Post-myocardial Infarction Express Report

Publication date: 2005-03-31

New Insights into the Antiarrhythmic Properties of Beta-blockers: A Class Effect?

This report was reviewed for medical and scientific accuracy by Ronald S. Freudenberger, MD, Director, Heart Failure and Transplant Cardiology, Associate Professor of Medicine, University of Medicine & Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Expert Commentary

Bramah N. Singh, MD, DSc, FRCP; Professor of Medicine, David Geffen School of Medicine at UCLA; Consultant Cardiologist, UCLA Medical Center, Cardio/VA Greater LA Healthcare System; Los Angeles, California

According to a published retrospective analysis of the Carvedilol Post-infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) trial,¹ carvedilol significantly suppresses atrial and ventricular arrhythmias in post-myocardial infarction patients already being treated with angiotensin-converting enzyme (ACE) inhibitors. The incidence of atrial fibrillation/flutter observed with carvedilol versus placebo was 2.3% versus 5.4%, respectively; the incidence of ventricular tachycardia/ flutter/fibrillation was 0.9% versus 3.9%, respectively. These results suggest that carvedilol may be the first beta-blocker in a controlled clinical trial to demonstrate reduction of both atrial and ventricular arrhythmias subsequent to acute myocardial infarction while given concomitantly with ACE inhibitor therapy.

Atrial and ventricular arrhythmias are common after myocardial infarction and are associated with poor prognosis.^2-5 The extent of atrial and ventricular arrhythmias predicts the degree of systolic dysfunction, indicated by left ventricular ejection fraction (LVEF), which is strongly associated with mortality after acute myocardial infarction.^2,6,7 Epidemiological examination of the relationship among ventricular arrhythmias, LVEF, and mortality two years after the occurrence of myocardial infarction shows that as left ventricular function decreases, the complexity and degree of ventricular arrhythmias increase, suggesting that LVEF is related to the presence of ventricular arrhythmia.⁸ The presence of ventricular arrhythmias is predictive of late mortality (after 6 months post-myocardial infarction), but the reduction or elimination of ventricular arrhythmias, in particular premature ventricular contractions (PVCs), may not portend a more favorable clinical outcome/prognosis. In this regard, beta-blockers are not powerful suppressants of PVCs, but they are highly effective in reducing sudden death and total mortality. Similar to ventricular arrhythmias, atrial arrhythmias, more specifically atrial fibrillation subsequent to myocardial infarction, are associated with worse clinical outcome, including a higher mortality.^3,5,9-11 ACE inhibitors have become standard therapy for post-myocardial infarction patients, especially in those with impaired ventricular function, having shown the ability to reduce both ventricular and atrial arrhythmias after myocardial infarction.^12-14 It is not known whether beta-blockers, in combination with ACE inhibitor therapy, will further reduce ventricular and atrial arrhythmias in post-myocardial infarction patients.

As a class, beta-blockers are a heterogeneous group of agents that vary with respect to pharmacology, receptor selectivity, hemodynamic effects, and tolerability. Although few studies have directly compared clinical outcomes among beta-blockers, meta-analyses have shown that beta-blockers possessing β₂- and/or α₁-adrenergic blockade were more effective at reducing all-cause mortality compared with β₁-selective blockers or beta-blockers with intrinsic sympathomimetic activity (ISA) (31% risk reduction versus 21% and 15%, respectively).^15-17

Carvedilol is a non-selective beta-blocker blocking both β₁- and β₂-receptors with selective α₁-adrenergic receptor blockade, antiendothelin effects, and, unlike other beta-blockers, potent antioxidant properties, which may protect