Post-myocardial Infarction Express Report

Publication date: 2004-06-10

Optimizing Treatment in the Post-myocardial Infarction Patient: The CAMIS Study

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

Barry H. Greenberg, MD, Professor of Medicine, University of California, San Diego; Director, Heart Failure/Cardiac Transplantation Program, UCSD Medical Center, San Diego, California

According to results presented at the 25^th Annual European Society of Cardiology Congress in September 2003 and at the 53^rd Annual Scientific Session of the American College of Cardiology in March 2004, carvedilol provides a superior beneficial clinical effect on cardiovascular endpoints after acute myocardial infarction when compared to treatment with atenolol.^1,2 The Carvedilol Acute Myocardial Infarction Study (CAMIS) evaluated global and regional left ventricular ejection fraction and cardiovascular endpoints in a total of 232 patients with normal ejection fractions (range 53% to 55%) randomly assigned to either carvedilol or atenolol therapy. Patients receiving carvedilol had significantly fewer total cardiovascular events compared to patients treated with atenolol. Interestingly, there was no difference in global or regional left ventricular ejection fraction, suggesting that mechanisms other than left ventricular remodeling likely contribute to the superiority of carvedilol over atenolol.

Multiple clinical trials have shown that β-blockade improves clinical outcomes in a variety of pathological settings, including chronic heart failure^3-6 and post-myocardial infarction.^7-12 However, it is not clear if all β-blockers provide similar beneficial cardiovascular effects. Indeed, available β-blockers are heterogeneous agents that vary with respect to pharmacology, receptor selectivity, hemodynamic effects, and tolerability. Although few studies have directly compared the clinical outcomes among β-blockers, a meta-analysis of 32 acute myocardial infarction clinical trials showed that β-blockers possessing β₂- and/or α₁-adrenergic blockade were more effective at reducing all-cause mortality compared with β₁-selective blockers or β-blockers with intrinsic sympatho-mimetic activity (ISA) (31% risk reduction versus 21% and 15%, respectively).¹³ Similar results were observed for a meta-analysis of 28 heart failure trials in which β-blockers possessing β₂- and/or α₁-adrenergic blockade produced a risk reduction of 42% compared to 33% and 10% for β₁-selective blockers or β-blockers with ISA, respectively.¹³ These results, as well as studies, suggest that there could be a difference in the clinical effectiveness among these agents.^13-17

Carvedilol is a lipophilic, nonspecific β-blocker with selective α₁-adrenergic receptor blockade and antioxidant properties.^18-20 In patients with chronic heart failure, carvedilol reduces mortality and morbidity and has a favorable effect on left ventricular remodeling.^3,21 Studies such as CAPRICORN have shown that carvedilol therapy reduces all-cause and cardiovascular mortality and lowers recurrent, non-fatal myocardial infarction in patients with left ventricular dysfunction after acute myocardial infarction treated with angiotensin-converting-enzyme (ACE) inhibitors.⁷ Echocardiography performed on a subset of post-myocardial infarction patients revealed that carvedilol inhibits left ventricular remodeling, with significant improvements in left ventricular systolic volume and left ventricular ejection fraction observed after 6 months of treatment compared with placebo.²²

The purpose of this Post-myocardial Infarction Express Report^TM is to review the results of the