Bivalirudin significantly reduced the risk of death after stenting for myocardial infarction compared with standard anticoagulants, researchers reported at a late breaking clinical trials session at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting in Washington, DC.

The prospective HORIZONS AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial included 3,602 patients with symptomatic ST-elevation myocardial infarction (STEMI) within 12 hours from symptom onset. In addition to dual antiplatelet therapy with aspirin and clopidogrel, patients were randomized to unfractionated heparin plus abciximab or eptifibatide plus unfractionated heparin or bivalirudin (0.75 mg/kg bolus then 1.75 mg/kg/hr).

"This is a landmark trial, which will help establish the guidelines for drug and stent therapy during primary angioplasty in patients with heart attacks for many years to come," said Gregg W. Stone, MD, Chairman of the Cardiovascular Research Foundation, Professor of Medicine, Columbia University Medical Center and Principal Investigator of the trial.

"This study determines that bivalirudin use is safer than previous standard anticoagulant therapy, without causing excess bleeding in these acutely ill patients with a heart attack undergoing angioplasty, which may translate into lower mortality," said Roxana Mehran, MD, Medical Director of the Data Coordinating and Analysis Center at the Cardiac Research Foundation stated.

At one year, patients who were randomized to bivalirudin had a 43% relative reduction (P=0.029) in all-cause mortality, and a 31% (P=0.005) relative reduction in cardiac-related mortality versus controls. Angiographic follow-up was available for 1,204 patients, and showed that percent binary restenosis per lesion was significantly lower in the Taxus group than in the Express group (10.0% vs. 22.9%; P<.0001).

Researchers suggest that the sustained mortality reduction was presumably caused by a reduction in bleeding events. The study found a 39% reduction in the rate of one-year bleeding in patients given the heparin regimen compared with the bivalarudin-only patients (9.2% versus 5.8%, P<0.001).

One-year results showed comparable overall safety outcomes (death, stroke, myocardial infarction or stent thrombosis) between the two stent groups (8.0 percent for the Express(R) bare-metal stent versus 8.1 percent for the TAXUS Express(R) Stent, p=0.92).

"In the HORIZONS AMI trial, the outcomes provide definitive evidence that, in patients with acute myocardial infarction (AMI), drug-eluting stents were superior in efficacy to bare-metal stents and had a comparable safety profile at one year," said Dr. Stone.

"Outcomes from prior registry studies of drug-eluting stents compared to bare-metal stents in AMI patients have been conflicting; this is the first prospective, large, international randomized clinical trial and provides conclusive evidence on this subject," continued Dr. Stone. "The findings from the HORIZONS AMI trial will have a major impact on how decisions are made regarding drug-eluting and bare-metal stents in the highest risk patients in this trial, those in the early hours of a heart attack. This study removes much of the uncertainty and concern about the efficacy and safety of drug-eluting stents in this clinical setting. Moreover, all of the patients in this trial will be followed for five years to ensure that these favorable results are maintained."

The study was supported by the Cardiovascular Research Foundation, with grant support from Boston Scientific and the Medicines Company.

This is the largest study to date to focus on the optimal use of stents and anticoagulation therapy in patients with STEMI.