NEW YORK, NY - March 16, 2015 - Data from the BRIGHT trial published today in the Journal of the American Medical Association demonstrated that bivalirudin was superior to both heparin monotherapy and heparin plus tirofiban for patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). Findings were first reported at last year's Transcatheter Cardiovascular Therapeutics (TCT), the annual scientific symposium of the Cardiovascular Research Foundation (CRF).
There has been recent controversy surrounding the optimal anticoagulant strategy for patients with AMI. Previous multicenter trials, such as HORIZONS-AMI and EUROMAX, have demonstrated superiority of bivalirudin to heparin plus glycoprotein IIb/IIIa inhibitors (GPI), but a recent single center trial, HEAT-PPCI, demonstrated the superiority of heparin monotherapy over bivalirudin alone, with concern for an increased rate of stent thrombosis observed in bivalirudin-treated patients. Due to these disparate results, the safety and efficacy of bivalirudin in patients with AMI undergoing PCI in contemporary practice is still controversial.
BRIGHT, a multicenter, open label trial was conducted with a 1:1:1 randomization that compared bivalirudin alone to heparin alone and heparin plus tirofiban in patients with AMI undergoing PCI. The trial randomized 2,194 patients with AMI eligible for emergency PCI from 82 Chinese sites to receive either bivalirudin with a post-PCI infusion (n=735), heparin alone (n=729), or heparin plus tirofiban with a post-PCI infusion (n=730).
The primary endpoint was 30-day net adverse clinical events (NACE), a composite of major adverse cardiac and cerebral events (MACCE; all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) or any bleeding as defined by the Bleeding Academic Research Consortium (BARC) definition. The secondary endpoints were NACE at one year, as well as MACCE and bleeding at 30 days and one year.
After 30 days, NACE occurred in 65 (8.8%) bivalirudin-treated patients compared to 96 (13.2%) heparin-treated patients (relative risk [RR]: 0.67, 95%CI: 0.50-0.90; difference: -4.3%, 95%CI: -7.5% - -1.1%; P=0.008); and 124 (17.0%) heparin plus tirofiban-treated patients (RR for bivalirudin vs. heparin plus tirofiban: 0.52, 95%CI: 0.39-0.69; difference: -8.1%, 95%CI: -11.6% - -4.7%; P<0.001). Bleeding at 30 days was reduced by bivalirudin compared to heparin and heparin plus tirofiban (4.1% vs. 7.5% vs. 12.3% respectively, P<0.001).
There were no statistically significant differences between treatments in the 30-day rates of MACCE (5.0% vs. 5.8% vs. 4.9% respectively, P=0.74) and stent thrombosis (0.6% vs. 0.9% vs. 0.7% respectively, P=0.77), nor in acute (<24 hour) stent thrombosis (0.3% in each group).
At one year, bivalirudin resulted in sustained reductions in NACE compared to heparin (12.8% vs. 16.5%, RR: 0.78, 95%CI: 0.61-0.99; difference: -3.7%, 95%CI: -7.3% - -0.1%; p=0.048) and compared to heparin plus tirofiban (12.8% vs. 20.5%, RR: 0.62, 95%CI: 0.49-0.79; difference: -7.8%, 95%CI: -11.6% - -4.0%; p<0.001), due to lower rates of bleeding. Rates of MACCE and stent thrombosis at one year were not significantly different between the treatment groups.
"By reducing bleeding with comparable rates of MACCE and stent thrombosis, bivalirudin significantly improved overall 30-day and one year outcomes, compared with both heparin alone and heparin plus tirofiban in patients with AMI undergoing primary PCI," said Gregg W. Stone, MD, the study's senior author. Dr. Stone is Co-Director of CRF's Medical Research and Education Division. He is also Professor of Medicine at Columbia University College of Physicians and Surgeons and Director of Cardiovascular Research and Education at the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/Columbia University Medical Center.
The BRIGHT trial was sponsored by the General Hospital of Shenyang Military Region, supported by a general research fund from the General Hospital of Shenyang Military Region, as well as nonprofit grants from the Chinese Government National Key R&D project for the 12th five-year plan (2011BAI11B07, 2012ZX093016-002), and a research grant and study drug supply from Salubris Pharmaceutical Co. (Shenzhen, China).
The Cardiovascular Research Foundation (CRF) is an independent, academically focused nonprofit organization dedicated to improving the survival and quality of life for people with heart disease through high quality research and education. Since its inception in 1991, CRF has played a major role in realizing dramatic improvements in the lives of countless numbers of patients by establishing the safe use of new technologies and therapies in interventional cardiovascular medicine. For more information, visit http://www.