Critical Appraisal of Bivalirudin versus Heparin for Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Trials

Abstract

Percutaneous coronary intervention with bivalirudin plus bail-out glycoprotein IIb/IIIa inhibitors has been shown to be as effective as unfractionated heparin plus routine glycoprotein IIb/IIIa inhibitors in preventing cardiac ischemic events, but with a lower bleeding risk. It is unknown whether bivalirudin would have the same beneficial effects if compared with heparin when the use of glycoprotein IIb/IIIa inhibitors was similar between treatment arms. We searched the MEDLINE, Web of Science, and Cochrane databases from inception until March 2015 for randomized trials that compared bivalirudin to heparin in patients undergoing percutaneous coronary intervention. We required that the intended use of glycoprotein IIb/IIIa inhibitors was similar between the study groups. Summary estimates were principally constructed by the Peto method. Fifteen trials met our inclusion criteria, which yielded 25,824 patients. Bivalirudin versus heparin was associated with an increased hazard of stent thrombosis (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.15-1.92, P = .002, I2 = 16.9%), with a similar hazard of myocardial infarction (OR 1.09, 95% CI 0.98-1.22, P = .11, I2 = 35.8%), all-cause mortality (OR 0.88, 95% CI 0.72-1.08, P = .21, I2 = 31.5%) and major adverse cardiac events (OR 1.04, 95% CI 0.94-1.14, P = .46, I2 = 53.9%). Bivalirudin was associated with a reduced hazard of major bleeding (OR 0.80, 95% CI 0.70-0.92, P = .001, I2 = 63.5%). The dose of heparin in the control arm modified this association; when the dose of unfractionated heparin in the control arm was ≥ 100 units/kg, bivalirudin was associated with a reduction in major bleeding (OR 0.55, 95% CI 0.45-0.68, P < .0001), but when the dose of unfractionated heparin was ≤ 75 units/kg, bivalirudin was not associated with reduction in bleeding (OR 1.09, 95% CI 0.91-1.31, P = .36). Among patients undergoing PCI, bivalirudin was associated with an increased hazard of stent thrombosis. Bivalirudin may be associated with a reduced hazard of major bleeding; however, this benefit was no longer apparent when compared with a dose of unfractionated heparin ≤ 75 units/kg.

What are the Factors that Could Contribute to the Lower Risk of Major Bleeding with Bivalirudin Compared with Unfractionated Heparin for Percutaneous Coronary Intervention?

“…The benefit was also noted only with higher doses of unfractionated heparin only, when the influence of glycoprotein IIb/IIIa inhibitors was balanced in both arms. Such results are similar to previous studies that explored the effect of bivalirudin versus unfractionated heparin on major bleeding, when the analysis was limited only to trials reporting balanced glycoprotein IIb/IIIa inhibitors use in both groups [5].…”

Will Bivalirudin Have an Impact in Peripheral Vascular Interventions?

“…We agree with the authors' postulate that reduction in bleeding may well explain the differences in mortality and major adverse clinical events observed because excess bleeding has consistently been demonstrated to increase mortality hazard in other data sets. [8][9][10][11] In this analysis, the addition of GPI was infrequent and did not affect the overall study outcome, further strengthening the hypothesis that bivalirudin reduces significant bleeding in PVI. It is worth noting that, although the arterial access site was not evaluated in this study, the vast majority of PVI procedures involving lower extremity PAD are performed via transfemoral access.…”

Bivalirudin versus Heparin plus Glycoprotein IIb/IIIa Inhibitors in Women Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials

“…On the contrary, the recently published HEAT-PPCI (How Effective are Antithrombotic Therapies in Primary PCI) trial [26] reported that bivalirudin compared with heparin alone resulted in a significantly higher rate of major adverse ischemic events with no decrease in bleeding complications. The diverging results among RCTs demonstrated that concomitant administration of a GPI with heparin might influence the benefit of bivalirudin [27]. Whether bivalirudin decreased the risk of bleeding regard less of routine GPI use remains unknow.…”