Bivalirudin superior as adjunct antithrombotic therapy in patients with acute MI undergoing PCI

Key Points

As a pharmacologic adjunct to stenting in patients with acute myocardial infarction (AMI), bivalirudin monotherapy outperformed the combination of a glycoprotein (GP) IIb/IIIa inhibitor and unfractionated heparin (UFH) over 1 year of follow-up, reported investigators at the 2008 Transcatheter Cardiovascular Therapeutics conference held in Washington, DC.

In the Harmonizing Outcomes with Revascularization and Stents in AMI (HORIZONS-AMI) study, bivalirudin monotherapy was associated with significant reductions in all-cause mortality, cardiac death, and bleeding compared with UFH plus either abciximab or eptifibatide in patients undergoing percutaneous coronary intervention (PCI).

The reduction in mortality with bivalirudin "is on the order of magnitude that surpasses statin therapy...in this time frame," said Deepak Bhatt, MD, chief of cardiology at the VA Boston Healthcare System and director of the integrated interventional cardiovascular program at Brigham and Women's Hospital, Boston. "The results are quite striking and define a new standard of care for PCI with respect to antithrombotic therapy."

Primary end points were the rate of net adverse clinical events, defined as the rates of major adverse cardiac events (MACE) plus major bleeding (non-coronary artery bypass graft [CABG] surgery), and the rate of non-CABG major bleeding; the incidence of MACE was a secondary end point.

The 30-day results, reported previously, demonstrated significant reductions in the rates of net adverse clinical events and major bleeding in the bivalirudin-treated patients and no significant difference in MACE between the 2 treatment groups.

The reductions in all-cause mortality and cardiac mortality in the bivalirudin arm were greater from 30 days to 1 year than they were from enrollment to 30 days, indicating a lasting effect of the therapy, said Roxana Mehran, MD, director of outcomes research, data coordination and analysis, Center for Interventional Vascular Therapy, New York-Presbyterian Hospital/Columbia University.

At 1 year, the incidence of net clinical adverse events was 15.7% with bivalirudin and 18.3% with UFH/GP IIb/IIIa inhibitor, corresponding to a 16% relative risk reduction with bivalirudin (P=.03). The major bleeding rate was 5.8% in patients assigned to bivalirudin and 9.2% in those assigned to UFH plus GP IIb/IIIa inhibitor, which corresponds to a 39% relative risk reduction with bivalirudin (P<.0001). In both groups, the rate of MACE was 11.9%.

All-cause mortality was 3.4% in bivalirudin recipients and 4.8% in recipients of UFH plus a GP IIb/IIIa inhibitor, which translates to a 43% relative risk reduction in the bivalirudin recipients (P =.029). Cardiac mortality was 2.1% in the bivalirudin arm versus 3.8% in the UFH plus GP IIb/IIIa arm, corresponding to a 31% relative risk reduction (P =.005) in bivalirudin-treated patients.

The rate of death/reinfarction was 6.6% in patients in the bivalirudin group versus 8.5% in the UFH plus GP IIb/IIIa group (P =.04). The rate of stent thrombosis was not significantly different between the bivalirudin and the UFH plus GP IIb/IIIa arms (3.5% vs 3.2%; P =.59).

These results were not altered by stent type, said Dr. Mehran.