Comparison of bivalirudin and conventional anticoagulation therapy in percutaneous coronary intervention: a systematic review and meta-analysis

Introduction Percutaneous coronary intervention (PCI) necessitates efficient periprocedural anticoagulation. Although traditional heparin-based protocols have been the norm, apprehensions about bleeding risk and variable responses remain. Bivalirudin, a direct thrombin inhibitor, presents a potential alternative; nonetheless, its relative efficacy and safety compared to heparin remain ambiguous due to inconsistent findings from previous trials and meta-analyses. This systematic review and meta-analysis seeks to offer a modern synthesis comparing bivalirudin with traditional anticoagulation in patients having percutaneous coronary intervention (PCI). Materials and Methods We performed a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Assessment of Multiple Systematic Reviews (AMSTAR) standards. A thorough search of PubMed, Embase, Cochrane Library, and Web of Science from inception to 15 December 2025, identified randomised controlled trials (RCTs) comparing bivalirudin versus heparin-based regimens (with or without glycoprotein IIb/IIIa inhibitors) in adult patients undergoing percutaneous coronary intervention (PCI). The primary outcomes comprised primary endpoint(death, MI or major bleeding), all-cause mortality(death), myocardial infarction (MI), stent thrombosis, revascularisation, significant bleeding and Stroke at 30 days. Two reviewers independently conducted study selection, data extraction, and risk of bias evaluation. The statistical analysis was conducted using the random or fixed effect model in Review Manager v5.3, and subgroup analyses were performed according to the publication year (before 2010 and after 2010), the type of STEMI, and whether Glycoprotein IIbIIIa was combined.The certainty of evidence was assessed with GRADE. Results Bivalirudin significantly reduced the primary endpoint (OR 0.86, 95% CI 0.76–0.98, P < 0.00001, I 2 = 76%) and major bleeding (OR 0.60, 95% CI 0.46–0.79, P < 0.00001, I 2 = 83%). All-cause mortality (OR 0.92, 95% CI 0.80–1.05, P = 0.23), MI, stent thrombosis, revascularization, and stroke did not differ significantly. The bleeding advantage of the group receiving heparin combined with GPI was the most significant (OR 0.51, 95% CI 0.45–0.59), while this benefit in the heparin monotherapy group was less pronounced (P = 0.05). The post-2010 subgroup showed a diminished but persistent bleeding benefit (OR 0.61, 95% CI 0.42–0.87). Certainty of evidence was high for bleeding, moderate for the primary endpoint and death, and low for ischemic outcomes. Conclusion In patients undergoing PCI, bivalirudin is associated with a significant reduction in the primary composite endpoint and major bleeding compared with heparin, but this finding is primarily driven by trials where heparin was combined with planned GPI. Against heparin monotherapy, the bleeding benefit is attenuated and not statistically robust. The bleeding benefit, though attenuated, persists in contemporary practice. All-cause mortality was not significantly reduced, and previous mortality claims should be interpreted cautiously. The choice of anticoagulant should be individualised based on bleeding risk, ischemic risk, access site, and bivalirudin infusion protocol. Clinical Trial Registration PROSPERO (CRD420261289024).