Are β-blockers as efficacious in patients with diabetes mellitus as in patients without diabetes mellitus who have chronic heart failure? A meta-analysis of large-scale clinical trials

Background Diabetes mellitus is a frequent comorbid condition in patients with chronic heart failure (CHF) and confers a worse prognosis. Furthermore, although patients with CHF derive considerable benefit from β-blockers, these agents are thought by many physicians to be contraindicated in patients with diabetes mellitus. Most published studies on β-blockers in CHF have been unable to reach definitive conclusions about the mortality benefits of these agents in patients with diabetes mellitus. We therefore performed a meta-analysis of β-blocker trials that reported mortality outcomes in patients with diabetes mellitus who had CHF to pool all available trial evidence on the benefits (or otherwise) of these agents in this setting. Methods All-cause mortality data on patients with diabetes mellitus were obtained from all completed β-blocker CHF randomized placebo-controlled trials involving >100 patients exposed to β-blockers, in which outcomes in patients with diabetes mellitus were described. When events were not directly reported, risk ratios (RRs) were derived from analysis of figures and other manuscript data. Results were pooled with the Mantel-Haenszel method. Results A total of 24.6% of patients were reported to have diabetes mellitus in the 6 studies analyzed (Australia and New Zealand [ANZ]-Carvedilol, Beta-blocker Evaluation of Survival Trial [BEST], Carvedilol US Trials, Cardiac Insufficiency Bisoprolol Study [CIBIS-II], Carvedilol Prospective Randomized Cumulative Survival Trial [COPERNICUS], and Metoprolol Controllled-release Randomized Intervention Trial in Heart Failure [MERIT-HF]). Patients with diabetes mellitus had increased mortality rates overall compared with subjects without diabetes mellitus (RR, 1.25; 95% CI, 1.15–1.36; P <.001). Compared with placebo, β-blocker therapy for CHF was beneficial in patients with diabetes mellitus (RR, 0.84; 95% CI, 0.73–0.96; P = .011) and in subjects without diabetes mellitus (RR, 0.72; 95% CI, 0.65–0.79; P <.001). The absolute risk reduction in mortality with β-blocker therapy was greater in patients with heart failure but without diabetes mellitus than in patients with diabetes mellitus (P = .023). Conclusions Patients with diabetes mellitus and CHF appear to derive prognostic benefit from β-blocker therapy, although the magnitude of that benefit is somewhat less than that observed in subjects without diabetes mellitus.