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.
Fahrni G., Wolfrum M., De Maria GL., Banning AP., Benedetto U., Kharbanda RK.
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.