ISAR-REACT 3A: a study of reduced dose of unfractionated heparin in biomarker negative patients undergoing percutaneous coronary intervention

• Published in: European heart journal 2010-10, Vol.31 (20), p.2482-2491
• Main Authors: Schulz, Stefanie, Mehilli, Julinda, Neumann, Franz-Josef, Schuster, Tibor, Massberg, Steffen, Valina, Christian, Seyfarth, Melchior, Pache, Jürgen, Laugwitz, Karl-Ludwig, Büttner, Hans-Joachim, Ndrepepa, Gjin, Schömig, Albert, Kastrati, Adnan
• Format: Article
• Language: English
• Subjects: Aged; Angina Pectoris - therapy; Angioplasty, Balloon, Coronary; Anticoagulants - administration & dosage; Biological and medical sciences; Biomarkers; Bivalirudin; Cardiology. Vascular system; Clopidogrel; Death, Sudden, Cardiac - prevention & control; Diseases of the cardiovascular system; Drug Therapy, Combination; Female; Follow-Up Studies; Heparin; Heparin - administration & dosage; Humans; Male; Medical sciences; Middle Aged; Myocardial Infarction - prevention & control; Myocardial Revascularization; Platelet Aggregation Inhibitors - administration & dosage; Postoperative Hemorrhage - prevention & control; Prospective Studies; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Stent; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Treatment Outcome
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehq330

Aims Although a 140 U/kg dose of unfractionated heparin (UFH) was comparable with bivalirudin in terms of net clinical outcome in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 3 trial, it was associated with a higher risk of bleeding. We designed this study to assess whether a reduction in the UFH dose from 140 to 100 U/kg is associated with improved net clinical outcome. Methods and results A total of 2505 biomarker negative patients undergoing percutaneous coronary intervention (PCI) after clopidogrel pre-treatment received a single bolus of 100 U/kg UFH. The primary endpoint was net clinical outcome—a quadruple endpoint of death, myocardial infarction, urgent target-vessel revascularization within 30 days, or in-hospital REPLACE 2 defined major bleeding. The primary comparison was with the historical UFH group of ISAR-REACT 3 (2281 patients). In a second analysis, we checked for non-inferiority against the historical bivalirudin arm of ISAR-REACT 3 (2289 patients). The incidence of the primary endpoint was 7.3% in the lower UFH dose group compared with 8.7% in the higher UFH dose group [hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.67–1.00; P = 0.045]. The incidence of major bleeding was 3.6% in the lower UFH dose group and 4.6% in the higher UFH dose group (HR 0.79; 95% CI 0.59–1.05; P = 0.11). The lower UFH dose met the criterion of non-inferiority compared with bivalirudin (P < 0.001). Conclusion In biomarker negative patients undergoing PCI after clopidogrel loading, a reduced dose of 100 U/kg UFH provided net clinical benefit compared with the historical control of 140 U/kg UFH in the ISAR-REACT 3 trial. The benefit was mostly driven by reduction in bleeding. Clinical trial registration information URL www.clinicaltrials.gov; Unique identifier NCT00735280.