The effect of carvedilol on mortality risk in heart failure patients with diabetes: results of a meta-analysis

BACKGROUND: Although beta-blocker therapy has been shown to improve survival in patients with chronic heart failure, this class of drugs tends to be underutilized in diabetic patients due to concerns about adverse metabolic effects, especially on glycemic control. No randomized clinical trial has specifically evaluated the effect of beta-blocker therapy on mortality in diabetic patients with heart failure. Previous meta-analyses combining results of heart failure trials with pharmacologically diverse beta-blockers suggest that the survival benefit in diabetic patients may be diminished compared to benefits in non-diabetic patients. However, some trial results indicate that carvedilol, which blocks beta1-, beta2-, and alpha1-receptors and is a potent antioxidant, may produce at least comparable effects in both patient groups. OBJECTIVES: To evaluate the effect of carvedilol in patients with heart failure and diabetes, specifically to determine if the survival benefit of carvedilol demonstrated in heart failure trials was as great in the subgroups of patients with diabetes. METHODS: A meta-analysis was performed that included 5757 patients with heart failure, 25% of whom had diabetes, from seven large placebo-controlled randomized trials with carvedilol. All large (> 100 patients) placebo-controlled, randomized trials with carvedilol in heart failure were included. The endpoint of all-cause mortality was examined in the overall population, patients without diabetes, and patients with diabetes. The number of patients needed to treat (NNT) for 1 year to prevent one death associated with carvedilol use in diabetic versus non-diabetic patients was also calculated. The log-rank test and the Cox proportional hazards regression were used to compare the event time distributions of carvedilol versus placebo with respect to the outcome of mortality. RESULTS: Similar survival benefits were seen with carvedilol use in diabetic and non-diabetic patients (relative risk reductions of 28% 95% confidence interval (CI) 3-46%; p = 0.03 and 37% 95% CI 22-48%; p < 0.001, respectively). There were no significant differences between the relative mortality risk reductions or the NNT with carvedilol use in diabetic versus non-diabetic patients. The NNT for 1 year to prevent one death was 23 for all patients, as well as for non-diabetic patients, and 25 for the diabetic group. CONCLUSIONS: This meta-analysis provides evidence that the same survival benefit may occur with carvedilol in heart failure patients with and without diabetes. The low NNT in the severe heart failure trial, COPERNICUS, and the diabetic subgroup in this meta-analysis suggests that severe heart failure patients and heart failure patients with diabetes may particularly derive benefit from therapy with carvedilol.