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Last Day of #AHA20: COVID-19 Galore!

The last day of the amazing #AHA20 featured a series of COVID-19-related research presentations.

First, data from the AHA COVID-19 Registry, a large database collecting data about COVID-19 patients and outcomes around the country, were shared. The registry includes data from 109 hospitals and over 22,500 records of patients who were hospitalized with COVID-19. Notably, large numbers of COVID-19 patients in this registry had cardiovascular risk factors such as hypertension and diabetes. Prior cardiovascular disease was also common. The disease was additionally noted to have a high morbidity and mortality rate, with more than 20% of hospitalized COVID-19 patients requiring mechanical ventilation.

One interesting study examined racial and ethnic differences in the AHA COVID-19 Registry of patients hospitalized with COVID-19, focusing primarily on the association of these factors with in-hospital death as the primary outcome and secondary outcomes such as major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, new onset heart failure or cardiogenic shock) or COVID-19 cardio-respiratory disease severity scale. Notably, Black and Hispanic patients accounted for >50% of hospitalizations in this Registry, suggesting significant over-representation of Black and Hispanic patients compared with the census demographics in their areas. Cardiovascular risk factors such as obesity and hypertension were also more common in Black and Hispanic patients. Mechanical ventilation and need for renal replacement therapy were more likely in Black patients. Overall in-hospital mortality was high at 18.4%, and particularly high for those older than 70 years old.

In fully adjusted models taking into account age, medical history and sociodemographic features, there was no statistically significant difference in mortality and MACE among different racial or ethnic groups, though Asian patients had a higher COVID-10 disease severity on presentation. These findings suggest that though race and ethnicity are not independently associated with worse in-hospital outcomes in COVID-19 patients, Black and Hispanic patients bear a greater burden of morbidity associated with COVID due to their disproportionate representation among patients hospitalized with CVOID-19. This study was simultaneously published online in Circulation.

One additional study examined the association between body mass index (BMI) with a composite of in-hospital death and/or mechanical ventilation (primary outcome), as well as with MACE (a composite of in-hospital all-cause death, stroke, heart failure, myocardial infarction), deep vein thrombosis and renal replacement therapy (secondary outcomes). Patients with a higher BMI were more likely to be admitted to the hospital with COVID-19. In analyses adjusting for age, sex, ethnicity, comorbidities, cardiovascular disease and chronic kidney disease, higher class obesity was associated with higher likelihood of in-hospital mortality or mechanical ventilation. MACE was not associated with obesity class. Deep venous thrombosis or pulmonary embolism were not associated with obesity class. Class I, II and III obesity, however, were noted to have a higher likelihood of need for mechanical ventilation, regardless of age. Moreover, when stratified by age, BMI >40 kg/m2 was associated with a higher risk of in-hospital death only in lower age groups (<50 years old). These findings suggest that better public health messaging may be required for younger obese individuals who may underestimate their own risk related to COVID-19. This study was also simultaneously published in Circulation.

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Late-Breaking Highlights: Fish Oils and Frustrations in Lipid Management

It was another exciting day of virtual sessions at #AHA20, led by intriguing findings from a few late-breaking trials!

 

First, the STRENGTH and OMEMI trials added nuance to ongoing discussions about the cardiovascular benefits of fish oils and cardiovascular risk reduction. The REDUCE-IT trial, published in the New England Journal of Medicine (NEJM) in 2019, showed that the highly purified fish oil icosapent ethyl improved cardiovascular outcomes in high-risk participants who had elevated triglycerides despite statin therapy. The STRENGTH and OMEMI trial, however, may temper enthusiasm about the use of fish oils in high-risk patients.

 

The STRENGTH trial randomized 13,000 participants in 22 countries to an omega-3 carboxylic acid or corn oil placebo, with a primary endpoint of cardiovascular death, myocardial infraction, stroke, coronary revascularization or hospitalization for unstable angina. The trial was stopped early due to “futility,” though it still achieved 1580 of the target 1600 endpoints needed for results to be sufficiently powered. Compared with those receiving corn oil placebo, participants in the omega-3 fatty acid group experienced a 19% reduction in triglycerides, 20% reduction in C-reactive protein and 269% increase in plasma eicosapentanoic acid (EPA; icosapent ethyl is a highly purified and stable version of this fatty acid). Despite these biochemical differences, there was no difference in the primary outcome between the two groups, 54 months after randomization. The major adverse outcome, atrial fibrillation, was significantly more likely in the treatment arm.

 

Why do STRENGTH findings differ from those of REDUCE-IT? STRENGTH and REDUCE-IT participants had similar triglyceride levels, but patients in the STRENGTH intervention arm had lower EPA levels than those in the REDUCE-IT treatment arm. Moreover, REDUCE-IT contained more participants with established CAD. Additionally, STRENGTH used a corn oil placebo, while REDUCE-IT used a mineral oil placebo. Corn oil has been shown to have a neutral effect on triglycerides and potentially some cardioprotective effects, while mineral oil may result in unfavorable increases in triglycerides and LDL. Some may argue that the use of mineral oil in REDUCE-IT might have exaggerated the efficacy of icosapent ethyl.

 

The OMEMI trial, meanwhile, randomized 1,000 elderly, 70-82 year old patients (who had had a myocardial infarction [MI] in the 2-8 weeks prior to enrollment) to 1.8 grams of omega-3 fatty acids or a matching corn oil placebo for 2 years. It excluded participants who could not tolerate fatty acids or who had diseases that would impact their ability to survive the 2 year study period. OMEMI found no difference in the composite primary outcome (non-fatal MI, unscheduled revascularization, stroke, hospitalization for heart failure or all-cause death). There were no significant differences in key clinical subgroup analyses, and there was a greater (though not statistically significant) risk of atrial fibrillation in the treatment arm. There was no difference in major bleeding.

 

Taken together, findings from STRENGTH and OMEMI complicate the picture of fish oil utilization and raise further questions about whether the cardiovascular effects of fish oils in some populations are beneficial or neutral. More work needs to be done to better elucidate the effects of fish oils on cardiovascular risk reduction in high-risk patients.

 

Nevertheless, while STRENGTH and OMEMI made waves owing to their potential practice-changing implications, I left the day feeling particularly inspired by the SAMSON trial. This ingeniously designed trial enrolled 60 participants who had stopped taking statins due to symptoms arising within two weeks. Any symptom was eligible if it was severe enough to lead to statin discontinuation in that time span. The most common symptoms were muscle aches, fatigue, and cramps. Participants were given four bottles containing atorvastatin 10 mg tablets, four bottles containing placebo pills and four empty bottles. Each month, they were randomly assigned to take the contents of one of the bottles, in a crossover fashion, with no washout between months. They were asked to rate the severity symptoms they experienced using a mobile phone app. They were also asked 6 months after the conclusion of the trial if they had resumed taking statins. Investigators combined symptom ratings, reporting average symptoms levels during “statin”, “placebo” and “no treatment” months.

 

SAMSON found that the severity of symptoms reported was substantially higher during statin months than during no treatment months; however, this was also true for placebo. Reported symptom levels during statin and placebo months were no different from each other. The nocebo proportion was 0.9; that is, 90% of symptoms reported during statin months were elicited by taking placebo tablets as well. Even more importantly, half of the participants resumed statins again after the trial!

 

SAMSON serves as a lesson to aspiring cardiovascular researchers that even a small study can have a major impact. It displays respect and empathy for the patient experience by acknowledging rather than denying that patients do experience side effects from statins. However, it also strongly suggests that these symptoms may be attributable to the act of taking a pill rather than the medication content of the pill itself. Lastly, SAMSON proves that patients who realize that statin side effects may not actually be specific to statins themselves may be willing to resume taking statins. These findings further support the foundational concept that we as physicians must respect our patients by engaging them in shared decision-making and give patients an opportunity to understand the science, rather than simply telling them what to do.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”