Meta-analysis gives clarity to bivalirudin’s risk-benefit profile

Compared with heparin, bivalirudin increases the risk of major adverse cardiac events (MACE) but reduces the risk of bleeding to varying degrees in patients undergoing PCI, a meta-analysis published in the Aug. 16 issue of The Lancet concluded.

Some clinical trials that evaluated the safety and efficacy of bivalirudin (Angiomax, The Medicines Company) against heparin showed an excess of MI and stent thrombosis in patients treated with the direct thrombin inhibitor but the findings were not statistically significant. Many studies also gave bivalirudin the advantage for bleeding, but patients in the heparin groups also often received glycoprotein IIb/IIIa inhibitors (GPI), which increases bleeding.

Matthew A. Cavender, MD, MPH, and Marc S. Sabatine, MD, MPH, of the TIMI Study Group at Brigham and Women’s Hospital in Boston, conducted a meta-analysis to try to better define the effects of the two regimens. By searching Medline and the Cochrane Library on April 9, 2014, they identified 16 suitable randomized, controlled clinical trials that enrolled almost 34,000 patients.

The primary efficacy endpoint was MACE, which the trials generally defined in a similar way. The secondary safety endpoint was major bleeding up to 30 days. While the trials set dosing regimens for bivalirudin similarly, they varied for heparin.

Cavender and Sabatine found a 9 percent relative increased risk of MACE with bivalirudin compared with heparin, mostly due to an increase in MI and ischemia-driven revascularization. Bivalirudin also showed an increased risk of stent thrombosis. The two regimens had no difference in mortality risk.

The risk of major bleeding was much lower with bivalirudin but the magnitude varied. “When GPI use was provisional in the bivalirudin arm but predominantly planned in the heparin arm, the risk of bleeding was 47% lower in the bivalirudin arm than in the heparin arm,” they wrote. “By contrast, when GPI use was provisional in both arms there was a non-significant 22% reduction, and when it was routine in both arms there was no difference in risk of bleeding.”

The results underscore the tradeoff between ischemic events and bleeding that physicians must consider when choosing anticoagulation strategies for PCI patients, they noted. They added that more research needs to be done to identify patient populations who would benefit from one approach or the other.