The thrill surrounding cardiovascular meetings and the promise of new science to be delivered have replaced what used to be my childhood excitement for holidays. I eagerly count down the days until the meeting, agonizing over what to expect from the late-breaking trials and wondering. While this year’s American College of Cardiology’s Scientific Session will be jam-packed with a diverse array of interesting and groundbreaking science, I am keenly excited to see if we will have potential changes to our pharmacotherapy recommendations for the management of MI patients. Will we be saying, “out with the old and in with the new?”
There are two trials specifically to which I am referring, one exploring the use of beta-blockers in patients who are post-MI with preserved ejection fraction (the old), and the other looking at the use of empagliflozin, a member of the sodium-glucose co-transporter type 2 (SGLT2) inhibitor wonder class (the new).
Current American College of Cardiology/American Heart Association guidelines have a Class Ia recommendation for the administration of beta-blockers during a hospital stay and continued thereafter for both ST-segment elevation MI (STEMI) as well as non-ST-segment elevation MI (NSTEMI) with an ejection fraction (EF) ≤ 40%. However, in patients with NSTEMI and preserved EF, the recommendation to continue beyond the acute phase is a class IIa. These recommendations are derived from data before the contemporary management of MI, and the benefits/harms are not known within the context of our current MI management. The results of the Randomized Evaluation of Decreased Usage of Beta-Blockers After Acute Myocardial Infarction (REDUCE-AMI) trial will shed some light on this matter. In this global, registry-based, open-label, multicenter trial, 5,000 patients with acute MI who have undergone coronary angiography with an EF ≥50% will be randomized to long-term treatment with beta-blockers or not, with the agent up to clinician discretion. The primary endpoint is a composite of death of any cause or new non-fatal MI. Secondary endpoints will include all-cause death, cardiovascular death, new MI, readmission because of heart failure, and atrial fibrillation, symptoms, functional status, and health-related quality of life after six–10 weeks and after one year of treatment. Safety will be assessed by exploration of bradycardia, heart block, hypotension, and the need for a pacemaker. These results could potentially provide the ability to streamline the MI pharmacotherapy regimen by removing the need for a beta-blocker if there is limited to no benefit with treatment. This could maybe improve adherence by reducing polypharmacy, if possible. I keep saying ‘if’ because the details of this trial will be key to help put this in context.
On the other hand, we are still learning about all the ways SGLT-2 inhibitors could be of benefit to our patients across the cardiovascular spectrum. All eyes are looking for signs of benefit, if any, for these agents after the mixed results of DAPA-MI results in November. DAPA-MI, a registry-based study, determined after one year there were significant benefits regarding improvement in cardiometabolic outcomes but no impact on the composite of cardiovascular death or hospitalization for heart failure in an acute MI population. The EMPAgliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction (EMPACT-MI) trial is a streamlined, multinational, randomized, double-blind, placebo-controlled trial of 5,000 participants with spontaneous MI with new signs or symptoms of pulmonary congestion requiring treatment or new left ventricular dysfunction (EF <45%) and at least one risk factor for heart failure. Patients will get empagliflozin at 10mg or placebo daily within 14 days of hospital admission. The primary endpoint is time to the first hospitalization for HF and all-cause mortality. The result of this trial will also come with a lot of ifs. The trial has a high bar, in my opinion: it needs to not just be positive but positive in a way that is meaningful, ideally in terms of mortality, in addition to other agents we know that are effective. If not, I fear people will have to debate about adding an agent, at more cost and additional pill burden, that only has modest benefits.
So, will it be out with the old and in with the new, or will it be old and new symbiotic, or something completely new? Only time will tell. However, I will continue to pine away until we arrive at the American College of Cardiology meeting. See you in Atlanta!
Dr. Beavers has no conflicts of interest to report.
Collage by Diana Connolly and Jennifer Bogartz
