Study Evaluates Factors Affecting Bleeding and Stent Thrombosis in Clinical Trials Comparing Bivalirudin With Heparin During PCI

December 23, 2015—John A. Bittl, MD, et al investigated factors affecting bleeding and stent thrombosis in clinical trials comparing bivalirudin with heparin during percutaneous coronary intervention (PCI). The findings were published online ahead of print in Circulation: Cardiovascular Interventions.

The background of the analysis is that patients treated with bivalirudin in randomized clinical trials of PCI generally have less bleeding but more acute stent thrombosis than patients treated with heparin, but differences have varied among trials.

As summarized in Circulation: Cardiovascular Interventions, the investigators modeled the risk of major hemorrhage and ischemic outcomes 30 days after PCI by treatment assignment and the use of adjunctive therapies in 18 randomized clinical trials enrolling 41,871 patients. Overall, bivalirudin caused less major bleeding (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53–0.76), more stent thrombosis (OR, 1.58; 95% CI, 1.19–2.09), and no difference in mortality (OR, 0.93; 95% CI, 0.77–1.14) as compared with heparin. 

The investigators reported that a risk–benefit analysis identified 19 fewer bleeds and five more stent thromboses for every 1,000 patients treated with bivalirudin in place of heparin. No significant bleeding advantage of bivalirudin over heparin could be identified when transradial access (OR, 0.89; 95% CI, 0.57–1.41) and planned glycoprotein IIb/IIIa inhibitors were used with bivalirudin in the majority of patients (OR, 1.07; 95% CI, 0.87–1.31). The use of prasugrel or ticagrelor eliminated bleeding differences (OR, 0.80; 95% CI, 0.63–1.03) but did not reduce the risk of stent thrombosis after bivalirudin (OR, 2.20; 95% CI, 1.48–3.27).

The investigators concluded that substituting bivalirudin for heparin conferred a tradeoff between bleeding and stent thrombosis and that transradial access, adjunctive glycoprotein IIb/IIIa inhibitors, and potent P2Y12 inhibitors attenuated the bleeding advantage of bivalirudin over heparin but had no apparent effect on early stent thrombosis. New approaches to reduce bleeding and ischemic complications during PCI warrant further investigation, advised the investigators in Circulation: Cardiovascular Interventions.