The New England Journal of Medicine, 2011, Vol.365(21), pp.1980-1989
Background The combination of glycoprotein IIb/IIIa inhibitors and heparin has not been compared with bivalirudin in studies specifically involving patients with non–ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). We compared the two treatments in this patient population. Methods Immediately before PCI, we randomly assigned, in a double-blind manner, 1721 patients with acute non–ST-segment elevation myocardial infarction to receive abciximab plus unfractionated heparin (861 patients) or bivalirudin (860 patients). The study tested the hypothesis that abciximab and heparin would be superior to bivalirudin with respect to the primary composite end point of death, large recurrent myocardial infarction, urgent target-vessel revascularization, or major bleeding within 30 days. Secondary end points included the composite of death, any recurrent myocardial infarction, or urgent target-vessel revascularization (efficacy end point) and major bleeding (safety end point) within 30 days. Results The primary end point occurred in 10.9% of the patients in the abciximab group (94 patients) and in 11.0% in the bivalirudin group (95 patients) (relative risk with abciximab, 0.99; 95% confidence interval [CI], 0.74 to 1.32; P=0.94). Death, any recurrent myocardial infarction, or urgent target-vessel revascularization occurred in 12.8% of the patients in the abciximab group (110 patients) and in 13.4% in the bivalirudin group (115 patients) (relative risk, 0.96; 95% CI, 0.74 to 1.25; P=0.76). Major bleeding occurred in 4.6% of the patients in the abciximab group (40 patients) as compared with 2.6% in the bivalirudin group (22 patients) (relative risk, 1.84; 95% CI, 1.10 to 3.07; P=0.02). Conclusions Abciximab and unfractionated heparin, as compared with bivalirudin, failed to reduce the rate of the primary end point and increased the risk of bleeding among patients with non–ST-segment elevation myocardial infarction who were undergoing PCI. (Funded by Nycomed Pharma and others; ISAR-REACT 4 ClinicalTrials.gov number, NCT00373451 .) This trial compared the combination of abciximab and unfractionated heparin with bivalirudin in patients with non–ST-segment elevation MI who were undergoing coronary stenting. The two regimens had similar efficacy, but there was more bleeding with abciximab and heparin. An invasive strategy of coronary angiography, with revascularization when appropriate, is recommended for high-risk patients who have an acute coronary syndrome.1,2 Owing to the key role that the rupture of an atherosclerotic plaque, which is highly prothrombotic, plays in the pathogenesis of these syndromes,3 identifying the most appropriate adjunctive antithrombotic therapy before, during, and after percutaneous coronary intervention (PCI) has been the target of extensive research for the past three decades. Abciximab is a glycoprotein IIb/IIIa inhibitor with potent platelet-antiaggregative effects.4 Although the administration of abciximab during PCI was not associated with a clinical benefit in patients in stable . . .
Adult–Drug Therapy ; Aged–Adverse Effects ; Angina Pectoris–Therapeutic Use ; Angioplasty, Balloon, Coronary–Adverse Effects ; Antibodies, Monoclonal–Therapeutic Use ; Anticoagulants–Chemically Induced ; Double-Blind Method–Adverse Effects ; Drug Therapy, Combination–Therapeutic Use ; Female–Adverse Effects ; Hemorrhage–Adverse Effects ; Heparin–Therapeutic Use ; Hirudins–Drug Therapy ; Humans–Mortality ; Immunoglobulin Fab Fragments–Therapy ; Male–Adverse Effects ; Middle Aged–Therapeutic Use ; Myocardial Infarction–Adverse Effects ; Peptide Fragments–Therapeutic Use ; Recombinant Proteins–Antagonists & Inhibitors ; Recurrence–Antagonists & Inhibitors ; Thrombin–Antagonists & Inhibitors ; Abridged ; Antibodies, Monoclonal ; Anticoagulants ; Hirudins ; Immunoglobulin Fab Fragments ; Peptide Fragments ; Recombinant Proteins ; Heparin ; Thrombin ; Bivalirudin ; Abciximab;