Patients treated with bivalirudin are still at higher risk of stent thrombosis: a comprehensive meta-analysis of randomised clinical trials of bivalirudin and heparin for percutaneous coronary interventions

Abstract

Background: Although the current practice guidelines recommend using both heparin and bivalirudin for percutaneous coronary interventions (PCI), the research data are ambiguous.

Aim: The aim of the study was to compare the impact of bivalirudin and heparin on major clinical endpoints in PCI patients with particular emphasis on periprocedural stent thrombosis.

Methods: A total of 18 randomised clinical trials involving 41,752 subjects were included. The endpoints comprised: net adverse clinical event (NACE: death, myocardial infarction [MI], unscheduled revascularisation, major bleeding), major adverse cardiovascular event (MACE: death, MI, or stroke), and acute/subacute stent thrombosis (ST). A subanalysis for planned and provisional glycoprotein IIb/IIIa inhibitor (GPI) use with heparin was performed. Results were presented as risk ratios (RR) and 95% confidence intervals (CI).

Results: Bivalirudin significantly reduced NACE risk (RR 0.85, 95% CI 0.76–0.96) and increased the incidence of MI (RR 1.09, 95% CI 1.01–1.18), ST (RR 1.50, 95% CI 1.13–1.99), and MACEs (RR 1.06, 95% CI 0.99–1.13). Comparing to heparin with provisional or planned GPI use, there was higher risk of acute ST with bivalirudin (RR 2.14, 95% CI 1.01–4.56 and RR 5.53, 95% CI 2.32–13.18, respectively). Comparing to heparin and provisional GPIs, bivalirudin failed to reduce NACEs and major bleeding. However, it decreased rates of NACEs (RR 0.81, 95% CI 0.69–0.96) and major bleeding (RR 0.64, 95% CI 0.48–0.85) compared with heparin and planned GPI use.

Conclusions: The advantages of bivalirudin are undoubtedly related to GPI use in the heparin arms. Bivalirudin-based regimens are more beneficial when compared with heparin and planned GPI use in terms of NACE and major bleedings; this was not observed when compared to heparin and provisional GPI use. Regardless of adjunctive GPI use, stent thrombosis episodes were significantly more common in bivalirudin-treated subjects. Therefore, the safety and economic issues may urge revision of this aspect of current clinical practice and guidelines.