Differential effects of nonselective versus selective β-blockers on cardiac sympathetic activity and hemostasis in patients with heart failure

Abstract

Carvedilol, a nonselective β-blocker, may be more effective than the selective β-blocker metoprolol in reducing the risk of thromboembolic events in heart failure. The aim of this study was, first, to assess whether there is a differential response in cardiac sympathetic activity by (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging when either β-blocker is used. Second, we assessed whether that response correlates with levels of various serum factors that serve as markers for coagulability.

Methods: In this prospective, randomized, open-label crossover study with masked outcome assessments, stable heart failure patients (left ventricular ejection fraction < 40%) homozygous for the Arg16/Gln27 (n = 13) or Gly16/Glu27 haplotype (n = 8) of the β2-receptor were randomized to equipotent dosages of carvedilol or metoprolol for two 6-wk periods. Primary outcome was sympathetic activity as measured by (123)I-MIBG myocardial washout. Secondary outcomes included markers of hemostasis.

Results: (123)I-MIBG cardiac washout was lower during carvedilol than metoprolol treatment (12.9% ± 3.9% vs. 22.1% ± 2.8%, respectively, P = 0.003), irrespective of β2-adrenergic receptor haplotype. In addition, treatment with carvedilol resulted in a lower von Willebrand factor than did metoprolol (149% ± 13% vs. 157% ± 13%, respectively, P = 0.01), irrespective of β2-adrenergic receptor haplotype.

Conclusion: Compared with metoprolol, carvedilol resulted in greater reduction of sympathetic activity after 6 wk of treatment and lower von Willebrand factor concentrations in both Arg16/Gln27 and Gly16/Glu27 individuals. Therefore, carvedilol may reduce the risk of thromboembolic events in patients with heart failure, irrespective of β2-receptor haplotype status.

Keywords: genetics, coagulation; heart failure; sympathetic nervous system; β-blockers.