Non-selective β-blockers decrease thrombotic events in patients with heart failure

Background: β-blockers are often prescribed to patients with heart failure (HF) without distinctions between types of β-blockers, although non-selective β-blockers may have a better effect on arterial thrombosis. The 2002 COMET study showed superiority of carvedilol (non-selective β-blocker) over metoprolol (selective β-blocker) on mortality and cardiovascular events in patients with HF, but this study was criticised for inappropriate formulation of metoprolol. Laboratory findings suggest a reduced prothrombotic response upon sympathetic activation by non-selective β-blockers. Objectives: To compare the incidence of thromboembolic events (acute coronary syndrome (ACS), stroke, or pulmonary embolism) between patients using selective and nonselective β-blockers. Methods: Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in The Netherlands. We identified a cohort of 24,398 patients admitted for HF in the period 1998-2007. Cox regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: The median follow up was 2.1 years (interquartile range: 0.8-4.0). In a 3-month time window after discharge, 6,864 patients were prescribed a selective and 2,356 patients a non-selective β-blocker. The incidence of thrombotic events during follow up was 3.3% for non-selective β-blockers and 4.6% for selective β-blockers, resulting in a crude HR of 0.69 (95%CI: 0.59-0.79). After adjustment for confounders, including age, sex, history of ACS, and other drug use, the difference remained significant (HR 0.75, 95%CI: 0.65-0.87). Conclusions: Non-selective β-blockers were associated with a lower risk of thromboembolic events compared to selective β-blockers in patients with HF. The hypothesis that non-selective β-blockers reduce the prothrombotic state in these patients should be explored further