Prolonged High‐Dose Bivalirudin Infusion Reduces Major Bleeding Without Increasing Stent Thrombosis in Patients Undergoing Primary Percutaneous Coronary Intervention: Novel Insights From an Updated Meta‐Analysis

BACKGROUND: The optimal antithrombotic therapy in patients with ST‐segment‐elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) remains a matter of debate. This updated meta‐analysis investigated the impact of (1) bivalirudin (with and without prolonged infusion) and (2) prolonged PCI‐dose (1.75 mg/hg per hour) bivalirudin infusion compared with conventional antithrombotic therapy on clinical outcomes in patients undergoing primary PCI. METHODS AND RESULTS: Eligible randomized trials were searched through MEDLINE, EMBASE, Cochrane database, and proceedings of major congresses. Prespecified outcomes were major bleeding (thrombolysis in myocardial infarction major and Bleeding Academic Research Consortium 3–5), acute stent thrombosis, as well as all‐cause and cardiac mortality at 30 days. Six randomized trials (n=17 294) were included. Bivalirudin compared with heparin (+/− glycoprotein‐IIb/IIIa inhibitor) was associated with reduction in major bleeding (odds ratio [OR]: 0.65, 95% CI: 0.48–0.88, P=0.006, derived from all 6 trials), increase in acute stent thrombosis (OR: 2.75, 95% CI: 1.46–5.18, P=0.002, 5 trials), and lower rate of all‐cause mortality (OR: 0.81, 95% CI: 0.67–0.98, P=0.03, 6 trials) as well as cardiac mortality (OR: 0.69, 95% CI: 0.55–0.87, P=0.001, 5 trials). The incidence of acute stent thrombosis did not differ between the prolonged PCI‐dose bivalirudin and comparator group (OR: 0.81, 95% CI: 0.27–2.46, P=0.71, 3 trials), whereas the risk of bleeding was reduced despite treatment with high‐dose bivalirudin infusion (OR: 0.28, 95% CI: 0.13–0.60, P=0.001, 3 trials). CONCLUSIONS: Bivalirudin (with and without prolonged infusion) compared with conventional antithrombotic therapy in ST‐segment‐elevation myocardial infarction patients undergoing primary PCI reduces major bleeding and death, but increases the rate of acute stent thrombosis. However, prolonging the bivalirudin infusion at PCI‐dose (1.75 mg/kg per hour) for 3 hours eliminates the excess risk of acute stent thrombosis, while maintaining the bleeding benefits.