Bivalirudin during Primary PCI in Acute Myocardial Infarction
Gregg W. Stone, M.D., Bernhard Witzenbichler, M.D., Giulio Guagliumi, M.D., Jan Z. Peruga, M.D., Bruce R. Brodie, M.D., Dariusz Dudek, M.D., Ran Kornowski, M.D., Franz Hartmann, M.D., Bernard J. Gersh, M.B., Ch.B., D.Phil., Stuart J. Pocock, Ph.D., George Dangas, M.D., Ph.D., S. Chiu Wong, M.D., Ajay J. Kirtane, M.D., Helen Parise, Sc.D., Roxana Mehran, M.D., for the HORIZONS-AMI Trial Investigators
Background Treatment with the direct thrombin inhibitor bivalirudin,as compared with heparin plus glycoprotein IIb/IIIa inhibitors,results in similar suppression of ischemia while reducing hemorrhagiccomplications in patients with stable angina and non–ST-segmentelevation acute coronary syndromes who are undergoing percutaneouscoronary intervention (PCI). The safety and efficacy of bivalirudinin high-risk patients are unknown.
Methods We randomly assigned 3602 patients with ST-segment elevationmyocardial infarction who presented within 12 hours after theonset of symptoms and who were undergoing primary PCI to treatmentwith heparin plus a glycoprotein IIb/IIIa inhibitor or to treatmentwith bivalirudin alone. The two primary end points of the studywere major bleeding and combined adverse clinical events, definedas the combination of major bleeding or major adverse cardiovascularevents, including death, reinfarction, target-vessel revascularizationfor ischemia, and stroke (hereinafter referred to as net adverseclinical events) within 30 days.
Results Anticoagulation with bivalirudin alone, as comparedwith heparin plus glycoprotein IIb/IIIa inhibitors, resultedin a reduced 30-day rate of net adverse clinical events (9.2%vs. 12.1%; relative risk, 0.76; 95% confidence interval [CI]0.63 to 0.92; P=0.005), owing to a lower rate of major bleeding(4.9% vs. 8.3%; relative risk, 0.60; 95% CI, 0.46 to 0.77; P<0.001).There was an increased risk of acute stent thrombosis within24 hours in the bivalirudin group, but no significant increasewas present by 30 days. Treatment with bivalirudin alone, ascompared with heparin plus glycoprotein IIb/IIIa inhibitors,resulted in significantly lower 30-day rates of death from cardiaccauses (1.8% vs. 2.9%; relative risk, 0.62; 95% CI, 0.40 to0.95; P=0.03) and death from all causes (2.1% vs. 3.1%; relativerisk, 0.66; 95% CI, 0.44 to 1.00; P=0.047).
Conclusions In patients with ST-segment elevation myocardialinfarction who are undergoing primary PCI, anticoagulation withbivalirudin alone, as compared with heparin plus glycoproteinIIb/IIIa inhibitors, results in significantly reduced 30-dayrates of major bleeding and net adverse clinical events. (ClinicalTrials.govnumber, NCT00433966
[ClinicalTrials.gov]
.)
Source Information
From Columbia University Medical Center and the Cardiovascular Research Foundation, New York (G.W.S., G.D., A.J.K., H.P., R.M.); Charité Campus Benjamin Franklin, Berlin (B.W.); Ospedali Riuniti di Bergamo, Bergamo, Italy (G.G.); Silesian Center for Heart Disease, Lodz, Poland (J.Z.P.); LeBauer Cardiovascular Research Foundation and Moses Cone Hospital, Greensboro, NC (B.R.B.); Jagiellonian University, Krakow, Poland (D.D.); Rabin Medical Center, Petach Tikva, Israel (R.K.); Universitätsklinikum Schleswig-Holstein, Lübeck, Germany (F.H.); Mayo Clinic, Rochester, MN (B.J.G.); London School of Hygiene and Tropical Medicine, London (S.J.P.); and New York–Presbyterian Hospital/Weill Cornell Medical Center, New York (S.C.W.).
Address reprint requests to Dr. Stone at Columbia University Medical Center, Cardiovascular Research Foundation, 111 E. 59th St., 11th Fl., New York, NY 10022, or at gs2184{at}columbia.edu.
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