Articles
Science Matters: Research Summary of the BETAMI - DANBLOCK Trial
About the Author: Michael Katsnelson MD, PhD, FACC is currently a research fellow at Washington University in St. Louis School of Medicine. He specializes in advanced heart failure/transplant cardiology and his main research interest lies in studying the role of the innate immune system in the progression of ischemic cardiomyopathy. In this article he provides a summary of a recent JACC publication.
Background: Beta blockers are commonly utilized therapeutic agents in patients with a history of myocardial infarction. These agents serve as a method of secondary prevention to decrease the likelihood of subsequent cardiovascular adverse events. However, the clinical trials which provided the underlying evidence for this recommendation were conducted in the 1980s. These studies demonstrated a reduction in all cause mortality as well as decreased risk of subsequent MI in patients who received beta blocker therapy following a myocardial infarction. However, there is a concern that advances in the management of acute coronary syndrome such as coronary reperfusion therapy, cholesterol lowering agents and anti-platelet therapy developed over the subsequent four decades may have obviated the requirement for life- long beta blocker therapy following MI. Beta blocker therapy is currently indicated in patients with ischemic cardiomyopathy and LVEF≤40%. However, the benefits of beta blocker therapy in patients with mid-range LVEF (40-50%) or preserved LVEF (≥50%) following MI are currently unclear.
Methods: The BETAMI and DANBLOCK trials were two clinical studies conducted in Norway and Denmark, respectively. The trials utilized a prospective, open-label, and blinded end-point evaluation approach to test the superiority of beta blocker therapy compared to no beta blocker therapy in patients following myocardial infarction. The trials utilized a similar study design as well as similar criteria for inclusion and exclusion. The data from the studies were pooled due to lower-than-expected enrollment in the individual trials in the setting of the COVID-19 pandemic. Inclusion criteria included patients within 14 days of sustaining a myocardial infarction and an LVEF≥40%. Key exclusion criteria were having a diagnosis of heart failure or another indication for beta blocker therapy as well as having any contraindication to beta blocker therapy. The primary endpoint of the trial was a composite of death from any cause or major cardiovascular adverse event (new myocardial infarction, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias).
Results: The authors observed a significant reduction in the incidence of the primary endpoint in those patients assigned to the beta blocker treatment group (14.2%) compared to those patients assigned to the no beta blocker therapy group (16.3%) [hazard ratio 0.85 with CI 0.75-0.98]. The incidence of subsequent myocardial infarction was reduced from 6.7% in the no beta blocker therapy group to 5.0% in the beta blocker treated group [HR 0.73 with 95% CI 0.59-0.92]. The incidence of serious adverse events including hospitalization for second- or third-degree heart block or pacemaker implantation were similar between the two groups. The average follow-up interval in the trial was 3.5 years. However, in a prespecified analysis restricted to 12 months of follow-up, the authors observed a similar reduction in the incidence of the primary endpoint in those patients on beta blocker therapy when compared to those patients who were not on beta blocker therapy.
Discussion: The results of the study demonstrate that the use of beta blocker therapy during the period following acute MI resulted in a modest reduction (2.1%) in the incidence of adverse cardiovascular events. This seemed to be mainly driven by reduced incidence of subsequent MI, although the study was not powered to evaluate each component of the primary endpoint individually. There are a number of mechanisms by which beta blocker therapy may reduce the risk of subsequent myocardial infarction including decreasing myocardial oxygen demand through negative inotropic and chronotropic effects, enhancing diastolic perfusion time, improving microvascular dysfunction by enhancing nitric oxide production and reducing platelet aggregation. Multiple studies have clearly demonstrated the benefit of beta blocker therapy in patients with LVEF≤40%. However, the effect of beta blockers on incidence of major adverse cardiac events (MACE) in patients with a mid-range LVEF 40-49% remains an area of active investigation. Previously this subset of patients was grouped together with those who had an LVEF≥50% in clinical trials of heart failure pharmacotherapy. The results of a recent meta-analysis by Joo et al utilizing a Korean MI registry indicated that beta blocker therapy in patients with mid-range LVEF was associated with a significantly lower risk of MACE, while there was no significant reduction in MACE in patients with LVEF≥50% who were treated with beta blockers. Thus, the modest reduction in MACE observed in patients on beta blocker therapy in the BETAMI-DANBLOCK trial may be due to a beneficial effect in the subset of patients with a mid-range LVEF (40-49%). Further studies are required to determine the optimal medical regimen in patients with a mid-range LVEF following acute MI.
Link to article https://www.nejm.org/doi/full/10.1056/NEJMoa2505985?query=featured_home
