Bivalirudin versus heparin in percutaneous coronary intervention-a systematic review and meta-analysis of randomized trials stratified by adjunctive glycoprotein IIb/IIIa strategy

Background: Bivalirudin has been shown to be associated with less major bleeding than heparin in patients undergoing percutaneous coronary intervention (PCI); but the confounding effect of concomitant glycoprotein IIb/IIIa inhibitors (GPI) limits meaningful comparison. We performed a systematic review and meta-analysis to compare bivalirudin to heparin, with and without adjunctive GPI in PCI. Methods: We searched PubMed, Cochrane, EMBASE, CINAHL and WOS from January 2000 to December 2017 for clinical trials comparing bivalirudin to heparin, with and without adjunctive GPI during PCI. Cochrane's Q statistics were used to determine heterogeneity. Random effects model was used. Results: Twenty-six comparison groups (22 original studies and 4 subgroup analyses) with 53,364 patients were included. Mean follow-up was 192 +/- 303 days. There was no difference between the two groups in all-cause mortality [risk ratio (RR: 0.93; 95% CI: 0.82-1.05, P=0.260), target vessel revascularization (TVR) (RR: 1.17; 95% CI: 0.93-1.46, P=0.174) or stroke (RR: 0.91; 95% CI: 0.71-1.18, P=0.490). Major bleeding was lower in the bivalirudin group with concomitant GPI in one or both arms (RR: 0.64; 95% CI: 0.53-0.77, P<0.001) and without (RR: 0.71; 95% CI: 0.51-0.99, P=0.041) provisional or routine GPIs. Bivalirudin appeared to have a higher risk of stent thrombosis (RR: 1.32; 95% CI: 1.04-1.68, P=0.022) and a trend towards more myocardial infarction (RR: 1.12; 95% CI: 0.98-1.28, P=0.098) though without statistical significance. However, exclusion of studies with GPI showed no difference in stent thrombosis or myocardial infarction with bivalirudin. Conclusions: Bivalirudin is associated with less major bleeding compared to heparin, regardless of GPI use. The lower anticoagulant effect of bivalirudin is linked with higher stent thrombosis and a trend towards more MI, however a confounding effect of GPI use in the heparin arm cannot be excluded.