MDedge Emergency Medicine

Significant improvement in the control of symptoms related to paroxysmal supraventricular tachycardia (PSVT) is resurrecting etripamil as a self-administered nasal spray a year after it failed to meet the primary endpoint in a phase 3 trial, according to a new analysis from this same study presented at the annual scientific sessions of the American College of Cardiology.

Thinkstock

In the phase 3 NODE-301 trial, presented at the 2020 Heart Rhythm Society annual meeting, etripamil did not show an advantage over placebo at 5 hours for achieving sinus rhythm. Nevertheless, a new presentation of the secondary outcomes suggests substantial clinical benefit.

These advantages include significant reductions in PSVT symptoms, a trend for fewer emergency room visits, and a degree of patient satisfaction that appears meaningful, according to Bruce S. Stambler, MD, an electrophysiologist affiliated with Piedmont Heart Institute, Atlanta.

The data, despite the phase 3 trial results, “support continued development of etripamil nasal spray acute treatment of PSVT,” Dr. Stambler said.
Etripamil is an L-type calcium channel blocker. When administered by nasal spray, it reaches peak effects within about 10 minutes. But the action is short, with a decline in antiarrhythmia effects beginning about 30 minutes after the peak effect. 

In the NODE-301 trial, which employed a 2:1 randomization ratio, 138 patients self-administered 70 mg of etripamil or placebo immediately upon experiencing a suspected episode of PSVT.

Up until 45 minutes, the proportion of episodes that converted to sinus rhythm was about 66% greater (hazard ratio, 1.66; P = .02) on etripamil than placebo, but the advantage was then lost. By predefined primary endpoint of 5 hours, when 100% of placebo patients but not all etripamil patients had converted, there was a slight but nonstatistical advantage for placebo (HR 1.08; P = .1212).

However, because of the rapid onset and then the rapid offset of this agent, the 5-hour time point for comparing effects might not have been the optimal duration to compare effects, according to Dr. Stambler.

On the basis of safety of etripamil, which was not associated with any significant adverse events in NODE-301, and the early clinical effect, the investigators have looked again at the data.

For relief of patient-reported symptoms and patient-reported satisfaction, which were secondary endpoints of the study, the data support a clinical role, according to this new analysis. 

Specifically, there were large differences on a 7-point scale for all of the measured symptoms of PSVT in favor of etripamil, including rapid pulse (P = .002), palpitations (P = .0001), dizziness (P = 0.01), shortness of breath (P = 0.008), and anxiety (P = 0.006). A numerical advantage for chest pain did not reach significance.

“In general, patients reported scores of 4 to 5 on this scale, which corresponds to ‘not satisfied’ to ‘satisfied,’ while the placebo-treated patients reported scores of 2 to 3, which corresponds to ‘dissatisfied’ or ‘very dissatisfied,’ ” Dr. Stambler reported.

The favorable patient experience is also reflected in the Treatment Satisfaction with Questionnaire for Medication (TSQM-9), which was another NODE-301 endpoint. Evaluated when patients were still blinded to their assigned therapy, the advantage of etripamil over placebo for both global satisfaction (P = .007) and treatment effectiveness (P = .002) were also highly statistically significant.

The subjective experience of patients appeared to be reflected in objective measures. When the two groups were compared for interventions in an emergency room, the need was reduced by about half (12.1% vs. 24.5%; P = .051) among those treated with etripamil. Although this just missed the conventional measure of statistical significance, it was close. Similarly, patients randomized to etripamil required numerically fewer rescue medications (14.0% vs. 26.5%; P = .059). 

Adenosine was the most common of the rescue medications, according to Dr. Stambler. He said there was no difference between the groups in use of rescue oral therapies.

When comparing etripamil and placebo in the subgroup that did visit an emergency room for PSVT, there was a delay in ER visits among those randomized to etripamil (116 vs. 79 minutes; P < 0.05), suggesting that this agent reduced the sense of urgency when PSVT symptoms develop, according to Dr. Stambler.

On average, the patients who enrolled in this trial had a PSVT history of about 1.5 years. In the year prior to enrollment, the mean number of ER visits was about nine. 

In the trial design, patients were required to take a test dose of etripamil under observation by a physician before being sent home with their assigned therapy, but Dr. Stambler does not believe that the requirement, if the drug is approved, will be in the label. 

Unexpectedly, many patients had symptom relief even without converting to sinus rhythm, Dr. Stambler acknowledged. He speculated that the reduction in heart rate associated with etripamil might have provided a relief of symptoms sufficient to relieve anxiety, producing the relative advantage for patient satisfaction.

Jodie L. Hurwitz, MD, director of the electrophysiology lab at Medical City Hospital, Dallas, indicated that there is a need for new options for PSVT. An expert panelist during the session where these data were presented, she was particularly interested in rapid symptom relief. 

“It would be great to have a therapy that could be self-administered at home. Patients would like it, too,” she said. 

Mary N. Walsh, MD, a heart failure specialist affiliated with Indiana University, Indianapolis, sees a potential role of a self-administered therapy like etripamil in conjunction with wearable devices. She noted that the proportion of patients using these devices to monitor arrhythmias is increasing, providing a role for an easily transportable therapy that could be used quickly when symptoms develop. 

However, after the negative phase 3 trial, more data must now be collected to satisfy the regulatory authorities that this agent is safe and effective. Dr. Stambler said that the developer is now committed to pursue these studies.

Dr. Stambler has a financial relationship with Milestone Pharmaceuticals, which is developing etripamil nasal spray and was the sponsor of this trial. Dr. Walsh and Dr. Hurwitz have no potential relevant conflicts of interest.
 

Significant improvement in the control of symptoms related to paroxysmal supraventricular tachycardia (PSVT) is resurrecting etripamil as a self-administered nasal spray a year after it failed to meet the primary endpoint in a phase 3 trial, according to a new analysis from this same study presented at the annual scientific sessions of the American College of Cardiology.

Thinkstock

In the phase 3 NODE-301 trial, presented at the 2020 Heart Rhythm Society annual meeting, etripamil did not show an advantage over placebo at 5 hours for achieving sinus rhythm. Nevertheless, a new presentation of the secondary outcomes suggests substantial clinical benefit.

These advantages include significant reductions in PSVT symptoms, a trend for fewer emergency room visits, and a degree of patient satisfaction that appears meaningful, according to Bruce S. Stambler, MD, an electrophysiologist affiliated with Piedmont Heart Institute, Atlanta.

The data, despite the phase 3 trial results, “support continued development of etripamil nasal spray acute treatment of PSVT,” Dr. Stambler said.
Etripamil is an L-type calcium channel blocker. When administered by nasal spray, it reaches peak effects within about 10 minutes. But the action is short, with a decline in antiarrhythmia effects beginning about 30 minutes after the peak effect. 

In the NODE-301 trial, which employed a 2:1 randomization ratio, 138 patients self-administered 70 mg of etripamil or placebo immediately upon experiencing a suspected episode of PSVT.

Up until 45 minutes, the proportion of episodes that converted to sinus rhythm was about 66% greater (hazard ratio, 1.66; P = .02) on etripamil than placebo, but the advantage was then lost. By predefined primary endpoint of 5 hours, when 100% of placebo patients but not all etripamil patients had converted, there was a slight but nonstatistical advantage for placebo (HR 1.08; P = .1212).

However, because of the rapid onset and then the rapid offset of this agent, the 5-hour time point for comparing effects might not have been the optimal duration to compare effects, according to Dr. Stambler.

On the basis of safety of etripamil, which was not associated with any significant adverse events in NODE-301, and the early clinical effect, the investigators have looked again at the data.

For relief of patient-reported symptoms and patient-reported satisfaction, which were secondary endpoints of the study, the data support a clinical role, according to this new analysis. 

Specifically, there were large differences on a 7-point scale for all of the measured symptoms of PSVT in favor of etripamil, including rapid pulse (P = .002), palpitations (P = .0001), dizziness (P = 0.01), shortness of breath (P = 0.008), and anxiety (P = 0.006). A numerical advantage for chest pain did not reach significance.

“In general, patients reported scores of 4 to 5 on this scale, which corresponds to ‘not satisfied’ to ‘satisfied,’ while the placebo-treated patients reported scores of 2 to 3, which corresponds to ‘dissatisfied’ or ‘very dissatisfied,’ ” Dr. Stambler reported.

The favorable patient experience is also reflected in the Treatment Satisfaction with Questionnaire for Medication (TSQM-9), which was another NODE-301 endpoint. Evaluated when patients were still blinded to their assigned therapy, the advantage of etripamil over placebo for both global satisfaction (P = .007) and treatment effectiveness (P = .002) were also highly statistically significant.

The subjective experience of patients appeared to be reflected in objective measures. When the two groups were compared for interventions in an emergency room, the need was reduced by about half (12.1% vs. 24.5%; P = .051) among those treated with etripamil. Although this just missed the conventional measure of statistical significance, it was close. Similarly, patients randomized to etripamil required numerically fewer rescue medications (14.0% vs. 26.5%; P = .059). 

Adenosine was the most common of the rescue medications, according to Dr. Stambler. He said there was no difference between the groups in use of rescue oral therapies.

When comparing etripamil and placebo in the subgroup that did visit an emergency room for PSVT, there was a delay in ER visits among those randomized to etripamil (116 vs. 79 minutes; P < 0.05), suggesting that this agent reduced the sense of urgency when PSVT symptoms develop, according to Dr. Stambler.

On average, the patients who enrolled in this trial had a PSVT history of about 1.5 years. In the year prior to enrollment, the mean number of ER visits was about nine. 

In the trial design, patients were required to take a test dose of etripamil under observation by a physician before being sent home with their assigned therapy, but Dr. Stambler does not believe that the requirement, if the drug is approved, will be in the label. 

Unexpectedly, many patients had symptom relief even without converting to sinus rhythm, Dr. Stambler acknowledged. He speculated that the reduction in heart rate associated with etripamil might have provided a relief of symptoms sufficient to relieve anxiety, producing the relative advantage for patient satisfaction.

Jodie L. Hurwitz, MD, director of the electrophysiology lab at Medical City Hospital, Dallas, indicated that there is a need for new options for PSVT. An expert panelist during the session where these data were presented, she was particularly interested in rapid symptom relief. 

“It would be great to have a therapy that could be self-administered at home. Patients would like it, too,” she said. 

Mary N. Walsh, MD, a heart failure specialist affiliated with Indiana University, Indianapolis, sees a potential role of a self-administered therapy like etripamil in conjunction with wearable devices. She noted that the proportion of patients using these devices to monitor arrhythmias is increasing, providing a role for an easily transportable therapy that could be used quickly when symptoms develop. 

However, after the negative phase 3 trial, more data must now be collected to satisfy the regulatory authorities that this agent is safe and effective. Dr. Stambler said that the developer is now committed to pursue these studies.

Dr. Stambler has a financial relationship with Milestone Pharmaceuticals, which is developing etripamil nasal spray and was the sponsor of this trial. Dr. Walsh and Dr. Hurwitz have no potential relevant conflicts of interest.
 

Significant improvement in the control of symptoms related to paroxysmal supraventricular tachycardia (PSVT) is resurrecting etripamil as a self-administered nasal spray a year after it failed to meet the primary endpoint in a phase 3 trial, according to a new analysis from this same study presented at the annual scientific sessions of the American College of Cardiology.

Thinkstock

In the phase 3 NODE-301 trial, presented at the 2020 Heart Rhythm Society annual meeting, etripamil did not show an advantage over placebo at 5 hours for achieving sinus rhythm. Nevertheless, a new presentation of the secondary outcomes suggests substantial clinical benefit.

These advantages include significant reductions in PSVT symptoms, a trend for fewer emergency room visits, and a degree of patient satisfaction that appears meaningful, according to Bruce S. Stambler, MD, an electrophysiologist affiliated with Piedmont Heart Institute, Atlanta.

The data, despite the phase 3 trial results, “support continued development of etripamil nasal spray acute treatment of PSVT,” Dr. Stambler said.
Etripamil is an L-type calcium channel blocker. When administered by nasal spray, it reaches peak effects within about 10 minutes. But the action is short, with a decline in antiarrhythmia effects beginning about 30 minutes after the peak effect. 

In the NODE-301 trial, which employed a 2:1 randomization ratio, 138 patients self-administered 70 mg of etripamil or placebo immediately upon experiencing a suspected episode of PSVT.

Up until 45 minutes, the proportion of episodes that converted to sinus rhythm was about 66% greater (hazard ratio, 1.66; P = .02) on etripamil than placebo, but the advantage was then lost. By predefined primary endpoint of 5 hours, when 100% of placebo patients but not all etripamil patients had converted, there was a slight but nonstatistical advantage for placebo (HR 1.08; P = .1212).

However, because of the rapid onset and then the rapid offset of this agent, the 5-hour time point for comparing effects might not have been the optimal duration to compare effects, according to Dr. Stambler.

On the basis of safety of etripamil, which was not associated with any significant adverse events in NODE-301, and the early clinical effect, the investigators have looked again at the data.

For relief of patient-reported symptoms and patient-reported satisfaction, which were secondary endpoints of the study, the data support a clinical role, according to this new analysis. 

Specifically, there were large differences on a 7-point scale for all of the measured symptoms of PSVT in favor of etripamil, including rapid pulse (P = .002), palpitations (P = .0001), dizziness (P = 0.01), shortness of breath (P = 0.008), and anxiety (P = 0.006). A numerical advantage for chest pain did not reach significance.

“In general, patients reported scores of 4 to 5 on this scale, which corresponds to ‘not satisfied’ to ‘satisfied,’ while the placebo-treated patients reported scores of 2 to 3, which corresponds to ‘dissatisfied’ or ‘very dissatisfied,’ ” Dr. Stambler reported.

The favorable patient experience is also reflected in the Treatment Satisfaction with Questionnaire for Medication (TSQM-9), which was another NODE-301 endpoint. Evaluated when patients were still blinded to their assigned therapy, the advantage of etripamil over placebo for both global satisfaction (P = .007) and treatment effectiveness (P = .002) were also highly statistically significant.

The subjective experience of patients appeared to be reflected in objective measures. When the two groups were compared for interventions in an emergency room, the need was reduced by about half (12.1% vs. 24.5%; P = .051) among those treated with etripamil. Although this just missed the conventional measure of statistical significance, it was close. Similarly, patients randomized to etripamil required numerically fewer rescue medications (14.0% vs. 26.5%; P = .059). 

Adenosine was the most common of the rescue medications, according to Dr. Stambler. He said there was no difference between the groups in use of rescue oral therapies.

When comparing etripamil and placebo in the subgroup that did visit an emergency room for PSVT, there was a delay in ER visits among those randomized to etripamil (116 vs. 79 minutes; P < 0.05), suggesting that this agent reduced the sense of urgency when PSVT symptoms develop, according to Dr. Stambler.

On average, the patients who enrolled in this trial had a PSVT history of about 1.5 years. In the year prior to enrollment, the mean number of ER visits was about nine. 

In the trial design, patients were required to take a test dose of etripamil under observation by a physician before being sent home with their assigned therapy, but Dr. Stambler does not believe that the requirement, if the drug is approved, will be in the label. 

Unexpectedly, many patients had symptom relief even without converting to sinus rhythm, Dr. Stambler acknowledged. He speculated that the reduction in heart rate associated with etripamil might have provided a relief of symptoms sufficient to relieve anxiety, producing the relative advantage for patient satisfaction.

Jodie L. Hurwitz, MD, director of the electrophysiology lab at Medical City Hospital, Dallas, indicated that there is a need for new options for PSVT. An expert panelist during the session where these data were presented, she was particularly interested in rapid symptom relief. 

“It would be great to have a therapy that could be self-administered at home. Patients would like it, too,” she said. 

Mary N. Walsh, MD, a heart failure specialist affiliated with Indiana University, Indianapolis, sees a potential role of a self-administered therapy like etripamil in conjunction with wearable devices. She noted that the proportion of patients using these devices to monitor arrhythmias is increasing, providing a role for an easily transportable therapy that could be used quickly when symptoms develop. 

However, after the negative phase 3 trial, more data must now be collected to satisfy the regulatory authorities that this agent is safe and effective. Dr. Stambler said that the developer is now committed to pursue these studies.

Dr. Stambler has a financial relationship with Milestone Pharmaceuticals, which is developing etripamil nasal spray and was the sponsor of this trial. Dr. Walsh and Dr. Hurwitz have no potential relevant conflicts of interest.
 

Left atrial appendage occlusion performed at the time of other heart surgery reduces the risk for stroke by about one-third in high-risk patients with atrial fibrillation (AFib), according to results of the Left Atrial Appendage Occlusion Study III (LAAOS III).

At 3.8 years’ follow-up, the primary endpoint of ischemic stroke or systemic embolism occurred in 4.8% of patients randomly assigned to left atrial appendage occlusion (LAAO) and 7.0% of those with no occlusion. This translated into a 33% relative risk reduction (hazard ratio, 0.67; 95% confidence interval, 0.53-0.85; P = .001).

In a landmark analysis, the effect was present early on but was more pronounced after the first 30 days, reducing the relative risk by 42% (HR, 0.58; 95% CI, 0.42-0.80), the researchers report.

The reduction in ongoing stroke risk was on top of oral anticoagulation (OAC) and consistent across all subgroups, Richard Whitlock, MD, PhD, professor of surgery, McMaster University, Hamilton, Ont., reported in a late-breaking trial session at the annual scientific sessions of the American College of Cardiology.

The procedure was safe and added, on average, just 6 minutes to cardiopulmonary bypass time, according to the results, simultaneously published in the New England Journal of Medicine.

“Any patient who comes to the operating room who fits the profile of a LAAOS III patient – so has atrial fibrillation and an elevated stroke risk based on their CHA₂DS₂-VASc score – the appendage should come off,” he said in an interview.

Commenting during the formal discussion, panelist Michael J. Mack, MD, of Baylor Health Care System in Houston, said, “This is potentially a game-changing, practice-changing study” but asked if there are any patients who shouldn’t undergo LAAO, such as those with heart failure (HF).

Dr. Whitlock said about 10%-15% of patients coming for heart surgery have a history of AFib and “as surgeons, you do need to individualize therapy. If you have a very frail patient, have concerns about tissue quality, you really need to think about how you would occlude the left atrial appendage or if you would occlude.”

Reassuringly, he noted, the data show no increase in HF hospitalizations and a beneficial effect on stroke among patients with HF and those with low ejection fractions, below 50%.

Observational data on surgical occlusion have been inconsistent, and current guidelines offer a weak recommendation in patients with AFib who have a contraindication to long-term anticoagulation. This is the first study to definitively prove that ischemic stroke is reduced by managing the left atrial appendage, he said in an interview.

“The previous percutaneous trials failed to demonstrate that; they demonstrated noninferiority but it was driven primarily by the avoidance of hemorrhagic events or strokes through taking patients off oral anticoagulation,” he said.

The results should translate into a class I guideline recommendation, he added. “This opens up a new paradigm of treatment for atrial fibrillation and stroke prevention in that it is really the first study that has looked at the additive effects of managing the left atrial appendage in addition to oral anticoagulation, and it’s protective on top of oral anticoagulation. That is a paradigm shift.”

In an accompanying editorial, Richard L. Page, MD, University of Vermont in Burlington, said the trial provides no insight on the possible benefit of surgical occlusion in patients unable to receive anticoagulation or with a lower CHA2DS2-VASc score, but he agreed a class I recommendation is likely for the population studied.

“I hope and anticipate that the results of this paper will strengthen the guideline indications for surgical left atrial appendage occlusion and will increase the number of cardiac surgeons who routinely perform this add-on procedure,” he said. “While many already perform this procedure, cardiac surgeons should now feel more comfortable that surgical left atrial appendage occlusion is indicated and supported by high-quality randomized data.”

Unfortunately, LAAOS III does not answer the question of whether patients can come off anticoagulation, but it does show surgical occlusion provides added protection from strokes, which can be huge with atrial fibrillation, Dr. Whitlock said.

“I spoke with a patient today who is an active 66-year-old individual on a [direct oral anticoagulant], and his stroke risk has been further reduced by 30%-40%, so he was ecstatic to hear the results,” Dr. Whitlock said. “I think it’s peace of mind.”

Global, nonindustry effort

LAAOS III investigators at 105 centers in 27 countries enrolled 4,811 patients undergoing cardiac surgery (mean age, 71 years; 68% male) who had a CHA₂DS₂-VASc score of at least 2.

In all, 4,770 were randomly assigned to no LAAO or occlusion via the preferred technique of amputation with suture closure of the stump as well as stapler occlusion, or epicardial device closure with the AtriClip (AtriCure) or TigerPaw (Maquet Medical). The treating team, researchers, and patients were blinded to assignment.

Patients were followed every 6 months with a validated stroke questionnaire. The trial was stopped early by the data safety monitoring board after the second interim analysis.

The mean CHA₂DS₂-VASc score was 4.2, one-third of patients had permanent AFib, 9% had a history of stroke, and more than two-thirds underwent a valve procedure, which makes LAAOS III unique, as many previous trials excluded valvular AFib, Dr. Whitlock pointed out.

Operative outcomes in the LAAO and no-LAAO groups were as follows:

• Bypass time: mean, 119 minutes vs. 113 minutes.  
• Cross-clamp time: mean, 86 minutes vs. 82 minutes.
• Chest tube output: median, 520 mL vs. 500 mL.
• Reoperation for bleeding: both, 4.0%.
• Prolonged hospitalization due to HF: 5 vs. 14 events.
• 30-day mortality: 3.7% vs 4.0%.

The primary safety outcome of HF hospitalization at 3.8 years occurred in 7.7% of patients with LAAO and 6.8% without occlusion (HR, 1.13; 95% CI, 0.92-1.40), despite concerns that taking off the appendage could worsen HF risk by impairing renal clearance of salt and water.

“There’s observational data on either side of the fence, so it was an important endpoint that people were concerned about,” Dr. Whitlock told this news organization. “We had a data collection firm dedicated to admission for heart failure to really tease that out and, in the end, we saw no adverse effect.”

Although rates of ischemic stroke at 3.8 years were lower with LAAO than without (4.2% vs. 6.6%; HR, 0.62; 95% CI, 0.48-0.80), there was no difference in systemic embolism (0.3% for both) or death (22.6% vs. 22.5%).

In LAAOS III, fewer than 2% of the deaths were attributed to stroke, which is consistent with large stroke registries, Dr. Whitlock said. “Stroke is not what causes people with atrial fibrillation to die; it’s actually the progression on to heart failure.”

The positive effect on stroke was consistent across all subgroups, including sex, age, rheumatic heart disease, type of OAC at baseline, CHA₂DS₂-VASc score (≤4 vs. >4), type of surgery, history of heart failure or hypertension, and prior stroke/transient ischemic attack/systemic embolism.

Panelist Anne B. Curtis, MD, State University of New York at Buffalo, expressed surprise that about half of patients at baseline were not receiving anticoagulation and questioned whether event rates varied among those who did and didn’t stay on OAC.

Dr. Whitlock noted that OAC is often underused in AFib and that analyses showed the effects were consistent whether patients were on or off anticoagulants.

The study was sponsored by the Population Health Research Institute, McMaster University. Dr. Whitlock reported no relevant disclosures. Dr. Curtis reported consultant fees/honoraria from Abbott, Janssen, Medtronic, Milestone Pharmaceuticals, and Sanofi Aventis, and data safety monitoring board participation for Medtronic.
 

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

Left atrial appendage occlusion performed at the time of other heart surgery reduces the risk for stroke by about one-third in high-risk patients with atrial fibrillation (AFib), according to results of the Left Atrial Appendage Occlusion Study III (LAAOS III).

At 3.8 years’ follow-up, the primary endpoint of ischemic stroke or systemic embolism occurred in 4.8% of patients randomly assigned to left atrial appendage occlusion (LAAO) and 7.0% of those with no occlusion. This translated into a 33% relative risk reduction (hazard ratio, 0.67; 95% confidence interval, 0.53-0.85; P = .001).

In a landmark analysis, the effect was present early on but was more pronounced after the first 30 days, reducing the relative risk by 42% (HR, 0.58; 95% CI, 0.42-0.80), the researchers report.

The reduction in ongoing stroke risk was on top of oral anticoagulation (OAC) and consistent across all subgroups, Richard Whitlock, MD, PhD, professor of surgery, McMaster University, Hamilton, Ont., reported in a late-breaking trial session at the annual scientific sessions of the American College of Cardiology.

The procedure was safe and added, on average, just 6 minutes to cardiopulmonary bypass time, according to the results, simultaneously published in the New England Journal of Medicine.

“Any patient who comes to the operating room who fits the profile of a LAAOS III patient – so has atrial fibrillation and an elevated stroke risk based on their CHA₂DS₂-VASc score – the appendage should come off,” he said in an interview.

Commenting during the formal discussion, panelist Michael J. Mack, MD, of Baylor Health Care System in Houston, said, “This is potentially a game-changing, practice-changing study” but asked if there are any patients who shouldn’t undergo LAAO, such as those with heart failure (HF).

Dr. Whitlock said about 10%-15% of patients coming for heart surgery have a history of AFib and “as surgeons, you do need to individualize therapy. If you have a very frail patient, have concerns about tissue quality, you really need to think about how you would occlude the left atrial appendage or if you would occlude.”

Reassuringly, he noted, the data show no increase in HF hospitalizations and a beneficial effect on stroke among patients with HF and those with low ejection fractions, below 50%.

Observational data on surgical occlusion have been inconsistent, and current guidelines offer a weak recommendation in patients with AFib who have a contraindication to long-term anticoagulation. This is the first study to definitively prove that ischemic stroke is reduced by managing the left atrial appendage, he said in an interview.

“The previous percutaneous trials failed to demonstrate that; they demonstrated noninferiority but it was driven primarily by the avoidance of hemorrhagic events or strokes through taking patients off oral anticoagulation,” he said.

The results should translate into a class I guideline recommendation, he added. “This opens up a new paradigm of treatment for atrial fibrillation and stroke prevention in that it is really the first study that has looked at the additive effects of managing the left atrial appendage in addition to oral anticoagulation, and it’s protective on top of oral anticoagulation. That is a paradigm shift.”

In an accompanying editorial, Richard L. Page, MD, University of Vermont in Burlington, said the trial provides no insight on the possible benefit of surgical occlusion in patients unable to receive anticoagulation or with a lower CHA2DS2-VASc score, but he agreed a class I recommendation is likely for the population studied.

“I hope and anticipate that the results of this paper will strengthen the guideline indications for surgical left atrial appendage occlusion and will increase the number of cardiac surgeons who routinely perform this add-on procedure,” he said. “While many already perform this procedure, cardiac surgeons should now feel more comfortable that surgical left atrial appendage occlusion is indicated and supported by high-quality randomized data.”

Unfortunately, LAAOS III does not answer the question of whether patients can come off anticoagulation, but it does show surgical occlusion provides added protection from strokes, which can be huge with atrial fibrillation, Dr. Whitlock said.

“I spoke with a patient today who is an active 66-year-old individual on a [direct oral anticoagulant], and his stroke risk has been further reduced by 30%-40%, so he was ecstatic to hear the results,” Dr. Whitlock said. “I think it’s peace of mind.”

Global, nonindustry effort

LAAOS III investigators at 105 centers in 27 countries enrolled 4,811 patients undergoing cardiac surgery (mean age, 71 years; 68% male) who had a CHA₂DS₂-VASc score of at least 2.

In all, 4,770 were randomly assigned to no LAAO or occlusion via the preferred technique of amputation with suture closure of the stump as well as stapler occlusion, or epicardial device closure with the AtriClip (AtriCure) or TigerPaw (Maquet Medical). The treating team, researchers, and patients were blinded to assignment.

Patients were followed every 6 months with a validated stroke questionnaire. The trial was stopped early by the data safety monitoring board after the second interim analysis.

The mean CHA₂DS₂-VASc score was 4.2, one-third of patients had permanent AFib, 9% had a history of stroke, and more than two-thirds underwent a valve procedure, which makes LAAOS III unique, as many previous trials excluded valvular AFib, Dr. Whitlock pointed out.

Operative outcomes in the LAAO and no-LAAO groups were as follows:

• Bypass time: mean, 119 minutes vs. 113 minutes.  
• Cross-clamp time: mean, 86 minutes vs. 82 minutes.
• Chest tube output: median, 520 mL vs. 500 mL.
• Reoperation for bleeding: both, 4.0%.
• Prolonged hospitalization due to HF: 5 vs. 14 events.
• 30-day mortality: 3.7% vs 4.0%.

The primary safety outcome of HF hospitalization at 3.8 years occurred in 7.7% of patients with LAAO and 6.8% without occlusion (HR, 1.13; 95% CI, 0.92-1.40), despite concerns that taking off the appendage could worsen HF risk by impairing renal clearance of salt and water.

“There’s observational data on either side of the fence, so it was an important endpoint that people were concerned about,” Dr. Whitlock told this news organization. “We had a data collection firm dedicated to admission for heart failure to really tease that out and, in the end, we saw no adverse effect.”

Although rates of ischemic stroke at 3.8 years were lower with LAAO than without (4.2% vs. 6.6%; HR, 0.62; 95% CI, 0.48-0.80), there was no difference in systemic embolism (0.3% for both) or death (22.6% vs. 22.5%).

In LAAOS III, fewer than 2% of the deaths were attributed to stroke, which is consistent with large stroke registries, Dr. Whitlock said. “Stroke is not what causes people with atrial fibrillation to die; it’s actually the progression on to heart failure.”

The positive effect on stroke was consistent across all subgroups, including sex, age, rheumatic heart disease, type of OAC at baseline, CHA₂DS₂-VASc score (≤4 vs. >4), type of surgery, history of heart failure or hypertension, and prior stroke/transient ischemic attack/systemic embolism.

Panelist Anne B. Curtis, MD, State University of New York at Buffalo, expressed surprise that about half of patients at baseline were not receiving anticoagulation and questioned whether event rates varied among those who did and didn’t stay on OAC.

Dr. Whitlock noted that OAC is often underused in AFib and that analyses showed the effects were consistent whether patients were on or off anticoagulants.

The study was sponsored by the Population Health Research Institute, McMaster University. Dr. Whitlock reported no relevant disclosures. Dr. Curtis reported consultant fees/honoraria from Abbott, Janssen, Medtronic, Milestone Pharmaceuticals, and Sanofi Aventis, and data safety monitoring board participation for Medtronic.
 

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

Left atrial appendage occlusion performed at the time of other heart surgery reduces the risk for stroke by about one-third in high-risk patients with atrial fibrillation (AFib), according to results of the Left Atrial Appendage Occlusion Study III (LAAOS III).

At 3.8 years’ follow-up, the primary endpoint of ischemic stroke or systemic embolism occurred in 4.8% of patients randomly assigned to left atrial appendage occlusion (LAAO) and 7.0% of those with no occlusion. This translated into a 33% relative risk reduction (hazard ratio, 0.67; 95% confidence interval, 0.53-0.85; P = .001).

In a landmark analysis, the effect was present early on but was more pronounced after the first 30 days, reducing the relative risk by 42% (HR, 0.58; 95% CI, 0.42-0.80), the researchers report.

The reduction in ongoing stroke risk was on top of oral anticoagulation (OAC) and consistent across all subgroups, Richard Whitlock, MD, PhD, professor of surgery, McMaster University, Hamilton, Ont., reported in a late-breaking trial session at the annual scientific sessions of the American College of Cardiology.

The procedure was safe and added, on average, just 6 minutes to cardiopulmonary bypass time, according to the results, simultaneously published in the New England Journal of Medicine.

“Any patient who comes to the operating room who fits the profile of a LAAOS III patient – so has atrial fibrillation and an elevated stroke risk based on their CHA₂DS₂-VASc score – the appendage should come off,” he said in an interview.

Commenting during the formal discussion, panelist Michael J. Mack, MD, of Baylor Health Care System in Houston, said, “This is potentially a game-changing, practice-changing study” but asked if there are any patients who shouldn’t undergo LAAO, such as those with heart failure (HF).

Dr. Whitlock said about 10%-15% of patients coming for heart surgery have a history of AFib and “as surgeons, you do need to individualize therapy. If you have a very frail patient, have concerns about tissue quality, you really need to think about how you would occlude the left atrial appendage or if you would occlude.”

Reassuringly, he noted, the data show no increase in HF hospitalizations and a beneficial effect on stroke among patients with HF and those with low ejection fractions, below 50%.

Observational data on surgical occlusion have been inconsistent, and current guidelines offer a weak recommendation in patients with AFib who have a contraindication to long-term anticoagulation. This is the first study to definitively prove that ischemic stroke is reduced by managing the left atrial appendage, he said in an interview.

“The previous percutaneous trials failed to demonstrate that; they demonstrated noninferiority but it was driven primarily by the avoidance of hemorrhagic events or strokes through taking patients off oral anticoagulation,” he said.

The results should translate into a class I guideline recommendation, he added. “This opens up a new paradigm of treatment for atrial fibrillation and stroke prevention in that it is really the first study that has looked at the additive effects of managing the left atrial appendage in addition to oral anticoagulation, and it’s protective on top of oral anticoagulation. That is a paradigm shift.”

In an accompanying editorial, Richard L. Page, MD, University of Vermont in Burlington, said the trial provides no insight on the possible benefit of surgical occlusion in patients unable to receive anticoagulation or with a lower CHA2DS2-VASc score, but he agreed a class I recommendation is likely for the population studied.

“I hope and anticipate that the results of this paper will strengthen the guideline indications for surgical left atrial appendage occlusion and will increase the number of cardiac surgeons who routinely perform this add-on procedure,” he said. “While many already perform this procedure, cardiac surgeons should now feel more comfortable that surgical left atrial appendage occlusion is indicated and supported by high-quality randomized data.”

Unfortunately, LAAOS III does not answer the question of whether patients can come off anticoagulation, but it does show surgical occlusion provides added protection from strokes, which can be huge with atrial fibrillation, Dr. Whitlock said.

“I spoke with a patient today who is an active 66-year-old individual on a [direct oral anticoagulant], and his stroke risk has been further reduced by 30%-40%, so he was ecstatic to hear the results,” Dr. Whitlock said. “I think it’s peace of mind.”

Global, nonindustry effort

LAAOS III investigators at 105 centers in 27 countries enrolled 4,811 patients undergoing cardiac surgery (mean age, 71 years; 68% male) who had a CHA₂DS₂-VASc score of at least 2.

In all, 4,770 were randomly assigned to no LAAO or occlusion via the preferred technique of amputation with suture closure of the stump as well as stapler occlusion, or epicardial device closure with the AtriClip (AtriCure) or TigerPaw (Maquet Medical). The treating team, researchers, and patients were blinded to assignment.

Patients were followed every 6 months with a validated stroke questionnaire. The trial was stopped early by the data safety monitoring board after the second interim analysis.

The mean CHA₂DS₂-VASc score was 4.2, one-third of patients had permanent AFib, 9% had a history of stroke, and more than two-thirds underwent a valve procedure, which makes LAAOS III unique, as many previous trials excluded valvular AFib, Dr. Whitlock pointed out.

Operative outcomes in the LAAO and no-LAAO groups were as follows:

• Bypass time: mean, 119 minutes vs. 113 minutes.  
• Cross-clamp time: mean, 86 minutes vs. 82 minutes.
• Chest tube output: median, 520 mL vs. 500 mL.
• Reoperation for bleeding: both, 4.0%.
• Prolonged hospitalization due to HF: 5 vs. 14 events.
• 30-day mortality: 3.7% vs 4.0%.

The primary safety outcome of HF hospitalization at 3.8 years occurred in 7.7% of patients with LAAO and 6.8% without occlusion (HR, 1.13; 95% CI, 0.92-1.40), despite concerns that taking off the appendage could worsen HF risk by impairing renal clearance of salt and water.

“There’s observational data on either side of the fence, so it was an important endpoint that people were concerned about,” Dr. Whitlock told this news organization. “We had a data collection firm dedicated to admission for heart failure to really tease that out and, in the end, we saw no adverse effect.”

Although rates of ischemic stroke at 3.8 years were lower with LAAO than without (4.2% vs. 6.6%; HR, 0.62; 95% CI, 0.48-0.80), there was no difference in systemic embolism (0.3% for both) or death (22.6% vs. 22.5%).

In LAAOS III, fewer than 2% of the deaths were attributed to stroke, which is consistent with large stroke registries, Dr. Whitlock said. “Stroke is not what causes people with atrial fibrillation to die; it’s actually the progression on to heart failure.”

The positive effect on stroke was consistent across all subgroups, including sex, age, rheumatic heart disease, type of OAC at baseline, CHA₂DS₂-VASc score (≤4 vs. >4), type of surgery, history of heart failure or hypertension, and prior stroke/transient ischemic attack/systemic embolism.

Panelist Anne B. Curtis, MD, State University of New York at Buffalo, expressed surprise that about half of patients at baseline were not receiving anticoagulation and questioned whether event rates varied among those who did and didn’t stay on OAC.

Dr. Whitlock noted that OAC is often underused in AFib and that analyses showed the effects were consistent whether patients were on or off anticoagulants.

The study was sponsored by the Population Health Research Institute, McMaster University. Dr. Whitlock reported no relevant disclosures. Dr. Curtis reported consultant fees/honoraria from Abbott, Janssen, Medtronic, Milestone Pharmaceuticals, and Sanofi Aventis, and data safety monitoring board participation for Medtronic.
 

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

No significant difference in cardiovascular events or major bleeding was shown between patients with established coronary heart disease assigned to a daily aspirin dose of 81 mg and those receiving a dose of 325 mg in the 15,000-patient ADAPTABLE trial.

Although substantial dose switching occurred in the trial, particularly from the higher to the lower dose, lead investigator W. Schuyler Jones, MD, believes the results support the use of the 81-mg dose in most patients.  

“While we would have liked to see higher adherence to the assigned doses, we think the results of the trial are reliable,” Dr. Jones said in an interview.

The real-world, open-label, pragmatic trial also involved an innovative low-cost design allowing researchers to identify and communicate with eligible patients directly, opening up a new cost-effective method to conduct clinical research going forward.

Dr. Jones, a cardiologist and associate professor of medicine at Duke University Medical Center, Durham, N.C., presented the ADAPTABLE results at the annual scientific sessions of the American College of Cardiology. They were simultaneously published online in the New England Journal of Medicine.   

He noted there were mixed signals in the results. “For example, the main intent-to-treat analysis showed a trend to a lower rate of all-cause death in the 81-mg group, but the subgroup of patients who stayed on the 325-mg dose throughout the study had a lower event rate. But overall, there was no difference.”

Dr. Jones said the investigators had the following take-home messages to patients: “If a patient is already taking 81 mg, staying on this dose is probably right given the similar study results for the primary endpoint and that we didn’t find conclusive evidence that 325 mg is better. But for patients who have tolerated 325 mg long term, then they may want to stay on this dose as it may be associated with moderate benefit.”

Dr. Jones pointed out that, overall, patients who switched doses tended to do worse, but he suggested this may have been more to do with underlying reasons for switching rather than the different dose itself. “For example, switching often happens after bleeding or bruising, which can also often preempt an ischemic event, and other illnesses, such as cancer or atrial fibrillation, can also lead patients to change doses.”

“With the caveat that this trial did not include new patients (the vast majority of patients had been taking aspirin previously) the results support the approach of starting new patients on 81 mg, which is what we have been seeing in evolving clinical practice in recent years,” he added.  

Dr. Jones explained that the trial set out to answer the simple but important question about the best dose of aspirin in patients with heart disease.

“Aspirin has been established as an appropriate long-term medication for patients with ischemic heart disease since the 1980s, but we really don’t have any good information on the correct dose.

He noted that the U.S. guidelines suggest any dose in the range of 81 mg to 325 mg daily can be used, whereas the European guidelines recommend 81 mg daily, although this is mainly based on observational data and expert opinion; there is little hard, randomized-trial evidence.

The ADAPTABLE trial randomly assigned 15,076 patients with established heart disease to receive 81 mg or 325 mg of aspirin. Before randomization, 96% of those with available information were already taking aspirin, 85% of whom were taking 81 mg.

After a mean follow-up of 26 months, the primary efficacy endpoint – a composite of all-cause death, myocardial infarction, or stroke – had occurred in 7.28% of the 81-mg group and 7.51% of the 325-mg group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14).     

The main safety endpoint, hospitalization for major bleeding with an associated blood transfusion, occurred in 0.63% of the 81-mg group and 0.60% of the 325-mg group (HR, 1.18; 95% CI, 0.79-1.77).

“The bleeding safety endpoint looked similar, which may be counterintuitive to what may have been expected,” Dr. Jones commented. “However, the safety endpoint was very stringent. We still haven’t analyzed all the less serious ADR [adverse drug event]/bleeding data, but overall, it does appear to be balanced.”

He added: “Most cardiologists probably may not have expected to see much difference in efficacy between these two doses but would maybe have anticipated a lower bleeding rate with the low dose. I was a little surprised to see such a low bleeding rate in the 325-mg group.”

Patients assigned to 325 mg had a higher incidence of dose switching (41.6%) than those assigned to 81 mg (7.1%) and were more likely to discontinue treatment (11.1% vs. 7.0%). This resulted in fewer median days of exposure to the assigned dose in the 325-mg group (434 vs. 650 days).

“This was an open-label study, and such studies always suffer from a degree of infidelity to the assigned treatment group,” Dr. Jones said. “In ADAPTABLE, this was unbalanced in that a much greater number of patients switched from 325 mg to 81 mg than the other way round.”   

“But our results do reflect what happens in normal life,” he added. “People behaved in the study like they do in the real world. They sometimes changed their dose and sometimes stopped taking aspirin altogether. So, I think the results are an accurate representation of the real world.”

A sensitivity analysis based on which dose the patient actually reported taking showed a higher risk for death, MI, or stroke in patients who took 81 mg than those who took 325 mg (HR, 1.25; 95% CI, 1.10-1.43). But as with any postrandomization analysis, this approach has many inherent biases, Dr. Jones cautioned.
 

Innovative study design  

The ADAPTABLE study used an innovative low-cost design, which involved direct communication with the patients themselves.

Using the National Patient-Centered Clinical Research Network (PCORnet), a group of 40 U.S. centers committed to compiling data in a common format, invitations to enroll in the study were sent to eligible patients identified from medical records. Consent and randomization took place on the patient web portal. 

Participants then purchased aspirin at the assigned dose themselves, and all follow-up was done virtually or on the phone, with outcomes ascertained remotely (from patient reports, electronic medical records, and insurance claims) without adjudication.   

“This is a pretty neat way to do clinical research, enabling us to conduct a 15,000-patient trial on a very tight budget,” Dr. Jones commented. 

He estimated that the trial cost around $18 to $19 million. “No industry funder would have sponsored such a study of aspirin, and a typical trial with this many patients conducted in the traditional way would have cost at least 5 or 10 times more,” he said.

“This is the first time this type of study has been done in the U.S. on such a large scale, and it opens up this method for future research.”

He explained that this design, communicating directly with patients, somewhat limits the questions that can be addressed. “As aspirin is purchased over the counter by patients themselves, this is a question that lent itself to be answered in this way.” 

Another innovative design feature was the inclusion of “patient partners,” with one patient nominated by each center to be part of the organization of the trial. “This helped keep the research relevant to what patients care about.

They also helped with the recruitment strategy and communication with participants. I think this is something we need to continue and prioritize in clinical research going forward,” Dr. Jones noted.

‘Pioneering’ trial

Discussants of the study at the ACC presentation congratulated the investigators on conducting such an innovative trial.

Donald Lloyd-Jones, MD, chair of preventive medicine at Northwestern University, Chicago, said, “This is really a pioneering large pragmatic trial, and we’re going to need to see more of these over the next few years. The most important legacy from this trial for me is that you did it, and that you showed us many of the promises and some of the pitfalls of these large pragmatic designs.”

Akshay Desai, MD, associate professor of medicine, Harvard Medical School, Boston, added: “This was an innovative approach to answering an important question for daily clinical practice.”

On the results of the study, Dr. Lloyd-Jones said, “Maybe the outcomes were not too surprising, and I certainly endorse your cautious status quo statement about patients staying on the dose that they are on.”

But he suggested that the bleeding safety outcomes were perhaps a little unexpected, being a little lower in the lower-dose group, and he asked whether there was a sensitivity analysis looking at bleeding on a per protocol basis. Dr. Jones answered that this was planned.

Dr. Desai also raised questions about the “unusual bleeding endpoint,” noting that the rates of bleeding were far lower than would be expected, compared with other clinical trials.

Dr. Jones replied that the bleeding endpoint with blood product transfusion was chosen to allow the researchers to accurately identify these events in claims codes. He said the endpoint probably mirrored the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding classification.

In an editorial accompanying the publication of ADAPTABLE, Colin Baigent, FMedSci, says the study provides proof of principle that large pragmatic randomized trials can be conducted in the United States.

But Dr. Baigent, who is professor of epidemiology and director of the Medical Research Council Population Health Research Unit at the University of Oxford (England), says that the high degree of switching between dosages that occurred during the trial gives rise to some uncertainty about the results.  

“Because switching was not likely to have been at random, bias arising from this degree of crossover could have obscured a true difference in efficacy or safety (or both), and moreover it is also not possible to conclude that the lack of any significant difference between the two dose groups implies equivalence of the effects of the doses,” he writes.

He suggests that a pilot study may have identified a preference for the 81-mg dose and allowed methods to facilitate equipoise, such as a run-in period with both doses, and only patients adhering being considered for randomization.  

But Dr. Baigent concludes that the ADAPTABLE trial is a “major achievement” in that it paves the way for low-cost randomized trials in the United States, which should allow many more clinical questions to be answered.

The trial was supported by an award from the Patient-Centred Outcomes Research Institute.  Dr. Schuyler Jones reports consultant fees/honoraria from Bayer Healthcare and Janssen and research grants from Boehringer Ingelheim, Bristol Myers Squibb, and the Patient-Centered Outcomes Research Institute. Dr. Baigent reports grants from Boehringer Ingelheim, Medical Research Council, British Heart Foundation, and National Institute of Health Research, outside the submitted work.
 

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

No significant difference in cardiovascular events or major bleeding was shown between patients with established coronary heart disease assigned to a daily aspirin dose of 81 mg and those receiving a dose of 325 mg in the 15,000-patient ADAPTABLE trial.

Although substantial dose switching occurred in the trial, particularly from the higher to the lower dose, lead investigator W. Schuyler Jones, MD, believes the results support the use of the 81-mg dose in most patients.  

“While we would have liked to see higher adherence to the assigned doses, we think the results of the trial are reliable,” Dr. Jones said in an interview.

The real-world, open-label, pragmatic trial also involved an innovative low-cost design allowing researchers to identify and communicate with eligible patients directly, opening up a new cost-effective method to conduct clinical research going forward.

Dr. Jones, a cardiologist and associate professor of medicine at Duke University Medical Center, Durham, N.C., presented the ADAPTABLE results at the annual scientific sessions of the American College of Cardiology. They were simultaneously published online in the New England Journal of Medicine.   

He noted there were mixed signals in the results. “For example, the main intent-to-treat analysis showed a trend to a lower rate of all-cause death in the 81-mg group, but the subgroup of patients who stayed on the 325-mg dose throughout the study had a lower event rate. But overall, there was no difference.”

Dr. Jones said the investigators had the following take-home messages to patients: “If a patient is already taking 81 mg, staying on this dose is probably right given the similar study results for the primary endpoint and that we didn’t find conclusive evidence that 325 mg is better. But for patients who have tolerated 325 mg long term, then they may want to stay on this dose as it may be associated with moderate benefit.”

Dr. Jones pointed out that, overall, patients who switched doses tended to do worse, but he suggested this may have been more to do with underlying reasons for switching rather than the different dose itself. “For example, switching often happens after bleeding or bruising, which can also often preempt an ischemic event, and other illnesses, such as cancer or atrial fibrillation, can also lead patients to change doses.”

“With the caveat that this trial did not include new patients (the vast majority of patients had been taking aspirin previously) the results support the approach of starting new patients on 81 mg, which is what we have been seeing in evolving clinical practice in recent years,” he added.  

Dr. Jones explained that the trial set out to answer the simple but important question about the best dose of aspirin in patients with heart disease.

“Aspirin has been established as an appropriate long-term medication for patients with ischemic heart disease since the 1980s, but we really don’t have any good information on the correct dose.

He noted that the U.S. guidelines suggest any dose in the range of 81 mg to 325 mg daily can be used, whereas the European guidelines recommend 81 mg daily, although this is mainly based on observational data and expert opinion; there is little hard, randomized-trial evidence.

The ADAPTABLE trial randomly assigned 15,076 patients with established heart disease to receive 81 mg or 325 mg of aspirin. Before randomization, 96% of those with available information were already taking aspirin, 85% of whom were taking 81 mg.

After a mean follow-up of 26 months, the primary efficacy endpoint – a composite of all-cause death, myocardial infarction, or stroke – had occurred in 7.28% of the 81-mg group and 7.51% of the 325-mg group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14).     

The main safety endpoint, hospitalization for major bleeding with an associated blood transfusion, occurred in 0.63% of the 81-mg group and 0.60% of the 325-mg group (HR, 1.18; 95% CI, 0.79-1.77).

“The bleeding safety endpoint looked similar, which may be counterintuitive to what may have been expected,” Dr. Jones commented. “However, the safety endpoint was very stringent. We still haven’t analyzed all the less serious ADR [adverse drug event]/bleeding data, but overall, it does appear to be balanced.”

He added: “Most cardiologists probably may not have expected to see much difference in efficacy between these two doses but would maybe have anticipated a lower bleeding rate with the low dose. I was a little surprised to see such a low bleeding rate in the 325-mg group.”

Patients assigned to 325 mg had a higher incidence of dose switching (41.6%) than those assigned to 81 mg (7.1%) and were more likely to discontinue treatment (11.1% vs. 7.0%). This resulted in fewer median days of exposure to the assigned dose in the 325-mg group (434 vs. 650 days).

“This was an open-label study, and such studies always suffer from a degree of infidelity to the assigned treatment group,” Dr. Jones said. “In ADAPTABLE, this was unbalanced in that a much greater number of patients switched from 325 mg to 81 mg than the other way round.”   

“But our results do reflect what happens in normal life,” he added. “People behaved in the study like they do in the real world. They sometimes changed their dose and sometimes stopped taking aspirin altogether. So, I think the results are an accurate representation of the real world.”

A sensitivity analysis based on which dose the patient actually reported taking showed a higher risk for death, MI, or stroke in patients who took 81 mg than those who took 325 mg (HR, 1.25; 95% CI, 1.10-1.43). But as with any postrandomization analysis, this approach has many inherent biases, Dr. Jones cautioned.
 

Innovative study design  

The ADAPTABLE study used an innovative low-cost design, which involved direct communication with the patients themselves.

Using the National Patient-Centered Clinical Research Network (PCORnet), a group of 40 U.S. centers committed to compiling data in a common format, invitations to enroll in the study were sent to eligible patients identified from medical records. Consent and randomization took place on the patient web portal. 

Participants then purchased aspirin at the assigned dose themselves, and all follow-up was done virtually or on the phone, with outcomes ascertained remotely (from patient reports, electronic medical records, and insurance claims) without adjudication.   

“This is a pretty neat way to do clinical research, enabling us to conduct a 15,000-patient trial on a very tight budget,” Dr. Jones commented. 

He estimated that the trial cost around $18 to $19 million. “No industry funder would have sponsored such a study of aspirin, and a typical trial with this many patients conducted in the traditional way would have cost at least 5 or 10 times more,” he said.

“This is the first time this type of study has been done in the U.S. on such a large scale, and it opens up this method for future research.”

He explained that this design, communicating directly with patients, somewhat limits the questions that can be addressed. “As aspirin is purchased over the counter by patients themselves, this is a question that lent itself to be answered in this way.” 

Another innovative design feature was the inclusion of “patient partners,” with one patient nominated by each center to be part of the organization of the trial. “This helped keep the research relevant to what patients care about.

They also helped with the recruitment strategy and communication with participants. I think this is something we need to continue and prioritize in clinical research going forward,” Dr. Jones noted.

‘Pioneering’ trial

Discussants of the study at the ACC presentation congratulated the investigators on conducting such an innovative trial.

Donald Lloyd-Jones, MD, chair of preventive medicine at Northwestern University, Chicago, said, “This is really a pioneering large pragmatic trial, and we’re going to need to see more of these over the next few years. The most important legacy from this trial for me is that you did it, and that you showed us many of the promises and some of the pitfalls of these large pragmatic designs.”

Akshay Desai, MD, associate professor of medicine, Harvard Medical School, Boston, added: “This was an innovative approach to answering an important question for daily clinical practice.”

On the results of the study, Dr. Lloyd-Jones said, “Maybe the outcomes were not too surprising, and I certainly endorse your cautious status quo statement about patients staying on the dose that they are on.”

But he suggested that the bleeding safety outcomes were perhaps a little unexpected, being a little lower in the lower-dose group, and he asked whether there was a sensitivity analysis looking at bleeding on a per protocol basis. Dr. Jones answered that this was planned.

Dr. Desai also raised questions about the “unusual bleeding endpoint,” noting that the rates of bleeding were far lower than would be expected, compared with other clinical trials.

Dr. Jones replied that the bleeding endpoint with blood product transfusion was chosen to allow the researchers to accurately identify these events in claims codes. He said the endpoint probably mirrored the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding classification.

In an editorial accompanying the publication of ADAPTABLE, Colin Baigent, FMedSci, says the study provides proof of principle that large pragmatic randomized trials can be conducted in the United States.

But Dr. Baigent, who is professor of epidemiology and director of the Medical Research Council Population Health Research Unit at the University of Oxford (England), says that the high degree of switching between dosages that occurred during the trial gives rise to some uncertainty about the results.  

“Because switching was not likely to have been at random, bias arising from this degree of crossover could have obscured a true difference in efficacy or safety (or both), and moreover it is also not possible to conclude that the lack of any significant difference between the two dose groups implies equivalence of the effects of the doses,” he writes.

He suggests that a pilot study may have identified a preference for the 81-mg dose and allowed methods to facilitate equipoise, such as a run-in period with both doses, and only patients adhering being considered for randomization.  

But Dr. Baigent concludes that the ADAPTABLE trial is a “major achievement” in that it paves the way for low-cost randomized trials in the United States, which should allow many more clinical questions to be answered.

The trial was supported by an award from the Patient-Centred Outcomes Research Institute.  Dr. Schuyler Jones reports consultant fees/honoraria from Bayer Healthcare and Janssen and research grants from Boehringer Ingelheim, Bristol Myers Squibb, and the Patient-Centered Outcomes Research Institute. Dr. Baigent reports grants from Boehringer Ingelheim, Medical Research Council, British Heart Foundation, and National Institute of Health Research, outside the submitted work.
 

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

No significant difference in cardiovascular events or major bleeding was shown between patients with established coronary heart disease assigned to a daily aspirin dose of 81 mg and those receiving a dose of 325 mg in the 15,000-patient ADAPTABLE trial.

Although substantial dose switching occurred in the trial, particularly from the higher to the lower dose, lead investigator W. Schuyler Jones, MD, believes the results support the use of the 81-mg dose in most patients.  

“While we would have liked to see higher adherence to the assigned doses, we think the results of the trial are reliable,” Dr. Jones said in an interview.

The real-world, open-label, pragmatic trial also involved an innovative low-cost design allowing researchers to identify and communicate with eligible patients directly, opening up a new cost-effective method to conduct clinical research going forward.

Dr. Jones, a cardiologist and associate professor of medicine at Duke University Medical Center, Durham, N.C., presented the ADAPTABLE results at the annual scientific sessions of the American College of Cardiology. They were simultaneously published online in the New England Journal of Medicine.   

He noted there were mixed signals in the results. “For example, the main intent-to-treat analysis showed a trend to a lower rate of all-cause death in the 81-mg group, but the subgroup of patients who stayed on the 325-mg dose throughout the study had a lower event rate. But overall, there was no difference.”

Dr. Jones said the investigators had the following take-home messages to patients: “If a patient is already taking 81 mg, staying on this dose is probably right given the similar study results for the primary endpoint and that we didn’t find conclusive evidence that 325 mg is better. But for patients who have tolerated 325 mg long term, then they may want to stay on this dose as it may be associated with moderate benefit.”

Dr. Jones pointed out that, overall, patients who switched doses tended to do worse, but he suggested this may have been more to do with underlying reasons for switching rather than the different dose itself. “For example, switching often happens after bleeding or bruising, which can also often preempt an ischemic event, and other illnesses, such as cancer or atrial fibrillation, can also lead patients to change doses.”

“With the caveat that this trial did not include new patients (the vast majority of patients had been taking aspirin previously) the results support the approach of starting new patients on 81 mg, which is what we have been seeing in evolving clinical practice in recent years,” he added.  

Dr. Jones explained that the trial set out to answer the simple but important question about the best dose of aspirin in patients with heart disease.

“Aspirin has been established as an appropriate long-term medication for patients with ischemic heart disease since the 1980s, but we really don’t have any good information on the correct dose.

He noted that the U.S. guidelines suggest any dose in the range of 81 mg to 325 mg daily can be used, whereas the European guidelines recommend 81 mg daily, although this is mainly based on observational data and expert opinion; there is little hard, randomized-trial evidence.

The ADAPTABLE trial randomly assigned 15,076 patients with established heart disease to receive 81 mg or 325 mg of aspirin. Before randomization, 96% of those with available information were already taking aspirin, 85% of whom were taking 81 mg.

After a mean follow-up of 26 months, the primary efficacy endpoint – a composite of all-cause death, myocardial infarction, or stroke – had occurred in 7.28% of the 81-mg group and 7.51% of the 325-mg group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14).     

The main safety endpoint, hospitalization for major bleeding with an associated blood transfusion, occurred in 0.63% of the 81-mg group and 0.60% of the 325-mg group (HR, 1.18; 95% CI, 0.79-1.77).

“The bleeding safety endpoint looked similar, which may be counterintuitive to what may have been expected,” Dr. Jones commented. “However, the safety endpoint was very stringent. We still haven’t analyzed all the less serious ADR [adverse drug event]/bleeding data, but overall, it does appear to be balanced.”

He added: “Most cardiologists probably may not have expected to see much difference in efficacy between these two doses but would maybe have anticipated a lower bleeding rate with the low dose. I was a little surprised to see such a low bleeding rate in the 325-mg group.”

Patients assigned to 325 mg had a higher incidence of dose switching (41.6%) than those assigned to 81 mg (7.1%) and were more likely to discontinue treatment (11.1% vs. 7.0%). This resulted in fewer median days of exposure to the assigned dose in the 325-mg group (434 vs. 650 days).

“This was an open-label study, and such studies always suffer from a degree of infidelity to the assigned treatment group,” Dr. Jones said. “In ADAPTABLE, this was unbalanced in that a much greater number of patients switched from 325 mg to 81 mg than the other way round.”   

“But our results do reflect what happens in normal life,” he added. “People behaved in the study like they do in the real world. They sometimes changed their dose and sometimes stopped taking aspirin altogether. So, I think the results are an accurate representation of the real world.”

A sensitivity analysis based on which dose the patient actually reported taking showed a higher risk for death, MI, or stroke in patients who took 81 mg than those who took 325 mg (HR, 1.25; 95% CI, 1.10-1.43). But as with any postrandomization analysis, this approach has many inherent biases, Dr. Jones cautioned.
 

Innovative study design  

The ADAPTABLE study used an innovative low-cost design, which involved direct communication with the patients themselves.

Using the National Patient-Centered Clinical Research Network (PCORnet), a group of 40 U.S. centers committed to compiling data in a common format, invitations to enroll in the study were sent to eligible patients identified from medical records. Consent and randomization took place on the patient web portal. 

Participants then purchased aspirin at the assigned dose themselves, and all follow-up was done virtually or on the phone, with outcomes ascertained remotely (from patient reports, electronic medical records, and insurance claims) without adjudication.   

“This is a pretty neat way to do clinical research, enabling us to conduct a 15,000-patient trial on a very tight budget,” Dr. Jones commented. 

He estimated that the trial cost around $18 to $19 million. “No industry funder would have sponsored such a study of aspirin, and a typical trial with this many patients conducted in the traditional way would have cost at least 5 or 10 times more,” he said.

“This is the first time this type of study has been done in the U.S. on such a large scale, and it opens up this method for future research.”

He explained that this design, communicating directly with patients, somewhat limits the questions that can be addressed. “As aspirin is purchased over the counter by patients themselves, this is a question that lent itself to be answered in this way.” 

Another innovative design feature was the inclusion of “patient partners,” with one patient nominated by each center to be part of the organization of the trial. “This helped keep the research relevant to what patients care about.

They also helped with the recruitment strategy and communication with participants. I think this is something we need to continue and prioritize in clinical research going forward,” Dr. Jones noted.

‘Pioneering’ trial

Discussants of the study at the ACC presentation congratulated the investigators on conducting such an innovative trial.

Donald Lloyd-Jones, MD, chair of preventive medicine at Northwestern University, Chicago, said, “This is really a pioneering large pragmatic trial, and we’re going to need to see more of these over the next few years. The most important legacy from this trial for me is that you did it, and that you showed us many of the promises and some of the pitfalls of these large pragmatic designs.”

Akshay Desai, MD, associate professor of medicine, Harvard Medical School, Boston, added: “This was an innovative approach to answering an important question for daily clinical practice.”

On the results of the study, Dr. Lloyd-Jones said, “Maybe the outcomes were not too surprising, and I certainly endorse your cautious status quo statement about patients staying on the dose that they are on.”

But he suggested that the bleeding safety outcomes were perhaps a little unexpected, being a little lower in the lower-dose group, and he asked whether there was a sensitivity analysis looking at bleeding on a per protocol basis. Dr. Jones answered that this was planned.

Dr. Desai also raised questions about the “unusual bleeding endpoint,” noting that the rates of bleeding were far lower than would be expected, compared with other clinical trials.

Dr. Jones replied that the bleeding endpoint with blood product transfusion was chosen to allow the researchers to accurately identify these events in claims codes. He said the endpoint probably mirrored the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding classification.

In an editorial accompanying the publication of ADAPTABLE, Colin Baigent, FMedSci, says the study provides proof of principle that large pragmatic randomized trials can be conducted in the United States.

But Dr. Baigent, who is professor of epidemiology and director of the Medical Research Council Population Health Research Unit at the University of Oxford (England), says that the high degree of switching between dosages that occurred during the trial gives rise to some uncertainty about the results.  

“Because switching was not likely to have been at random, bias arising from this degree of crossover could have obscured a true difference in efficacy or safety (or both), and moreover it is also not possible to conclude that the lack of any significant difference between the two dose groups implies equivalence of the effects of the doses,” he writes.

He suggests that a pilot study may have identified a preference for the 81-mg dose and allowed methods to facilitate equipoise, such as a run-in period with both doses, and only patients adhering being considered for randomization.  

But Dr. Baigent concludes that the ADAPTABLE trial is a “major achievement” in that it paves the way for low-cost randomized trials in the United States, which should allow many more clinical questions to be answered.

The trial was supported by an award from the Patient-Centred Outcomes Research Institute.  Dr. Schuyler Jones reports consultant fees/honoraria from Bayer Healthcare and Janssen and research grants from Boehringer Ingelheim, Bristol Myers Squibb, and the Patient-Centered Outcomes Research Institute. Dr. Baigent reports grants from Boehringer Ingelheim, Medical Research Council, British Heart Foundation, and National Institute of Health Research, outside the submitted work.
 

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

Treatment with sacubitril/valsartan, a pillar of therapy for patients with chronic heart failure with below-normal ejection fraction, came suggestively close to showing efficacy for preventing cardiovascular death or heart failure events in patients who have just had an MI but have no history of heart failure in a controlled trial with more than 5,600 patients.

Although sacubitril/valsartan (Entresto) fell short of producing a significant benefit, it did show good safety that was similar to the study’s comparator treatment, ramipril, an agent from the angiotensin-converting enzyme inhibitor class that is a mainstay of treatment in these patients.

“To say that, with no run-in, sacubitril/valsartan is as well tolerated and as safe as one of the best-studied ACE inhibitors – ramipril – in acutely ill MI patients, is a big statement,” said Marc A. Pfeffer, MD, at the annual scientific sessions of the American College of Cardiology. This high level of safety without gradual uptitration of sacubitril/valsartan (Entresto) “should lower barriers” to broader use of the dual-drug formulation for its approved indication in patients with chronic heart failure, especially patients with a left ventricular ejection fraction that is below normal. In addition, results from the PARADISE-MI trial suggested that “patients seemed to benefit before they develop heart failure. We couldn’t prove that, but we should build on this, and make it easier for patients to use this treatment,” Dr. Pfeffer said during a press briefing following his talk at the sessions.

Preventing heart failures to come

Treatment with sacubitril/valsartan in acute MI patients within a few days of their event “is perhaps addressing prevention of the heart failure that’s to come,” commented Lynne W. Stevenson, MD, designated discussant for the report and professor of medicine at Vanderbilt University Medical Center in Nashville. “Patients who are destined to develop heart failure are beginning their treatment early. The subgroup analyses suggest that it’s the sicker patients who benefited the most,” she said.

But Dr. Pfeffer stressed that “I don’t think this is a subgroup discussion. I would like to pursue this, but that’s up to the sponsor,” Novartis, the company that markets sacubitril/valsartan.

‘Exceedingly reassuring’ safety

The safety data that Dr. Pfeffer reported “are exceedingly reassuring. We didn’t see a signal of harm, and in some of the exploratory endpoints there was some evidence of benefit, so we need to encourage you to continue,” commented Mary N. Walsh, MD, medical director of the heart failure and cardiac transplantation program at Ascension St. Vincent Heart Center of Indiana in Indianapolis.

The PARADISE-MI (Prospective ARNI vs. ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI) trial enrolled 5,669 patients with no history of heart failure within an average of 4 days following an acute MI at 495 sites in 41 countries during 2016-2020, with 8% of enrolled patients from the United States. Patients averaged 64 years of age, about three-quarters were men, about 43% had a history of diabetes, and only 1% were Black; Dr. Pfeffer noted that this is because most patients came from countries with low Black populations. The enrollment criteria required a left ventricular ejection fraction no greater than 40%, and among the enrolled patients this averaged about 37%.

A 10% nonsignificant relative risk reduction for the primary endpoint

The study’s primary endpoint was the combined first-event rate of cardiovascular death, hospitalization for heart failure, or an outpatient visit for heart failure. During a median follow-up of 23 months, this occurred at a rate of 7.4/100 patient years in the ramipril arm and 6.7/100 patient years in the sacubitril/valsartan arm, a 10% relative risk reduction with sacubitril/valsartan that was not significant, which meant all other efficacy analyses were exploratory, Dr. Pfeffer stressed.

Several secondary efficacy analyses showed significant benefits from sacubitril/valsartan, compared with ramipril, including the total number of events that comprised the primary endpoint, with a 21% relative risk reduction associated with sacubitril/valsartan, as well as investigator-reported events. The primary-endpoint benefit from sacubitril/valsartan was also significant in two subgroup analyses: patients aged 65 years or older (roughly half the study cohort), who had a 24% relative risk reduction on sacubitril/valsartan, compared with ramipril, and the 88% of patients who received treatment with percutaneous coronary intervention for their acute MI, who had a 19% relative risk reduction on sacubitril/valsartan, compared with patients who received ramipril.

The study’s safety data showed nearly identical rates in the two treatment arms for total adverse events, serious adverse events, adverse events that led to stopping the study drug, as well as in laboratory measures. The biggest between-treatment differences were a modest excess of hypotension on sacubitril valsartan, 28%, compared with 22% on ramipril, and a modest excess rate of cough on ramipril, 13%, compared with 9% on sacubitril/valsartan.

The added insight the results provide about sacubitril/valsartan comes at a time when U.S. patients continue to struggle to get health insurance coverage for an agent that has been approved for U.S. use in treating heart failure since 2015.

“Our patients do not have access to this important treatment,” declared Dr. Walsh during the press briefing. “The prior authorization process is unbelievable, and some patients have no access unless they pay the full cost on their own. This is an important, real-world problem that we face with this drug.”

PARADISE-MI was sponsored by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. Pfeffer has received research funding from and is a consultant to Novartis. He is also a consultant to AstraZeneca, Boehringer Ingelheim, Corvidia, DalCor, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Peerbridge, and Sanofi, and he holds equity in DalCor and Peerbridge. Dr. Stevenson has received honoraria from LivaNova and has received research support from Abbott. Dr. Walsh had no disclosures.

[email protected]

Treatment with sacubitril/valsartan, a pillar of therapy for patients with chronic heart failure with below-normal ejection fraction, came suggestively close to showing efficacy for preventing cardiovascular death or heart failure events in patients who have just had an MI but have no history of heart failure in a controlled trial with more than 5,600 patients.

Although sacubitril/valsartan (Entresto) fell short of producing a significant benefit, it did show good safety that was similar to the study’s comparator treatment, ramipril, an agent from the angiotensin-converting enzyme inhibitor class that is a mainstay of treatment in these patients.

“To say that, with no run-in, sacubitril/valsartan is as well tolerated and as safe as one of the best-studied ACE inhibitors – ramipril – in acutely ill MI patients, is a big statement,” said Marc A. Pfeffer, MD, at the annual scientific sessions of the American College of Cardiology. This high level of safety without gradual uptitration of sacubitril/valsartan (Entresto) “should lower barriers” to broader use of the dual-drug formulation for its approved indication in patients with chronic heart failure, especially patients with a left ventricular ejection fraction that is below normal. In addition, results from the PARADISE-MI trial suggested that “patients seemed to benefit before they develop heart failure. We couldn’t prove that, but we should build on this, and make it easier for patients to use this treatment,” Dr. Pfeffer said during a press briefing following his talk at the sessions.

Preventing heart failures to come

Treatment with sacubitril/valsartan in acute MI patients within a few days of their event “is perhaps addressing prevention of the heart failure that’s to come,” commented Lynne W. Stevenson, MD, designated discussant for the report and professor of medicine at Vanderbilt University Medical Center in Nashville. “Patients who are destined to develop heart failure are beginning their treatment early. The subgroup analyses suggest that it’s the sicker patients who benefited the most,” she said.

But Dr. Pfeffer stressed that “I don’t think this is a subgroup discussion. I would like to pursue this, but that’s up to the sponsor,” Novartis, the company that markets sacubitril/valsartan.

‘Exceedingly reassuring’ safety

The safety data that Dr. Pfeffer reported “are exceedingly reassuring. We didn’t see a signal of harm, and in some of the exploratory endpoints there was some evidence of benefit, so we need to encourage you to continue,” commented Mary N. Walsh, MD, medical director of the heart failure and cardiac transplantation program at Ascension St. Vincent Heart Center of Indiana in Indianapolis.

The PARADISE-MI (Prospective ARNI vs. ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI) trial enrolled 5,669 patients with no history of heart failure within an average of 4 days following an acute MI at 495 sites in 41 countries during 2016-2020, with 8% of enrolled patients from the United States. Patients averaged 64 years of age, about three-quarters were men, about 43% had a history of diabetes, and only 1% were Black; Dr. Pfeffer noted that this is because most patients came from countries with low Black populations. The enrollment criteria required a left ventricular ejection fraction no greater than 40%, and among the enrolled patients this averaged about 37%.

A 10% nonsignificant relative risk reduction for the primary endpoint

The study’s primary endpoint was the combined first-event rate of cardiovascular death, hospitalization for heart failure, or an outpatient visit for heart failure. During a median follow-up of 23 months, this occurred at a rate of 7.4/100 patient years in the ramipril arm and 6.7/100 patient years in the sacubitril/valsartan arm, a 10% relative risk reduction with sacubitril/valsartan that was not significant, which meant all other efficacy analyses were exploratory, Dr. Pfeffer stressed.

Several secondary efficacy analyses showed significant benefits from sacubitril/valsartan, compared with ramipril, including the total number of events that comprised the primary endpoint, with a 21% relative risk reduction associated with sacubitril/valsartan, as well as investigator-reported events. The primary-endpoint benefit from sacubitril/valsartan was also significant in two subgroup analyses: patients aged 65 years or older (roughly half the study cohort), who had a 24% relative risk reduction on sacubitril/valsartan, compared with ramipril, and the 88% of patients who received treatment with percutaneous coronary intervention for their acute MI, who had a 19% relative risk reduction on sacubitril/valsartan, compared with patients who received ramipril.

The study’s safety data showed nearly identical rates in the two treatment arms for total adverse events, serious adverse events, adverse events that led to stopping the study drug, as well as in laboratory measures. The biggest between-treatment differences were a modest excess of hypotension on sacubitril valsartan, 28%, compared with 22% on ramipril, and a modest excess rate of cough on ramipril, 13%, compared with 9% on sacubitril/valsartan.

The added insight the results provide about sacubitril/valsartan comes at a time when U.S. patients continue to struggle to get health insurance coverage for an agent that has been approved for U.S. use in treating heart failure since 2015.

“Our patients do not have access to this important treatment,” declared Dr. Walsh during the press briefing. “The prior authorization process is unbelievable, and some patients have no access unless they pay the full cost on their own. This is an important, real-world problem that we face with this drug.”

PARADISE-MI was sponsored by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. Pfeffer has received research funding from and is a consultant to Novartis. He is also a consultant to AstraZeneca, Boehringer Ingelheim, Corvidia, DalCor, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Peerbridge, and Sanofi, and he holds equity in DalCor and Peerbridge. Dr. Stevenson has received honoraria from LivaNova and has received research support from Abbott. Dr. Walsh had no disclosures.

[email protected]

Treatment with sacubitril/valsartan, a pillar of therapy for patients with chronic heart failure with below-normal ejection fraction, came suggestively close to showing efficacy for preventing cardiovascular death or heart failure events in patients who have just had an MI but have no history of heart failure in a controlled trial with more than 5,600 patients.

Although sacubitril/valsartan (Entresto) fell short of producing a significant benefit, it did show good safety that was similar to the study’s comparator treatment, ramipril, an agent from the angiotensin-converting enzyme inhibitor class that is a mainstay of treatment in these patients.

“To say that, with no run-in, sacubitril/valsartan is as well tolerated and as safe as one of the best-studied ACE inhibitors – ramipril – in acutely ill MI patients, is a big statement,” said Marc A. Pfeffer, MD, at the annual scientific sessions of the American College of Cardiology. This high level of safety without gradual uptitration of sacubitril/valsartan (Entresto) “should lower barriers” to broader use of the dual-drug formulation for its approved indication in patients with chronic heart failure, especially patients with a left ventricular ejection fraction that is below normal. In addition, results from the PARADISE-MI trial suggested that “patients seemed to benefit before they develop heart failure. We couldn’t prove that, but we should build on this, and make it easier for patients to use this treatment,” Dr. Pfeffer said during a press briefing following his talk at the sessions.

Preventing heart failures to come

Treatment with sacubitril/valsartan in acute MI patients within a few days of their event “is perhaps addressing prevention of the heart failure that’s to come,” commented Lynne W. Stevenson, MD, designated discussant for the report and professor of medicine at Vanderbilt University Medical Center in Nashville. “Patients who are destined to develop heart failure are beginning their treatment early. The subgroup analyses suggest that it’s the sicker patients who benefited the most,” she said.

But Dr. Pfeffer stressed that “I don’t think this is a subgroup discussion. I would like to pursue this, but that’s up to the sponsor,” Novartis, the company that markets sacubitril/valsartan.

‘Exceedingly reassuring’ safety

The safety data that Dr. Pfeffer reported “are exceedingly reassuring. We didn’t see a signal of harm, and in some of the exploratory endpoints there was some evidence of benefit, so we need to encourage you to continue,” commented Mary N. Walsh, MD, medical director of the heart failure and cardiac transplantation program at Ascension St. Vincent Heart Center of Indiana in Indianapolis.

The PARADISE-MI (Prospective ARNI vs. ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI) trial enrolled 5,669 patients with no history of heart failure within an average of 4 days following an acute MI at 495 sites in 41 countries during 2016-2020, with 8% of enrolled patients from the United States. Patients averaged 64 years of age, about three-quarters were men, about 43% had a history of diabetes, and only 1% were Black; Dr. Pfeffer noted that this is because most patients came from countries with low Black populations. The enrollment criteria required a left ventricular ejection fraction no greater than 40%, and among the enrolled patients this averaged about 37%.

A 10% nonsignificant relative risk reduction for the primary endpoint

The study’s primary endpoint was the combined first-event rate of cardiovascular death, hospitalization for heart failure, or an outpatient visit for heart failure. During a median follow-up of 23 months, this occurred at a rate of 7.4/100 patient years in the ramipril arm and 6.7/100 patient years in the sacubitril/valsartan arm, a 10% relative risk reduction with sacubitril/valsartan that was not significant, which meant all other efficacy analyses were exploratory, Dr. Pfeffer stressed.

Several secondary efficacy analyses showed significant benefits from sacubitril/valsartan, compared with ramipril, including the total number of events that comprised the primary endpoint, with a 21% relative risk reduction associated with sacubitril/valsartan, as well as investigator-reported events. The primary-endpoint benefit from sacubitril/valsartan was also significant in two subgroup analyses: patients aged 65 years or older (roughly half the study cohort), who had a 24% relative risk reduction on sacubitril/valsartan, compared with ramipril, and the 88% of patients who received treatment with percutaneous coronary intervention for their acute MI, who had a 19% relative risk reduction on sacubitril/valsartan, compared with patients who received ramipril.

The study’s safety data showed nearly identical rates in the two treatment arms for total adverse events, serious adverse events, adverse events that led to stopping the study drug, as well as in laboratory measures. The biggest between-treatment differences were a modest excess of hypotension on sacubitril valsartan, 28%, compared with 22% on ramipril, and a modest excess rate of cough on ramipril, 13%, compared with 9% on sacubitril/valsartan.

The added insight the results provide about sacubitril/valsartan comes at a time when U.S. patients continue to struggle to get health insurance coverage for an agent that has been approved for U.S. use in treating heart failure since 2015.

“Our patients do not have access to this important treatment,” declared Dr. Walsh during the press briefing. “The prior authorization process is unbelievable, and some patients have no access unless they pay the full cost on their own. This is an important, real-world problem that we face with this drug.”

PARADISE-MI was sponsored by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. Pfeffer has received research funding from and is a consultant to Novartis. He is also a consultant to AstraZeneca, Boehringer Ingelheim, Corvidia, DalCor, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Peerbridge, and Sanofi, and he holds equity in DalCor and Peerbridge. Dr. Stevenson has received honoraria from LivaNova and has received research support from Abbott. Dr. Walsh had no disclosures.

[email protected]

The Food and Drug Administration is recommending patients and caregivers keep cell phones and smart watches at least 6 inches away from implanted medical devices, such as pacemakers and defibrillators.

Terry Rudd/MDedge News

The warning, published on May 13, comes on the heels of recent research reporting that high–field strength magnets in newer smartphones may cause some implanted medical devices to switch to “magnet mode” and suspend normal lifesaving operations until the magnet is moved away.

This, for example, may cause a cardiac defibrillator to be unable to detect tachycardia events, the agency noted. The magnets may also change the operational mode such as turning on asynchronous mode in a pacemaker.

“The FDA is aware of published articles which describe the effect that sufficiently strong magnetic fields can turn on the magnetic safe mode when in close contact,” it said. “The FDA also conducted its own testing on some products that use the high–field strength magnet feature and have confirmed the magnetic field is both consistent with the publications and strong enough to turn on the magnetic safety mode of the medical devices in question.”

The FDA said it believes the risk to patients is low and is not aware of any adverse events associated with this issue at this time.

The American Heart Association has also cautioned that magnetic fields can inhibit the pulse generators for implantable cardioverter defibrillators and pacemakers.

The FDA offered the following simple precautions for individuals with implanted medical devices:

• Keep the consumer electronics, such as certain cell phones and smart watches, 6 inches away from implanted medical devices.
• Do not carry consumer electronics in a pocket over the medical device.
• Check your device using your home monitoring system, if you have one.
• Talk to your health care provider if you are experiencing any symptoms or have questions regarding magnets in consumer electronics and implanted medical devices.

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

The Food and Drug Administration is recommending patients and caregivers keep cell phones and smart watches at least 6 inches away from implanted medical devices, such as pacemakers and defibrillators.

Terry Rudd/MDedge News

The warning, published on May 13, comes on the heels of recent research reporting that high–field strength magnets in newer smartphones may cause some implanted medical devices to switch to “magnet mode” and suspend normal lifesaving operations until the magnet is moved away.

This, for example, may cause a cardiac defibrillator to be unable to detect tachycardia events, the agency noted. The magnets may also change the operational mode such as turning on asynchronous mode in a pacemaker.

“The FDA is aware of published articles which describe the effect that sufficiently strong magnetic fields can turn on the magnetic safe mode when in close contact,” it said. “The FDA also conducted its own testing on some products that use the high–field strength magnet feature and have confirmed the magnetic field is both consistent with the publications and strong enough to turn on the magnetic safety mode of the medical devices in question.”

The FDA said it believes the risk to patients is low and is not aware of any adverse events associated with this issue at this time.

The American Heart Association has also cautioned that magnetic fields can inhibit the pulse generators for implantable cardioverter defibrillators and pacemakers.

The FDA offered the following simple precautions for individuals with implanted medical devices:

• Keep the consumer electronics, such as certain cell phones and smart watches, 6 inches away from implanted medical devices.
• Do not carry consumer electronics in a pocket over the medical device.
• Check your device using your home monitoring system, if you have one.
• Talk to your health care provider if you are experiencing any symptoms or have questions regarding magnets in consumer electronics and implanted medical devices.

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

The Food and Drug Administration is recommending patients and caregivers keep cell phones and smart watches at least 6 inches away from implanted medical devices, such as pacemakers and defibrillators.

Terry Rudd/MDedge News

The warning, published on May 13, comes on the heels of recent research reporting that high–field strength magnets in newer smartphones may cause some implanted medical devices to switch to “magnet mode” and suspend normal lifesaving operations until the magnet is moved away.

This, for example, may cause a cardiac defibrillator to be unable to detect tachycardia events, the agency noted. The magnets may also change the operational mode such as turning on asynchronous mode in a pacemaker.

“The FDA is aware of published articles which describe the effect that sufficiently strong magnetic fields can turn on the magnetic safe mode when in close contact,” it said. “The FDA also conducted its own testing on some products that use the high–field strength magnet feature and have confirmed the magnetic field is both consistent with the publications and strong enough to turn on the magnetic safety mode of the medical devices in question.”

The FDA said it believes the risk to patients is low and is not aware of any adverse events associated with this issue at this time.

The American Heart Association has also cautioned that magnetic fields can inhibit the pulse generators for implantable cardioverter defibrillators and pacemakers.

The FDA offered the following simple precautions for individuals with implanted medical devices:

• Keep the consumer electronics, such as certain cell phones and smart watches, 6 inches away from implanted medical devices.
• Do not carry consumer electronics in a pocket over the medical device.
• Check your device using your home monitoring system, if you have one.
• Talk to your health care provider if you are experiencing any symptoms or have questions regarding magnets in consumer electronics and implanted medical devices.

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

Primary care physicians are more likely to write a prescription for statins for their patients at risk for cardiovascular adverse events in the morning than in the afternoon, new research suggests.

RogerAshford/Thinkstock

In an observational cohort study, researchers from the nudge unit, University of Pennsylvania, Philadelphia, found that patients who had the first appointments of the day were most likely to have statins prescribed for them, and that this likelihood decreased as the day went on.

The study was published online May 11, 2021, in JAMA Network Open.

“Physicians are faced with decision fatigue, where they are seeing 20 patients in a day and may not have the mental bandwidth or cognitive bandwidth to fully think through every decision for every patient and to make all the appropriate decisions all of the time,” lead author Allison J. Hare, medical student and clinical informatics fellow in the nudge unit, said in an interview.

The Penn Medicine nudge unit attempts to better align clinician decision-making with current standards in best practices for the provision of various therapies, Ms. Hare explained.

“As we see more and more best-practice guidelines come out, we also see that there is a gap in the intention to treat and actual provision of these therapies,” she said. “There are also increasing expectations for clinicians to provide all of these different evidence-backed therapies. It can be hard to keep up with all these guidelines, especially when you are expected to take care of more and more patients, more and more efficiently.”

Guideline-directed statin therapy has been demonstrated to reduce the risk for major adverse cardiovascular events, yet 50% of statin-eligible patients have not been prescribed one.

“In our prior work at the nudge unit, we observed that rates of preventive care, including flu vaccination and cancer screening, declined as the clinic day progressed. We wanted to see if this occurred with statin scripts,” Ms. Hare said.

The researchers obtained data from 28 Penn Medicine primary care practices that included 10,757 patients at risk for heart disease for the period from March 2019 to February 2020.

Their mean age was 66.0 years (standard deviation, 10.5 years), 5,072 (47.2%) were female, and 7,071 (65.7%) were White. Patient characteristics were similar between morning and afternoon appointments.

All patients had clinical atherosclerotic cardiovascular disease, familial hypercholesterolemia, or LDL cholesterol of at least 190 mg/dL, conditions which qualified them for statins based on the U.S. Preventive Services Task Force guidelines.

The appointment times for each patient were broken down into hour blocks, ranging from the 8:00 a.m. hour to the 4:00 p.m. hour, which bookend open times in most practices.

Overall, statins were prescribed in 36% (n = 3,864) of visits.

The data showed a clear decline in statin prescribing as the day went on. For example, compared with patients who came in at 8:00 a.m. (the reference group), patients who came in at 9:00 a.m. were 12% less likely to get a prescription.

Patients coming in for noon appointments were 37% less likely to get a statin prescription, which made them the least likely to get a script. After the noon visits, there was a slight increase, but the likelihood of a statin prescription remained 27% less likely or worse for the rest of the day.

“In the context of the myriad tasks that clinicians are faced with doing for a single patient, and then also within the context of seeing 20 patients in 15-minute increments, it is easy to see how certain things fall through the cracks,” Ms. Hare said. “It’s impossible for any clinician to remember every single little thing for their patient every single time, so if we can augment the clinician’s ability to make those appropriate decisions with electronic tools, we can narrow that gap a little bit.”
 

Why the variability?

“The nudge unit uses prompts to ask the physician about prescribing statins. The question is, what is causing the variability in statin prescriptions?” Nieca Goldberg, MD, medical director of the New York University women’s heart program, said in an interview.

“Is it fatigue, lack of familiarity of guidelines, or is this due to the volume of patients and lack of time to discuss the therapy and make a shared decision with their patient? The answer to these questions was not part of the study,” said Dr. Goldberg, who is also an American Heart Association volunteer expert. “It would be interesting to know the thoughts of the physicians who were studied after they were informed of the results. Also, having a nudge to write the prescription will increase the prescriptions of statins, but will patients take the medication?”

The study was funded in part by a grant from the National Institute on Aging. Ms. Hare and Dr. Goldberg reported no relevant financial relationships.

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

Primary care physicians are more likely to write a prescription for statins for their patients at risk for cardiovascular adverse events in the morning than in the afternoon, new research suggests.

RogerAshford/Thinkstock

In an observational cohort study, researchers from the nudge unit, University of Pennsylvania, Philadelphia, found that patients who had the first appointments of the day were most likely to have statins prescribed for them, and that this likelihood decreased as the day went on.

The study was published online May 11, 2021, in JAMA Network Open.

“Physicians are faced with decision fatigue, where they are seeing 20 patients in a day and may not have the mental bandwidth or cognitive bandwidth to fully think through every decision for every patient and to make all the appropriate decisions all of the time,” lead author Allison J. Hare, medical student and clinical informatics fellow in the nudge unit, said in an interview.

The Penn Medicine nudge unit attempts to better align clinician decision-making with current standards in best practices for the provision of various therapies, Ms. Hare explained.

“As we see more and more best-practice guidelines come out, we also see that there is a gap in the intention to treat and actual provision of these therapies,” she said. “There are also increasing expectations for clinicians to provide all of these different evidence-backed therapies. It can be hard to keep up with all these guidelines, especially when you are expected to take care of more and more patients, more and more efficiently.”

Guideline-directed statin therapy has been demonstrated to reduce the risk for major adverse cardiovascular events, yet 50% of statin-eligible patients have not been prescribed one.

“In our prior work at the nudge unit, we observed that rates of preventive care, including flu vaccination and cancer screening, declined as the clinic day progressed. We wanted to see if this occurred with statin scripts,” Ms. Hare said.

The researchers obtained data from 28 Penn Medicine primary care practices that included 10,757 patients at risk for heart disease for the period from March 2019 to February 2020.

Their mean age was 66.0 years (standard deviation, 10.5 years), 5,072 (47.2%) were female, and 7,071 (65.7%) were White. Patient characteristics were similar between morning and afternoon appointments.

All patients had clinical atherosclerotic cardiovascular disease, familial hypercholesterolemia, or LDL cholesterol of at least 190 mg/dL, conditions which qualified them for statins based on the U.S. Preventive Services Task Force guidelines.

The appointment times for each patient were broken down into hour blocks, ranging from the 8:00 a.m. hour to the 4:00 p.m. hour, which bookend open times in most practices.

Overall, statins were prescribed in 36% (n = 3,864) of visits.

The data showed a clear decline in statin prescribing as the day went on. For example, compared with patients who came in at 8:00 a.m. (the reference group), patients who came in at 9:00 a.m. were 12% less likely to get a prescription.

Patients coming in for noon appointments were 37% less likely to get a statin prescription, which made them the least likely to get a script. After the noon visits, there was a slight increase, but the likelihood of a statin prescription remained 27% less likely or worse for the rest of the day.

“In the context of the myriad tasks that clinicians are faced with doing for a single patient, and then also within the context of seeing 20 patients in 15-minute increments, it is easy to see how certain things fall through the cracks,” Ms. Hare said. “It’s impossible for any clinician to remember every single little thing for their patient every single time, so if we can augment the clinician’s ability to make those appropriate decisions with electronic tools, we can narrow that gap a little bit.”
 

Why the variability?

“The nudge unit uses prompts to ask the physician about prescribing statins. The question is, what is causing the variability in statin prescriptions?” Nieca Goldberg, MD, medical director of the New York University women’s heart program, said in an interview.

“Is it fatigue, lack of familiarity of guidelines, or is this due to the volume of patients and lack of time to discuss the therapy and make a shared decision with their patient? The answer to these questions was not part of the study,” said Dr. Goldberg, who is also an American Heart Association volunteer expert. “It would be interesting to know the thoughts of the physicians who were studied after they were informed of the results. Also, having a nudge to write the prescription will increase the prescriptions of statins, but will patients take the medication?”

The study was funded in part by a grant from the National Institute on Aging. Ms. Hare and Dr. Goldberg reported no relevant financial relationships.

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

Primary care physicians are more likely to write a prescription for statins for their patients at risk for cardiovascular adverse events in the morning than in the afternoon, new research suggests.

RogerAshford/Thinkstock

In an observational cohort study, researchers from the nudge unit, University of Pennsylvania, Philadelphia, found that patients who had the first appointments of the day were most likely to have statins prescribed for them, and that this likelihood decreased as the day went on.

The study was published online May 11, 2021, in JAMA Network Open.

“Physicians are faced with decision fatigue, where they are seeing 20 patients in a day and may not have the mental bandwidth or cognitive bandwidth to fully think through every decision for every patient and to make all the appropriate decisions all of the time,” lead author Allison J. Hare, medical student and clinical informatics fellow in the nudge unit, said in an interview.

The Penn Medicine nudge unit attempts to better align clinician decision-making with current standards in best practices for the provision of various therapies, Ms. Hare explained.

“As we see more and more best-practice guidelines come out, we also see that there is a gap in the intention to treat and actual provision of these therapies,” she said. “There are also increasing expectations for clinicians to provide all of these different evidence-backed therapies. It can be hard to keep up with all these guidelines, especially when you are expected to take care of more and more patients, more and more efficiently.”

Guideline-directed statin therapy has been demonstrated to reduce the risk for major adverse cardiovascular events, yet 50% of statin-eligible patients have not been prescribed one.

“In our prior work at the nudge unit, we observed that rates of preventive care, including flu vaccination and cancer screening, declined as the clinic day progressed. We wanted to see if this occurred with statin scripts,” Ms. Hare said.

The researchers obtained data from 28 Penn Medicine primary care practices that included 10,757 patients at risk for heart disease for the period from March 2019 to February 2020.

Their mean age was 66.0 years (standard deviation, 10.5 years), 5,072 (47.2%) were female, and 7,071 (65.7%) were White. Patient characteristics were similar between morning and afternoon appointments.

All patients had clinical atherosclerotic cardiovascular disease, familial hypercholesterolemia, or LDL cholesterol of at least 190 mg/dL, conditions which qualified them for statins based on the U.S. Preventive Services Task Force guidelines.

The appointment times for each patient were broken down into hour blocks, ranging from the 8:00 a.m. hour to the 4:00 p.m. hour, which bookend open times in most practices.

Overall, statins were prescribed in 36% (n = 3,864) of visits.

The data showed a clear decline in statin prescribing as the day went on. For example, compared with patients who came in at 8:00 a.m. (the reference group), patients who came in at 9:00 a.m. were 12% less likely to get a prescription.

Patients coming in for noon appointments were 37% less likely to get a statin prescription, which made them the least likely to get a script. After the noon visits, there was a slight increase, but the likelihood of a statin prescription remained 27% less likely or worse for the rest of the day.

“In the context of the myriad tasks that clinicians are faced with doing for a single patient, and then also within the context of seeing 20 patients in 15-minute increments, it is easy to see how certain things fall through the cracks,” Ms. Hare said. “It’s impossible for any clinician to remember every single little thing for their patient every single time, so if we can augment the clinician’s ability to make those appropriate decisions with electronic tools, we can narrow that gap a little bit.”
 

Why the variability?

“The nudge unit uses prompts to ask the physician about prescribing statins. The question is, what is causing the variability in statin prescriptions?” Nieca Goldberg, MD, medical director of the New York University women’s heart program, said in an interview.

“Is it fatigue, lack of familiarity of guidelines, or is this due to the volume of patients and lack of time to discuss the therapy and make a shared decision with their patient? The answer to these questions was not part of the study,” said Dr. Goldberg, who is also an American Heart Association volunteer expert. “It would be interesting to know the thoughts of the physicians who were studied after they were informed of the results. Also, having a nudge to write the prescription will increase the prescriptions of statins, but will patients take the medication?”

The study was funded in part by a grant from the National Institute on Aging. Ms. Hare and Dr. Goldberg reported no relevant financial relationships.

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

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

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

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

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

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

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

The American Medical Association has released a 3-year strategic plan to counter longstanding health inequities that hurt marginalized communities and to improve the AMA’s own performance in this regard.

The 82-page report, which was created by the association’s Center for Health Equity, argues for both internal changes at the AMA and changes in how the association addresses race-based inequities in general.

The report was released just 2 months after this news organization reported that a podcast hosted by AMA’s top journal was lambasted as racist and out of touch. In the podcast – entitled “Stuctural Racism for Doctors – What Is It?” – one JAMA editor argued that structural racism doesn’t exist. He eventually resigned and the journal’s top editor was placed on administration leave.

The new AMA report’s strategic framework “is driven by the immense need for equity-centered solutions to confront harms produced by systemic racism and other forms of oppression for Black, Latinx, Indigenous, Asian, and other people of color, as well as people who identify as LGBTQ+ and people with disabilities,” the AMA said in a news release. “Its urgency is underscored by ongoing circumstances including inequities exacerbated by the COVID-19 pandemic, ongoing police brutality, and hate crimes targeting Asian, Black, and Brown communities.”

The plan includes five main approaches to addressing inequities in health care and the AMA:

• Implement antiracist equity strategies through AMA practices, programming, policies, and culture.
• Build alliances with marginalized doctors and other stakeholders to elevate the experiences and ideas of historically marginalized and minority health care leaders.
• Strengthen, empower, and equip doctors with the knowledge and tools to dismantle structural and social health inequities.
• Ensure equitable opportunities in innovation.
• Foster truth, racial healing, reconciliation, and transformation for AMA’s past by accounting for how policies and processes excluded, discriminated, and harmed communities.

As the report acknowledges, the AMA has a long history of exclusion of and discrimination against Black physicians, for which the association publicly apologized in 2008. Within the past year, the AMA has reaffirmed its commitment to addressing this legacy and to be proactive on health equity.

Among other things, the association has described racism as a public health crisis, stated that race has nothing to do with biology, said police brutality is a product of structural racism, and called on the federal government to collect and release COVID-19 race/ethnicity data. It also removed the name of AMA founder Nathan Davis, MD, from an annual award and display because of his contribution to explicit racist practices.
 

Equity-centered solutions

The AMA launched its Center for Health Equity in 2019 with a mandate “to embed health equity across the organization.” Aletha Maybank, MD, was named the AMA’s chief health equity officer to lead the center.

In the report that Dr. Maybank helped write, the AMA discusses the consequences of individual and systemic injustice toward minorities. Among these consequences, the report said, is “segregated and inequitable health care systems.”

The “equity-centered solutions” listed in the report include:

• End segregated health care.
• Establish national health care equity and racial justice standards.
• End the use of race-based clinical decision models.
• Eliminate all forms of discrimination, exclusion and oppression in medical and physician education, training, hiring, and promotion.
• Prevent exclusion of and ensure equal representation of Black, Indigenous and Latinx people in medical school admissions as well as medical school and hospital leadership ranks.
• Ensure equity in innovation, including design, development, implementation along with support for equitable innovation opportunities and entrepreneurship.
• Solidify connections and coordination between health care and public health.
• Acknowledge and repair past harms committed by institutions.
•  

Changing medical education

In an exclusive interview, Gerald E. Harmon, MD, president-elect of the AMA, singled out medical education as an area that is ripe for change. “One of the most threatened phenotypes on the planet is the Black male physician,” he said. “Their numbers among medical school applicants continue to drop. We have increasing numbers of women in medical schools – over 50% of trainees are women – and more Black women are entering medical school, but Black men in medical school are an endangered species.

“We’re trying to get the physician workforce to look like the patient workforce.”

Dr. Harmon cited the “pipeline program” at the Morehouse School of Medicine in Atlanta and the AMA’s “doctors back to school” program as examples of efforts to attract minority high school students to health care careers. Much more needs to be done, he added. “We have to put equity and representation into our medical workforce so we can provide better high quality, more reliable care for underrepresented patients.”
 

Putting the AMA’s house in order

In its report, the AMA also makes recommendations about how it can improve equity within its own organization. Over the next 3 years, among other things, the association plans to improve the diversity of leadership at the AMA and its journal, JAMA; train all staff on equity requirements; and develop a plan to recruit more racial and ethnic minorities, LGBTQ+ people, and disabled people.

Dr. Maybank, the AMA’s chief health equity officer, said in an interview that she wouldn’t describe these efforts as affirmative action. “This is beyond affirmative action. It’s about intentional activity and action to ensure equity and justice within the AMA.”

The AMA has to thoroughly examine its own processes and determine “how inequity shows up on a day-to-day basis,” she said. “Whether it’s through hiring, innovation, publishing or communications, everybody needs to know how inequity shows up and how their own mental models can exacerbate inequities. People need tools to challenge themselves and ask themselves critical questions about racism in their processes and what they can do to mitigate those.”

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

The American Medical Association has released a 3-year strategic plan to counter longstanding health inequities that hurt marginalized communities and to improve the AMA’s own performance in this regard.

The 82-page report, which was created by the association’s Center for Health Equity, argues for both internal changes at the AMA and changes in how the association addresses race-based inequities in general.

The report was released just 2 months after this news organization reported that a podcast hosted by AMA’s top journal was lambasted as racist and out of touch. In the podcast – entitled “Stuctural Racism for Doctors – What Is It?” – one JAMA editor argued that structural racism doesn’t exist. He eventually resigned and the journal’s top editor was placed on administration leave.

The new AMA report’s strategic framework “is driven by the immense need for equity-centered solutions to confront harms produced by systemic racism and other forms of oppression for Black, Latinx, Indigenous, Asian, and other people of color, as well as people who identify as LGBTQ+ and people with disabilities,” the AMA said in a news release. “Its urgency is underscored by ongoing circumstances including inequities exacerbated by the COVID-19 pandemic, ongoing police brutality, and hate crimes targeting Asian, Black, and Brown communities.”

The plan includes five main approaches to addressing inequities in health care and the AMA:

• Implement antiracist equity strategies through AMA practices, programming, policies, and culture.
• Build alliances with marginalized doctors and other stakeholders to elevate the experiences and ideas of historically marginalized and minority health care leaders.
• Strengthen, empower, and equip doctors with the knowledge and tools to dismantle structural and social health inequities.
• Ensure equitable opportunities in innovation.
• Foster truth, racial healing, reconciliation, and transformation for AMA’s past by accounting for how policies and processes excluded, discriminated, and harmed communities.

As the report acknowledges, the AMA has a long history of exclusion of and discrimination against Black physicians, for which the association publicly apologized in 2008. Within the past year, the AMA has reaffirmed its commitment to addressing this legacy and to be proactive on health equity.

Among other things, the association has described racism as a public health crisis, stated that race has nothing to do with biology, said police brutality is a product of structural racism, and called on the federal government to collect and release COVID-19 race/ethnicity data. It also removed the name of AMA founder Nathan Davis, MD, from an annual award and display because of his contribution to explicit racist practices.
 

Equity-centered solutions

The AMA launched its Center for Health Equity in 2019 with a mandate “to embed health equity across the organization.” Aletha Maybank, MD, was named the AMA’s chief health equity officer to lead the center.

In the report that Dr. Maybank helped write, the AMA discusses the consequences of individual and systemic injustice toward minorities. Among these consequences, the report said, is “segregated and inequitable health care systems.”

The “equity-centered solutions” listed in the report include:

• End segregated health care.
• Establish national health care equity and racial justice standards.
• End the use of race-based clinical decision models.
• Eliminate all forms of discrimination, exclusion and oppression in medical and physician education, training, hiring, and promotion.
• Prevent exclusion of and ensure equal representation of Black, Indigenous and Latinx people in medical school admissions as well as medical school and hospital leadership ranks.
• Ensure equity in innovation, including design, development, implementation along with support for equitable innovation opportunities and entrepreneurship.
• Solidify connections and coordination between health care and public health.
• Acknowledge and repair past harms committed by institutions.
•  

Changing medical education

In an exclusive interview, Gerald E. Harmon, MD, president-elect of the AMA, singled out medical education as an area that is ripe for change. “One of the most threatened phenotypes on the planet is the Black male physician,” he said. “Their numbers among medical school applicants continue to drop. We have increasing numbers of women in medical schools – over 50% of trainees are women – and more Black women are entering medical school, but Black men in medical school are an endangered species.

“We’re trying to get the physician workforce to look like the patient workforce.”

Dr. Harmon cited the “pipeline program” at the Morehouse School of Medicine in Atlanta and the AMA’s “doctors back to school” program as examples of efforts to attract minority high school students to health care careers. Much more needs to be done, he added. “We have to put equity and representation into our medical workforce so we can provide better high quality, more reliable care for underrepresented patients.”
 

Putting the AMA’s house in order

In its report, the AMA also makes recommendations about how it can improve equity within its own organization. Over the next 3 years, among other things, the association plans to improve the diversity of leadership at the AMA and its journal, JAMA; train all staff on equity requirements; and develop a plan to recruit more racial and ethnic minorities, LGBTQ+ people, and disabled people.

Dr. Maybank, the AMA’s chief health equity officer, said in an interview that she wouldn’t describe these efforts as affirmative action. “This is beyond affirmative action. It’s about intentional activity and action to ensure equity and justice within the AMA.”

The AMA has to thoroughly examine its own processes and determine “how inequity shows up on a day-to-day basis,” she said. “Whether it’s through hiring, innovation, publishing or communications, everybody needs to know how inequity shows up and how their own mental models can exacerbate inequities. People need tools to challenge themselves and ask themselves critical questions about racism in their processes and what they can do to mitigate those.”

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

The American Medical Association has released a 3-year strategic plan to counter longstanding health inequities that hurt marginalized communities and to improve the AMA’s own performance in this regard.

The 82-page report, which was created by the association’s Center for Health Equity, argues for both internal changes at the AMA and changes in how the association addresses race-based inequities in general.

The report was released just 2 months after this news organization reported that a podcast hosted by AMA’s top journal was lambasted as racist and out of touch. In the podcast – entitled “Stuctural Racism for Doctors – What Is It?” – one JAMA editor argued that structural racism doesn’t exist. He eventually resigned and the journal’s top editor was placed on administration leave.

The new AMA report’s strategic framework “is driven by the immense need for equity-centered solutions to confront harms produced by systemic racism and other forms of oppression for Black, Latinx, Indigenous, Asian, and other people of color, as well as people who identify as LGBTQ+ and people with disabilities,” the AMA said in a news release. “Its urgency is underscored by ongoing circumstances including inequities exacerbated by the COVID-19 pandemic, ongoing police brutality, and hate crimes targeting Asian, Black, and Brown communities.”

The plan includes five main approaches to addressing inequities in health care and the AMA:

• Implement antiracist equity strategies through AMA practices, programming, policies, and culture.
• Build alliances with marginalized doctors and other stakeholders to elevate the experiences and ideas of historically marginalized and minority health care leaders.
• Strengthen, empower, and equip doctors with the knowledge and tools to dismantle structural and social health inequities.
• Ensure equitable opportunities in innovation.
• Foster truth, racial healing, reconciliation, and transformation for AMA’s past by accounting for how policies and processes excluded, discriminated, and harmed communities.

As the report acknowledges, the AMA has a long history of exclusion of and discrimination against Black physicians, for which the association publicly apologized in 2008. Within the past year, the AMA has reaffirmed its commitment to addressing this legacy and to be proactive on health equity.

Among other things, the association has described racism as a public health crisis, stated that race has nothing to do with biology, said police brutality is a product of structural racism, and called on the federal government to collect and release COVID-19 race/ethnicity data. It also removed the name of AMA founder Nathan Davis, MD, from an annual award and display because of his contribution to explicit racist practices.
 

Equity-centered solutions

The AMA launched its Center for Health Equity in 2019 with a mandate “to embed health equity across the organization.” Aletha Maybank, MD, was named the AMA’s chief health equity officer to lead the center.

In the report that Dr. Maybank helped write, the AMA discusses the consequences of individual and systemic injustice toward minorities. Among these consequences, the report said, is “segregated and inequitable health care systems.”

The “equity-centered solutions” listed in the report include:

• End segregated health care.
• Establish national health care equity and racial justice standards.
• End the use of race-based clinical decision models.
• Eliminate all forms of discrimination, exclusion and oppression in medical and physician education, training, hiring, and promotion.
• Prevent exclusion of and ensure equal representation of Black, Indigenous and Latinx people in medical school admissions as well as medical school and hospital leadership ranks.
• Ensure equity in innovation, including design, development, implementation along with support for equitable innovation opportunities and entrepreneurship.
• Solidify connections and coordination between health care and public health.
• Acknowledge and repair past harms committed by institutions.
•  

Changing medical education

In an exclusive interview, Gerald E. Harmon, MD, president-elect of the AMA, singled out medical education as an area that is ripe for change. “One of the most threatened phenotypes on the planet is the Black male physician,” he said. “Their numbers among medical school applicants continue to drop. We have increasing numbers of women in medical schools – over 50% of trainees are women – and more Black women are entering medical school, but Black men in medical school are an endangered species.

“We’re trying to get the physician workforce to look like the patient workforce.”

Dr. Harmon cited the “pipeline program” at the Morehouse School of Medicine in Atlanta and the AMA’s “doctors back to school” program as examples of efforts to attract minority high school students to health care careers. Much more needs to be done, he added. “We have to put equity and representation into our medical workforce so we can provide better high quality, more reliable care for underrepresented patients.”
 

Putting the AMA’s house in order

In its report, the AMA also makes recommendations about how it can improve equity within its own organization. Over the next 3 years, among other things, the association plans to improve the diversity of leadership at the AMA and its journal, JAMA; train all staff on equity requirements; and develop a plan to recruit more racial and ethnic minorities, LGBTQ+ people, and disabled people.

Dr. Maybank, the AMA’s chief health equity officer, said in an interview that she wouldn’t describe these efforts as affirmative action. “This is beyond affirmative action. It’s about intentional activity and action to ensure equity and justice within the AMA.”

The AMA has to thoroughly examine its own processes and determine “how inequity shows up on a day-to-day basis,” she said. “Whether it’s through hiring, innovation, publishing or communications, everybody needs to know how inequity shows up and how their own mental models can exacerbate inequities. People need tools to challenge themselves and ask themselves critical questions about racism in their processes and what they can do to mitigate those.”

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

Lower blood sugar with sardines

Brand X Pictures/thinkstock.com

If you’ve ever turned your nose up at someone eating sardines straight from the can, you could be the one missing out on a good way to boost your own health.

New research from Open University of Catalonia (Spain) has found that eating two cans of whole sardines a week can help prevent people from developing type 2 diabetes (T2D). Now you might be thinking: That’s a lot of fish, can’t I just take a supplement pill? Actually, no.

“Nutrients can play an essential role in the prevention and treatment of many different pathologies, but their effect is usually caused by the synergy that exists between them and the food that they are contained in,” study coauthor Diana Rizzolo, PhD, said in a written statement. See, we told you.

In a study of 152 patients with prediabetes, each participant was put on a specific diet to reduce their chances of developing T2D. Among the patients who were not given sardines each week, the proportion considered to be at the highest risk fell from 27% to 22% after 1 year, but for those who did get the sardines, the size of the high-risk group shrank from 37% to just 8%.

Suggesting sardines during checkups could make eating them more widely accepted, Dr. Rizzolo and associates said. Sardines are cheap, easy to find, and also have the benefits of other oily fish, like boosting insulin resistance and increasing good cholesterol.

So why not have a can with a couple of saltine crackers for lunch? Your blood sugar will thank you. Just please avoid indulging on a plane or in your office, where workers are slowly returning – no need to give them another excuse to avoid their cubicle.
 

Come for the torture, stay for the vaccine

MMZ84 from Pixabay

Bran Castle. Home of Dracula and Vlad the Impaler (at least in pop culture’s eyes). A moody Gothic structure atop a hill. You can practically hear the ancient screams of thousands of tortured souls as you wander the grounds and its cursed halls. Naturally, it’s a major tourist destination.

Unfortunately for Romania, the pandemic has rather put a damper on tourism. The restrictions have done their damage, but here’s a quick LOTME theory: Perhaps people don’t want to be reminded of medieval tortures when we’ve got plenty of modern-day ones right now.

The management of Bran Castle has developed a new gimmick to drum up attendance – come to Bran Castle and get your COVID vaccine. Anyone can come and get jabbed with the Pfizer vaccine on all weekends in May, and when they do, they gain free admittance to the castle and the exhibit within, home to 52 medieval torture instruments. “The idea … was to show how people got jabbed 500-600 years ago in Europe,” the castle’s marketing director said.

While it may not be kind of the jabbing ole Vladdy got his name for – fully impaling people on hundreds of wooden stakes while you eat a nice dinner isn’t exactly smiled upon in today’s world – we’re sure he’d approve of this more limited but ultimately beneficial version. Jabbing people while helping them really is the dream.
 

Fuzzy little COVID detectors

temmuzcan/Getty Images

Before we get started, we need a moment to get our deep, movie trailer announcer-type voice ready. Okay, here goes.

“In a world where an organism too tiny to see brings entire economies to a standstill and pits scientists against doofuses, who can humanity turn to for help?”

How about bees? That’s right, we said bees. But not just any bees. Specially trained bees. Specially trained Dutch bees. Bees trained to sniff out our greatest nemesis. No, we’re not talking about Ted Cruz anymore. Let it go, that was just a joke. We’re talking COVID.

We’ll let Wim van der Poel, professor of virology at Wageningen (the Netherlands) University, explain the process: “We collect normal honeybees from a beekeeper, and we put the bees in harnesses.” And you thought their tulips were pretty great – the Dutch are putting harnesses on bees! (Which is much better than our previous story of bees involving a Taiwanese patient.)

The researchers presented the bees with two types of samples: COVID infected and non–COVID infected. The infected samples came with a sugary water reward and the noninfected samples did not, so the bees quickly learned to tell the difference.

The bees, then, could cut the waiting time for test results down to seconds, and at a fraction of the cost, making them an option in countries without a lot of testing infrastructure, the research team suggested.

The plan is not without its flaws, of course, but we’re convinced. More than that, we are true bee-lievers.
 

A little slice of … well, not heaven

risalbudiman006/Pixaby

If you’ve been around for the last 2 decades, you’ve seen your share of Internet trends: Remember the ice bucket challenge? Tide pod eating? We know what you’re thinking: Sigh, what could they be doing now?

Well, people are eating old meat, and before you think about the expired ground beef you got on special from the grocery store yesterday, that’s not quite what we mean. We all know expiration dates are “suggestions,” like yield signs and yellow lights. People are eating rotten, decomposing, borderline moldy meat.

They claim that the meat tastes better. We’re not so sure, but don’t worry, because it gets weirder. Some folks, apparently, are getting high from eating this meat, experiencing a feeling of euphoria. Personally, we think that rotten fumes probably knocked these people out and made them hallucinate.

Singaporean dietitian Naras Lapsys says that eating rotten meat can possibly cause a person to go into another state of consciousness, but it’s not a good thing. We don’t think you have to be a dietitian to know that.

It has not been definitively proven that eating rotting meat makes you high, but it’s definitely proven that this is disgusting … and very dangerous.
 

Lower blood sugar with sardines

Brand X Pictures/thinkstock.com

If you’ve ever turned your nose up at someone eating sardines straight from the can, you could be the one missing out on a good way to boost your own health.

New research from Open University of Catalonia (Spain) has found that eating two cans of whole sardines a week can help prevent people from developing type 2 diabetes (T2D). Now you might be thinking: That’s a lot of fish, can’t I just take a supplement pill? Actually, no.

“Nutrients can play an essential role in the prevention and treatment of many different pathologies, but their effect is usually caused by the synergy that exists between them and the food that they are contained in,” study coauthor Diana Rizzolo, PhD, said in a written statement. See, we told you.

In a study of 152 patients with prediabetes, each participant was put on a specific diet to reduce their chances of developing T2D. Among the patients who were not given sardines each week, the proportion considered to be at the highest risk fell from 27% to 22% after 1 year, but for those who did get the sardines, the size of the high-risk group shrank from 37% to just 8%.

Suggesting sardines during checkups could make eating them more widely accepted, Dr. Rizzolo and associates said. Sardines are cheap, easy to find, and also have the benefits of other oily fish, like boosting insulin resistance and increasing good cholesterol.

So why not have a can with a couple of saltine crackers for lunch? Your blood sugar will thank you. Just please avoid indulging on a plane or in your office, where workers are slowly returning – no need to give them another excuse to avoid their cubicle.
 

Come for the torture, stay for the vaccine

MMZ84 from Pixabay

Bran Castle. Home of Dracula and Vlad the Impaler (at least in pop culture’s eyes). A moody Gothic structure atop a hill. You can practically hear the ancient screams of thousands of tortured souls as you wander the grounds and its cursed halls. Naturally, it’s a major tourist destination.

Unfortunately for Romania, the pandemic has rather put a damper on tourism. The restrictions have done their damage, but here’s a quick LOTME theory: Perhaps people don’t want to be reminded of medieval tortures when we’ve got plenty of modern-day ones right now.

The management of Bran Castle has developed a new gimmick to drum up attendance – come to Bran Castle and get your COVID vaccine. Anyone can come and get jabbed with the Pfizer vaccine on all weekends in May, and when they do, they gain free admittance to the castle and the exhibit within, home to 52 medieval torture instruments. “The idea … was to show how people got jabbed 500-600 years ago in Europe,” the castle’s marketing director said.

While it may not be kind of the jabbing ole Vladdy got his name for – fully impaling people on hundreds of wooden stakes while you eat a nice dinner isn’t exactly smiled upon in today’s world – we’re sure he’d approve of this more limited but ultimately beneficial version. Jabbing people while helping them really is the dream.
 

Fuzzy little COVID detectors

temmuzcan/Getty Images

Before we get started, we need a moment to get our deep, movie trailer announcer-type voice ready. Okay, here goes.

“In a world where an organism too tiny to see brings entire economies to a standstill and pits scientists against doofuses, who can humanity turn to for help?”

How about bees? That’s right, we said bees. But not just any bees. Specially trained bees. Specially trained Dutch bees. Bees trained to sniff out our greatest nemesis. No, we’re not talking about Ted Cruz anymore. Let it go, that was just a joke. We’re talking COVID.

We’ll let Wim van der Poel, professor of virology at Wageningen (the Netherlands) University, explain the process: “We collect normal honeybees from a beekeeper, and we put the bees in harnesses.” And you thought their tulips were pretty great – the Dutch are putting harnesses on bees! (Which is much better than our previous story of bees involving a Taiwanese patient.)

The researchers presented the bees with two types of samples: COVID infected and non–COVID infected. The infected samples came with a sugary water reward and the noninfected samples did not, so the bees quickly learned to tell the difference.

The bees, then, could cut the waiting time for test results down to seconds, and at a fraction of the cost, making them an option in countries without a lot of testing infrastructure, the research team suggested.

The plan is not without its flaws, of course, but we’re convinced. More than that, we are true bee-lievers.
 

A little slice of … well, not heaven

risalbudiman006/Pixaby

If you’ve been around for the last 2 decades, you’ve seen your share of Internet trends: Remember the ice bucket challenge? Tide pod eating? We know what you’re thinking: Sigh, what could they be doing now?

Well, people are eating old meat, and before you think about the expired ground beef you got on special from the grocery store yesterday, that’s not quite what we mean. We all know expiration dates are “suggestions,” like yield signs and yellow lights. People are eating rotten, decomposing, borderline moldy meat.

They claim that the meat tastes better. We’re not so sure, but don’t worry, because it gets weirder. Some folks, apparently, are getting high from eating this meat, experiencing a feeling of euphoria. Personally, we think that rotten fumes probably knocked these people out and made them hallucinate.

Singaporean dietitian Naras Lapsys says that eating rotten meat can possibly cause a person to go into another state of consciousness, but it’s not a good thing. We don’t think you have to be a dietitian to know that.

It has not been definitively proven that eating rotting meat makes you high, but it’s definitely proven that this is disgusting … and very dangerous.
 

Lower blood sugar with sardines

Brand X Pictures/thinkstock.com

If you’ve ever turned your nose up at someone eating sardines straight from the can, you could be the one missing out on a good way to boost your own health.

New research from Open University of Catalonia (Spain) has found that eating two cans of whole sardines a week can help prevent people from developing type 2 diabetes (T2D). Now you might be thinking: That’s a lot of fish, can’t I just take a supplement pill? Actually, no.

“Nutrients can play an essential role in the prevention and treatment of many different pathologies, but their effect is usually caused by the synergy that exists between them and the food that they are contained in,” study coauthor Diana Rizzolo, PhD, said in a written statement. See, we told you.

In a study of 152 patients with prediabetes, each participant was put on a specific diet to reduce their chances of developing T2D. Among the patients who were not given sardines each week, the proportion considered to be at the highest risk fell from 27% to 22% after 1 year, but for those who did get the sardines, the size of the high-risk group shrank from 37% to just 8%.

Suggesting sardines during checkups could make eating them more widely accepted, Dr. Rizzolo and associates said. Sardines are cheap, easy to find, and also have the benefits of other oily fish, like boosting insulin resistance and increasing good cholesterol.

So why not have a can with a couple of saltine crackers for lunch? Your blood sugar will thank you. Just please avoid indulging on a plane or in your office, where workers are slowly returning – no need to give them another excuse to avoid their cubicle.
 

Come for the torture, stay for the vaccine

MMZ84 from Pixabay

Bran Castle. Home of Dracula and Vlad the Impaler (at least in pop culture’s eyes). A moody Gothic structure atop a hill. You can practically hear the ancient screams of thousands of tortured souls as you wander the grounds and its cursed halls. Naturally, it’s a major tourist destination.

Unfortunately for Romania, the pandemic has rather put a damper on tourism. The restrictions have done their damage, but here’s a quick LOTME theory: Perhaps people don’t want to be reminded of medieval tortures when we’ve got plenty of modern-day ones right now.

The management of Bran Castle has developed a new gimmick to drum up attendance – come to Bran Castle and get your COVID vaccine. Anyone can come and get jabbed with the Pfizer vaccine on all weekends in May, and when they do, they gain free admittance to the castle and the exhibit within, home to 52 medieval torture instruments. “The idea … was to show how people got jabbed 500-600 years ago in Europe,” the castle’s marketing director said.

While it may not be kind of the jabbing ole Vladdy got his name for – fully impaling people on hundreds of wooden stakes while you eat a nice dinner isn’t exactly smiled upon in today’s world – we’re sure he’d approve of this more limited but ultimately beneficial version. Jabbing people while helping them really is the dream.
 

Fuzzy little COVID detectors

temmuzcan/Getty Images

Before we get started, we need a moment to get our deep, movie trailer announcer-type voice ready. Okay, here goes.

“In a world where an organism too tiny to see brings entire economies to a standstill and pits scientists against doofuses, who can humanity turn to for help?”

How about bees? That’s right, we said bees. But not just any bees. Specially trained bees. Specially trained Dutch bees. Bees trained to sniff out our greatest nemesis. No, we’re not talking about Ted Cruz anymore. Let it go, that was just a joke. We’re talking COVID.

We’ll let Wim van der Poel, professor of virology at Wageningen (the Netherlands) University, explain the process: “We collect normal honeybees from a beekeeper, and we put the bees in harnesses.” And you thought their tulips were pretty great – the Dutch are putting harnesses on bees! (Which is much better than our previous story of bees involving a Taiwanese patient.)

The researchers presented the bees with two types of samples: COVID infected and non–COVID infected. The infected samples came with a sugary water reward and the noninfected samples did not, so the bees quickly learned to tell the difference.

The bees, then, could cut the waiting time for test results down to seconds, and at a fraction of the cost, making them an option in countries without a lot of testing infrastructure, the research team suggested.

The plan is not without its flaws, of course, but we’re convinced. More than that, we are true bee-lievers.
 

A little slice of … well, not heaven

risalbudiman006/Pixaby

If you’ve been around for the last 2 decades, you’ve seen your share of Internet trends: Remember the ice bucket challenge? Tide pod eating? We know what you’re thinking: Sigh, what could they be doing now?

Well, people are eating old meat, and before you think about the expired ground beef you got on special from the grocery store yesterday, that’s not quite what we mean. We all know expiration dates are “suggestions,” like yield signs and yellow lights. People are eating rotten, decomposing, borderline moldy meat.

They claim that the meat tastes better. We’re not so sure, but don’t worry, because it gets weirder. Some folks, apparently, are getting high from eating this meat, experiencing a feeling of euphoria. Personally, we think that rotten fumes probably knocked these people out and made them hallucinate.

Singaporean dietitian Naras Lapsys says that eating rotten meat can possibly cause a person to go into another state of consciousness, but it’s not a good thing. We don’t think you have to be a dietitian to know that.

It has not been definitively proven that eating rotting meat makes you high, but it’s definitely proven that this is disgusting … and very dangerous.
 

The Centers for Disease Control and Prevention’s director Rochelle Walensky, MD, signed off on an advisory panel’s recommendation May 12 endorsing the use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12-15 years.

Earlier in the day the CDC’s Advisory Committee on Immunization Practices voted 14-0 in favor of the safety and effectiveness of the vaccine in younger teens.

“CDC now recommends that this vaccine be used among this population, and providers may begin vaccinating them right away,” Dr. Walensky said in an official statement.

The Food and Drug Administration on May 10 issued an emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine for the prevention of COVID-19 in individuals 12-15 years old. The FDA first cleared the Pfizer-BioNTech vaccine through an EUA in December 2020 for those ages 16 and older. Pfizer this month also initiated steps with the FDA toward a full approval of its vaccine.

Dr. Walenksy urged parents to seriously consider vaccinating their children.

“Understandably, some parents want more information before their children receive a vaccine,” she said. “I encourage parents with questions to talk to your child’s healthcare provider or your family doctor to learn more about the vaccine.”
 

Vaccine “safe and effective”

Separately, the American Academy of Pediatrics issued a statement May 12 in support of vaccinating all children ages 12 and older who are eligible for the federally authorized COVID-19 vaccine.

“As a pediatrician and a parent, I have looked forward to getting my own children and patients vaccinated, and I am thrilled that those ages 12 and older can now be protected,” said AAP President Lee Savio Beers, MD, in a statement. “The data continue to show that this vaccine is safe and effective. I urge all parents to call their pediatrician to learn more about how to get their children and teens vaccinated.”

The expanded clearance for the Pfizer vaccine is seen as a critical step for allowing teens to resume activities on which they missed out during the pandemic.

“We’ve seen the harm done to children’s mental and emotional health as they’ve missed out on so many experiences during the pandemic,” Dr. Beers said. “Vaccinating children will protect them and allow them to fully engage in all of the activities – school, sports, socializing with friends and family – that are so important to their health and development.”

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

The Centers for Disease Control and Prevention’s director Rochelle Walensky, MD, signed off on an advisory panel’s recommendation May 12 endorsing the use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12-15 years.

Earlier in the day the CDC’s Advisory Committee on Immunization Practices voted 14-0 in favor of the safety and effectiveness of the vaccine in younger teens.

“CDC now recommends that this vaccine be used among this population, and providers may begin vaccinating them right away,” Dr. Walensky said in an official statement.

The Food and Drug Administration on May 10 issued an emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine for the prevention of COVID-19 in individuals 12-15 years old. The FDA first cleared the Pfizer-BioNTech vaccine through an EUA in December 2020 for those ages 16 and older. Pfizer this month also initiated steps with the FDA toward a full approval of its vaccine.

Dr. Walenksy urged parents to seriously consider vaccinating their children.

“Understandably, some parents want more information before their children receive a vaccine,” she said. “I encourage parents with questions to talk to your child’s healthcare provider or your family doctor to learn more about the vaccine.”
 

Vaccine “safe and effective”

Separately, the American Academy of Pediatrics issued a statement May 12 in support of vaccinating all children ages 12 and older who are eligible for the federally authorized COVID-19 vaccine.

“As a pediatrician and a parent, I have looked forward to getting my own children and patients vaccinated, and I am thrilled that those ages 12 and older can now be protected,” said AAP President Lee Savio Beers, MD, in a statement. “The data continue to show that this vaccine is safe and effective. I urge all parents to call their pediatrician to learn more about how to get their children and teens vaccinated.”

The expanded clearance for the Pfizer vaccine is seen as a critical step for allowing teens to resume activities on which they missed out during the pandemic.

“We’ve seen the harm done to children’s mental and emotional health as they’ve missed out on so many experiences during the pandemic,” Dr. Beers said. “Vaccinating children will protect them and allow them to fully engage in all of the activities – school, sports, socializing with friends and family – that are so important to their health and development.”

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

The Centers for Disease Control and Prevention’s director Rochelle Walensky, MD, signed off on an advisory panel’s recommendation May 12 endorsing the use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12-15 years.

Earlier in the day the CDC’s Advisory Committee on Immunization Practices voted 14-0 in favor of the safety and effectiveness of the vaccine in younger teens.

“CDC now recommends that this vaccine be used among this population, and providers may begin vaccinating them right away,” Dr. Walensky said in an official statement.

The Food and Drug Administration on May 10 issued an emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine for the prevention of COVID-19 in individuals 12-15 years old. The FDA first cleared the Pfizer-BioNTech vaccine through an EUA in December 2020 for those ages 16 and older. Pfizer this month also initiated steps with the FDA toward a full approval of its vaccine.

Dr. Walenksy urged parents to seriously consider vaccinating their children.

“Understandably, some parents want more information before their children receive a vaccine,” she said. “I encourage parents with questions to talk to your child’s healthcare provider or your family doctor to learn more about the vaccine.”
 

Vaccine “safe and effective”

Separately, the American Academy of Pediatrics issued a statement May 12 in support of vaccinating all children ages 12 and older who are eligible for the federally authorized COVID-19 vaccine.

“As a pediatrician and a parent, I have looked forward to getting my own children and patients vaccinated, and I am thrilled that those ages 12 and older can now be protected,” said AAP President Lee Savio Beers, MD, in a statement. “The data continue to show that this vaccine is safe and effective. I urge all parents to call their pediatrician to learn more about how to get their children and teens vaccinated.”

The expanded clearance for the Pfizer vaccine is seen as a critical step for allowing teens to resume activities on which they missed out during the pandemic.

“We’ve seen the harm done to children’s mental and emotional health as they’ve missed out on so many experiences during the pandemic,” Dr. Beers said. “Vaccinating children will protect them and allow them to fully engage in all of the activities – school, sports, socializing with friends and family – that are so important to their health and development.”

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