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

Stefanie Schulz, Julinda Mehilli, Franz-Josef Neumann, Tibor Schuster, Steffen Massberg, Christian Valina, Melchior Seyfarth, Jürgen Pache, Karl-Ludwig Laugwitz, Hans-Joachim Büttner, Gjin Ndrepepa, Albert Schömig, Adnan Kastrati
DOI: http://dx.doi.org/10.1093/eurheartj/ehq330 First published online: 30 August 2010

Abstract

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.

  • Heparin
  • Bivalirudin
  • Clopidogrel
  • Stent
    • Received July 30, 2010.
    • Revision received August 11, 2010.
    • Accepted August 13, 2010.
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