The influence of carvedilol vs. metoprolol on sympathetic activity and hemostasis in patients with heart failure

Background: Carvedilol, a non-selective beta-blocker, may be more effective in reducing the risk of thromboembolic events in heart failure, compared to metoprolol, a selective beta-blocker (De Peuter et al., Eur J Heart Fail, in press/ISTH 2009). We hypothesized that carvedilol lowers this risk through more effective downregulation of the sympathetic hyperactivity and the associated prothrombotic state compared to metoprolol. This effect may be mediated through common haplotypes of the beta2-adrenergic receptor. Methods: In this prospective, randomized, open-label with blinded outcome assessments, crossover study, stable heart failure patients (left ventricular ejection fraction <40%) homozygous for the Arg16/Gln27 (n = 13) or Gly16/Glu27 haplotype (n = 8) of the beta2-receptor were randomized to equipotent dosages of carvedilol or metoprolol for two 6-week periods. Primary outcome was sympathetic activity as measured by 123I-meta-iodobenzylguanidine (MIBG) myocardial washout. Secondary outcomes included markers of hemostasis. Data are presented as mean ± standard error of the mean. Results: 123I-MIBG washout was lower during carvedilol than metoprolol treatment (12.9 ± 3.9% vs. 22.1 ± 2.8%, respectively, P = 0.01). This difference was present in both Arg16/Gln27 and Gly16/Glu27 individuals. Treatment with carvedilol lowered von Willebrand factor (149 ± 13% vs. 157 ± 13%, respectively, P = 0.01). There were no differences in other hemostatic markers. Conclusion: Treatment with carvedilol resulted in greater reduction of sympathetic activity after 6-weeks treatment and lower von Willebrand factor concentrations, compared to metoprolol, in both Arg16/ Gln27 and Gly16/Glu27 individuals. Carvedilol may reduce the risk of thromboembolic event risk in heart failure, irrespective of beta2- receptor haplotype status