Highlights from #AHA21: Coffee and SGLT2 inhibitors!

So much great work is being shared at the AHA. I’d like to put a spotlight on two studies that stood out from Day 2 of #AHA21!

The CRAVE  Trial

The Coffee and Real-Time Assessment of Atrial and Ventricular Ectopy (CRAVE) trial attempted to address an urban myth that has been around for decades: coffee could contribute to arrhythmias. But is this actually true? The objective of this study was to assess in a more structured and scientific way to study the effects of coffee on individuals in the ambulatory setting. In this randomized crossover trial, 100 participants were each given a Fitbit Flex 2 (an accelerometer that can records step counts and number of hours of sleep), a Zio Patch (a continuously recording electrocardiogram [ECG] device), and a continuous glucose monitor to measure glucose levels. Study investigators also obtained blood samples to extract DNA to determine whether participants exhibited fast or slow caffeine metabolism genetic variants.

Participants were randomly assigned using a mobile app to either consume or avoid coffee on a day-to-day basis. Coffee consumption was validated via geo-location trackers, money incentives and daily surveys. Study investigators then compared days when people were assigned to drink coffee with those in which they were assigned to avoid it. Increased coffee consumption did not lead to an increase in atrial arrhythmias (in fact, it was associated with less supraventricular tachycardias [SVT]). However, increased coffee consumption was associated with more premature ventricular contractions (PVCs). Genetic analyses of DNA samples from participants showed that faster metabolizers were more likely to have more PVCs.

In the analysis of the Fitbit data, coffee intake was associated with 1000 additional steps on those days in which coffee was consumed, but with less sleep that same evening. Slow metabolizers of caffeine were more affected and were more likely to have reduced sleep. There were no differences in serum glucose levels with regard to coffee intake.

Study investigators concluded that coffee consumption did not lead to increased atrial arrhythmias but did increase PVCs and that coffee consumption. It also led to more physical activity, may lead to less sleep, with differential effects depending on how well people can metabolize caffeine. This is further evidence that the physiologic effects of caffeine intake are complex and varied in different populations, and should be further studied.



The Empagliflozin in Patients Hospitalized for Acute Heart Failure  (EMPULSE) trial was a randomized, placebo-controlled trial that assessed the safety and efficacy of the sodium glucose transporter cotransporter-2 (SGLT2) inhibitor empagliflozin in 500 patients who were hospitalized for acute decompensated heart failure (regardless of whether or not they had diabetes, HFpEF or HFrEF). This last distinction is key as many recent studies of empagliflozin have focused specifically on diabetic patients or patients with heart failure with reduced left ventricular ejection fraction (HFrEF). Primary outcomes included death, number of heart failure events (HFE), time to first heart failure event, change in baseline Kansas City Cardiomyopathy Questionnaire (KCCQ-TSS) after 90 days of treatment. Participants were randomized to empagliflozin 10 mg daily (and continued for at least 90 days) or to a placebo during their acute heart failure hospitalization.

After 90 days of treatment starting during their hospitalization for acute decompensated heart failure, participants who received empagliflozin were 36% more likely to see a clinical benefit (a composite of time to death, number of HFEs, time to HFE, and change from baseline KCCQ-TSS). There was a 35% percent reduction in death or first heart failure event. There was also greater weight loss, greater reduction in NT-proBNP and there were no safety concerns associated with taking the medication. Findings were similar in patients without and with diabetes, those with HFpEF and HFrEF as well as those with a new heart failure diagnosis or those with chronic heart failure.

In conclusion, this study showed that empagliflozin was both safe for patients to start taking during a hospitalization for acute decompensated heart failure and led to lower likelihood of death or new heart failure events – among other benefits – if the medication was started during that hospitalization, regardless of one’s diabetes status or ejection fraction. More work needs to be done to better understand the mechanism by which SGLT2 improve these clinical outcomes, though some speculate that their benefits have to do with the diuretic effect of the medication. In a similar vein, EMPEROR-Preserved Trial published in the New England Journal of Medicine earlier this year showed that empagliflozin reduced the risk of cardiovascular death or hospitalization in patients with heart failure with a left ventricular ejection fraction of at least 40%, regardless of whether or not they have diabetes.

Studies such as EMPULSE and EMPEROR-Preserved provide further support for utilization of empagliflozin in all patients with heart failure – not just those with a reduced ejection fraction (for which a number of studies have already shown clinical benefit, and for which SGLT2 inhibitors are already standard of care). Lively discussions in the medical community are ongoing as to whether we should be placing all patients – with reduced and preserved ejection fraction –  who are hospitalized with heart failure on an SGLT2 inhibitor, prior to discharge.



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