Cardiology Express Report

Publication date: 2004-05-10

Best Practices for Post-myocardial Infarction with Left Ventricular Dysfunction: Update on Treatment Options

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

William T. Abraham, MD, FACP, FACC, Professor of Medicine, Chief, Division of Cardiovascular Medicine, Associate Director, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio

According to the recently published results of an echocardiographic substudy of the Carvedilol Post-infarct Survival Control in LV Dysfunction (CAPRICORN) trial,¹ carvedilol significantly reverses the process of progressive pathological left ventricular remodeling which occurs in patients with left ventricular dysfunction after acute myocardial infarction.² Specifically, statistically significant improvements in both left ventricular end-systolic volume and left ventricular ejection fraction were observed in carvedilol-treated patients compared to those treated with placebo after 6 months of therapy. The results of this substudy augment earlier findings that carvedilol improves clinical outcome and left ventricular remodeling in patients with heart failure,^3,4 and support the primary findings from CAPRICORN that optimal management of patients with left ventricular dysfunction after acute myocardial infarction should include the addition of carvedilol to currently accepted therapies.¹

Although cardiac remodeling is perceived as an initially compensatory response to maintain normal cardiac function following injury to the heart, progressive left ventricular remodeling (dilation and systolic dysfunction) leads to cardiac decompen-sation⁵ and is associated with poor prognosis following an acute myocardial infarction.^5,6 Therapeutic interventions that arrest, attenuate, or reverse this remodeling process could favorably alter the progression of cardiovascular diseases such as myocardial infarction, valvular heart diseases, myocarditis, heart failure and dilated cardiomyopathy.^5,6

It has been well established that the use of angiotensin-converting-enzyme (ACE) inhibitors has beneficial effects on left ventricular remodeling and improves clinical outcome in patients after acute myocardial infarction.^7-11 Beta-adrenergic antagonists have also shown favorable effects on left ventricular remodeling and improve clinical outcome in patients with chronic heart failure.^3,12-14 However, until recently, the effects of beta-adrenergic antagonism in patients with left ventricular dysfunction after acute myocardial infarction in combination with ACE inhibitors had not been conclusively studied. Results from CAPRICORN demonstrated that the use of carvedilol resulted in improved clinical outcome in this patient population. Specifically, all-cause mortality was significantly lower in carvedilol-treated patients compared with placebo (12% vs 15%, relative risk reduction 23%; P = .03).¹ To understand the underlying mechanism of the substantial beneficial effects of carvedilol in this setting, an echocardiographic substudy was undertaken to investigate the effects of carvedilol on left ventricular remodeling.

The purpose of this Cardiology Express Report^TM is to review the CAPRICORN echocardiographic substudy and discuss its implications on clinical practice.

Beneficial Effect of Carvedilol on Left Ventricular Remodeling

randomized, international, multicenter, placebo-controlled, echocardiographic substudy of the CAPRICORN trial was conducted to evaluate the effects of carvedilol on left ventricular remodeling in patients with left ventricular dysfunction after acute myocardial infarction treated with ACE inhibitors.² A total of 127 patients from 13 international study sites were randomly assigned to receive 6.25 mg carvedilol twice daily