Efficacy and safety of vorapaxar for the prevention of adverse cardiac events in patients with coronary artery disease: a meta-analysis.

Background: Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Vorapaxar, a protease-activated receptor-1 (PAR-1) antagonist, is a novel antiplatelet agent that may provide us a new way in antithrombotic therapy. Several studies had been conducted to evaluate the efficacy of vorapaxar in the treatment of CAD, but the results were inconsistent. Here a meta-analysis was made to assess the efficacy and safety of vorapaxar in reducing adverse cardiac events in patients with CAD.

Methods: A comprehensive literature search was conducted. The primary efficacy endpoint was the major adverse cardiac events, which was defined as a composite of cardiovascular death, myocardial infarction (MI), stroke, urgent coronary revascularization, or recurrent ischemia with rehospitalization. The primary safety endpoint was the composite of major or minor bleeding events. Pooled effects were measured by odds ratios (ORs) with 95% confidence intervals (CIs). A random-effect or fixed model was used in this meta-analysis.

Results: Totally, 31,388 patients from four randomized controlled trials (RCTs) were included in this meta-analysis. Patients who took vorapaxar combined with standard dual anti-platelet therapy (aspirin and thienopyridine) showed a lower incidence in major adverse cardiac events (OR, 0.86, 95% CI: 0.75-0.99, P=0.03), MI (OR, 0.79, 95% CI: 0.67-0.95, P=0.01) and ischemic stroke (OR, 0.72, 95% CI: 0.58-0.89, P=0.003) than those who only took placebo instead. But there was no significant reduction in cardiovascular death (OR, 0.95, 95% CI: 0.82-1.09, P=0.45). Nevertheless, the vorapaxar group were associated with a higher risk of bleeding events (P<0.001).

Conclusions: The result of this meta-analysis indicated that adding vorapaxar to the standard dual anti-platelet therapy may be efficient in reducing the incidence of major adverse cardiac events at the cost of increasing risk of bleeding events.