared with the control group.

A post hoc analysis adjusted for sex and baseline BP showed an average 4.3 mm Hg reduction (P = .056) in those following the MB-BP program, compared with controls.

There were no observed significant effects on diastolic BP.

The study offered clues to how engagement in the MB-BP program might promote reductions in systolic BP, Dr. Loucks observed. For example, it may have led to increased activity levels, reduced sodium intake, and other dietary improvements.

Indeed, program participants averaged about 351 minutes less sedentary time (P = .02) and showed a 0.32-point improvement in Dietary Approaches to Stop Hypertension scores (P = .08), compared with the control group, Dr. Loucks reported. Other modifiable risk factors for elevated BP that could have responded to the mindfulness-based training, he proposed, include obesity, alcohol intake, and reaction to stress.

Dr. Loucks reports that he developed the MB-BP training and was a program instructor but did not receive related financial compensation; he had no other disclosures. Dr. Khera, Dr. Touyz, and Dr. Rangaswami had no relevant financial relationships.

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

U.K. researchers have established that hypertension is associated with a 22% greater risk of severe COVID-19, with the odds of severe COVID-19 unaffected by medication type.

Hypertension “appears to be one of the commonest comorbidities in COVID-19 patients”, explained the authors of a new study, published in PLOS ONE. The authors highlighted that previous research had shown that hypertension was more prevalent in severe and fatal cases compared with all cases of COVID-19.

They pointed out, however, that whether hypertensive individuals have a higher risk of severe COVID-19, compared with nonhypertensives, and whether the absolute level of systolic blood pressure or the type of antihypertensive medication is related to this risk, remained “unclear.”

To try to answer these questions, the research team, led by University of Cambridge researchers, analyzed data from 16,134 individuals who tested positive for COVID-19 (mean age 65.3 years, 47% male, 90% white), 40% were diagnosed with essential hypertension at the analysis baseline – 22% of whom had developed severe COVID-19.

Systolic blood pressure (SBP) was categorized by 10–mm Hg ranges, starting from < 120 mm Hg up to 180+ mm Hg, with the reference category defined as 120-129 mm Hg, based on data from the SPRINT study, which demonstrated that intensive SBP lowering to below 120 mm Hg, as compared with the traditional threshold of 140 mm Hg, was beneficial. Diastolic blood pressure was categorized by 10–mm Hg ranges, starting from < 60 mm Hg up to 100+ mm Hg with 80-90 mm Hg being the reference category.

In their analyses the researchers adjusted for age, sex, body mass index, ethnicity, smoking status, diabetes status, socioeconomic status, and inflammation (C-reactive protein [CRP]), as these were proposed as potential confounders. To assess the direct effect of hypertension on COVID-19, they also adjusted for intermediate variables, including cardiovascular comorbidities and stroke, on the causal pathway between hypertension and severe COVID-19.
 

Majority of effect of hypertension on severe COVID-19 was direct

The unadjusted odds ratio of the association between hypertension and severe COVID-19 was 2.33 (95% confidence interval, 2.16-2.51), the authors emphasized. They found that, after adjusting for all confounding variables, hypertension was associated with 22% higher odds of severe COVID-19 (OR, 1.22; 95% CI, 1.12-1.33), compared with normotension.

Individuals with severe COVID-19 were marginally older, more likely to be male, and more deprived, the authors said. “They were also more likely to be hypertensive, compared with individuals without severe COVID-19, and a greater proportion of individuals with severe COVID-19 had cardiovascular comorbidities.”

The majority of the effect of hypertension on development of severe COVID-19 was “direct,” they said. However, a modest proportion of the effect was mediated via cardiovascular comorbidities such as peripheral vascular disease, MI, coronary heart disease, arrhythmias, and stroke. Of note, those with a history of stroke had a 47% higher risk of severe COVID-19 and those with a history of other cardiovascular comorbidities had a 30% higher risk of severe COVID-19, the authors commented.
 

J-shaped relationship

Of the total of 6,517 (40%) individuals who had a diagnosis of essential hypertension at baseline, 67% were treated (41% with monotherapy, 59% with combination therapy), and 33% were untreated.

There were similar numbers of severe COVID-19 in each medication group: ACE inhibitors, 34%; angiotensin receptor blockers (ARBs), 36%; and “other” medications 34%.

In hypertensive individuals receiving antihypertensive medications, there was a “J-shaped relationship” between the level of blood pressure and risk of severe COVID-19 when using a systolic blood pressure level of 120-129 mm Hg as a reference – 150-159 mm Hg versus 120-129 mm Hg (OR 1.91; 95% CI, 1.44-2.53), > 180+ mm Hg versus 120-129 mm Hg (OR 1.93; 95% CI, 1.06-3.51).

The authors commented that there was no evidence of a higher risk of severe COVID-19 until systolic blood pressure “exceeded 150 mm Hg.”

They said it was an interesting finding that “very well-controlled” systolic blood pressure < 120 mm Hg was associated with a 40% (OR, 1.40; 95% CI, 1.11-1.78) greater odds of severe COVID-19. “This may be due to reverse causality, where low systolic blood pressure levels may indicate poorer health, such that the occurrence of severe COVID-19 may be related to underlying disease rather than the level of SBP per se,” they suggested.

The J-shaped association observed remained after multiple adjustments, including presence of known cardiovascular comorbidities, which suggested a possible “real effect” of low SBP on severe COVID-19, “at least in treated hypertensive individuals.”

Their analyses also identified that, compared with a “normal” diastolic blood pressure (80-90 mm Hg), having a diastolic blood pressure higher than 90 mm Hg was associated with higher odds of severe COVID-19.

The association between hypertension and COVID-19 was “amplified” if the individuals were treated and their BP remained uncontrolled, the authors pointed out.

There did not appear to be any difference in the risk of severe COVID-19 between individuals taking ACE inhibitors and those taking ARBs or other antihypertensive medications, the authors said.
 

Better understanding of underlying mechanisms needed

Individuals with hypertension who tested positive for COVID-19 had “over twice” the risk of developing severe COVID-19, compared with nonhypertensive individuals, the authors said.

They highlighted that their findings also suggest that there are “further effects” influencing the severity of COVID-19 beyond a “dichotomous” diagnosis of hypertension.

“Individuals with a higher-than-target systolic blood pressure may be less healthy, less active, suffering more severe hypertension, or have developed drug-resistant hypertension, all suggesting that the effects of hypertension have already had detrimental physiological effects on the cardiovascular system, which in turn may offer some explanation for the higher risk of severe COVID-19 with uncontrolled SBP,” they explained.

“Hypertension is an important risk factor for COVID-19,” reiterated the authors, who emphasized that a better understanding of the underlying mechanisms driving this increased risk is warranted in case of “more severe strains or other viruses” in the future.

The authors have declared no competing interests.

A version of this article first appeared on Medscape UK.

U.K. researchers have established that hypertension is associated with a 22% greater risk of severe COVID-19, with the odds of severe COVID-19 unaffected by medication type.

Hypertension “appears to be one of the commonest comorbidities in COVID-19 patients”, explained the authors of a new study, published in PLOS ONE. The authors highlighted that previous research had shown that hypertension was more prevalent in severe and fatal cases compared with all cases of COVID-19.

They pointed out, however, that whether hypertensive individuals have a higher risk of severe COVID-19, compared with nonhypertensives, and whether the absolute level of systolic blood pressure or the type of antihypertensive medication is related to this risk, remained “unclear.”

To try to answer these questions, the research team, led by University of Cambridge researchers, analyzed data from 16,134 individuals who tested positive for COVID-19 (mean age 65.3 years, 47% male, 90% white), 40% were diagnosed with essential hypertension at the analysis baseline – 22% of whom had developed severe COVID-19.

Systolic blood pressure (SBP) was categorized by 10–mm Hg ranges, starting from < 120 mm Hg up to 180+ mm Hg, with the reference category defined as 120-129 mm Hg, based on data from the SPRINT study, which demonstrated that intensive SBP lowering to below 120 mm Hg, as compared with the traditional threshold of 140 mm Hg, was beneficial. Diastolic blood pressure was categorized by 10–mm Hg ranges, starting from < 60 mm Hg up to 100+ mm Hg with 80-90 mm Hg being the reference category.

In their analyses the researchers adjusted for age, sex, body mass index, ethnicity, smoking status, diabetes status, socioeconomic status, and inflammation (C-reactive protein [CRP]), as these were proposed as potential confounders. To assess the direct effect of hypertension on COVID-19, they also adjusted for intermediate variables, including cardiovascular comorbidities and stroke, on the causal pathway between hypertension and severe COVID-19.
 

Majority of effect of hypertension on severe COVID-19 was direct

The unadjusted odds ratio of the association between hypertension and severe COVID-19 was 2.33 (95% confidence interval, 2.16-2.51), the authors emphasized. They found that, after adjusting for all confounding variables, hypertension was associated with 22% higher odds of severe COVID-19 (OR, 1.22; 95% CI, 1.12-1.33), compared with normotension.

Individuals with severe COVID-19 were marginally older, more likely to be male, and more deprived, the authors said. “They were also more likely to be hypertensive, compared with individuals without severe COVID-19, and a greater proportion of individuals with severe COVID-19 had cardiovascular comorbidities.”

The majority of the effect of hypertension on development of severe COVID-19 was “direct,” they said. However, a modest proportion of the effect was mediated via cardiovascular comorbidities such as peripheral vascular disease, MI, coronary heart disease, arrhythmias, and stroke. Of note, those with a history of stroke had a 47% higher risk of severe COVID-19 and those with a history of other cardiovascular comorbidities had a 30% higher risk of severe COVID-19, the authors commented.
 

J-shaped relationship

Of the total of 6,517 (40%) individuals who had a diagnosis of essential hypertension at baseline, 67% were treated (41% with monotherapy, 59% with combination therapy), and 33% were untreated.

There were similar numbers of severe COVID-19 in each medication group: ACE inhibitors, 34%; angiotensin receptor blockers (ARBs), 36%; and “other” medications 34%.

In hypertensive individuals receiving antihypertensive medications, there was a “J-shaped relationship” between the level of blood pressure and risk of severe COVID-19 when using a systolic blood pressure level of 120-129 mm Hg as a reference – 150-159 mm Hg versus 120-129 mm Hg (OR 1.91; 95% CI, 1.44-2.53), > 180+ mm Hg versus 120-129 mm Hg (OR 1.93; 95% CI, 1.06-3.51).

The authors commented that there was no evidence of a higher risk of severe COVID-19 until systolic blood pressure “exceeded 150 mm Hg.”

They said it was an interesting finding that “very well-controlled” systolic blood pressure < 120 mm Hg was associated with a 40% (OR, 1.40; 95% CI, 1.11-1.78) greater odds of severe COVID-19. “This may be due to reverse causality, where low systolic blood pressure levels may indicate poorer health, such that the occurrence of severe COVID-19 may be related to underlying disease rather than the level of SBP per se,” they suggested.

The J-shaped association observed remained after multiple adjustments, including presence of known cardiovascular comorbidities, which suggested a possible “real effect” of low SBP on severe COVID-19, “at least in treated hypertensive individuals.”

Their analyses also identified that, compared with a “normal” diastolic blood pressure (80-90 mm Hg), having a diastolic blood pressure higher than 90 mm Hg was associated with higher odds of severe COVID-19.

The association between hypertension and COVID-19 was “amplified” if the individuals were treated and their BP remained uncontrolled, the authors pointed out.

There did not appear to be any difference in the risk of severe COVID-19 between individuals taking ACE inhibitors and those taking ARBs or other antihypertensive medications, the authors said.
 

Better understanding of underlying mechanisms needed

Individuals with hypertension who tested positive for COVID-19 had “over twice” the risk of developing severe COVID-19, compared with nonhypertensive individuals, the authors said.

They highlighted that their findings also suggest that there are “further effects” influencing the severity of COVID-19 beyond a “dichotomous” diagnosis of hypertension.

“Individuals with a higher-than-target systolic blood pressure may be less healthy, less active, suffering more severe hypertension, or have developed drug-resistant hypertension, all suggesting that the effects of hypertension have already had detrimental physiological effects on the cardiovascular system, which in turn may offer some explanation for the higher risk of severe COVID-19 with uncontrolled SBP,” they explained.

“Hypertension is an important risk factor for COVID-19,” reiterated the authors, who emphasized that a better understanding of the underlying mechanisms driving this increased risk is warranted in case of “more severe strains or other viruses” in the future.

The authors have declared no competing interests.

A version of this article first appeared on Medscape UK.

U.K. researchers have established that hypertension is associated with a 22% greater risk of severe COVID-19, with the odds of severe COVID-19 unaffected by medication type.

Hypertension “appears to be one of the commonest comorbidities in COVID-19 patients”, explained the authors of a new study, published in PLOS ONE. The authors highlighted that previous research had shown that hypertension was more prevalent in severe and fatal cases compared with all cases of COVID-19.

They pointed out, however, that whether hypertensive individuals have a higher risk of severe COVID-19, compared with nonhypertensives, and whether the absolute level of systolic blood pressure or the type of antihypertensive medication is related to this risk, remained “unclear.”

To try to answer these questions, the research team, led by University of Cambridge researchers, analyzed data from 16,134 individuals who tested positive for COVID-19 (mean age 65.3 years, 47% male, 90% white), 40% were diagnosed with essential hypertension at the analysis baseline – 22% of whom had developed severe COVID-19.

Systolic blood pressure (SBP) was categorized by 10–mm Hg ranges, starting from < 120 mm Hg up to 180+ mm Hg, with the reference category defined as 120-129 mm Hg, based on data from the SPRINT study, which demonstrated that intensive SBP lowering to below 120 mm Hg, as compared with the traditional threshold of 140 mm Hg, was beneficial. Diastolic blood pressure was categorized by 10–mm Hg ranges, starting from < 60 mm Hg up to 100+ mm Hg with 80-90 mm Hg being the reference category.

In their analyses the researchers adjusted for age, sex, body mass index, ethnicity, smoking status, diabetes status, socioeconomic status, and inflammation (C-reactive protein [CRP]), as these were proposed as potential confounders. To assess the direct effect of hypertension on COVID-19, they also adjusted for intermediate variables, including cardiovascular comorbidities and stroke, on the causal pathway between hypertension and severe COVID-19.
 

Majority of effect of hypertension on severe COVID-19 was direct

The unadjusted odds ratio of the association between hypertension and severe COVID-19 was 2.33 (95% confidence interval, 2.16-2.51), the authors emphasized. They found that, after adjusting for all confounding variables, hypertension was associated with 22% higher odds of severe COVID-19 (OR, 1.22; 95% CI, 1.12-1.33), compared with normotension.

Individuals with severe COVID-19 were marginally older, more likely to be male, and more deprived, the authors said. “They were also more likely to be hypertensive, compared with individuals without severe COVID-19, and a greater proportion of individuals with severe COVID-19 had cardiovascular comorbidities.”

The majority of the effect of hypertension on development of severe COVID-19 was “direct,” they said. However, a modest proportion of the effect was mediated via cardiovascular comorbidities such as peripheral vascular disease, MI, coronary heart disease, arrhythmias, and stroke. Of note, those with a history of stroke had a 47% higher risk of severe COVID-19 and those with a history of other cardiovascular comorbidities had a 30% higher risk of severe COVID-19, the authors commented.
 

J-shaped relationship

Of the total of 6,517 (40%) individuals who had a diagnosis of essential hypertension at baseline, 67% were treated (41% with monotherapy, 59% with combination therapy), and 33% were untreated.

There were similar numbers of severe COVID-19 in each medication group: ACE inhibitors, 34%; angiotensin receptor blockers (ARBs), 36%; and “other” medications 34%.

In hypertensive individuals receiving antihypertensive medications, there was a “J-shaped relationship” between the level of blood pressure and risk of severe COVID-19 when using a systolic blood pressure level of 120-129 mm Hg as a reference – 150-159 mm Hg versus 120-129 mm Hg (OR 1.91; 95% CI, 1.44-2.53), > 180+ mm Hg versus 120-129 mm Hg (OR 1.93; 95% CI, 1.06-3.51).

The authors commented that there was no evidence of a higher risk of severe COVID-19 until systolic blood pressure “exceeded 150 mm Hg.”

They said it was an interesting finding that “very well-controlled” systolic blood pressure < 120 mm Hg was associated with a 40% (OR, 1.40; 95% CI, 1.11-1.78) greater odds of severe COVID-19. “This may be due to reverse causality, where low systolic blood pressure levels may indicate poorer health, such that the occurrence of severe COVID-19 may be related to underlying disease rather than the level of SBP per se,” they suggested.

The J-shaped association observed remained after multiple adjustments, including presence of known cardiovascular comorbidities, which suggested a possible “real effect” of low SBP on severe COVID-19, “at least in treated hypertensive individuals.”

Their analyses also identified that, compared with a “normal” diastolic blood pressure (80-90 mm Hg), having a diastolic blood pressure higher than 90 mm Hg was associated with higher odds of severe COVID-19.

The association between hypertension and COVID-19 was “amplified” if the individuals were treated and their BP remained uncontrolled, the authors pointed out.

There did not appear to be any difference in the risk of severe COVID-19 between individuals taking ACE inhibitors and those taking ARBs or other antihypertensive medications, the authors said.
 

Better understanding of underlying mechanisms needed

Individuals with hypertension who tested positive for COVID-19 had “over twice” the risk of developing severe COVID-19, compared with nonhypertensive individuals, the authors said.

They highlighted that their findings also suggest that there are “further effects” influencing the severity of COVID-19 beyond a “dichotomous” diagnosis of hypertension.

“Individuals with a higher-than-target systolic blood pressure may be less healthy, less active, suffering more severe hypertension, or have developed drug-resistant hypertension, all suggesting that the effects of hypertension have already had detrimental physiological effects on the cardiovascular system, which in turn may offer some explanation for the higher risk of severe COVID-19 with uncontrolled SBP,” they explained.

“Hypertension is an important risk factor for COVID-19,” reiterated the authors, who emphasized that a better understanding of the underlying mechanisms driving this increased risk is warranted in case of “more severe strains or other viruses” in the future.

The authors have declared no competing interests.

A version of this article first appeared on Medscape UK.

Farshad Fani Marvasti, MD, MPH, is part of a growing movement to fundamentally shift medical education to include training on how to cook healthy meals.

The way he sees it, the stakes couldn’t be higher. He believes doctors need to see food as medicine to be able to stem the tide of chronic disease.

About 6 in 10 adults in the United States live with chronic diseases, according to the Centers for Disease Control and Prevention, costing $4.1 trillion in annual health care costs. Adult obesity rates are rising, as are obesity-related conditions such as heart disease, stroke, type 2 diabetes, and certain types of cancer.

To turn the tide, Dr. Marvasti created a culinary medicine program in 2020 in collaboration with the University of Arizona Cooperative Extension and local chefs.

Dr. Marvasti, who is board certified in family medicine, graduated from the University of Arizona, Phoenix, where he serves as the director of the medical school’s Culinary Medicine Program.

The program offers an elective course for third- and fourth-year medical students, which introduces the evidence-based field of culinary medicine. Dr Marvasti’s goal is for the course to teach students how to use this science and the joy of cooking to improve long-term health outcomes for their patients.

As part of Dr. Marvasti’s program, students learn cooking fundamentals through chef demonstrations and hands-on practice – to teach students how food can be used to prevent and treat many chronic diseases.

One of the dishes students learn to make includes a quinoa salad made with cucumber, onion, bell peppers, corn, cherry tomatoes, beans, garlic, olive oil, and lemon juice. Another recipe includes a healthier take on dessert: Dark chocolate mousse made with three large, ripe avocados, dark chocolate powder, three tablespoons of agave or maple, coconut cream, nondairy milk, salt, and vanilla. Dr. Marvasti and his team are set to build out the existing program to develop additional resources for medically underserved and rural communities in Arizona, according to a statement from the university. These plans will be funded by a $750,000 grant from Novo Nordisk.

“We’re going to develop an open education curriculum to share, so it’s open access to everyone,” said Dr. Marvasti, who is also director of Public Health, Prevention and Health Promotion and an associate professor at the university. “It can be adaptable at the undergraduate, graduate, and postgraduate level.”

Dr. Marvasti and his colleagues at the University of Arizona aren’t alone. In fact, culinary medicine programs are sprouting some serious legs.
 

Culinary medicine programs catch on

Jaclyn Albin, MD, CCMS, an associate professor in the departments of internal medicine and pediatrics at UT Southwestern Medical Center, Dallas, conducted a scoping review of the literature on culinary medicine programs for medical students.* Her purpose was to learn how the programs were structured and how they assessed student knowledge and attitudes regarding nutrition counseling for patients.

Dr. Albin and her colleagues performed an initial literature search between June 1 and Aug. 1, 2020, of papers published between Jan. 1, 2012, and Aug. 1, 2020 – excluding some newer programs such as the one at the University of Arizona. The results of their research were published in Academic Medicine.

Ultimately, the authors identified and examined 34 programs offering medical student–focused culinary medicine courses.

Program instructors typically included a team of physicians, dietitians, chefs, and other professionals, the study found.

Most program participants exclusively taught medical students, though the training years of participants varied among programs, and they included first-, second-, third-, and fourth-year students. Some programs allowed students from outside their respective medical school to participate in the trainings.

As for the formats of the program, most included cohorts of 10-20 students attending multiple 2- to 3-hour sessions over the course of several months. The University of Alabama at Birmingham offers one of the longest courses, which spans 4-5 months, according to the paper. In contrast, the University of Rochester (N.Y.) program offers only a 1-day lab divided into four sessions, with each session lasting about 2 hours.

The culinary medicine programs’ course sessions tended to include a 10- to 30-minute didactic session involving videos, research articles, culinary theories, and other lectures, a 60- to 90-minute hands-on cooking session, and a 30-minute discussion around nutrition, culture, and patient care.

Most programs used pre- and post-program surveys to evaluate outcomes, though results varied between programs, according to the study. While each program evaluation had different metrics, the surveys generally revealed students felt more confident discussing dietary interventions with patients and in their own cooking skills following completion.
 

Course correction

Most of those programs are unfunded or minimally funded, Dr. Albin said.

Her own program, which is immensely popular with medical students, is one she teaches on a volunteer basis.

“I do this for free, in the evenings, because I believe in it,” she said.

Medical school education real estate is limited, so convincing medical schools to add something to the curriculum is difficult, Dr. Albin noted.

But it’s worth it, she said, because nutrition is the underpinning of so many diseases.

“Food is the top risk factor for early death in the U.S.,” Dr. Albin said. “I like to say that five times in a row. People have not digested it.”

During her culinary medicine courses, she also asks her medical students: “Who is comfortable in the kitchen?” Some sheepishly raise their hands, she said. Some don’t. Many don’t know anything about cooking.

Then she teaches students about healthy food and how to make it. As part of her program, medical students are given a pantry starter kit with olive oil and a variety of spices to take home and use.

Some recipes Dr. Albin teaches includes mango chili shrimp salad with lime vinaigrette, eggplant sliders, yellow vegetable curry, and strawberry banana chia pudding.

“If you figure out how to do it for your own busy, everyday life, you are now empowered to tell someone else about it,” she said.
 

A dietitian’s involvement

Milette Siler, RD, LD, CCMS, works with Dr. Albin to educate medical students and patients about food as medicine. A significant chunk of her job involves teaching future doctors what dietitians do.

When the class starts, many students don’t know two of the five basic things dietitians do, Ms. Siler said. By the end of the class, all students know what a dietitian does.

That’s important as students go on to become doctors.

“For us to remove barriers to care, we have to acknowledge most patients’ entry into health care is their physician,” she said. “The dietitian is often a referral. Doctors need to know enough to do no harm.”

Clinicians are often siloed, she said, and the key to better serving patients is partnership, transparency, and relationships. “I think everybody is at a point where everyone is saying what we’re doing isn’t working,” she said. “The American public deserves better, physicians deserve better, and clinicians deserve better.”
 

Popular with students

While the old guard has been slow to embrace the shift, her students have helped drive the growth of the culinary medicine field, Dr. Albin said.

“They are not settling for the inadequacy that somehow the rest of us did,” she continued. “I’m so hopeful for the future of the health system. We have a generation of people who will not stand for neglecting the most vital elements.”

Courtesy Farshad Fani Marvasti, MD, MPH

Lyndon Bui, a second-year medical student at the University of Arizona, Phoenix, is an example of one of these people.

As a member of a culinary medicine interest group on campus, he said, he has learned a lot about the importance of diet for long-term health. This has given him confidence to talk about food and nutrition.

His group does cooking demos at the Phoenix Farmers Market using food from various local vendors. They usually make a salad from local greens and cook seasonal veggies in a stir fry, he said.

They’ve previously made salad with microgreens – young seedlings of edible vegetables and herbs – and pomegranate seeds with a honey mustard vinaigrette, eggplant or cucumber, and hummus on pita bread, as well as almond butter and honey sandwiches, according to the university.

The group also talks with people in the community, answers questions, and learns about community needs.

Mr. Bui’s participation in this group has helped him cultivate a passion for community outreach that he wants to incorporate into his career.

“I feel like I have the knowledge to provide better advice to patients,” he said. “Knowing all these things about food, I feel more comfortable talking about it and more inclined to refer to a dietitian when maybe I wouldn’t have before.”
 

Family physician applauds culinary medicine programs

When Angie Neison, MD, CCMS, went to medical school, she was surprised there wasn’t more education on nutrition.

In fact, on average, physicians receive less than 20 hours of nutrition education, according to the University of Arizona.

Now 15 years into her career as a family physician, Dr. Neison says nutrition is a huge part of her practice. She spends time working to bust myths about nutrition for her patients – including that healthy food is boring and bland, that making it is time consuming, and that healthy food is expensive. She also spends time teaching aspects of culinary medicine to her colleagues – many of whom are well into their careers – so they can better serve their patients.

It’s worth it to spend time learning about nutrition, she said, whether that’s as a medical student in a culinary medicine program or a practicing physician taking additional courses.

Nutrition education in medical school hasn’t been a priority, she said, maybe because there is so much to learn, or maybe because there is no money to be made in prevention.

“If doctors learn it, they are able to better guide patients,” she said.

Correction, 11/29/22: An earlier version of this article misstated Dr. Albin's institution.
 

Farshad Fani Marvasti, MD, MPH, is part of a growing movement to fundamentally shift medical education to include training on how to cook healthy meals.

The way he sees it, the stakes couldn’t be higher. He believes doctors need to see food as medicine to be able to stem the tide of chronic disease.

About 6 in 10 adults in the United States live with chronic diseases, according to the Centers for Disease Control and Prevention, costing $4.1 trillion in annual health care costs. Adult obesity rates are rising, as are obesity-related conditions such as heart disease, stroke, type 2 diabetes, and certain types of cancer.

To turn the tide, Dr. Marvasti created a culinary medicine program in 2020 in collaboration with the University of Arizona Cooperative Extension and local chefs.

Dr. Marvasti, who is board certified in family medicine, graduated from the University of Arizona, Phoenix, where he serves as the director of the medical school’s Culinary Medicine Program.

The program offers an elective course for third- and fourth-year medical students, which introduces the evidence-based field of culinary medicine. Dr Marvasti’s goal is for the course to teach students how to use this science and the joy of cooking to improve long-term health outcomes for their patients.

As part of Dr. Marvasti’s program, students learn cooking fundamentals through chef demonstrations and hands-on practice – to teach students how food can be used to prevent and treat many chronic diseases.

One of the dishes students learn to make includes a quinoa salad made with cucumber, onion, bell peppers, corn, cherry tomatoes, beans, garlic, olive oil, and lemon juice. Another recipe includes a healthier take on dessert: Dark chocolate mousse made with three large, ripe avocados, dark chocolate powder, three tablespoons of agave or maple, coconut cream, nondairy milk, salt, and vanilla. Dr. Marvasti and his team are set to build out the existing program to develop additional resources for medically underserved and rural communities in Arizona, according to a statement from the university. These plans will be funded by a $750,000 grant from Novo Nordisk.

“We’re going to develop an open education curriculum to share, so it’s open access to everyone,” said Dr. Marvasti, who is also director of Public Health, Prevention and Health Promotion and an associate professor at the university. “It can be adaptable at the undergraduate, graduate, and postgraduate level.”

Dr. Marvasti and his colleagues at the University of Arizona aren’t alone. In fact, culinary medicine programs are sprouting some serious legs.
 

Culinary medicine programs catch on

Jaclyn Albin, MD, CCMS, an associate professor in the departments of internal medicine and pediatrics at UT Southwestern Medical Center, Dallas, conducted a scoping review of the literature on culinary medicine programs for medical students.* Her purpose was to learn how the programs were structured and how they assessed student knowledge and attitudes regarding nutrition counseling for patients.

Dr. Albin and her colleagues performed an initial literature search between June 1 and Aug. 1, 2020, of papers published between Jan. 1, 2012, and Aug. 1, 2020 – excluding some newer programs such as the one at the University of Arizona. The results of their research were published in Academic Medicine.

Ultimately, the authors identified and examined 34 programs offering medical student–focused culinary medicine courses.

Program instructors typically included a team of physicians, dietitians, chefs, and other professionals, the study found.

Most program participants exclusively taught medical students, though the training years of participants varied among programs, and they included first-, second-, third-, and fourth-year students. Some programs allowed students from outside their respective medical school to participate in the trainings.

As for the formats of the program, most included cohorts of 10-20 students attending multiple 2- to 3-hour sessions over the course of several months. The University of Alabama at Birmingham offers one of the longest courses, which spans 4-5 months, according to the paper. In contrast, the University of Rochester (N.Y.) program offers only a 1-day lab divided into four sessions, with each session lasting about 2 hours.

The culinary medicine programs’ course sessions tended to include a 10- to 30-minute didactic session involving videos, research articles, culinary theories, and other lectures, a 60- to 90-minute hands-on cooking session, and a 30-minute discussion around nutrition, culture, and patient care.

Most programs used pre- and post-program surveys to evaluate outcomes, though results varied between programs, according to the study. While each program evaluation had different metrics, the surveys generally revealed students felt more confident discussing dietary interventions with patients and in their own cooking skills following completion.
 

Course correction

Most of those programs are unfunded or minimally funded, Dr. Albin said.

Her own program, which is immensely popular with medical students, is one she teaches on a volunteer basis.

“I do this for free, in the evenings, because I believe in it,” she said.

Medical school education real estate is limited, so convincing medical schools to add something to the curriculum is difficult, Dr. Albin noted.

But it’s worth it, she said, because nutrition is the underpinning of so many diseases.

“Food is the top risk factor for early death in the U.S.,” Dr. Albin said. “I like to say that five times in a row. People have not digested it.”

During her culinary medicine courses, she also asks her medical students: “Who is comfortable in the kitchen?” Some sheepishly raise their hands, she said. Some don’t. Many don’t know anything about cooking.

Then she teaches students about healthy food and how to make it. As part of her program, medical students are given a pantry starter kit with olive oil and a variety of spices to take home and use.

Some recipes Dr. Albin teaches includes mango chili shrimp salad with lime vinaigrette, eggplant sliders, yellow vegetable curry, and strawberry banana chia pudding.

“If you figure out how to do it for your own busy, everyday life, you are now empowered to tell someone else about it,” she said.
 

A dietitian’s involvement

Milette Siler, RD, LD, CCMS, works with Dr. Albin to educate medical students and patients about food as medicine. A significant chunk of her job involves teaching future doctors what dietitians do.

When the class starts, many students don’t know two of the five basic things dietitians do, Ms. Siler said. By the end of the class, all students know what a dietitian does.

That’s important as students go on to become doctors.

“For us to remove barriers to care, we have to acknowledge most patients’ entry into health care is their physician,” she said. “The dietitian is often a referral. Doctors need to know enough to do no harm.”

Clinicians are often siloed, she said, and the key to better serving patients is partnership, transparency, and relationships. “I think everybody is at a point where everyone is saying what we’re doing isn’t working,” she said. “The American public deserves better, physicians deserve better, and clinicians deserve better.”
 

Popular with students

While the old guard has been slow to embrace the shift, her students have helped drive the growth of the culinary medicine field, Dr. Albin said.

“They are not settling for the inadequacy that somehow the rest of us did,” she continued. “I’m so hopeful for the future of the health system. We have a generation of people who will not stand for neglecting the most vital elements.”

Courtesy Farshad Fani Marvasti, MD, MPH

Lyndon Bui, a second-year medical student at the University of Arizona, Phoenix, is an example of one of these people.

As a member of a culinary medicine interest group on campus, he said, he has learned a lot about the importance of diet for long-term health. This has given him confidence to talk about food and nutrition.

His group does cooking demos at the Phoenix Farmers Market using food from various local vendors. They usually make a salad from local greens and cook seasonal veggies in a stir fry, he said.

They’ve previously made salad with microgreens – young seedlings of edible vegetables and herbs – and pomegranate seeds with a honey mustard vinaigrette, eggplant or cucumber, and hummus on pita bread, as well as almond butter and honey sandwiches, according to the university.

The group also talks with people in the community, answers questions, and learns about community needs.

Mr. Bui’s participation in this group has helped him cultivate a passion for community outreach that he wants to incorporate into his career.

“I feel like I have the knowledge to provide better advice to patients,” he said. “Knowing all these things about food, I feel more comfortable talking about it and more inclined to refer to a dietitian when maybe I wouldn’t have before.”
 

Family physician applauds culinary medicine programs

When Angie Neison, MD, CCMS, went to medical school, she was surprised there wasn’t more education on nutrition.

In fact, on average, physicians receive less than 20 hours of nutrition education, according to the University of Arizona.

Now 15 years into her career as a family physician, Dr. Neison says nutrition is a huge part of her practice. She spends time working to bust myths about nutrition for her patients – including that healthy food is boring and bland, that making it is time consuming, and that healthy food is expensive. She also spends time teaching aspects of culinary medicine to her colleagues – many of whom are well into their careers – so they can better serve their patients.

It’s worth it to spend time learning about nutrition, she said, whether that’s as a medical student in a culinary medicine program or a practicing physician taking additional courses.

Nutrition education in medical school hasn’t been a priority, she said, maybe because there is so much to learn, or maybe because there is no money to be made in prevention.

“If doctors learn it, they are able to better guide patients,” she said.

Correction, 11/29/22: An earlier version of this article misstated Dr. Albin's institution.
 

Farshad Fani Marvasti, MD, MPH, is part of a growing movement to fundamentally shift medical education to include training on how to cook healthy meals.

The way he sees it, the stakes couldn’t be higher. He believes doctors need to see food as medicine to be able to stem the tide of chronic disease.

About 6 in 10 adults in the United States live with chronic diseases, according to the Centers for Disease Control and Prevention, costing $4.1 trillion in annual health care costs. Adult obesity rates are rising, as are obesity-related conditions such as heart disease, stroke, type 2 diabetes, and certain types of cancer.

To turn the tide, Dr. Marvasti created a culinary medicine program in 2020 in collaboration with the University of Arizona Cooperative Extension and local chefs.

Dr. Marvasti, who is board certified in family medicine, graduated from the University of Arizona, Phoenix, where he serves as the director of the medical school’s Culinary Medicine Program.

The program offers an elective course for third- and fourth-year medical students, which introduces the evidence-based field of culinary medicine. Dr Marvasti’s goal is for the course to teach students how to use this science and the joy of cooking to improve long-term health outcomes for their patients.

As part of Dr. Marvasti’s program, students learn cooking fundamentals through chef demonstrations and hands-on practice – to teach students how food can be used to prevent and treat many chronic diseases.

One of the dishes students learn to make includes a quinoa salad made with cucumber, onion, bell peppers, corn, cherry tomatoes, beans, garlic, olive oil, and lemon juice. Another recipe includes a healthier take on dessert: Dark chocolate mousse made with three large, ripe avocados, dark chocolate powder, three tablespoons of agave or maple, coconut cream, nondairy milk, salt, and vanilla. Dr. Marvasti and his team are set to build out the existing program to develop additional resources for medically underserved and rural communities in Arizona, according to a statement from the university. These plans will be funded by a $750,000 grant from Novo Nordisk.

“We’re going to develop an open education curriculum to share, so it’s open access to everyone,” said Dr. Marvasti, who is also director of Public Health, Prevention and Health Promotion and an associate professor at the university. “It can be adaptable at the undergraduate, graduate, and postgraduate level.”

Dr. Marvasti and his colleagues at the University of Arizona aren’t alone. In fact, culinary medicine programs are sprouting some serious legs.
 

Culinary medicine programs catch on

Jaclyn Albin, MD, CCMS, an associate professor in the departments of internal medicine and pediatrics at UT Southwestern Medical Center, Dallas, conducted a scoping review of the literature on culinary medicine programs for medical students.* Her purpose was to learn how the programs were structured and how they assessed student knowledge and attitudes regarding nutrition counseling for patients.

Dr. Albin and her colleagues performed an initial literature search between June 1 and Aug. 1, 2020, of papers published between Jan. 1, 2012, and Aug. 1, 2020 – excluding some newer programs such as the one at the University of Arizona. The results of their research were published in Academic Medicine.

Ultimately, the authors identified and examined 34 programs offering medical student–focused culinary medicine courses.

Program instructors typically included a team of physicians, dietitians, chefs, and other professionals, the study found.

Most program participants exclusively taught medical students, though the training years of participants varied among programs, and they included first-, second-, third-, and fourth-year students. Some programs allowed students from outside their respective medical school to participate in the trainings.

As for the formats of the program, most included cohorts of 10-20 students attending multiple 2- to 3-hour sessions over the course of several months. The University of Alabama at Birmingham offers one of the longest courses, which spans 4-5 months, according to the paper. In contrast, the University of Rochester (N.Y.) program offers only a 1-day lab divided into four sessions, with each session lasting about 2 hours.

The culinary medicine programs’ course sessions tended to include a 10- to 30-minute didactic session involving videos, research articles, culinary theories, and other lectures, a 60- to 90-minute hands-on cooking session, and a 30-minute discussion around nutrition, culture, and patient care.

Most programs used pre- and post-program surveys to evaluate outcomes, though results varied between programs, according to the study. While each program evaluation had different metrics, the surveys generally revealed students felt more confident discussing dietary interventions with patients and in their own cooking skills following completion.
 

Course correction

Most of those programs are unfunded or minimally funded, Dr. Albin said.

Her own program, which is immensely popular with medical students, is one she teaches on a volunteer basis.

“I do this for free, in the evenings, because I believe in it,” she said.

Medical school education real estate is limited, so convincing medical schools to add something to the curriculum is difficult, Dr. Albin noted.

But it’s worth it, she said, because nutrition is the underpinning of so many diseases.

“Food is the top risk factor for early death in the U.S.,” Dr. Albin said. “I like to say that five times in a row. People have not digested it.”

During her culinary medicine courses, she also asks her medical students: “Who is comfortable in the kitchen?” Some sheepishly raise their hands, she said. Some don’t. Many don’t know anything about cooking.

Then she teaches students about healthy food and how to make it. As part of her program, medical students are given a pantry starter kit with olive oil and a variety of spices to take home and use.

Some recipes Dr. Albin teaches includes mango chili shrimp salad with lime vinaigrette, eggplant sliders, yellow vegetable curry, and strawberry banana chia pudding.

“If you figure out how to do it for your own busy, everyday life, you are now empowered to tell someone else about it,” she said.
 

A dietitian’s involvement

Milette Siler, RD, LD, CCMS, works with Dr. Albin to educate medical students and patients about food as medicine. A significant chunk of her job involves teaching future doctors what dietitians do.

When the class starts, many students don’t know two of the five basic things dietitians do, Ms. Siler said. By the end of the class, all students know what a dietitian does.

That’s important as students go on to become doctors.

“For us to remove barriers to care, we have to acknowledge most patients’ entry into health care is their physician,” she said. “The dietitian is often a referral. Doctors need to know enough to do no harm.”

Clinicians are often siloed, she said, and the key to better serving patients is partnership, transparency, and relationships. “I think everybody is at a point where everyone is saying what we’re doing isn’t working,” she said. “The American public deserves better, physicians deserve better, and clinicians deserve better.”
 

Popular with students

While the old guard has been slow to embrace the shift, her students have helped drive the growth of the culinary medicine field, Dr. Albin said.

“They are not settling for the inadequacy that somehow the rest of us did,” she continued. “I’m so hopeful for the future of the health system. We have a generation of people who will not stand for neglecting the most vital elements.”

Courtesy Farshad Fani Marvasti, MD, MPH

Lyndon Bui, a second-year medical student at the University of Arizona, Phoenix, is an example of one of these people.

As a member of a culinary medicine interest group on campus, he said, he has learned a lot about the importance of diet for long-term health. This has given him confidence to talk about food and nutrition.

His group does cooking demos at the Phoenix Farmers Market using food from various local vendors. They usually make a salad from local greens and cook seasonal veggies in a stir fry, he said.

They’ve previously made salad with microgreens – young seedlings of edible vegetables and herbs – and pomegranate seeds with a honey mustard vinaigrette, eggplant or cucumber, and hummus on pita bread, as well as almond butter and honey sandwiches, according to the university.

The group also talks with people in the community, answers questions, and learns about community needs.

Mr. Bui’s participation in this group has helped him cultivate a passion for community outreach that he wants to incorporate into his career.

“I feel like I have the knowledge to provide better advice to patients,” he said. “Knowing all these things about food, I feel more comfortable talking about it and more inclined to refer to a dietitian when maybe I wouldn’t have before.”
 

Family physician applauds culinary medicine programs

When Angie Neison, MD, CCMS, went to medical school, she was surprised there wasn’t more education on nutrition.

In fact, on average, physicians receive less than 20 hours of nutrition education, according to the University of Arizona.

Now 15 years into her career as a family physician, Dr. Neison says nutrition is a huge part of her practice. She spends time working to bust myths about nutrition for her patients – including that healthy food is boring and bland, that making it is time consuming, and that healthy food is expensive. She also spends time teaching aspects of culinary medicine to her colleagues – many of whom are well into their careers – so they can better serve their patients.

It’s worth it to spend time learning about nutrition, she said, whether that’s as a medical student in a culinary medicine program or a practicing physician taking additional courses.

Nutrition education in medical school hasn’t been a priority, she said, maybe because there is so much to learn, or maybe because there is no money to be made in prevention.

“If doctors learn it, they are able to better guide patients,” she said.

Correction, 11/29/22: An earlier version of this article misstated Dr. Albin's institution.
 

CHICAGO – An investigational aldosterone synthase inhibitor could be an effective new treatment to reduce blood pressure in patients with treatment-resistant hypertension, reslts of a phase 2 study suggest.

The BrigHTN trial showed systolic blood pressure fell by an average of 20.3 mm Hg, 17.5 mm Hg, and 12.1 mm Hg with baxdrostat 2 mg, 1 mg, and 0.5 mg after 12 weeks follow-up in 248 patients unable to achieve target blood pressure on stable doses of at least three antihypertensive agents, including a diuretic.

After adjustment for the –9.4 mm Hg change observed in the placebo group, there was a statistically significant difference of 11.0 mm Hg in the 2-mg baxdrostat group (P = .0001) and of 8.1 mm Hg in the 1-mg baxdrostat group (P = .003).

The adjusted change in diastolic blood pressure was significant only for the 2-mg dose (–5.2 mm Hg; P = .004).

Once-daily oral baxdrostat had an acceptable side-effect profile and no patients died.

The study, which was stopped early after meeting criteria for overwhelming efficacy, was presented in the final late-breaking science session at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.
 

Threading the needle

For at least 20 years, researchers have tried to create a drug that would lower aldosterone levels directly by inhibiting hormone synthesis rather than blocking the mineralocorticoid receptor.

What’s made this extraordinarily difficult is that the enzyme that makes aldosterone synthase and the enzyme required for cortisol synthase, 11-beta-hydroxylase, are 93% sequence similar. Baxdrostat, however, is able to selectively block aldosterone synthase, and thus the production of aldosterone, without also blocking the production of cortisol, explained Mason W. Freeman, MD, lead author of the study and executive vice president of clinical development at CinCor Pharma, which is developing the agent.

“We have beautiful biomarker evidence of not only blood pressure lowering but the mechanism by which that blood pressure reduction is occurring,” he said.

Over 12 weeks of follow-up in the new study, the use of baxdrostat led to decreases in serum aldosterone levels ranging from 3.0 ng/dL with the 0.5-mg dose to 4.9 ng/dL with the 2-mg dose. The 24-hour urinary aldosterone levels decreased with all three doses tested.

Baxdrostat increased plasma renin activity by 3.6, 5.0, and 13.8 mg/mL per hr with the 0.5, 1.0, and 2.0 mg doses, respectively, an indicator of its effect on lowering salt and fluid retention, Dr. Freeman said. Serum cortisol levels were not reduced in any of the baxdrostat groups throughout the study.
 

‘A bright future’

“It seems to have a bright future in the area of resistant hypertension, particularly in patients who are producing too much aldosterone,” said Suzanne Oparil, MD, invited discussant for the study and director of the Vascular Biology and Hypertension program at the University of Alabama at Birmingham.

She noted that aldosterone is a major contributor to the pathogenesis of resistant hypertension, which afflicts about 20% of the hypertensive population. Aldosterone antagonists are considered by many to be the best add-on treatment for resistant hypertension and do lower blood pressure.

“But they have major problems,” Dr. Oparil added. “Spironolactone, for example, causes hyperkalemia in many patients and adverse effects such as gynecomastia, erectile dysfunction, and feminization.”

Baxdrostat was well tolerated with no serious adverse events deemed related to treatment, Dr. Freeman reported. A total of 18 serious adverse events occurred in 10 patients, 6 of which were in a patient with urosepsis.

Ten adverse events of special interest occurred in eight patients, including one case of hypotension, three cases of hyponatremia, and six cases of hyperkalemia.

Potassium levels ranged from 6.0 to 6.3 mmol/L (6.0-6.3 mEq/L) in three patients and between 5.5 and 5.9 mmol/L (5.5-5.9 mEq/L) on at least two consecutive occasions in three others. Four of the patients were able to resume baxdrostat and complete the trial, whereas two patients discontinued treatment, one of whom was the patient with urosepsis.

Dr. Freeman pointed out that the study population was relatively diverse, with 33%-48% of participants of Hispanic or Latinx ethnicity and 23%-32% being Black.

At baseline, all patients had a seated blood pressure of at least 130/80 mm Hg (average 147.8/87.9 mm Hg) on a background therapy that included a diuretic in 100%, an agent targeting the renin-angiotensin-aldosterone system in 91%-96%, a beta-blocker in 52%-68%, and a calcium channel blocker in 64%-70%.

The study was not designed to test the benefits and risks of aldosterone synthase inhibition beyond 12 weeks and baxdrostat was not compared to alternative antihypertensives, he said. Additional limitations are that medication adherence was based on pill counts rather than drug analysis and enrolling only patients with an estimated glomerular filtration rate over 45 mL/min per 1.73m² reduced the likelihood of hyperkalemia and other adverse events.

Nevertheless, “we think that these data suggest that baxdrostat has the potential to treat disorders associated with aldosterone excess, including hypertension and primary hyperaldosteronism,” Dr. Freeman said.

The intention is to carry the drug forward into additional phase 2 studies in chronic kidney disease and to begin a phase 3 study in hypertension in 2023, he noted.

The study was funded by CinCor Pharma. Dr. Freeman and three coauthors are employees of CinCor and receive stock-based compensation. The remaining authors have a financial relationship with CinRx Pharma, which has an equity stake in CinCor. Dr. Oparil reports grant/research support from Bayer, Higi, and Novartis; and serving on the scientific advisory board/expert committee for CinCor Pharma and Preventric Diagnostics.

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

CHICAGO – An investigational aldosterone synthase inhibitor could be an effective new treatment to reduce blood pressure in patients with treatment-resistant hypertension, reslts of a phase 2 study suggest.

The BrigHTN trial showed systolic blood pressure fell by an average of 20.3 mm Hg, 17.5 mm Hg, and 12.1 mm Hg with baxdrostat 2 mg, 1 mg, and 0.5 mg after 12 weeks follow-up in 248 patients unable to achieve target blood pressure on stable doses of at least three antihypertensive agents, including a diuretic.

After adjustment for the –9.4 mm Hg change observed in the placebo group, there was a statistically significant difference of 11.0 mm Hg in the 2-mg baxdrostat group (P = .0001) and of 8.1 mm Hg in the 1-mg baxdrostat group (P = .003).

The adjusted change in diastolic blood pressure was significant only for the 2-mg dose (–5.2 mm Hg; P = .004).

Once-daily oral baxdrostat had an acceptable side-effect profile and no patients died.

The study, which was stopped early after meeting criteria for overwhelming efficacy, was presented in the final late-breaking science session at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.
 

Threading the needle

For at least 20 years, researchers have tried to create a drug that would lower aldosterone levels directly by inhibiting hormone synthesis rather than blocking the mineralocorticoid receptor.

What’s made this extraordinarily difficult is that the enzyme that makes aldosterone synthase and the enzyme required for cortisol synthase, 11-beta-hydroxylase, are 93% sequence similar. Baxdrostat, however, is able to selectively block aldosterone synthase, and thus the production of aldosterone, without also blocking the production of cortisol, explained Mason W. Freeman, MD, lead author of the study and executive vice president of clinical development at CinCor Pharma, which is developing the agent.

“We have beautiful biomarker evidence of not only blood pressure lowering but the mechanism by which that blood pressure reduction is occurring,” he said.

Over 12 weeks of follow-up in the new study, the use of baxdrostat led to decreases in serum aldosterone levels ranging from 3.0 ng/dL with the 0.5-mg dose to 4.9 ng/dL with the 2-mg dose. The 24-hour urinary aldosterone levels decreased with all three doses tested.

Baxdrostat increased plasma renin activity by 3.6, 5.0, and 13.8 mg/mL per hr with the 0.5, 1.0, and 2.0 mg doses, respectively, an indicator of its effect on lowering salt and fluid retention, Dr. Freeman said. Serum cortisol levels were not reduced in any of the baxdrostat groups throughout the study.
 

‘A bright future’

“It seems to have a bright future in the area of resistant hypertension, particularly in patients who are producing too much aldosterone,” said Suzanne Oparil, MD, invited discussant for the study and director of the Vascular Biology and Hypertension program at the University of Alabama at Birmingham.

She noted that aldosterone is a major contributor to the pathogenesis of resistant hypertension, which afflicts about 20% of the hypertensive population. Aldosterone antagonists are considered by many to be the best add-on treatment for resistant hypertension and do lower blood pressure.

“But they have major problems,” Dr. Oparil added. “Spironolactone, for example, causes hyperkalemia in many patients and adverse effects such as gynecomastia, erectile dysfunction, and feminization.”

Baxdrostat was well tolerated with no serious adverse events deemed related to treatment, Dr. Freeman reported. A total of 18 serious adverse events occurred in 10 patients, 6 of which were in a patient with urosepsis.

Ten adverse events of special interest occurred in eight patients, including one case of hypotension, three cases of hyponatremia, and six cases of hyperkalemia.

Potassium levels ranged from 6.0 to 6.3 mmol/L (6.0-6.3 mEq/L) in three patients and between 5.5 and 5.9 mmol/L (5.5-5.9 mEq/L) on at least two consecutive occasions in three others. Four of the patients were able to resume baxdrostat and complete the trial, whereas two patients discontinued treatment, one of whom was the patient with urosepsis.

Dr. Freeman pointed out that the study population was relatively diverse, with 33%-48% of participants of Hispanic or Latinx ethnicity and 23%-32% being Black.

At baseline, all patients had a seated blood pressure of at least 130/80 mm Hg (average 147.8/87.9 mm Hg) on a background therapy that included a diuretic in 100%, an agent targeting the renin-angiotensin-aldosterone system in 91%-96%, a beta-blocker in 52%-68%, and a calcium channel blocker in 64%-70%.

The study was not designed to test the benefits and risks of aldosterone synthase inhibition beyond 12 weeks and baxdrostat was not compared to alternative antihypertensives, he said. Additional limitations are that medication adherence was based on pill counts rather than drug analysis and enrolling only patients with an estimated glomerular filtration rate over 45 mL/min per 1.73m² reduced the likelihood of hyperkalemia and other adverse events.

Nevertheless, “we think that these data suggest that baxdrostat has the potential to treat disorders associated with aldosterone excess, including hypertension and primary hyperaldosteronism,” Dr. Freeman said.

The intention is to carry the drug forward into additional phase 2 studies in chronic kidney disease and to begin a phase 3 study in hypertension in 2023, he noted.

The study was funded by CinCor Pharma. Dr. Freeman and three coauthors are employees of CinCor and receive stock-based compensation. The remaining authors have a financial relationship with CinRx Pharma, which has an equity stake in CinCor. Dr. Oparil reports grant/research support from Bayer, Higi, and Novartis; and serving on the scientific advisory board/expert committee for CinCor Pharma and Preventric Diagnostics.

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

CHICAGO – An investigational aldosterone synthase inhibitor could be an effective new treatment to reduce blood pressure in patients with treatment-resistant hypertension, reslts of a phase 2 study suggest.

The BrigHTN trial showed systolic blood pressure fell by an average of 20.3 mm Hg, 17.5 mm Hg, and 12.1 mm Hg with baxdrostat 2 mg, 1 mg, and 0.5 mg after 12 weeks follow-up in 248 patients unable to achieve target blood pressure on stable doses of at least three antihypertensive agents, including a diuretic.

After adjustment for the –9.4 mm Hg change observed in the placebo group, there was a statistically significant difference of 11.0 mm Hg in the 2-mg baxdrostat group (P = .0001) and of 8.1 mm Hg in the 1-mg baxdrostat group (P = .003).

The adjusted change in diastolic blood pressure was significant only for the 2-mg dose (–5.2 mm Hg; P = .004).

Once-daily oral baxdrostat had an acceptable side-effect profile and no patients died.

The study, which was stopped early after meeting criteria for overwhelming efficacy, was presented in the final late-breaking science session at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.
 

Threading the needle

For at least 20 years, researchers have tried to create a drug that would lower aldosterone levels directly by inhibiting hormone synthesis rather than blocking the mineralocorticoid receptor.

What’s made this extraordinarily difficult is that the enzyme that makes aldosterone synthase and the enzyme required for cortisol synthase, 11-beta-hydroxylase, are 93% sequence similar. Baxdrostat, however, is able to selectively block aldosterone synthase, and thus the production of aldosterone, without also blocking the production of cortisol, explained Mason W. Freeman, MD, lead author of the study and executive vice president of clinical development at CinCor Pharma, which is developing the agent.

“We have beautiful biomarker evidence of not only blood pressure lowering but the mechanism by which that blood pressure reduction is occurring,” he said.

Over 12 weeks of follow-up in the new study, the use of baxdrostat led to decreases in serum aldosterone levels ranging from 3.0 ng/dL with the 0.5-mg dose to 4.9 ng/dL with the 2-mg dose. The 24-hour urinary aldosterone levels decreased with all three doses tested.

Baxdrostat increased plasma renin activity by 3.6, 5.0, and 13.8 mg/mL per hr with the 0.5, 1.0, and 2.0 mg doses, respectively, an indicator of its effect on lowering salt and fluid retention, Dr. Freeman said. Serum cortisol levels were not reduced in any of the baxdrostat groups throughout the study.
 

‘A bright future’

“It seems to have a bright future in the area of resistant hypertension, particularly in patients who are producing too much aldosterone,” said Suzanne Oparil, MD, invited discussant for the study and director of the Vascular Biology and Hypertension program at the University of Alabama at Birmingham.

She noted that aldosterone is a major contributor to the pathogenesis of resistant hypertension, which afflicts about 20% of the hypertensive population. Aldosterone antagonists are considered by many to be the best add-on treatment for resistant hypertension and do lower blood pressure.

“But they have major problems,” Dr. Oparil added. “Spironolactone, for example, causes hyperkalemia in many patients and adverse effects such as gynecomastia, erectile dysfunction, and feminization.”

Baxdrostat was well tolerated with no serious adverse events deemed related to treatment, Dr. Freeman reported. A total of 18 serious adverse events occurred in 10 patients, 6 of which were in a patient with urosepsis.

Ten adverse events of special interest occurred in eight patients, including one case of hypotension, three cases of hyponatremia, and six cases of hyperkalemia.

Potassium levels ranged from 6.0 to 6.3 mmol/L (6.0-6.3 mEq/L) in three patients and between 5.5 and 5.9 mmol/L (5.5-5.9 mEq/L) on at least two consecutive occasions in three others. Four of the patients were able to resume baxdrostat and complete the trial, whereas two patients discontinued treatment, one of whom was the patient with urosepsis.

Dr. Freeman pointed out that the study population was relatively diverse, with 33%-48% of participants of Hispanic or Latinx ethnicity and 23%-32% being Black.

At baseline, all patients had a seated blood pressure of at least 130/80 mm Hg (average 147.8/87.9 mm Hg) on a background therapy that included a diuretic in 100%, an agent targeting the renin-angiotensin-aldosterone system in 91%-96%, a beta-blocker in 52%-68%, and a calcium channel blocker in 64%-70%.

The study was not designed to test the benefits and risks of aldosterone synthase inhibition beyond 12 weeks and baxdrostat was not compared to alternative antihypertensives, he said. Additional limitations are that medication adherence was based on pill counts rather than drug analysis and enrolling only patients with an estimated glomerular filtration rate over 45 mL/min per 1.73m² reduced the likelihood of hyperkalemia and other adverse events.

Nevertheless, “we think that these data suggest that baxdrostat has the potential to treat disorders associated with aldosterone excess, including hypertension and primary hyperaldosteronism,” Dr. Freeman said.

The intention is to carry the drug forward into additional phase 2 studies in chronic kidney disease and to begin a phase 3 study in hypertension in 2023, he noted.

The study was funded by CinCor Pharma. Dr. Freeman and three coauthors are employees of CinCor and receive stock-based compensation. The remaining authors have a financial relationship with CinRx Pharma, which has an equity stake in CinCor. Dr. Oparil reports grant/research support from Bayer, Higi, and Novartis; and serving on the scientific advisory board/expert committee for CinCor Pharma and Preventric Diagnostics.

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

Study 1 Overview (STICHES Investigators)

Objective: To assess the survival benefit of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, compared to optimal medical therapy (OMT) alone, in patients with coronary artery disease, heart failure, and severe left ventricular dysfunction. Design: Multicenter, randomized, prospective study with extended follow-up (median duration of 9.8 years).

Setting and participants: A total of 1212 patients with left ventricular ejection fraction (LVEF) of 35% or less and coronary artery disease were randomized to medical therapy plus CABG or OMT alone at 127 clinical sites in 26 countries.

Main outcome measures: The primary endpoint was death from any cause. Main secondary endpoints were death from cardiovascular causes and a composite outcome of death from any cause or hospitalization for cardiovascular causes.

Main results: There were 359 primary outcome all-cause deaths (58.9%) in the CABG group and 398 (66.1%) in the medical therapy group (hazard ratio [HR], 0.84; 95% CI, 0.73-0.97; P = .02). Death from cardiovascular causes was reported in 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical therapy group (HR, 0.79; 95% CI, 0.66-0.93; P < .01). The composite outcome of death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and 467 patients (87.0%) in the medical therapy group (HR, 0.72; 95% CI, 0.64-0.82; P < .01).

Conclusion: Over a median follow-up of 9.8 years in patients with ischemic cardiomyopathy with severely reduced ejection fraction, the rates of death from any cause, death from cardiovascular causes, and the composite of death from any cause or hospitalization for cardiovascular causes were significantly lower in patients undergoing CABG than in patients receiving medical therapy alone.

Study 2 Overview (REVIVED BCIS Trial Group)

Objective: To assess whether percutaneous coronary intervention (PCI) can improve survival and left ventricular function in patients with severe left ventricular systolic dysfunction as compared to OMT alone.

Design: Multicenter, randomized, prospective study.

Setting and participants: A total of 700 patients with LVEF <35% with severe coronary artery disease amendable to PCI and demonstrable myocardial viability were randomly assigned to either PCI plus optimal medical therapy (PCI group) or OMT alone (OMT group).

Main outcome measures: The primary outcome was death from any cause or hospitalization for heart failure. The main secondary outcomes were LVEF at 6 and 12 months and quality of life (QOL) scores.

Main results: Over a median follow-up of 41 months, the primary outcome was reported in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the OMT group (HR, 0.99; 95% CI, 0.78-1.27; P = .96). The LVEF was similar in the 2 groups at 6 months (mean difference, –1.6 percentage points; 95% CI, –3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, –1.7 to 3.4). QOL scores at 6 and 12 months favored the PCI group, but the difference had diminished at 24 months.

Conclusion: In patients with severe ischemic cardiomyopathy, revascularization by PCI in addition to OMT did not result in a lower incidence of death from any cause or hospitalization from heart failure.

Commentary

Coronary artery disease is the most common cause of heart failure with reduced ejection fraction and an important cause of mortality.¹ Patients with ischemic cardiomyopathy with reduced ejection fraction are often considered for revascularization in addition to OMT and device therapies. Although there have been multiple retrospective studies and registries suggesting that cardiac outcomes and LVEF improve with revascularization, the number of large-scale prospective studies that assessed this clinical question and randomized patients to revascularization plus OMT compared to OMT alone has been limited.

In the Surgical Treatment for Ischemic Heart Failure (STICH) study,^2,3 eligible patients had coronary artery disease amendable to CABG and a LVEF of 35% or less. Patients (N = 1212) were randomly assigned to CABG plus OMT or OMT alone between July 2002 and May 2007. The original study, with a median follow-up of 5 years, did not show survival benefit, but the investigators reported that the primary outcome of death from any cause was significantly lower in the CABG group compared to OMT alone when follow-up of the same study population was extended to 9.8 years (58.9% vs 66.1%, P = .02). The findings from this study led to a class I guideline recommendation of CABG over medical therapy in patients with multivessel disease and low ejection fraction.⁴

Since the STICH trial was designed, there have been significant improvements in devices and techniques used for PCI, and the procedure is now widely performed in patients with multivessel disease.⁵ The advantages of PCI over CABG include shorter recovery times and lower risk of immediate complications. In this context, the recently reported Revascularization for Ischemic Ventricular Dysfunction (REVIVED) study assessed clinical outcomes in patients with severe coronary artery disease and reduced ejection fraction by randomizing patients to either PCI with OMT or OMT alone.⁶ At a median follow-up of 3.5 years, the investigators found no difference in the primary outcome of death from any cause or hospitalization for heart failure (37.2% vs 38.0%; 95% CI, 0.78-1.28; P = .96). Moreover, the degree of LVEF improvement, assessed by follow-up echocardiogram read by the core lab, showed no difference in the degree of LVEF improvement between groups at 6 and 12 months. Finally, although results of the QOL assessment using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated, patient-reported, heart-failure-specific QOL scale, favored the PCI group at 6 and 12 months of follow-up, the difference had diminished at 24 months.

The main strength of the REVIVED study was that it targeted a patient population with severe coronary artery disease, including left main disease and severely reduced ejection fraction, that historically have been excluded from large-scale randomized controlled studies evaluating PCI with OMT compared to OMT alone.⁷ However, there are several points to consider when interpreting the results of this study. First, further details of the PCI procedures are necessary. The REVIVED study recommended revascularization of all territories with viable myocardium; the anatomical revascularization index utilizing the British Cardiovascular Intervention Society (BCIS) Jeopardy Score was 71%. It is important to note that this jeopardy score was operator-reported and the core-lab adjudicated anatomical revascularization rate may be lower. Although viability testing primarily utilizing cardiac magnetic resonance imaging was performed in most patients, correlation between the revascularization territory and the viable segments has yet to be reported. Moreover, procedural details such as use of intravascular ultrasound and physiological testing, known to improve clinical outcome, need to be reported.^8,9

Second, there is a high prevalence of ischemic cardiomyopathy, and it is important to note that the patients included in this study were highly selected from daily clinical practice, as evidenced by the prolonged enrollment period (8 years). Individuals were largely stable patients with less complex coronary anatomy as evidenced by the median interval from angiography to randomization of 80 days. Taking into consideration the degree of left ventricular dysfunction for patients included in the trial, only 14% of the patients had left main disease and half of the patients only had 2-vessel disease. The severity of the left main disease also needs to be clarified as it is likely that patients the operator determined to be critical were not enrolled in the study. Furthermore, the standard of care based on the STICH trial is to refer patients with severe multivessel coronary artery disease to CABG, making it more likely that patients with more severe and complex disease were not included in this trial. It is also important to note that this study enrolled patients with stable ischemic heart disease, and the data do not apply to patients presenting with acute coronary syndrome.

Third, although the primary outcome was similar between the groups, the secondary outcome of unplanned revascularization was lower in the PCI group. In addition, the rate of acute myocardial infarction (MI) was similar between the 2 groups, but the rate of spontaneous MI was lower in the PCI group compared to the OMT group (5.2% vs 9.3%) as 40% of MI cases in the PCI group were periprocedural MIs. The correlation between periprocedural MI and long-term outcomes has been modest compared to spontaneous MI. Moreover, with the longer follow-up, the number of spontaneous MI cases is expected to rise while the number of periprocedural MI cases is not. Extending the follow-up period is also important, as the STICH extension trial showed a statistically significant difference at 10-year follow up despite negative results at the time of the original publication.

Fourth, the REVIVED trial randomized a significantly lower number of patients compared to the STICH trial, and the authors reported fewer primary-outcome events than the estimated number needed to achieve the power to assess the primary hypothesis. In addition, significant improvements in medical treatment for heart failure with reduced ejection fraction since the STICH trial make comparison of PCI vs CABG in this patient population unfeasible.

Finally, although severe angina was not an exclusion criterion, two-thirds of the patients enrolled had no angina, and only 2% of the patients had baseline severe angina. This is important to consider when interpreting the results of the patient-reported health status as previous studies have shown that patients with worse angina at baseline derive the largest improvement in their QOL,^10,11 and symptom improvement is the main indication for PCI in patients with stable ischemic heart disease.

Applications for Clinical Practice and System Implementation

In patients with severe left ventricular systolic dysfunction and multivessel stable ischemic heart disease who are well compensated and have little or no angina at baseline, OMT alone as an initial strategy may be considered against the addition of PCI after careful risk and benefit discussion. Further details about revascularization and extended follow-up data from the REVIVED trial are necessary.

Practice Points

• Patients with ischemic cardiomyopathy with reduced ejection fraction have been an understudied population in previous studies.
• Further studies are necessary to understand the benefits of revascularization and the role of viability testing in this population.

– Taishi Hirai MD, and Ziad Sayed Ahmad, MD
University of Missouri, Columbia, MO

Study 1 Overview (STICHES Investigators)

Objective: To assess the survival benefit of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, compared to optimal medical therapy (OMT) alone, in patients with coronary artery disease, heart failure, and severe left ventricular dysfunction. Design: Multicenter, randomized, prospective study with extended follow-up (median duration of 9.8 years).

Setting and participants: A total of 1212 patients with left ventricular ejection fraction (LVEF) of 35% or less and coronary artery disease were randomized to medical therapy plus CABG or OMT alone at 127 clinical sites in 26 countries.

Main outcome measures: The primary endpoint was death from any cause. Main secondary endpoints were death from cardiovascular causes and a composite outcome of death from any cause or hospitalization for cardiovascular causes.

Main results: There were 359 primary outcome all-cause deaths (58.9%) in the CABG group and 398 (66.1%) in the medical therapy group (hazard ratio [HR], 0.84; 95% CI, 0.73-0.97; P = .02). Death from cardiovascular causes was reported in 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical therapy group (HR, 0.79; 95% CI, 0.66-0.93; P < .01). The composite outcome of death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and 467 patients (87.0%) in the medical therapy group (HR, 0.72; 95% CI, 0.64-0.82; P < .01).

Conclusion: Over a median follow-up of 9.8 years in patients with ischemic cardiomyopathy with severely reduced ejection fraction, the rates of death from any cause, death from cardiovascular causes, and the composite of death from any cause or hospitalization for cardiovascular causes were significantly lower in patients undergoing CABG than in patients receiving medical therapy alone.

Study 2 Overview (REVIVED BCIS Trial Group)

Objective: To assess whether percutaneous coronary intervention (PCI) can improve survival and left ventricular function in patients with severe left ventricular systolic dysfunction as compared to OMT alone.

Design: Multicenter, randomized, prospective study.

Setting and participants: A total of 700 patients with LVEF <35% with severe coronary artery disease amendable to PCI and demonstrable myocardial viability were randomly assigned to either PCI plus optimal medical therapy (PCI group) or OMT alone (OMT group).

Main outcome measures: The primary outcome was death from any cause or hospitalization for heart failure. The main secondary outcomes were LVEF at 6 and 12 months and quality of life (QOL) scores.

Main results: Over a median follow-up of 41 months, the primary outcome was reported in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the OMT group (HR, 0.99; 95% CI, 0.78-1.27; P = .96). The LVEF was similar in the 2 groups at 6 months (mean difference, –1.6 percentage points; 95% CI, –3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, –1.7 to 3.4). QOL scores at 6 and 12 months favored the PCI group, but the difference had diminished at 24 months.

Conclusion: In patients with severe ischemic cardiomyopathy, revascularization by PCI in addition to OMT did not result in a lower incidence of death from any cause or hospitalization from heart failure.

Commentary

Coronary artery disease is the most common cause of heart failure with reduced ejection fraction and an important cause of mortality.¹ Patients with ischemic cardiomyopathy with reduced ejection fraction are often considered for revascularization in addition to OMT and device therapies. Although there have been multiple retrospective studies and registries suggesting that cardiac outcomes and LVEF improve with revascularization, the number of large-scale prospective studies that assessed this clinical question and randomized patients to revascularization plus OMT compared to OMT alone has been limited.

In the Surgical Treatment for Ischemic Heart Failure (STICH) study,^2,3 eligible patients had coronary artery disease amendable to CABG and a LVEF of 35% or less. Patients (N = 1212) were randomly assigned to CABG plus OMT or OMT alone between July 2002 and May 2007. The original study, with a median follow-up of 5 years, did not show survival benefit, but the investigators reported that the primary outcome of death from any cause was significantly lower in the CABG group compared to OMT alone when follow-up of the same study population was extended to 9.8 years (58.9% vs 66.1%, P = .02). The findings from this study led to a class I guideline recommendation of CABG over medical therapy in patients with multivessel disease and low ejection fraction.⁴

Since the STICH trial was designed, there have been significant improvements in devices and techniques used for PCI, and the procedure is now widely performed in patients with multivessel disease.⁵ The advantages of PCI over CABG include shorter recovery times and lower risk of immediate complications. In this context, the recently reported Revascularization for Ischemic Ventricular Dysfunction (REVIVED) study assessed clinical outcomes in patients with severe coronary artery disease and reduced ejection fraction by randomizing patients to either PCI with OMT or OMT alone.⁶ At a median follow-up of 3.5 years, the investigators found no difference in the primary outcome of death from any cause or hospitalization for heart failure (37.2% vs 38.0%; 95% CI, 0.78-1.28; P = .96). Moreover, the degree of LVEF improvement, assessed by follow-up echocardiogram read by the core lab, showed no difference in the degree of LVEF improvement between groups at 6 and 12 months. Finally, although results of the QOL assessment using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated, patient-reported, heart-failure-specific QOL scale, favored the PCI group at 6 and 12 months of follow-up, the difference had diminished at 24 months.

The main strength of the REVIVED study was that it targeted a patient population with severe coronary artery disease, including left main disease and severely reduced ejection fraction, that historically have been excluded from large-scale randomized controlled studies evaluating PCI with OMT compared to OMT alone.⁷ However, there are several points to consider when interpreting the results of this study. First, further details of the PCI procedures are necessary. The REVIVED study recommended revascularization of all territories with viable myocardium; the anatomical revascularization index utilizing the British Cardiovascular Intervention Society (BCIS) Jeopardy Score was 71%. It is important to note that this jeopardy score was operator-reported and the core-lab adjudicated anatomical revascularization rate may be lower. Although viability testing primarily utilizing cardiac magnetic resonance imaging was performed in most patients, correlation between the revascularization territory and the viable segments has yet to be reported. Moreover, procedural details such as use of intravascular ultrasound and physiological testing, known to improve clinical outcome, need to be reported.^8,9

Second, there is a high prevalence of ischemic cardiomyopathy, and it is important to note that the patients included in this study were highly selected from daily clinical practice, as evidenced by the prolonged enrollment period (8 years). Individuals were largely stable patients with less complex coronary anatomy as evidenced by the median interval from angiography to randomization of 80 days. Taking into consideration the degree of left ventricular dysfunction for patients included in the trial, only 14% of the patients had left main disease and half of the patients only had 2-vessel disease. The severity of the left main disease also needs to be clarified as it is likely that patients the operator determined to be critical were not enrolled in the study. Furthermore, the standard of care based on the STICH trial is to refer patients with severe multivessel coronary artery disease to CABG, making it more likely that patients with more severe and complex disease were not included in this trial. It is also important to note that this study enrolled patients with stable ischemic heart disease, and the data do not apply to patients presenting with acute coronary syndrome.

Third, although the primary outcome was similar between the groups, the secondary outcome of unplanned revascularization was lower in the PCI group. In addition, the rate of acute myocardial infarction (MI) was similar between the 2 groups, but the rate of spontaneous MI was lower in the PCI group compared to the OMT group (5.2% vs 9.3%) as 40% of MI cases in the PCI group were periprocedural MIs. The correlation between periprocedural MI and long-term outcomes has been modest compared to spontaneous MI. Moreover, with the longer follow-up, the number of spontaneous MI cases is expected to rise while the number of periprocedural MI cases is not. Extending the follow-up period is also important, as the STICH extension trial showed a statistically significant difference at 10-year follow up despite negative results at the time of the original publication.

Fourth, the REVIVED trial randomized a significantly lower number of patients compared to the STICH trial, and the authors reported fewer primary-outcome events than the estimated number needed to achieve the power to assess the primary hypothesis. In addition, significant improvements in medical treatment for heart failure with reduced ejection fraction since the STICH trial make comparison of PCI vs CABG in this patient population unfeasible.

Finally, although severe angina was not an exclusion criterion, two-thirds of the patients enrolled had no angina, and only 2% of the patients had baseline severe angina. This is important to consider when interpreting the results of the patient-reported health status as previous studies have shown that patients with worse angina at baseline derive the largest improvement in their QOL,^10,11 and symptom improvement is the main indication for PCI in patients with stable ischemic heart disease.

Applications for Clinical Practice and System Implementation

In patients with severe left ventricular systolic dysfunction and multivessel stable ischemic heart disease who are well compensated and have little or no angina at baseline, OMT alone as an initial strategy may be considered against the addition of PCI after careful risk and benefit discussion. Further details about revascularization and extended follow-up data from the REVIVED trial are necessary.

Practice Points

• Patients with ischemic cardiomyopathy with reduced ejection fraction have been an understudied population in previous studies.
• Further studies are necessary to understand the benefits of revascularization and the role of viability testing in this population.

– Taishi Hirai MD, and Ziad Sayed Ahmad, MD
University of Missouri, Columbia, MO

Study 1 Overview (STICHES Investigators)

Objective: To assess the survival benefit of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, compared to optimal medical therapy (OMT) alone, in patients with coronary artery disease, heart failure, and severe left ventricular dysfunction. Design: Multicenter, randomized, prospective study with extended follow-up (median duration of 9.8 years).

Setting and participants: A total of 1212 patients with left ventricular ejection fraction (LVEF) of 35% or less and coronary artery disease were randomized to medical therapy plus CABG or OMT alone at 127 clinical sites in 26 countries.

Main outcome measures: The primary endpoint was death from any cause. Main secondary endpoints were death from cardiovascular causes and a composite outcome of death from any cause or hospitalization for cardiovascular causes.

Main results: There were 359 primary outcome all-cause deaths (58.9%) in the CABG group and 398 (66.1%) in the medical therapy group (hazard ratio [HR], 0.84; 95% CI, 0.73-0.97; P = .02). Death from cardiovascular causes was reported in 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical therapy group (HR, 0.79; 95% CI, 0.66-0.93; P < .01). The composite outcome of death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and 467 patients (87.0%) in the medical therapy group (HR, 0.72; 95% CI, 0.64-0.82; P < .01).

Conclusion: Over a median follow-up of 9.8 years in patients with ischemic cardiomyopathy with severely reduced ejection fraction, the rates of death from any cause, death from cardiovascular causes, and the composite of death from any cause or hospitalization for cardiovascular causes were significantly lower in patients undergoing CABG than in patients receiving medical therapy alone.

Study 2 Overview (REVIVED BCIS Trial Group)

Objective: To assess whether percutaneous coronary intervention (PCI) can improve survival and left ventricular function in patients with severe left ventricular systolic dysfunction as compared to OMT alone.

Design: Multicenter, randomized, prospective study.

Setting and participants: A total of 700 patients with LVEF <35% with severe coronary artery disease amendable to PCI and demonstrable myocardial viability were randomly assigned to either PCI plus optimal medical therapy (PCI group) or OMT alone (OMT group).

Main outcome measures: The primary outcome was death from any cause or hospitalization for heart failure. The main secondary outcomes were LVEF at 6 and 12 months and quality of life (QOL) scores.

Main results: Over a median follow-up of 41 months, the primary outcome was reported in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the OMT group (HR, 0.99; 95% CI, 0.78-1.27; P = .96). The LVEF was similar in the 2 groups at 6 months (mean difference, –1.6 percentage points; 95% CI, –3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, –1.7 to 3.4). QOL scores at 6 and 12 months favored the PCI group, but the difference had diminished at 24 months.

Conclusion: In patients with severe ischemic cardiomyopathy, revascularization by PCI in addition to OMT did not result in a lower incidence of death from any cause or hospitalization from heart failure.

Commentary

Coronary artery disease is the most common cause of heart failure with reduced ejection fraction and an important cause of mortality.¹ Patients with ischemic cardiomyopathy with reduced ejection fraction are often considered for revascularization in addition to OMT and device therapies. Although there have been multiple retrospective studies and registries suggesting that cardiac outcomes and LVEF improve with revascularization, the number of large-scale prospective studies that assessed this clinical question and randomized patients to revascularization plus OMT compared to OMT alone has been limited.

In the Surgical Treatment for Ischemic Heart Failure (STICH) study,^2,3 eligible patients had coronary artery disease amendable to CABG and a LVEF of 35% or less. Patients (N = 1212) were randomly assigned to CABG plus OMT or OMT alone between July 2002 and May 2007. The original study, with a median follow-up of 5 years, did not show survival benefit, but the investigators reported that the primary outcome of death from any cause was significantly lower in the CABG group compared to OMT alone when follow-up of the same study population was extended to 9.8 years (58.9% vs 66.1%, P = .02). The findings from this study led to a class I guideline recommendation of CABG over medical therapy in patients with multivessel disease and low ejection fraction.⁴

Since the STICH trial was designed, there have been significant improvements in devices and techniques used for PCI, and the procedure is now widely performed in patients with multivessel disease.⁵ The advantages of PCI over CABG include shorter recovery times and lower risk of immediate complications. In this context, the recently reported Revascularization for Ischemic Ventricular Dysfunction (REVIVED) study assessed clinical outcomes in patients with severe coronary artery disease and reduced ejection fraction by randomizing patients to either PCI with OMT or OMT alone.⁶ At a median follow-up of 3.5 years, the investigators found no difference in the primary outcome of death from any cause or hospitalization for heart failure (37.2% vs 38.0%; 95% CI, 0.78-1.28; P = .96). Moreover, the degree of LVEF improvement, assessed by follow-up echocardiogram read by the core lab, showed no difference in the degree of LVEF improvement between groups at 6 and 12 months. Finally, although results of the QOL assessment using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated, patient-reported, heart-failure-specific QOL scale, favored the PCI group at 6 and 12 months of follow-up, the difference had diminished at 24 months.

The main strength of the REVIVED study was that it targeted a patient population with severe coronary artery disease, including left main disease and severely reduced ejection fraction, that historically have been excluded from large-scale randomized controlled studies evaluating PCI with OMT compared to OMT alone.⁷ However, there are several points to consider when interpreting the results of this study. First, further details of the PCI procedures are necessary. The REVIVED study recommended revascularization of all territories with viable myocardium; the anatomical revascularization index utilizing the British Cardiovascular Intervention Society (BCIS) Jeopardy Score was 71%. It is important to note that this jeopardy score was operator-reported and the core-lab adjudicated anatomical revascularization rate may be lower. Although viability testing primarily utilizing cardiac magnetic resonance imaging was performed in most patients, correlation between the revascularization territory and the viable segments has yet to be reported. Moreover, procedural details such as use of intravascular ultrasound and physiological testing, known to improve clinical outcome, need to be reported.^8,9

Second, there is a high prevalence of ischemic cardiomyopathy, and it is important to note that the patients included in this study were highly selected from daily clinical practice, as evidenced by the prolonged enrollment period (8 years). Individuals were largely stable patients with less complex coronary anatomy as evidenced by the median interval from angiography to randomization of 80 days. Taking into consideration the degree of left ventricular dysfunction for patients included in the trial, only 14% of the patients had left main disease and half of the patients only had 2-vessel disease. The severity of the left main disease also needs to be clarified as it is likely that patients the operator determined to be critical were not enrolled in the study. Furthermore, the standard of care based on the STICH trial is to refer patients with severe multivessel coronary artery disease to CABG, making it more likely that patients with more severe and complex disease were not included in this trial. It is also important to note that this study enrolled patients with stable ischemic heart disease, and the data do not apply to patients presenting with acute coronary syndrome.

Third, although the primary outcome was similar between the groups, the secondary outcome of unplanned revascularization was lower in the PCI group. In addition, the rate of acute myocardial infarction (MI) was similar between the 2 groups, but the rate of spontaneous MI was lower in the PCI group compared to the OMT group (5.2% vs 9.3%) as 40% of MI cases in the PCI group were periprocedural MIs. The correlation between periprocedural MI and long-term outcomes has been modest compared to spontaneous MI. Moreover, with the longer follow-up, the number of spontaneous MI cases is expected to rise while the number of periprocedural MI cases is not. Extending the follow-up period is also important, as the STICH extension trial showed a statistically significant difference at 10-year follow up despite negative results at the time of the original publication.

Fourth, the REVIVED trial randomized a significantly lower number of patients compared to the STICH trial, and the authors reported fewer primary-outcome events than the estimated number needed to achieve the power to assess the primary hypothesis. In addition, significant improvements in medical treatment for heart failure with reduced ejection fraction since the STICH trial make comparison of PCI vs CABG in this patient population unfeasible.

Finally, although severe angina was not an exclusion criterion, two-thirds of the patients enrolled had no angina, and only 2% of the patients had baseline severe angina. This is important to consider when interpreting the results of the patient-reported health status as previous studies have shown that patients with worse angina at baseline derive the largest improvement in their QOL,^10,11 and symptom improvement is the main indication for PCI in patients with stable ischemic heart disease.

Applications for Clinical Practice and System Implementation

In patients with severe left ventricular systolic dysfunction and multivessel stable ischemic heart disease who are well compensated and have little or no angina at baseline, OMT alone as an initial strategy may be considered against the addition of PCI after careful risk and benefit discussion. Further details about revascularization and extended follow-up data from the REVIVED trial are necessary.

Practice Points

• Patients with ischemic cardiomyopathy with reduced ejection fraction have been an understudied population in previous studies.
• Further studies are necessary to understand the benefits of revascularization and the role of viability testing in this population.

– Taishi Hirai MD, and Ziad Sayed Ahmad, MD
University of Missouri, Columbia, MO

Emergencies happen anywhere, anytime – and sometimes physicians find themselves in situations where they are the only ones who can help. “Is There a Doctor in the House?” is a new series telling these stories.

When the plane crashed, I was asleep. I had arrived the evening before with my wife and three sons at a house on Kezar Lake on the Maine–New Hampshire border. We were going to spend a week there with my wife’s four brothers and their families. I was woken by people screaming my name. I jumped out of bed and ran downstairs. My kids had been watching a float plane circling and gliding along the lake. It had crashed into the water and flipped upside down. My oldest brother-in-law jumped into his ski boat and we sped out to the scene.

All we can see are the plane’s pontoons. The rest is underwater. A woman has already surfaced, screaming. I dive in.

I find the woman’s husband and 3-year-old son struggling to get free from the plane through the smashed windshield. They manage to get to the surface. The pilot is dead, impaled through the chest by the left wing strut.

The big problem: A little girl, whom I would learn later is named Lauren, remained trapped. The water is murky but I can see her, a 5- or 6-year-old girl with this long hair, strapped in upside down and unconscious.

The mom and I dive down over and over, pulling and ripping at the door. We cannot get it open. Finally, I’m able to bend the door open enough where I can reach in, but I can’t undo the seatbelt. In my mind, I’m debating, should I try and go through the front windshield? I’m getting really tired, I can tell there’s fuel in the water, and I don’t want to drown in the plane. So I pop up to the surface and yell, “Does anyone have a knife?”

My brother-in-law shoots back to shore in the boat, screaming, “Get a knife!” My niece gets in the boat with one. I’m standing on the pontoon, and my niece is in the front of the boat calling, “Uncle Todd! Uncle Todd!” and she throws the knife. It goes way over my head. I can’t even jump for it, it’s so high.

I have to get the knife. So, I dive into the water to try and find it. Somehow, the black knife has landed on the white wing, 4 or 5 feet under the water. Pure luck. It could have sunk down a hundred feet into the lake. I grab the knife and hand it to the mom, Beth. She’s able to cut the seatbelt, and we both pull Lauren to the surface.

I lay her out on the pontoon. She has no pulse and her pupils are fixed and dilated. Her mom is yelling, “She’s dead, isn’t she?” I start CPR. My skin and eyes are burning from the airplane fuel in the water. I get her breathing, and her heart comes back very quickly. Lauren starts to vomit and I’m trying to keep her airway clear. She’s breathing spontaneously and she has a pulse, so I decide it’s time to move her to shore.

We pull the boat up to the dock and Lauren’s now having anoxic seizures. Her brain has been without oxygen, and now she’s getting perfused again. We get her to shore and lay her on the lawn. I’m still doing mouth-to-mouth, but she’s seizing like crazy, and I don’t have any way to control that. Beth is crying and wants to hold her daughter gently while I’m working.

Someone had called 911, and finally this dude shows up with an ambulance, and it’s like something out of World War II. All he has is an oxygen tank, but the mask is old and cracked. It’s too big for Lauren, but it sort of fits me, so I’m sucking in oxygen and blowing it into the girl’s mouth. I’m doing whatever I can, but I don’t have an IV to start. I have no fluids. I got nothing.

As it happens, I’d done my emergency medicine training at Maine Medical Center, so I tell someone to call them and get a Life Flight chopper. We have to drive somewhere where the chopper can land, so we take the ambulance to the parking lot of the closest store called the Wicked Good Store. That’s a common thing in Maine. Everything is “wicked good.”

The whole town is there by that point. The chopper arrives. The ambulance doors pop open and a woman says, “Todd?” And I say, “Heather?”

Heather is an emergency flight nurse whom I’d trained with many years ago. There’s immediate trust. She has all the right equipment. We put in breathing tubes and IVs. We stop Lauren from seizing. The kid is soon stable.

There is only one extra seat in the chopper, so I tell Beth to go. They take off.

Suddenly, I begin to doubt my decision. Lauren had been underwater for 15 minutes at minimum. I know how long that is. Did I do the right thing? Did I resuscitate a brain-dead child? I didn’t think about it at the time, but if that patient had come to me in the emergency department, I’m honestly not sure what I would have done.

So, I go home. And I don’t get a call. The FAA and sheriff arrive to take statements from us. I don’t hear from anyone.

The next day I start calling. No one will tell me anything, so I finally get to one of the pediatric ICU attendings who had trained me. He says Lauren literally woke up and said, “I have to go pee.” And that was it. She was 100% normal. I couldn’t believe it.

Here’s a theory: In kids, there’s something called the glottic reflex. I think her glottic reflex went off as soon as she hit the water, which basically closed her airway. So when she passed out, she could never get enough water in her lungs and still had enough air in there to keep her alive. Later, I got a call from her uncle. He could barely get the words out because he was in tears. He said Lauren was doing beautifully.  

Three days later, I drove to Lauren’s house with my wife and kids. I had her read to me. I watched her play on the jungle gym for motor function. All sorts of stuff. She was totally normal.

Beth told us that the night before the accident, her mother had given the women in her family what she called a “miracle bracelet,” a bracelet that is supposed to give you one miracle in your life. Beth said she had the bracelet on her wrist the day of the accident, and now it’s gone. “Saving Lauren’s life was my miracle,” she said.

Funny thing: For 20 years, I ran all the EMS, police, fire, ambulance, in Boulder, Colo., where I live. I wrote all the protocols, and I would never advise any of my paramedics to dive into jet fuel to save someone. That was risky. But at the time, it was totally automatic. I think it taught me not to give up in certain situations, because you really don’t know.

Dr. Dorfman is an emergency medicine physician in Boulder, Colo., and medical director at Cedalion Health.
 

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

Emergencies happen anywhere, anytime – and sometimes physicians find themselves in situations where they are the only ones who can help. “Is There a Doctor in the House?” is a new series telling these stories.

When the plane crashed, I was asleep. I had arrived the evening before with my wife and three sons at a house on Kezar Lake on the Maine–New Hampshire border. We were going to spend a week there with my wife’s four brothers and their families. I was woken by people screaming my name. I jumped out of bed and ran downstairs. My kids had been watching a float plane circling and gliding along the lake. It had crashed into the water and flipped upside down. My oldest brother-in-law jumped into his ski boat and we sped out to the scene.

All we can see are the plane’s pontoons. The rest is underwater. A woman has already surfaced, screaming. I dive in.

I find the woman’s husband and 3-year-old son struggling to get free from the plane through the smashed windshield. They manage to get to the surface. The pilot is dead, impaled through the chest by the left wing strut.

The big problem: A little girl, whom I would learn later is named Lauren, remained trapped. The water is murky but I can see her, a 5- or 6-year-old girl with this long hair, strapped in upside down and unconscious.

The mom and I dive down over and over, pulling and ripping at the door. We cannot get it open. Finally, I’m able to bend the door open enough where I can reach in, but I can’t undo the seatbelt. In my mind, I’m debating, should I try and go through the front windshield? I’m getting really tired, I can tell there’s fuel in the water, and I don’t want to drown in the plane. So I pop up to the surface and yell, “Does anyone have a knife?”

My brother-in-law shoots back to shore in the boat, screaming, “Get a knife!” My niece gets in the boat with one. I’m standing on the pontoon, and my niece is in the front of the boat calling, “Uncle Todd! Uncle Todd!” and she throws the knife. It goes way over my head. I can’t even jump for it, it’s so high.

I have to get the knife. So, I dive into the water to try and find it. Somehow, the black knife has landed on the white wing, 4 or 5 feet under the water. Pure luck. It could have sunk down a hundred feet into the lake. I grab the knife and hand it to the mom, Beth. She’s able to cut the seatbelt, and we both pull Lauren to the surface.

I lay her out on the pontoon. She has no pulse and her pupils are fixed and dilated. Her mom is yelling, “She’s dead, isn’t she?” I start CPR. My skin and eyes are burning from the airplane fuel in the water. I get her breathing, and her heart comes back very quickly. Lauren starts to vomit and I’m trying to keep her airway clear. She’s breathing spontaneously and she has a pulse, so I decide it’s time to move her to shore.

We pull the boat up to the dock and Lauren’s now having anoxic seizures. Her brain has been without oxygen, and now she’s getting perfused again. We get her to shore and lay her on the lawn. I’m still doing mouth-to-mouth, but she’s seizing like crazy, and I don’t have any way to control that. Beth is crying and wants to hold her daughter gently while I’m working.

Someone had called 911, and finally this dude shows up with an ambulance, and it’s like something out of World War II. All he has is an oxygen tank, but the mask is old and cracked. It’s too big for Lauren, but it sort of fits me, so I’m sucking in oxygen and blowing it into the girl’s mouth. I’m doing whatever I can, but I don’t have an IV to start. I have no fluids. I got nothing.

As it happens, I’d done my emergency medicine training at Maine Medical Center, so I tell someone to call them and get a Life Flight chopper. We have to drive somewhere where the chopper can land, so we take the ambulance to the parking lot of the closest store called the Wicked Good Store. That’s a common thing in Maine. Everything is “wicked good.”

The whole town is there by that point. The chopper arrives. The ambulance doors pop open and a woman says, “Todd?” And I say, “Heather?”

Heather is an emergency flight nurse whom I’d trained with many years ago. There’s immediate trust. She has all the right equipment. We put in breathing tubes and IVs. We stop Lauren from seizing. The kid is soon stable.

There is only one extra seat in the chopper, so I tell Beth to go. They take off.

Suddenly, I begin to doubt my decision. Lauren had been underwater for 15 minutes at minimum. I know how long that is. Did I do the right thing? Did I resuscitate a brain-dead child? I didn’t think about it at the time, but if that patient had come to me in the emergency department, I’m honestly not sure what I would have done.

So, I go home. And I don’t get a call. The FAA and sheriff arrive to take statements from us. I don’t hear from anyone.

The next day I start calling. No one will tell me anything, so I finally get to one of the pediatric ICU attendings who had trained me. He says Lauren literally woke up and said, “I have to go pee.” And that was it. She was 100% normal. I couldn’t believe it.

Here’s a theory: In kids, there’s something called the glottic reflex. I think her glottic reflex went off as soon as she hit the water, which basically closed her airway. So when she passed out, she could never get enough water in her lungs and still had enough air in there to keep her alive. Later, I got a call from her uncle. He could barely get the words out because he was in tears. He said Lauren was doing beautifully.  

Three days later, I drove to Lauren’s house with my wife and kids. I had her read to me. I watched her play on the jungle gym for motor function. All sorts of stuff. She was totally normal.

Beth told us that the night before the accident, her mother had given the women in her family what she called a “miracle bracelet,” a bracelet that is supposed to give you one miracle in your life. Beth said she had the bracelet on her wrist the day of the accident, and now it’s gone. “Saving Lauren’s life was my miracle,” she said.

Funny thing: For 20 years, I ran all the EMS, police, fire, ambulance, in Boulder, Colo., where I live. I wrote all the protocols, and I would never advise any of my paramedics to dive into jet fuel to save someone. That was risky. But at the time, it was totally automatic. I think it taught me not to give up in certain situations, because you really don’t know.

Dr. Dorfman is an emergency medicine physician in Boulder, Colo., and medical director at Cedalion Health.
 

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

Emergencies happen anywhere, anytime – and sometimes physicians find themselves in situations where they are the only ones who can help. “Is There a Doctor in the House?” is a new series telling these stories.

When the plane crashed, I was asleep. I had arrived the evening before with my wife and three sons at a house on Kezar Lake on the Maine–New Hampshire border. We were going to spend a week there with my wife’s four brothers and their families. I was woken by people screaming my name. I jumped out of bed and ran downstairs. My kids had been watching a float plane circling and gliding along the lake. It had crashed into the water and flipped upside down. My oldest brother-in-law jumped into his ski boat and we sped out to the scene.

All we can see are the plane’s pontoons. The rest is underwater. A woman has already surfaced, screaming. I dive in.

I find the woman’s husband and 3-year-old son struggling to get free from the plane through the smashed windshield. They manage to get to the surface. The pilot is dead, impaled through the chest by the left wing strut.

The big problem: A little girl, whom I would learn later is named Lauren, remained trapped. The water is murky but I can see her, a 5- or 6-year-old girl with this long hair, strapped in upside down and unconscious.

The mom and I dive down over and over, pulling and ripping at the door. We cannot get it open. Finally, I’m able to bend the door open enough where I can reach in, but I can’t undo the seatbelt. In my mind, I’m debating, should I try and go through the front windshield? I’m getting really tired, I can tell there’s fuel in the water, and I don’t want to drown in the plane. So I pop up to the surface and yell, “Does anyone have a knife?”

My brother-in-law shoots back to shore in the boat, screaming, “Get a knife!” My niece gets in the boat with one. I’m standing on the pontoon, and my niece is in the front of the boat calling, “Uncle Todd! Uncle Todd!” and she throws the knife. It goes way over my head. I can’t even jump for it, it’s so high.

I have to get the knife. So, I dive into the water to try and find it. Somehow, the black knife has landed on the white wing, 4 or 5 feet under the water. Pure luck. It could have sunk down a hundred feet into the lake. I grab the knife and hand it to the mom, Beth. She’s able to cut the seatbelt, and we both pull Lauren to the surface.

I lay her out on the pontoon. She has no pulse and her pupils are fixed and dilated. Her mom is yelling, “She’s dead, isn’t she?” I start CPR. My skin and eyes are burning from the airplane fuel in the water. I get her breathing, and her heart comes back very quickly. Lauren starts to vomit and I’m trying to keep her airway clear. She’s breathing spontaneously and she has a pulse, so I decide it’s time to move her to shore.

We pull the boat up to the dock and Lauren’s now having anoxic seizures. Her brain has been without oxygen, and now she’s getting perfused again. We get her to shore and lay her on the lawn. I’m still doing mouth-to-mouth, but she’s seizing like crazy, and I don’t have any way to control that. Beth is crying and wants to hold her daughter gently while I’m working.

Someone had called 911, and finally this dude shows up with an ambulance, and it’s like something out of World War II. All he has is an oxygen tank, but the mask is old and cracked. It’s too big for Lauren, but it sort of fits me, so I’m sucking in oxygen and blowing it into the girl’s mouth. I’m doing whatever I can, but I don’t have an IV to start. I have no fluids. I got nothing.

As it happens, I’d done my emergency medicine training at Maine Medical Center, so I tell someone to call them and get a Life Flight chopper. We have to drive somewhere where the chopper can land, so we take the ambulance to the parking lot of the closest store called the Wicked Good Store. That’s a common thing in Maine. Everything is “wicked good.”

The whole town is there by that point. The chopper arrives. The ambulance doors pop open and a woman says, “Todd?” And I say, “Heather?”

Heather is an emergency flight nurse whom I’d trained with many years ago. There’s immediate trust. She has all the right equipment. We put in breathing tubes and IVs. We stop Lauren from seizing. The kid is soon stable.

There is only one extra seat in the chopper, so I tell Beth to go. They take off.

Suddenly, I begin to doubt my decision. Lauren had been underwater for 15 minutes at minimum. I know how long that is. Did I do the right thing? Did I resuscitate a brain-dead child? I didn’t think about it at the time, but if that patient had come to me in the emergency department, I’m honestly not sure what I would have done.

So, I go home. And I don’t get a call. The FAA and sheriff arrive to take statements from us. I don’t hear from anyone.

The next day I start calling. No one will tell me anything, so I finally get to one of the pediatric ICU attendings who had trained me. He says Lauren literally woke up and said, “I have to go pee.” And that was it. She was 100% normal. I couldn’t believe it.

Here’s a theory: In kids, there’s something called the glottic reflex. I think her glottic reflex went off as soon as she hit the water, which basically closed her airway. So when she passed out, she could never get enough water in her lungs and still had enough air in there to keep her alive. Later, I got a call from her uncle. He could barely get the words out because he was in tears. He said Lauren was doing beautifully.  

Three days later, I drove to Lauren’s house with my wife and kids. I had her read to me. I watched her play on the jungle gym for motor function. All sorts of stuff. She was totally normal.

Beth told us that the night before the accident, her mother had given the women in her family what she called a “miracle bracelet,” a bracelet that is supposed to give you one miracle in your life. Beth said she had the bracelet on her wrist the day of the accident, and now it’s gone. “Saving Lauren’s life was my miracle,” she said.

Funny thing: For 20 years, I ran all the EMS, police, fire, ambulance, in Boulder, Colo., where I live. I wrote all the protocols, and I would never advise any of my paramedics to dive into jet fuel to save someone. That was risky. But at the time, it was totally automatic. I think it taught me not to give up in certain situations, because you really don’t know.

Dr. Dorfman is an emergency medicine physician in Boulder, Colo., and medical director at Cedalion Health.
 

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

CHICAGO – Clinicians who prescribe heart failure meds are holding the best hand they’ve ever had, but with so much underuse and suboptimal dosing in actual practice, it seems many may not appreciate the value of their cards. But a major randomized trial that has captured the field’s attention may embolden them to go all in.

Results showed that a strategy of early, rapid up-titration of multiple guideline-directed meds in patients hospitalized with heart failure, compared with a usual-care approach, cut their 6-month risk for death or HF readmission by a steep 34% (P = .002).

The drugs had been started and partly up-titrated in the hospital with the goal of full up-titration within 2 weeks after discharge.

Patients well tolerated the high-intensity approach, researchers said. Their quality-of-life scores improved (P < .0001) compared with the usual-care group, and adverse events were considered few and manageable in the international trial with more than 1,000 patients.

Safety on the high-intensity strategy depended on close patient monitoring at frequently planned clinic visits along with guidance for the up-titrations from clinical signs and natriuretic peptide levels, observed Alexandre Mebazaa, MD, PhD, University of Paris and Public Hospitals of Paris.

Dr. Mebazaa is principal investigator on the trial, called STRONG-HF, which he presented at the American Heart Association scientific sessions, held in Chicago and virtually. He is also lead author on the study’s same-day publication in the Lancet.

The high-intensity strategy’s superiority emerged early in the trial, which was halted early on the data safety monitoring board’s recommendation, with about 90% of follow-ups completed. The board “felt it was unethical to keep patients in usual care,” Dr. Mebazaa said at a press conference.
 

A dramatic change

The next step, he said, will be to educate the heart failure community on the high-intensity care technique so it can swiftly enter clinical practice. Currently in acute heart failure, “very few patients are monitored after discharge and treated with full doses of heart failure therapies.”

Adoption of the strategy “would be a dramatic change from what’s currently being done,” said Martin B. Leon, MD, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, who moderated the press conference.

Only an estimated 5% of patients with HF in the United States receive full guideline-directed medical therapy, Dr. Leon said, “so the generalizability of this strategy, with careful follow-up that has safety involved in it, is absolutely crucial.”

But the potential impact of this high-intensity approach on resource use is unknown, raising questions about how widely and consistently it could be implemented, said Dr. Leon, who is not connected with STRONG-HF.

The trial called for in-hospital initiation of the three distinct drug classes that, at the time, were the core of guideline-directed HF therapy, with up-titration to 50% of recommended dosage by hospital discharge, and then to 100% within 2 weeks later.

The meds included a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system inhibitor (RASI). The latter could be an ACE inhibitor, angiotensin-receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI).
 

How about a fourth drug?

Conspicuously absent from the list, for contemporary practice, was an SGLT2 inhibitor, a class that entered the HF guidelines well after STRONG-HF was designed. They would undoubtedly join the other three agents were the high-intensity strategy to enter practice, potentially changing its complexity and safety profile.

But Dr. Mebazaa and other experts don’t see that as a big challenge and would expect a smooth transition to a high-intensity approach that also includes the SGLT2 inhibitors.

STRONG-HF was necessary in part because many clinicians have been “reluctant” to take full advantage of three agents that had been the basis of guideline-directed therapy, he told this news organization.

That reluctance stemmed from concerns that beta-blockers might worsen the heart failure, ACE inhibitors could hurt the kidneys, or MRAs might cause hyperkalemia, Dr. Mebazaa said. The STRONG-HF high-intensity regimen, therefore, demanded multiple clinic visits for close follow-up.

But the SGLT2 inhibitors “are known to be rather safe drugs, at least much safer than the three others,” he said. So, it seems unlikely that their addition to a beta-blocker, RASI, and MRA in patients with HF would worsen the risk of adverse events.

John G.F. Cleland, MD, PhD, agrees. With addition of the fourth agent, “You may need to be a little bit more careful with renal function, just in that first couple of weeks,” he told this news organization. “But I think it would be easy to add an SGLT2 inhibitor into this regimen. And in general, there’s no titration with an SGLT2 inhibitor, so they’ll all be on full dose predischarge.”

Given the drugs’ diuretic-like action, moreover, some patients might be able to pull back on their loop diuretics, speculated Dr. Cleland, from the University of Glasgow’s School of Health and Wellbeing.

The prospect of a high-intensity strategy’s wide implementation in practice presents both “challenges and opportunities,” Amanda R. Vest, MBBS, MPH, Tufts University, Boston, told this news organization.

“There may be additional challenges in terms of ensuring we avoid hypotension or acute kidney injury in the up-titration phase,” said Dr. Vest, who is medical director of her center’s cardiac transplantation program but not connected with STRONG-HF.

“But it also gives us opportunities,” she added, “because there are some patients, especially in that vulnerable postdischarge phase, who are actually much more able to tolerate introduction of an SGLT2 inhibitor than, for example, an ACE inhibitor, ARB, or ARNI – or maybe a beta-blocker if they’ve been in a low cardiac-output state.” Effective dosing would depend on “the personalization and skill of the clinician in optimizing the medications in their correct sequence,” Dr. Vest said.

“It’s challenging to think that we would ever get to 100% up-titration,” she added, “and even in this excellent study, they didn’t get to 100%.” But as clinicians gain experience with the high-intensity strategy, especially as the SGLT2 inhibitors are included, “I think we can reasonably expect more progress to be made in these up-titration skills.”
 

No restrictions on LVEF

The researchers entered 1,078 patients hospitalized with acute HF in 14 countries across Africa, Europe, the Middle East, and South America, and randomly assigned them to the high-intensity management strategy or usual care.

About 60% of the patients were male and 77% were White. There were no entry restrictions based on left ventricular ejection fraction (LVEF), which exceeded 40% in almost a third of cases.

In the high-intensity care group’s 542 patients, the three agents were up-titrated to 50% of the maximum guideline-recommended dosage prior to hospital discharge, and to 100% within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were monitored closely at four planned clinical visits over the following 6 weeks.

The 536 patients assigned to usual care were discharged and managed according to local standards, with their meds handled by their own primary care doctors or cardiologists, the published report notes. They were reevaluated by STRONG-HF clinicians 90 days after discharge.

The number of clinic visits in the first 90 postdischarge days averaged 4.8 in the high-intensity care group and 1.0 for those receiving usual care. Full up-titration was far more likely in the high-intensity care group: 55% vs. 2% for RASI agents, 49% vs. 4% for beta-blockers, and 84% vs. 46% for MRAs.

They also fared significantly better on all measured parameters associated with decongestion, including weight, prevalence of peripheral edema, jugular venous pressure, NYHA functional class, and natriuretic peptide levels, the researchers said.

The primary endpoint of 180-day death from any cause or HF readmission was met by 15.2% of the high-intensity care group and 23.3% of usual-care patients, for an adjusted risk ratio (RR) of 0.66 (95% CI, 0.50-0.86; P = .0021).

Subgroup analyses saw no significant interactions by age, sex, race, geography, or baseline blood pressure, renal function, or LVEF. Patients with higher vs. lower baseline natriuretic peptide levels trend toward better responses to high-intensity care (P = .08)
 

The COVID effect

The group performed a sensitivity analysis that excluded deaths attributed to COVID-19 in STRONG-HF, which launched prior to the pandemic. The high-intensity strategy’s benefit for the primary endpoint grew, with an adjusted RR of 0.61 (95% CI, 0.46-0.82; P = .0005). There was no corresponding effect on death from any cause (P = .15).

Treatment-related adverse effects in the overall trial were seen in 41.1% of the high-intensity care group and in 29.5% of those assigned to usual care.

The higher rate in the high-intensity care arm “may be related to their higher number of [clinic] visits compared to usual care,” Dr. Mebazaa said. “However, serious adverse events and fatal adverse events were similar in both arms.”

Cardiac failure was the most common adverse event, developing in about 15% in both groups. It was followed by hypotension, hyperkalemia, and renal impairment, according to the published report.

Dr. Cleland cautioned that the risk of adverse events would potentially be higher should the high-intensity strategy become common clinical practice. The median age in STRONG-HF was 63, which is “10-15 years younger, on average, than the population with recently admitted heart failure that we see. There’s no doubt that older people have more multimorbidity.”

STRONG-HF was funded by Roche Diagnostics. Dr. Mebazaa discloses receiving grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and Merck, Sharp & Dohme; and consulting for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and to being a co-inventor on a patent involving combination therapy for patients having acute or persistent dyspnea.

Dr. Vest reports modest relationships with Boehringer Ingelheim, Corvia, and CareDx; and receiving research grants from the American Heart Association and the National Institutes of Health. Dr. Cleland discloses receiving honoraria from Idorsia; and research grants from Vifor Pharma, Medtronic, Bayer, and Bristol-Myers Squibb. Dr. Leon had no disclosures.

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

CHICAGO – Clinicians who prescribe heart failure meds are holding the best hand they’ve ever had, but with so much underuse and suboptimal dosing in actual practice, it seems many may not appreciate the value of their cards. But a major randomized trial that has captured the field’s attention may embolden them to go all in.

Results showed that a strategy of early, rapid up-titration of multiple guideline-directed meds in patients hospitalized with heart failure, compared with a usual-care approach, cut their 6-month risk for death or HF readmission by a steep 34% (P = .002).

The drugs had been started and partly up-titrated in the hospital with the goal of full up-titration within 2 weeks after discharge.

Patients well tolerated the high-intensity approach, researchers said. Their quality-of-life scores improved (P < .0001) compared with the usual-care group, and adverse events were considered few and manageable in the international trial with more than 1,000 patients.

Safety on the high-intensity strategy depended on close patient monitoring at frequently planned clinic visits along with guidance for the up-titrations from clinical signs and natriuretic peptide levels, observed Alexandre Mebazaa, MD, PhD, University of Paris and Public Hospitals of Paris.

Dr. Mebazaa is principal investigator on the trial, called STRONG-HF, which he presented at the American Heart Association scientific sessions, held in Chicago and virtually. He is also lead author on the study’s same-day publication in the Lancet.

The high-intensity strategy’s superiority emerged early in the trial, which was halted early on the data safety monitoring board’s recommendation, with about 90% of follow-ups completed. The board “felt it was unethical to keep patients in usual care,” Dr. Mebazaa said at a press conference.
 

A dramatic change

The next step, he said, will be to educate the heart failure community on the high-intensity care technique so it can swiftly enter clinical practice. Currently in acute heart failure, “very few patients are monitored after discharge and treated with full doses of heart failure therapies.”

Adoption of the strategy “would be a dramatic change from what’s currently being done,” said Martin B. Leon, MD, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, who moderated the press conference.

Only an estimated 5% of patients with HF in the United States receive full guideline-directed medical therapy, Dr. Leon said, “so the generalizability of this strategy, with careful follow-up that has safety involved in it, is absolutely crucial.”

But the potential impact of this high-intensity approach on resource use is unknown, raising questions about how widely and consistently it could be implemented, said Dr. Leon, who is not connected with STRONG-HF.

The trial called for in-hospital initiation of the three distinct drug classes that, at the time, were the core of guideline-directed HF therapy, with up-titration to 50% of recommended dosage by hospital discharge, and then to 100% within 2 weeks later.

The meds included a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system inhibitor (RASI). The latter could be an ACE inhibitor, angiotensin-receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI).
 

How about a fourth drug?

Conspicuously absent from the list, for contemporary practice, was an SGLT2 inhibitor, a class that entered the HF guidelines well after STRONG-HF was designed. They would undoubtedly join the other three agents were the high-intensity strategy to enter practice, potentially changing its complexity and safety profile.

But Dr. Mebazaa and other experts don’t see that as a big challenge and would expect a smooth transition to a high-intensity approach that also includes the SGLT2 inhibitors.

STRONG-HF was necessary in part because many clinicians have been “reluctant” to take full advantage of three agents that had been the basis of guideline-directed therapy, he told this news organization.

That reluctance stemmed from concerns that beta-blockers might worsen the heart failure, ACE inhibitors could hurt the kidneys, or MRAs might cause hyperkalemia, Dr. Mebazaa said. The STRONG-HF high-intensity regimen, therefore, demanded multiple clinic visits for close follow-up.

But the SGLT2 inhibitors “are known to be rather safe drugs, at least much safer than the three others,” he said. So, it seems unlikely that their addition to a beta-blocker, RASI, and MRA in patients with HF would worsen the risk of adverse events.

John G.F. Cleland, MD, PhD, agrees. With addition of the fourth agent, “You may need to be a little bit more careful with renal function, just in that first couple of weeks,” he told this news organization. “But I think it would be easy to add an SGLT2 inhibitor into this regimen. And in general, there’s no titration with an SGLT2 inhibitor, so they’ll all be on full dose predischarge.”

Given the drugs’ diuretic-like action, moreover, some patients might be able to pull back on their loop diuretics, speculated Dr. Cleland, from the University of Glasgow’s School of Health and Wellbeing.

The prospect of a high-intensity strategy’s wide implementation in practice presents both “challenges and opportunities,” Amanda R. Vest, MBBS, MPH, Tufts University, Boston, told this news organization.

“There may be additional challenges in terms of ensuring we avoid hypotension or acute kidney injury in the up-titration phase,” said Dr. Vest, who is medical director of her center’s cardiac transplantation program but not connected with STRONG-HF.

“But it also gives us opportunities,” she added, “because there are some patients, especially in that vulnerable postdischarge phase, who are actually much more able to tolerate introduction of an SGLT2 inhibitor than, for example, an ACE inhibitor, ARB, or ARNI – or maybe a beta-blocker if they’ve been in a low cardiac-output state.” Effective dosing would depend on “the personalization and skill of the clinician in optimizing the medications in their correct sequence,” Dr. Vest said.

“It’s challenging to think that we would ever get to 100% up-titration,” she added, “and even in this excellent study, they didn’t get to 100%.” But as clinicians gain experience with the high-intensity strategy, especially as the SGLT2 inhibitors are included, “I think we can reasonably expect more progress to be made in these up-titration skills.”
 

No restrictions on LVEF

The researchers entered 1,078 patients hospitalized with acute HF in 14 countries across Africa, Europe, the Middle East, and South America, and randomly assigned them to the high-intensity management strategy or usual care.

About 60% of the patients were male and 77% were White. There were no entry restrictions based on left ventricular ejection fraction (LVEF), which exceeded 40% in almost a third of cases.

In the high-intensity care group’s 542 patients, the three agents were up-titrated to 50% of the maximum guideline-recommended dosage prior to hospital discharge, and to 100% within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were monitored closely at four planned clinical visits over the following 6 weeks.

The 536 patients assigned to usual care were discharged and managed according to local standards, with their meds handled by their own primary care doctors or cardiologists, the published report notes. They were reevaluated by STRONG-HF clinicians 90 days after discharge.

The number of clinic visits in the first 90 postdischarge days averaged 4.8 in the high-intensity care group and 1.0 for those receiving usual care. Full up-titration was far more likely in the high-intensity care group: 55% vs. 2% for RASI agents, 49% vs. 4% for beta-blockers, and 84% vs. 46% for MRAs.

They also fared significantly better on all measured parameters associated with decongestion, including weight, prevalence of peripheral edema, jugular venous pressure, NYHA functional class, and natriuretic peptide levels, the researchers said.

The primary endpoint of 180-day death from any cause or HF readmission was met by 15.2% of the high-intensity care group and 23.3% of usual-care patients, for an adjusted risk ratio (RR) of 0.66 (95% CI, 0.50-0.86; P = .0021).

Subgroup analyses saw no significant interactions by age, sex, race, geography, or baseline blood pressure, renal function, or LVEF. Patients with higher vs. lower baseline natriuretic peptide levels trend toward better responses to high-intensity care (P = .08)
 

The COVID effect

The group performed a sensitivity analysis that excluded deaths attributed to COVID-19 in STRONG-HF, which launched prior to the pandemic. The high-intensity strategy’s benefit for the primary endpoint grew, with an adjusted RR of 0.61 (95% CI, 0.46-0.82; P = .0005). There was no corresponding effect on death from any cause (P = .15).

Treatment-related adverse effects in the overall trial were seen in 41.1% of the high-intensity care group and in 29.5% of those assigned to usual care.

The higher rate in the high-intensity care arm “may be related to their higher number of [clinic] visits compared to usual care,” Dr. Mebazaa said. “However, serious adverse events and fatal adverse events were similar in both arms.”

Cardiac failure was the most common adverse event, developing in about 15% in both groups. It was followed by hypotension, hyperkalemia, and renal impairment, according to the published report.

Dr. Cleland cautioned that the risk of adverse events would potentially be higher should the high-intensity strategy become common clinical practice. The median age in STRONG-HF was 63, which is “10-15 years younger, on average, than the population with recently admitted heart failure that we see. There’s no doubt that older people have more multimorbidity.”

STRONG-HF was funded by Roche Diagnostics. Dr. Mebazaa discloses receiving grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and Merck, Sharp & Dohme; and consulting for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and to being a co-inventor on a patent involving combination therapy for patients having acute or persistent dyspnea.

Dr. Vest reports modest relationships with Boehringer Ingelheim, Corvia, and CareDx; and receiving research grants from the American Heart Association and the National Institutes of Health. Dr. Cleland discloses receiving honoraria from Idorsia; and research grants from Vifor Pharma, Medtronic, Bayer, and Bristol-Myers Squibb. Dr. Leon had no disclosures.

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

CHICAGO – Clinicians who prescribe heart failure meds are holding the best hand they’ve ever had, but with so much underuse and suboptimal dosing in actual practice, it seems many may not appreciate the value of their cards. But a major randomized trial that has captured the field’s attention may embolden them to go all in.

Results showed that a strategy of early, rapid up-titration of multiple guideline-directed meds in patients hospitalized with heart failure, compared with a usual-care approach, cut their 6-month risk for death or HF readmission by a steep 34% (P = .002).

The drugs had been started and partly up-titrated in the hospital with the goal of full up-titration within 2 weeks after discharge.

Patients well tolerated the high-intensity approach, researchers said. Their quality-of-life scores improved (P < .0001) compared with the usual-care group, and adverse events were considered few and manageable in the international trial with more than 1,000 patients.

Safety on the high-intensity strategy depended on close patient monitoring at frequently planned clinic visits along with guidance for the up-titrations from clinical signs and natriuretic peptide levels, observed Alexandre Mebazaa, MD, PhD, University of Paris and Public Hospitals of Paris.

Dr. Mebazaa is principal investigator on the trial, called STRONG-HF, which he presented at the American Heart Association scientific sessions, held in Chicago and virtually. He is also lead author on the study’s same-day publication in the Lancet.

The high-intensity strategy’s superiority emerged early in the trial, which was halted early on the data safety monitoring board’s recommendation, with about 90% of follow-ups completed. The board “felt it was unethical to keep patients in usual care,” Dr. Mebazaa said at a press conference.
 

A dramatic change

The next step, he said, will be to educate the heart failure community on the high-intensity care technique so it can swiftly enter clinical practice. Currently in acute heart failure, “very few patients are monitored after discharge and treated with full doses of heart failure therapies.”

Adoption of the strategy “would be a dramatic change from what’s currently being done,” said Martin B. Leon, MD, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, who moderated the press conference.

Only an estimated 5% of patients with HF in the United States receive full guideline-directed medical therapy, Dr. Leon said, “so the generalizability of this strategy, with careful follow-up that has safety involved in it, is absolutely crucial.”

But the potential impact of this high-intensity approach on resource use is unknown, raising questions about how widely and consistently it could be implemented, said Dr. Leon, who is not connected with STRONG-HF.

The trial called for in-hospital initiation of the three distinct drug classes that, at the time, were the core of guideline-directed HF therapy, with up-titration to 50% of recommended dosage by hospital discharge, and then to 100% within 2 weeks later.

The meds included a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system inhibitor (RASI). The latter could be an ACE inhibitor, angiotensin-receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI).
 

How about a fourth drug?

Conspicuously absent from the list, for contemporary practice, was an SGLT2 inhibitor, a class that entered the HF guidelines well after STRONG-HF was designed. They would undoubtedly join the other three agents were the high-intensity strategy to enter practice, potentially changing its complexity and safety profile.

But Dr. Mebazaa and other experts don’t see that as a big challenge and would expect a smooth transition to a high-intensity approach that also includes the SGLT2 inhibitors.

STRONG-HF was necessary in part because many clinicians have been “reluctant” to take full advantage of three agents that had been the basis of guideline-directed therapy, he told this news organization.

That reluctance stemmed from concerns that beta-blockers might worsen the heart failure, ACE inhibitors could hurt the kidneys, or MRAs might cause hyperkalemia, Dr. Mebazaa said. The STRONG-HF high-intensity regimen, therefore, demanded multiple clinic visits for close follow-up.

But the SGLT2 inhibitors “are known to be rather safe drugs, at least much safer than the three others,” he said. So, it seems unlikely that their addition to a beta-blocker, RASI, and MRA in patients with HF would worsen the risk of adverse events.

John G.F. Cleland, MD, PhD, agrees. With addition of the fourth agent, “You may need to be a little bit more careful with renal function, just in that first couple of weeks,” he told this news organization. “But I think it would be easy to add an SGLT2 inhibitor into this regimen. And in general, there’s no titration with an SGLT2 inhibitor, so they’ll all be on full dose predischarge.”

Given the drugs’ diuretic-like action, moreover, some patients might be able to pull back on their loop diuretics, speculated Dr. Cleland, from the University of Glasgow’s School of Health and Wellbeing.

The prospect of a high-intensity strategy’s wide implementation in practice presents both “challenges and opportunities,” Amanda R. Vest, MBBS, MPH, Tufts University, Boston, told this news organization.

“There may be additional challenges in terms of ensuring we avoid hypotension or acute kidney injury in the up-titration phase,” said Dr. Vest, who is medical director of her center’s cardiac transplantation program but not connected with STRONG-HF.

“But it also gives us opportunities,” she added, “because there are some patients, especially in that vulnerable postdischarge phase, who are actually much more able to tolerate introduction of an SGLT2 inhibitor than, for example, an ACE inhibitor, ARB, or ARNI – or maybe a beta-blocker if they’ve been in a low cardiac-output state.” Effective dosing would depend on “the personalization and skill of the clinician in optimizing the medications in their correct sequence,” Dr. Vest said.

“It’s challenging to think that we would ever get to 100% up-titration,” she added, “and even in this excellent study, they didn’t get to 100%.” But as clinicians gain experience with the high-intensity strategy, especially as the SGLT2 inhibitors are included, “I think we can reasonably expect more progress to be made in these up-titration skills.”
 

No restrictions on LVEF

The researchers entered 1,078 patients hospitalized with acute HF in 14 countries across Africa, Europe, the Middle East, and South America, and randomly assigned them to the high-intensity management strategy or usual care.

About 60% of the patients were male and 77% were White. There were no entry restrictions based on left ventricular ejection fraction (LVEF), which exceeded 40% in almost a third of cases.

In the high-intensity care group’s 542 patients, the three agents were up-titrated to 50% of the maximum guideline-recommended dosage prior to hospital discharge, and to 100% within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were monitored closely at four planned clinical visits over the following 6 weeks.

The 536 patients assigned to usual care were discharged and managed according to local standards, with their meds handled by their own primary care doctors or cardiologists, the published report notes. They were reevaluated by STRONG-HF clinicians 90 days after discharge.

The number of clinic visits in the first 90 postdischarge days averaged 4.8 in the high-intensity care group and 1.0 for those receiving usual care. Full up-titration was far more likely in the high-intensity care group: 55% vs. 2% for RASI agents, 49% vs. 4% for beta-blockers, and 84% vs. 46% for MRAs.

They also fared significantly better on all measured parameters associated with decongestion, including weight, prevalence of peripheral edema, jugular venous pressure, NYHA functional class, and natriuretic peptide levels, the researchers said.

The primary endpoint of 180-day death from any cause or HF readmission was met by 15.2% of the high-intensity care group and 23.3% of usual-care patients, for an adjusted risk ratio (RR) of 0.66 (95% CI, 0.50-0.86; P = .0021).

Subgroup analyses saw no significant interactions by age, sex, race, geography, or baseline blood pressure, renal function, or LVEF. Patients with higher vs. lower baseline natriuretic peptide levels trend toward better responses to high-intensity care (P = .08)
 

The COVID effect

The group performed a sensitivity analysis that excluded deaths attributed to COVID-19 in STRONG-HF, which launched prior to the pandemic. The high-intensity strategy’s benefit for the primary endpoint grew, with an adjusted RR of 0.61 (95% CI, 0.46-0.82; P = .0005). There was no corresponding effect on death from any cause (P = .15).

Treatment-related adverse effects in the overall trial were seen in 41.1% of the high-intensity care group and in 29.5% of those assigned to usual care.

The higher rate in the high-intensity care arm “may be related to their higher number of [clinic] visits compared to usual care,” Dr. Mebazaa said. “However, serious adverse events and fatal adverse events were similar in both arms.”

Cardiac failure was the most common adverse event, developing in about 15% in both groups. It was followed by hypotension, hyperkalemia, and renal impairment, according to the published report.

Dr. Cleland cautioned that the risk of adverse events would potentially be higher should the high-intensity strategy become common clinical practice. The median age in STRONG-HF was 63, which is “10-15 years younger, on average, than the population with recently admitted heart failure that we see. There’s no doubt that older people have more multimorbidity.”

STRONG-HF was funded by Roche Diagnostics. Dr. Mebazaa discloses receiving grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and Merck, Sharp & Dohme; and consulting for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and to being a co-inventor on a patent involving combination therapy for patients having acute or persistent dyspnea.

Dr. Vest reports modest relationships with Boehringer Ingelheim, Corvia, and CareDx; and receiving research grants from the American Heart Association and the National Institutes of Health. Dr. Cleland discloses receiving honoraria from Idorsia; and research grants from Vifor Pharma, Medtronic, Bayer, and Bristol-Myers Squibb. Dr. Leon had no disclosures.

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

In most cases, passengers on an airline flight are representative of the general population, which means that anyone could have an emergency at any time.

A study published in the New England Journal of Medicine in 2013 showed that a medical emergency occurred in 1 per 604 flights, as determined on the basis of in-flight medical emergencies that resulted in calls to a physician-directed medical communications center, said Amy Faith Ho, MD, MPH of Integrative Emergency Services, Dallas–Fort Worth, in a presentation at the annual meeting of the American College of Emergency Physicians.

The study authors reviewed records of 11,920 in-flight medical emergencies between Jan. 1, 2008, and Oct. 31, 2010. The data showed that physician passengers provided medical assistance in nearly half of in-flight emergencies (48.1%) and that flights were diverted because of the emergency in 7.3% of cases.

The majority of the in-flight emergencies involved syncope or presyncope (37.4% of cases), followed by respiratory symptoms (12.1%) and nausea or vomiting (9.5%), according to the study.

The in-flight medical bag

Tools in a physician’s in-flight toolbox start with the first-aid kit. Airplanes also have an emergency medical kit (EMK), an oxygen tank, and an AED.

The minimum EMK contents are mandated by the Federal Aviation Administration, said Dr. Ho. The standard equipment includes a stethoscope, a sphygmomanometer, and three sizes of oropharyngeal airways. Other items include self-inflating manual resuscitation devices and CPR masks in thee sizes, alcohol sponges, gloves, adhesive tape, scissors, a tourniquet, as well as saline solution, needles, syringes, and an intravenous administration set consisting of tubing and two Y connectors.

An EMK also should contain the following medications: nonnarcotic analgesic tablets, antihistamine tablets, an injectable antihistamine, atropine, aspirin tablets, a bronchodilator, and epinephrine (both 1:1000; 1 injectable cc and 1:10,000; two injectable cc). Nitroglycerin tablets and 5 cc of 20 mg/mL injectable cardiac lidocaine are part of the mandated kit as well, according to Dr. Ho.

Some airlines carry additional supplies on all their flights, said Dr. Ho. Notably, American Airlines and British Airways carry EpiPens for adults and children, as well as opioid reversal medication (naloxone) and glucose for managing low blood sugar. American Airlines and Delta stock antiemetics, and Delta also carries naloxone. British Airways is unique in stocking additional cardiac medications, both oral and injectable.
 

How to handle an in-flight emergency

Physicians should always carry a copy of their medical license when traveling for documentation by the airline if they assist in a medical emergency during a flight, Dr. Ho emphasized. “Staff” personnel should be used. These include the flight attendants, medical ground control, and other passengers who might have useful skills, such as nursing, the ability to perform CPR, or therapy/counseling to calm a frightened patient. If needed, “crowdsource additional supplies from passengers,” such as a glucometer or pulse oximeter.

Legal lessons

Physicians are not obligated to assist during an in-flight medical emergency, said Dr. Ho. Legal jurisdiction can vary. In the United States, a bystander who assists in an emergency is generally protected by Good Samaritan laws; for international airlines, the laws may vary; those where the airline is based usually apply.

The Aviation Medical Assistance Act, passed in 1998, protects individuals from being sued for negligence while providing medical assistance, “unless the individual, while rendering such assistance, is guilty of gross negligence of willful misconduct,” Dr. Ho noted. The Aviation Medical Assistance Act also protects the airline itself “if the carrier in good faith believes that the passenger is a medically qualified individual.”

Dr. Ho disclosed no relevant financial relationships.

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

In most cases, passengers on an airline flight are representative of the general population, which means that anyone could have an emergency at any time.

A study published in the New England Journal of Medicine in 2013 showed that a medical emergency occurred in 1 per 604 flights, as determined on the basis of in-flight medical emergencies that resulted in calls to a physician-directed medical communications center, said Amy Faith Ho, MD, MPH of Integrative Emergency Services, Dallas–Fort Worth, in a presentation at the annual meeting of the American College of Emergency Physicians.

The study authors reviewed records of 11,920 in-flight medical emergencies between Jan. 1, 2008, and Oct. 31, 2010. The data showed that physician passengers provided medical assistance in nearly half of in-flight emergencies (48.1%) and that flights were diverted because of the emergency in 7.3% of cases.

The majority of the in-flight emergencies involved syncope or presyncope (37.4% of cases), followed by respiratory symptoms (12.1%) and nausea or vomiting (9.5%), according to the study.

The in-flight medical bag

Tools in a physician’s in-flight toolbox start with the first-aid kit. Airplanes also have an emergency medical kit (EMK), an oxygen tank, and an AED.

The minimum EMK contents are mandated by the Federal Aviation Administration, said Dr. Ho. The standard equipment includes a stethoscope, a sphygmomanometer, and three sizes of oropharyngeal airways. Other items include self-inflating manual resuscitation devices and CPR masks in thee sizes, alcohol sponges, gloves, adhesive tape, scissors, a tourniquet, as well as saline solution, needles, syringes, and an intravenous administration set consisting of tubing and two Y connectors.

An EMK also should contain the following medications: nonnarcotic analgesic tablets, antihistamine tablets, an injectable antihistamine, atropine, aspirin tablets, a bronchodilator, and epinephrine (both 1:1000; 1 injectable cc and 1:10,000; two injectable cc). Nitroglycerin tablets and 5 cc of 20 mg/mL injectable cardiac lidocaine are part of the mandated kit as well, according to Dr. Ho.

Some airlines carry additional supplies on all their flights, said Dr. Ho. Notably, American Airlines and British Airways carry EpiPens for adults and children, as well as opioid reversal medication (naloxone) and glucose for managing low blood sugar. American Airlines and Delta stock antiemetics, and Delta also carries naloxone. British Airways is unique in stocking additional cardiac medications, both oral and injectable.
 

How to handle an in-flight emergency

Physicians should always carry a copy of their medical license when traveling for documentation by the airline if they assist in a medical emergency during a flight, Dr. Ho emphasized. “Staff” personnel should be used. These include the flight attendants, medical ground control, and other passengers who might have useful skills, such as nursing, the ability to perform CPR, or therapy/counseling to calm a frightened patient. If needed, “crowdsource additional supplies from passengers,” such as a glucometer or pulse oximeter.

Legal lessons

Physicians are not obligated to assist during an in-flight medical emergency, said Dr. Ho. Legal jurisdiction can vary. In the United States, a bystander who assists in an emergency is generally protected by Good Samaritan laws; for international airlines, the laws may vary; those where the airline is based usually apply.

The Aviation Medical Assistance Act, passed in 1998, protects individuals from being sued for negligence while providing medical assistance, “unless the individual, while rendering such assistance, is guilty of gross negligence of willful misconduct,” Dr. Ho noted. The Aviation Medical Assistance Act also protects the airline itself “if the carrier in good faith believes that the passenger is a medically qualified individual.”

Dr. Ho disclosed no relevant financial relationships.

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

In most cases, passengers on an airline flight are representative of the general population, which means that anyone could have an emergency at any time.

A study published in the New England Journal of Medicine in 2013 showed that a medical emergency occurred in 1 per 604 flights, as determined on the basis of in-flight medical emergencies that resulted in calls to a physician-directed medical communications center, said Amy Faith Ho, MD, MPH of Integrative Emergency Services, Dallas–Fort Worth, in a presentation at the annual meeting of the American College of Emergency Physicians.

The study authors reviewed records of 11,920 in-flight medical emergencies between Jan. 1, 2008, and Oct. 31, 2010. The data showed that physician passengers provided medical assistance in nearly half of in-flight emergencies (48.1%) and that flights were diverted because of the emergency in 7.3% of cases.

The majority of the in-flight emergencies involved syncope or presyncope (37.4% of cases), followed by respiratory symptoms (12.1%) and nausea or vomiting (9.5%), according to the study.

The in-flight medical bag

Tools in a physician’s in-flight toolbox start with the first-aid kit. Airplanes also have an emergency medical kit (EMK), an oxygen tank, and an AED.

The minimum EMK contents are mandated by the Federal Aviation Administration, said Dr. Ho. The standard equipment includes a stethoscope, a sphygmomanometer, and three sizes of oropharyngeal airways. Other items include self-inflating manual resuscitation devices and CPR masks in thee sizes, alcohol sponges, gloves, adhesive tape, scissors, a tourniquet, as well as saline solution, needles, syringes, and an intravenous administration set consisting of tubing and two Y connectors.

An EMK also should contain the following medications: nonnarcotic analgesic tablets, antihistamine tablets, an injectable antihistamine, atropine, aspirin tablets, a bronchodilator, and epinephrine (both 1:1000; 1 injectable cc and 1:10,000; two injectable cc). Nitroglycerin tablets and 5 cc of 20 mg/mL injectable cardiac lidocaine are part of the mandated kit as well, according to Dr. Ho.

Some airlines carry additional supplies on all their flights, said Dr. Ho. Notably, American Airlines and British Airways carry EpiPens for adults and children, as well as opioid reversal medication (naloxone) and glucose for managing low blood sugar. American Airlines and Delta stock antiemetics, and Delta also carries naloxone. British Airways is unique in stocking additional cardiac medications, both oral and injectable.
 

How to handle an in-flight emergency

Physicians should always carry a copy of their medical license when traveling for documentation by the airline if they assist in a medical emergency during a flight, Dr. Ho emphasized. “Staff” personnel should be used. These include the flight attendants, medical ground control, and other passengers who might have useful skills, such as nursing, the ability to perform CPR, or therapy/counseling to calm a frightened patient. If needed, “crowdsource additional supplies from passengers,” such as a glucometer or pulse oximeter.

Legal lessons

Physicians are not obligated to assist during an in-flight medical emergency, said Dr. Ho. Legal jurisdiction can vary. In the United States, a bystander who assists in an emergency is generally protected by Good Samaritan laws; for international airlines, the laws may vary; those where the airline is based usually apply.

The Aviation Medical Assistance Act, passed in 1998, protects individuals from being sued for negligence while providing medical assistance, “unless the individual, while rendering such assistance, is guilty of gross negligence of willful misconduct,” Dr. Ho noted. The Aviation Medical Assistance Act also protects the airline itself “if the carrier in good faith believes that the passenger is a medically qualified individual.”

Dr. Ho disclosed no relevant financial relationships.

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

ILLUSTRATIVE CASE

A frail 76-year-old woman with a history of hypertension and hyperlipidemia presents for evaluation of palpitations. An in-office electrocardiogram reveals that the patient is in AF. Her CHA₂DS₂-VASc score is 4 and her HAS-BLED score is 2.^2,3 Using shared decision making, you decide to start medications for her AF. You plan to initiate a beta-blocker for rate control and must now decide on anticoagulation. Which oral anticoagulant would you prescribe for this patient’s AF, given her frail status?

Frailty is defined as a state of vulnerability with a decreased ability to recover from an acute stressful event.⁴ The prevalence of frailty varies by the measurements used and the population studied. A 2021 meta-analysis found that frailty prevalence ranges from 12% to 24% worldwide in patients older than 50 years⁵ and may increase to > 30% among those ages 85 years and older.⁶ Frailty increases rates of AEs such as falls⁷ and fracture,⁸ leading to disability,⁹ decreased quality of life,¹⁰ increased utilization of health care,¹¹ and increased mortality.¹² A number of validated approaches are available to screen for and measure frailty.^13-18

Given the association with negative health outcomes and high health care utilization, frailty is an important clinical factor for physicians to consider when treating elderly patients. Frailty assessment may allow for more tailored treatment choices for patients, with a potential reduction in complications. Although CHA₂DS₂-VASc and HAS-BLED scores assist in the decision-making process of whether to start anticoagulation,these tools do not take frailty into consideration or guide anticoagulant choice.^2,3 The purpose of this study was to analyze how levels of frailty affect the association of 3 different direct oral anticoagulants (DOACs) vs warfarin with various AEs (death, stroke, or major bleeding).

STUDY SUMMARY

This DOAC rose above the others

This retrospective cohort study compared the safety of 3 DOACs—dabigatran, rivaroxaban, and apixaban—vs warfarin in Medicare beneficiaries with AF, using 1:1 propensity score (PS)–matched analysis. Eligible patients were ages 65 years or older, with a filled prescription for a DOAC or warfarin, no prior oral anticoagulant exposure in the previous 183 days, a diagnostic code of AF, and continuous enrollment in Medicare Parts A, B, and D only. Patients were excluded if they had missing demographic data, received hospice care, resided in a nursing facility at drug initiation, had another indication for anticoagulation, or had a contraindication to either a DOAC or warfarin.

Frailty was measured using a claims-based frailty index (CFI), which applies health care utilization data to estimate a frailty index, with cut points for nonfrailty, prefrailty, and frailty. The CFI score has 93 claims-based variables, including wheelchairs and durable medical equipment, open wounds, diseases such as chronic obstructive pulmonary disease and ischemic heart disease, and transportation services.^15-17 In this study, nonfrailty was defined as a CFI < 0.15, prefrailty as a CFI of 0.15 to 0.24, and frailty as a CFI ≥ 0.25.

Among older patients treated with anticoagulation for atrial fibrillation, apixaban had the lowest adverse event rate vs warfarin among frail patients, compared with dabigatran and rivaroxaban.

The primary outcome—a composite endpoint of death, ischemic stroke, or major bleeding—was measured for each of the DOAC–warfarin cohorts in the overall population and stratified by frailty classification. Patients were followed until the occurrence of a study outcome, Medicare disenrollment, the end of the study period, discontinuation of the index drug (defined as > 5 days), change to a different anticoagulant, admission to a nursing facility, enrollment in hospice, initiation of dialysis, or kidney transplant. The authors conducted a PS-matched analysis to reduce any imbalances in clinical characteristics between the DOAC- and warfarin-­treated groups, as well as a sensitivity analysis to assess the strength of the data findings using different assumptions.

The authors created 3 DOAC–warfarin cohorts: dabigatran (n = 81,863) vs warfarin (n = 256,722), rivaroxaban (n = 185,011) vs warfarin (n = 228,028), and apixaban (n = 222,478) vs warfarin (n = 206,031). After PS matching, the mean age in all cohorts was 76 to 77 years, about 50% were female, and 91% were White. The mean HAS-BLED score was 2 and the mean CHA₂DS₂-VASc score was 4. The mean CFI was 0.19 to 0.20, defined as prefrail. Patients classified as frail were older, more likely to be female, and more likely to have greater comorbidities, higher scores on CHA₂DS₂-VASc and HAS-BLED, and higher health care utilization.

Continue to: In the dabigatran-warfarin...

In the dabigatran–warfarin cohort (median follow-up, 72 days), the event rate of the composite endpoint per 1000 person-years (PY) was 63.5 for dabigatran and 65.6 for warfarin (hazard ratio [HR] = 0.98; 95% CI, 0.92 to 1.05; rate difference [RD] per 1000 PY = –2.2; 95% CI, –6.5 to 2.1). A lower rate of the composite endpoint was associated with dabigatran than warfarin for the nonfrail subgroup but not the prefrail or frail groups.

In the rivaroxaban–warfarin cohort (median follow-up, 82 days), the composite endpoint rate per 1000 PY was 77.8 for rivaroxaban and 83.7 for warfarin (HR = 0.98; 95% CI, 0.94 to 1.02; RD per 1000 PY = –5.9; 95% CI, –9.4 to –2.4). When stratifying by frailty category, both dabigatran and rivaroxaban were associated with a lower composite endpoint rate than warfarin for the nonfrail population only (HR = 0.81; 95% CI, 0.68 to 0.97, and HR = 0.88; 95% CI, 0.77 to 0.99, respectively).

In the apixaban–warfarin cohort (median follow-up, 84 days), the rate of the composite endpoint per 1000 PY was 60.1 for apixaban and 92.3 for warfarin (HR = 0.68; 95% CI, 0.65 to 0.72; RD per 1000 PY = –32.2; 95% CI, –36.1 to –28.3). The beneficial association for apixaban was present in all frailty categories, with an HR of 0.61 (95% CI, 0.52 to 0.71) for nonfrail patients, 0.66 (95% CI, 0.61 to 0.70) for prefrail patients, and 0.73 (95% CI, 0.67 to 0.80) for frail patients. Apixaban was the only DOAC with a relative reduction in the hazard of death, ischemic stroke, or major bleeding among all frailty groups.

WHAT’S NEW

Only apixaban had lower AE rates vs warfarin across frailty levels

Three DOACs (dabigatran, rivaroxaban, and apixaban) reduced the risk of death, ischemic stroke, or major bleeding compared with warfarin in older adults with AF, but only apixaban was associated with a relative reduction of these adverse outcomes in patients of all frailty classifications.

CAVEATS

Important data but RCTs are needed

The power of this observational study is considerable. However, it remains a retrospective observational study. The authors attempted to account for these limitations and potential confounders by performing a PS-matched analysis and sensitivity analysis; however, these findings should be confirmed with randomized controlled trials.

Continue to: Additionally, the study...

Additionally, the study collected data on each of the DOAC–warfarin cohorts for < 90 days. Trials to address long-term outcomes are warranted.

Finally, there was no control group in comparison with anticoagulation. It is possible that choosing not to use an anticoagulant is the best choice for frail elderly patients.

CHALLENGES TO IMPLEMENTATION

Doctors need a practical frailty scale, patients need an affordable Rx

Frailty is not often considered a measurable trait. The approach used in the study to determine the CFI is not a practical clinical tool. Studies comparing a frailty calculation software application or an easily implementable survey may help bring this clinically impactful information to the hands of primary care physicians. The Clinical Frailty Scale—a brief, 7-point scale based on the physician’s clinical impression of the patient—has been found to correlate with other established frailty measures¹⁸ and might be an option for busy clinicians. However, the current study did not utilize this measurement, and the validity of its use by primary care physicians in the outpatient setting requires further study.

Cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D.

In addition, cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D. The average monthly cost of the DOACs ranges from $560 for dabigatran¹⁹ to $600 for rivaroxaban²⁰ and $623 for apixaban.²¹ As always, the choice of anticoagulant therapy is a clinical judgment and a joint decision of the patient and physician.

ILLUSTRATIVE CASE

A frail 76-year-old woman with a history of hypertension and hyperlipidemia presents for evaluation of palpitations. An in-office electrocardiogram reveals that the patient is in AF. Her CHA₂DS₂-VASc score is 4 and her HAS-BLED score is 2.^2,3 Using shared decision making, you decide to start medications for her AF. You plan to initiate a beta-blocker for rate control and must now decide on anticoagulation. Which oral anticoagulant would you prescribe for this patient’s AF, given her frail status?

Frailty is defined as a state of vulnerability with a decreased ability to recover from an acute stressful event.⁴ The prevalence of frailty varies by the measurements used and the population studied. A 2021 meta-analysis found that frailty prevalence ranges from 12% to 24% worldwide in patients older than 50 years⁵ and may increase to > 30% among those ages 85 years and older.⁶ Frailty increases rates of AEs such as falls⁷ and fracture,⁸ leading to disability,⁹ decreased quality of life,¹⁰ increased utilization of health care,¹¹ and increased mortality.¹² A number of validated approaches are available to screen for and measure frailty.^13-18

Given the association with negative health outcomes and high health care utilization, frailty is an important clinical factor for physicians to consider when treating elderly patients. Frailty assessment may allow for more tailored treatment choices for patients, with a potential reduction in complications. Although CHA₂DS₂-VASc and HAS-BLED scores assist in the decision-making process of whether to start anticoagulation,these tools do not take frailty into consideration or guide anticoagulant choice.^2,3 The purpose of this study was to analyze how levels of frailty affect the association of 3 different direct oral anticoagulants (DOACs) vs warfarin with various AEs (death, stroke, or major bleeding).

STUDY SUMMARY

This DOAC rose above the others

This retrospective cohort study compared the safety of 3 DOACs—dabigatran, rivaroxaban, and apixaban—vs warfarin in Medicare beneficiaries with AF, using 1:1 propensity score (PS)–matched analysis. Eligible patients were ages 65 years or older, with a filled prescription for a DOAC or warfarin, no prior oral anticoagulant exposure in the previous 183 days, a diagnostic code of AF, and continuous enrollment in Medicare Parts A, B, and D only. Patients were excluded if they had missing demographic data, received hospice care, resided in a nursing facility at drug initiation, had another indication for anticoagulation, or had a contraindication to either a DOAC or warfarin.

Frailty was measured using a claims-based frailty index (CFI), which applies health care utilization data to estimate a frailty index, with cut points for nonfrailty, prefrailty, and frailty. The CFI score has 93 claims-based variables, including wheelchairs and durable medical equipment, open wounds, diseases such as chronic obstructive pulmonary disease and ischemic heart disease, and transportation services.^15-17 In this study, nonfrailty was defined as a CFI < 0.15, prefrailty as a CFI of 0.15 to 0.24, and frailty as a CFI ≥ 0.25.

Among older patients treated with anticoagulation for atrial fibrillation, apixaban had the lowest adverse event rate vs warfarin among frail patients, compared with dabigatran and rivaroxaban.

The primary outcome—a composite endpoint of death, ischemic stroke, or major bleeding—was measured for each of the DOAC–warfarin cohorts in the overall population and stratified by frailty classification. Patients were followed until the occurrence of a study outcome, Medicare disenrollment, the end of the study period, discontinuation of the index drug (defined as > 5 days), change to a different anticoagulant, admission to a nursing facility, enrollment in hospice, initiation of dialysis, or kidney transplant. The authors conducted a PS-matched analysis to reduce any imbalances in clinical characteristics between the DOAC- and warfarin-­treated groups, as well as a sensitivity analysis to assess the strength of the data findings using different assumptions.

The authors created 3 DOAC–warfarin cohorts: dabigatran (n = 81,863) vs warfarin (n = 256,722), rivaroxaban (n = 185,011) vs warfarin (n = 228,028), and apixaban (n = 222,478) vs warfarin (n = 206,031). After PS matching, the mean age in all cohorts was 76 to 77 years, about 50% were female, and 91% were White. The mean HAS-BLED score was 2 and the mean CHA₂DS₂-VASc score was 4. The mean CFI was 0.19 to 0.20, defined as prefrail. Patients classified as frail were older, more likely to be female, and more likely to have greater comorbidities, higher scores on CHA₂DS₂-VASc and HAS-BLED, and higher health care utilization.

Continue to: In the dabigatran-warfarin...

In the dabigatran–warfarin cohort (median follow-up, 72 days), the event rate of the composite endpoint per 1000 person-years (PY) was 63.5 for dabigatran and 65.6 for warfarin (hazard ratio [HR] = 0.98; 95% CI, 0.92 to 1.05; rate difference [RD] per 1000 PY = –2.2; 95% CI, –6.5 to 2.1). A lower rate of the composite endpoint was associated with dabigatran than warfarin for the nonfrail subgroup but not the prefrail or frail groups.

In the rivaroxaban–warfarin cohort (median follow-up, 82 days), the composite endpoint rate per 1000 PY was 77.8 for rivaroxaban and 83.7 for warfarin (HR = 0.98; 95% CI, 0.94 to 1.02; RD per 1000 PY = –5.9; 95% CI, –9.4 to –2.4). When stratifying by frailty category, both dabigatran and rivaroxaban were associated with a lower composite endpoint rate than warfarin for the nonfrail population only (HR = 0.81; 95% CI, 0.68 to 0.97, and HR = 0.88; 95% CI, 0.77 to 0.99, respectively).

In the apixaban–warfarin cohort (median follow-up, 84 days), the rate of the composite endpoint per 1000 PY was 60.1 for apixaban and 92.3 for warfarin (HR = 0.68; 95% CI, 0.65 to 0.72; RD per 1000 PY = –32.2; 95% CI, –36.1 to –28.3). The beneficial association for apixaban was present in all frailty categories, with an HR of 0.61 (95% CI, 0.52 to 0.71) for nonfrail patients, 0.66 (95% CI, 0.61 to 0.70) for prefrail patients, and 0.73 (95% CI, 0.67 to 0.80) for frail patients. Apixaban was the only DOAC with a relative reduction in the hazard of death, ischemic stroke, or major bleeding among all frailty groups.

WHAT’S NEW

Only apixaban had lower AE rates vs warfarin across frailty levels

Three DOACs (dabigatran, rivaroxaban, and apixaban) reduced the risk of death, ischemic stroke, or major bleeding compared with warfarin in older adults with AF, but only apixaban was associated with a relative reduction of these adverse outcomes in patients of all frailty classifications.

CAVEATS

Important data but RCTs are needed

The power of this observational study is considerable. However, it remains a retrospective observational study. The authors attempted to account for these limitations and potential confounders by performing a PS-matched analysis and sensitivity analysis; however, these findings should be confirmed with randomized controlled trials.

Continue to: Additionally, the study...

Additionally, the study collected data on each of the DOAC–warfarin cohorts for < 90 days. Trials to address long-term outcomes are warranted.

Finally, there was no control group in comparison with anticoagulation. It is possible that choosing not to use an anticoagulant is the best choice for frail elderly patients.

CHALLENGES TO IMPLEMENTATION

Doctors need a practical frailty scale, patients need an affordable Rx

Frailty is not often considered a measurable trait. The approach used in the study to determine the CFI is not a practical clinical tool. Studies comparing a frailty calculation software application or an easily implementable survey may help bring this clinically impactful information to the hands of primary care physicians. The Clinical Frailty Scale—a brief, 7-point scale based on the physician’s clinical impression of the patient—has been found to correlate with other established frailty measures¹⁸ and might be an option for busy clinicians. However, the current study did not utilize this measurement, and the validity of its use by primary care physicians in the outpatient setting requires further study.

Cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D.

In addition, cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D. The average monthly cost of the DOACs ranges from $560 for dabigatran¹⁹ to $600 for rivaroxaban²⁰ and $623 for apixaban.²¹ As always, the choice of anticoagulant therapy is a clinical judgment and a joint decision of the patient and physician.

ILLUSTRATIVE CASE

A frail 76-year-old woman with a history of hypertension and hyperlipidemia presents for evaluation of palpitations. An in-office electrocardiogram reveals that the patient is in AF. Her CHA₂DS₂-VASc score is 4 and her HAS-BLED score is 2.^2,3 Using shared decision making, you decide to start medications for her AF. You plan to initiate a beta-blocker for rate control and must now decide on anticoagulation. Which oral anticoagulant would you prescribe for this patient’s AF, given her frail status?

Frailty is defined as a state of vulnerability with a decreased ability to recover from an acute stressful event.⁴ The prevalence of frailty varies by the measurements used and the population studied. A 2021 meta-analysis found that frailty prevalence ranges from 12% to 24% worldwide in patients older than 50 years⁵ and may increase to > 30% among those ages 85 years and older.⁶ Frailty increases rates of AEs such as falls⁷ and fracture,⁸ leading to disability,⁹ decreased quality of life,¹⁰ increased utilization of health care,¹¹ and increased mortality.¹² A number of validated approaches are available to screen for and measure frailty.^13-18

Given the association with negative health outcomes and high health care utilization, frailty is an important clinical factor for physicians to consider when treating elderly patients. Frailty assessment may allow for more tailored treatment choices for patients, with a potential reduction in complications. Although CHA₂DS₂-VASc and HAS-BLED scores assist in the decision-making process of whether to start anticoagulation,these tools do not take frailty into consideration or guide anticoagulant choice.^2,3 The purpose of this study was to analyze how levels of frailty affect the association of 3 different direct oral anticoagulants (DOACs) vs warfarin with various AEs (death, stroke, or major bleeding).

STUDY SUMMARY

This DOAC rose above the others

This retrospective cohort study compared the safety of 3 DOACs—dabigatran, rivaroxaban, and apixaban—vs warfarin in Medicare beneficiaries with AF, using 1:1 propensity score (PS)–matched analysis. Eligible patients were ages 65 years or older, with a filled prescription for a DOAC or warfarin, no prior oral anticoagulant exposure in the previous 183 days, a diagnostic code of AF, and continuous enrollment in Medicare Parts A, B, and D only. Patients were excluded if they had missing demographic data, received hospice care, resided in a nursing facility at drug initiation, had another indication for anticoagulation, or had a contraindication to either a DOAC or warfarin.

Frailty was measured using a claims-based frailty index (CFI), which applies health care utilization data to estimate a frailty index, with cut points for nonfrailty, prefrailty, and frailty. The CFI score has 93 claims-based variables, including wheelchairs and durable medical equipment, open wounds, diseases such as chronic obstructive pulmonary disease and ischemic heart disease, and transportation services.^15-17 In this study, nonfrailty was defined as a CFI < 0.15, prefrailty as a CFI of 0.15 to 0.24, and frailty as a CFI ≥ 0.25.

Among older patients treated with anticoagulation for atrial fibrillation, apixaban had the lowest adverse event rate vs warfarin among frail patients, compared with dabigatran and rivaroxaban.

The primary outcome—a composite endpoint of death, ischemic stroke, or major bleeding—was measured for each of the DOAC–warfarin cohorts in the overall population and stratified by frailty classification. Patients were followed until the occurrence of a study outcome, Medicare disenrollment, the end of the study period, discontinuation of the index drug (defined as > 5 days), change to a different anticoagulant, admission to a nursing facility, enrollment in hospice, initiation of dialysis, or kidney transplant. The authors conducted a PS-matched analysis to reduce any imbalances in clinical characteristics between the DOAC- and warfarin-­treated groups, as well as a sensitivity analysis to assess the strength of the data findings using different assumptions.

The authors created 3 DOAC–warfarin cohorts: dabigatran (n = 81,863) vs warfarin (n = 256,722), rivaroxaban (n = 185,011) vs warfarin (n = 228,028), and apixaban (n = 222,478) vs warfarin (n = 206,031). After PS matching, the mean age in all cohorts was 76 to 77 years, about 50% were female, and 91% were White. The mean HAS-BLED score was 2 and the mean CHA₂DS₂-VASc score was 4. The mean CFI was 0.19 to 0.20, defined as prefrail. Patients classified as frail were older, more likely to be female, and more likely to have greater comorbidities, higher scores on CHA₂DS₂-VASc and HAS-BLED, and higher health care utilization.

Continue to: In the dabigatran-warfarin...

In the dabigatran–warfarin cohort (median follow-up, 72 days), the event rate of the composite endpoint per 1000 person-years (PY) was 63.5 for dabigatran and 65.6 for warfarin (hazard ratio [HR] = 0.98; 95% CI, 0.92 to 1.05; rate difference [RD] per 1000 PY = –2.2; 95% CI, –6.5 to 2.1). A lower rate of the composite endpoint was associated with dabigatran than warfarin for the nonfrail subgroup but not the prefrail or frail groups.

In the rivaroxaban–warfarin cohort (median follow-up, 82 days), the composite endpoint rate per 1000 PY was 77.8 for rivaroxaban and 83.7 for warfarin (HR = 0.98; 95% CI, 0.94 to 1.02; RD per 1000 PY = –5.9; 95% CI, –9.4 to –2.4). When stratifying by frailty category, both dabigatran and rivaroxaban were associated with a lower composite endpoint rate than warfarin for the nonfrail population only (HR = 0.81; 95% CI, 0.68 to 0.97, and HR = 0.88; 95% CI, 0.77 to 0.99, respectively).

In the apixaban–warfarin cohort (median follow-up, 84 days), the rate of the composite endpoint per 1000 PY was 60.1 for apixaban and 92.3 for warfarin (HR = 0.68; 95% CI, 0.65 to 0.72; RD per 1000 PY = –32.2; 95% CI, –36.1 to –28.3). The beneficial association for apixaban was present in all frailty categories, with an HR of 0.61 (95% CI, 0.52 to 0.71) for nonfrail patients, 0.66 (95% CI, 0.61 to 0.70) for prefrail patients, and 0.73 (95% CI, 0.67 to 0.80) for frail patients. Apixaban was the only DOAC with a relative reduction in the hazard of death, ischemic stroke, or major bleeding among all frailty groups.

WHAT’S NEW

Only apixaban had lower AE rates vs warfarin across frailty levels

Three DOACs (dabigatran, rivaroxaban, and apixaban) reduced the risk of death, ischemic stroke, or major bleeding compared with warfarin in older adults with AF, but only apixaban was associated with a relative reduction of these adverse outcomes in patients of all frailty classifications.

CAVEATS

Important data but RCTs are needed

The power of this observational study is considerable. However, it remains a retrospective observational study. The authors attempted to account for these limitations and potential confounders by performing a PS-matched analysis and sensitivity analysis; however, these findings should be confirmed with randomized controlled trials.

Continue to: Additionally, the study...

Additionally, the study collected data on each of the DOAC–warfarin cohorts for < 90 days. Trials to address long-term outcomes are warranted.

Finally, there was no control group in comparison with anticoagulation. It is possible that choosing not to use an anticoagulant is the best choice for frail elderly patients.

CHALLENGES TO IMPLEMENTATION

Doctors need a practical frailty scale, patients need an affordable Rx

Frailty is not often considered a measurable trait. The approach used in the study to determine the CFI is not a practical clinical tool. Studies comparing a frailty calculation software application or an easily implementable survey may help bring this clinically impactful information to the hands of primary care physicians. The Clinical Frailty Scale—a brief, 7-point scale based on the physician’s clinical impression of the patient—has been found to correlate with other established frailty measures¹⁸ and might be an option for busy clinicians. However, the current study did not utilize this measurement, and the validity of its use by primary care physicians in the outpatient setting requires further study.

Cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D.

In addition, cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D. The average monthly cost of the DOACs ranges from $560 for dabigatran¹⁹ to $600 for rivaroxaban²⁰ and $623 for apixaban.²¹ As always, the choice of anticoagulant therapy is a clinical judgment and a joint decision of the patient and physician.

Undiagnosed atrial fibrillation (AFib) was significantly more common among adults with obstructive sleep apnea (OSA), compared with controls, based on data from 303 individuals.

OSA has become a common chronic disease, and cardiovascular diseases including AFib also are known independent risk factors associated with OSA, Anna Hojager, MD, of Zealand University Hospital, Roskilde, Denmark, and colleagues wrote. Previous studies have shown a significant increase in AFib risk in OSA patients with severe disease, but the prevalence of undiagnosed AFib in OSA patients has not been explored.

In a study published in Sleep Medicine, the researchers enrolled 238 adults with severe OSA (based on apnea-hypopnea index of 15 or higher) and 65 with mild or no OSA (based on an AHI of less than 15). The mean AHI across all participants was 34.2, and ranged from 0.2 to 115.8.

Participants underwent heart rhythm monitoring using a home system or standard ECG for 7 days; they were instructed to carry the device at all times except when showering or sweating heavily. The primary outcome was the detection of AFib, defined as at least one period of 30 seconds or longer with an irregular heart rhythm but without detectable evidence of another diagnosis. Sleep was assessed for one night using a portable sleep monitoring device. All participants were examined at baseline and measured for blood pressure, body mass index, waist-to-hip ratio, and ECG.

Overall, AFib occurred in 21 patients with moderate to severe OSA and 1 patient with mild/no OSA (8.8% vs. 1.5%, P = .045). The majority of patients across both groups had hypertension (66%) and dyslipidemia (77.6%), but the severe OSA group was more likely to be dysregulated and to have unknown prediabetes. Participants who were deemed candidates for anticoagulation therapy were referred for additional treatment. None of the 22 total patients with AFib had heart failure with reduced ejection fraction, and 68.2% had normal ejection fraction and ventricle function.

The researchers noted that no guidelines currently exist for systematic opportunistic screening for comorbidities in OSA patients, although the American Academy of Sleep Medicine recommends patient education as part of a multidisciplinary chronic disease management strategy. The high prevalence of AFib in OSA patients, as seen in the current study, “might warrant a recommendation of screening for paroxysmal [AFib] and could be valuable in the management of modifiable cardiovascular risk factors in patients with OSA,” they wrote.

The study findings were limited by several factors including the observational design and absence of polysomnography to assess OSA, the researchers noted. However, the study has the highest known prevalence of silent AFib in patients with moderate to severe OSA, and supports the value of screening and management for known comorbidities of OSA.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Undiagnosed atrial fibrillation (AFib) was significantly more common among adults with obstructive sleep apnea (OSA), compared with controls, based on data from 303 individuals.

OSA has become a common chronic disease, and cardiovascular diseases including AFib also are known independent risk factors associated with OSA, Anna Hojager, MD, of Zealand University Hospital, Roskilde, Denmark, and colleagues wrote. Previous studies have shown a significant increase in AFib risk in OSA patients with severe disease, but the prevalence of undiagnosed AFib in OSA patients has not been explored.

In a study published in Sleep Medicine, the researchers enrolled 238 adults with severe OSA (based on apnea-hypopnea index of 15 or higher) and 65 with mild or no OSA (based on an AHI of less than 15). The mean AHI across all participants was 34.2, and ranged from 0.2 to 115.8.

Participants underwent heart rhythm monitoring using a home system or standard ECG for 7 days; they were instructed to carry the device at all times except when showering or sweating heavily. The primary outcome was the detection of AFib, defined as at least one period of 30 seconds or longer with an irregular heart rhythm but without detectable evidence of another diagnosis. Sleep was assessed for one night using a portable sleep monitoring device. All participants were examined at baseline and measured for blood pressure, body mass index, waist-to-hip ratio, and ECG.

Overall, AFib occurred in 21 patients with moderate to severe OSA and 1 patient with mild/no OSA (8.8% vs. 1.5%, P = .045). The majority of patients across both groups had hypertension (66%) and dyslipidemia (77.6%), but the severe OSA group was more likely to be dysregulated and to have unknown prediabetes. Participants who were deemed candidates for anticoagulation therapy were referred for additional treatment. None of the 22 total patients with AFib had heart failure with reduced ejection fraction, and 68.2% had normal ejection fraction and ventricle function.

The researchers noted that no guidelines currently exist for systematic opportunistic screening for comorbidities in OSA patients, although the American Academy of Sleep Medicine recommends patient education as part of a multidisciplinary chronic disease management strategy. The high prevalence of AFib in OSA patients, as seen in the current study, “might warrant a recommendation of screening for paroxysmal [AFib] and could be valuable in the management of modifiable cardiovascular risk factors in patients with OSA,” they wrote.

The study findings were limited by several factors including the observational design and absence of polysomnography to assess OSA, the researchers noted. However, the study has the highest known prevalence of silent AFib in patients with moderate to severe OSA, and supports the value of screening and management for known comorbidities of OSA.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Undiagnosed atrial fibrillation (AFib) was significantly more common among adults with obstructive sleep apnea (OSA), compared with controls, based on data from 303 individuals.

OSA has become a common chronic disease, and cardiovascular diseases including AFib also are known independent risk factors associated with OSA, Anna Hojager, MD, of Zealand University Hospital, Roskilde, Denmark, and colleagues wrote. Previous studies have shown a significant increase in AFib risk in OSA patients with severe disease, but the prevalence of undiagnosed AFib in OSA patients has not been explored.

In a study published in Sleep Medicine, the researchers enrolled 238 adults with severe OSA (based on apnea-hypopnea index of 15 or higher) and 65 with mild or no OSA (based on an AHI of less than 15). The mean AHI across all participants was 34.2, and ranged from 0.2 to 115.8.

Participants underwent heart rhythm monitoring using a home system or standard ECG for 7 days; they were instructed to carry the device at all times except when showering or sweating heavily. The primary outcome was the detection of AFib, defined as at least one period of 30 seconds or longer with an irregular heart rhythm but without detectable evidence of another diagnosis. Sleep was assessed for one night using a portable sleep monitoring device. All participants were examined at baseline and measured for blood pressure, body mass index, waist-to-hip ratio, and ECG.

Overall, AFib occurred in 21 patients with moderate to severe OSA and 1 patient with mild/no OSA (8.8% vs. 1.5%, P = .045). The majority of patients across both groups had hypertension (66%) and dyslipidemia (77.6%), but the severe OSA group was more likely to be dysregulated and to have unknown prediabetes. Participants who were deemed candidates for anticoagulation therapy were referred for additional treatment. None of the 22 total patients with AFib had heart failure with reduced ejection fraction, and 68.2% had normal ejection fraction and ventricle function.

The researchers noted that no guidelines currently exist for systematic opportunistic screening for comorbidities in OSA patients, although the American Academy of Sleep Medicine recommends patient education as part of a multidisciplinary chronic disease management strategy. The high prevalence of AFib in OSA patients, as seen in the current study, “might warrant a recommendation of screening for paroxysmal [AFib] and could be valuable in the management of modifiable cardiovascular risk factors in patients with OSA,” they wrote.

The study findings were limited by several factors including the observational design and absence of polysomnography to assess OSA, the researchers noted. However, the study has the highest known prevalence of silent AFib in patients with moderate to severe OSA, and supports the value of screening and management for known comorbidities of OSA.

The study received no outside funding. The researchers had no financial conflicts to disclose.