Tolerability of carvedilol in heart failure: clinical trials experience

An extensive clinical trials database now exists to support the therapeutic efficacy of beta-blockers in systolic heart failure. However, concerns remain about the tolerability of these agents. These concerns relate to perceived complexity in initiation and uptitration, risk of worsening heart failure clinical status, and delay in beneficial effects on outcomes. All of the above concerns are thought especially relevant in patients with advanced disease. However, these perceptions are not borne out in the controlled clinical trial experience or in open-label studies and postmarketing surveillance programs with carvedilol. Specifically, in clinical studies, discontinuation rates (because of adverse events), serious adverse event rates, mean achieved dose, and percentage reaching target dose strongly suggest good tolerability. This is especially notable, considering that beta-blockade is used in addition to other background neurohormonal antagonists, such as angiotensin-converting enzyme inhibitors. Furthermore, tolerability in the everyday community setting also appears to be high. Carvedilol, specifically, is also well tolerated during initiation of therapy, with fewer withdrawals for heart failure during the first 8 weeks of uptitration, and no delay in the accrual of beneficial clinical outcomes, as observed in the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study. Thus, in contrast to widely held perceptions about tolerability of beta-blockade in heart failure, carvedilol appears to be an extremely well-tolerated agent, even during initiation and in the most advanced patients.