Antithrombotic effects of beta2-adrenergic receptor blockade on top of beta1-receptor blockade in patients with acute coronary syndrome or heart failure: a systematic review

Background: Non-selective beta1 + 2 blockers may have specific antithrombotic effects not present in eta1-blockers, due to a eta2-specific effect on sympathetic activity. Our aim was to assess the influence of eta2-receptor suppression on top of selective beta1-receptor blockade on the occurrence of vascular events and on all cause mortality in patients with acute coronary syndrome (ACS) or heart failure (HF). Methods: Systematic review and analysis of studies published since 1980. Randomised controlled trials directly comparing beta1 blockers with beta1 + 2 blockers, or comparing the two beta-blockers with placebo were included. Studies had a minimum treatment period of 3 months and total mortality or vascular events as their outcome. Results: Five studies directly compared beta-blockers (3733 patients) and 28 compared with placebo (30 889 patients). These latter studies were heterogeneous in study population, dose and type of beta-blockers. In ACS, the only study directly comparing different beta-blockers was underpowered to detect a difference on mortality, while in HF beta1 + 2 blockers significantly decreased mortality compared to beta1-blockers (RR 0.86, 95% CI 0.78-0.94). In ACS, beta1 blockers in placebo-controlled trials had no significant effect on total mortality (RR 0.82, 0.67-1.01) or vascular events (RR 0.68, 0.42-1.11). Beta1 + 2 blockers were associated with a significant decrease in total mortality (RR 0.73, 0.64-0.82), and vascular events (RR 0.71, 0.59-0.84). In HF, beta1 and beta1 + 2 blockers reduced total mortality, while only beta1 + 2 blockers decreased vascular events (RR 0.80, 0.64-1.00). Conclusions: Although only few studies directly compared beta- blockers, and indirect comparisons were subject to heterogeneity, additional beta2-receptor blockade seems more effective than beta1- receptor blockade alone in preventing total mortality and vascular events in patients with ACS or, to a lesser extent, HF. This effect may be due to different antithrombotic activity of beta-blockers.