Effects of carvedilol versus metoprolol on hemostasis and fibrinolysis in patients with chronic heart failure

Abstract

Background: Mechanisms behind the beneficial effects of beta-blockers are unclear as well as the cause of differential effects of these agents. In COMET (Carvedilol or Metoprolol European Trial) carvedilol (C) compared with metoprolol (M) significantly reduced mortality as well as incidence of stroke and myocardial infarction in patients with chronic heart failure (CHF). We hypothesized that the antiproliferative and antioxidative properties of C might be beneficial on endothelial derived hemostatic factors as compared to M. Aim: To study the effects of carvedilol and metoprolol on mass-concentrations of tissue plasminogen activator (tPA), its inhibitor PAI-1 and von Willebrand factor (vWF) in patients with CHF. Methods: Among Swedish patients entered in a prespecified substudy of COMET, we measured tPA, PAI-1 and von Willebrand factor (vWf) at baseline, after one and two years of treatment. Results: We recruited 260 patients (134 on C, 126 on M), 84 percent were males, aged 65.5 years. Comparing the two treatments, there were no significant differences at baseline in plasma concentrations of tPA, PAI-1, and a borderline difference for vWF at baseline (248 vs. 220 %, p=0.06,) and after one or two years of treatment. Plasma median levels of PAI-1 decreased from 32.6 to 32.0 and 31.1 μg/l, respectively (p<0.05) in the C group while there was a non-significant increase in the M group, 32.2 to 36.4 and 36.8 μg/l, respectively. Also median levels of vWF decreased significantly in the C group from baseline to one year (248.6 vs. 223.3%, p<0.05) without any decrease in the metoprolol group. Plasma tPA increased significantly in both treatment groups (p<0.05). Conclusion: In patients with chronic heart failure, carvedilol was associated with beneficial effects on plasma levels of PAI-1 and vWF while no such effects were seen with metoprolol. These effects might have clinical implications in reducing the risk for atherothrombotic events.