Prognostic value of a high on-clopidogrel treatment platelet reactivity in bivalirudin versus abciximab treated non-ST-segment elevation myocardial infarction patients. ISAR-REACT 4 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment-4) platelet substudy

J Am Coll Cardiol. 2012 Jul 31;60(5):369-77. doi: 10.1016/j.jacc.2012.02.044. Epub 2012 Jun 6.

Abstract

Objectives: The ISAR-REACT 4 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment-4) platelet substudy aimed to determine the relevance of high on-clopidogrel treatment platelet reactivity (HPR) in non-ST-segment elevation myocardial infarction patients that received abciximab with unfractionated heparin (UFH) or bivalirudin during percutaneous coronary intervention (PCI).

Background: In patients undergoing PCI, HPR has been linked to a higher risk for ischemic events. The influence of HPR on clinical outcomes may differ with regard to the adjunctive antithrombotic treatment administered. In ISAR-REACT 4, bivalirudin treatment showed similar efficacy profiles as compared to abciximab with UFH. The impact of HPR on clinical outcomes in abciximab with UFH versus bivalirudin treated non-ST-segment elevation myocardial infarction patients has never been investigated specifically.

Methods: A total of 564 patients (274 in abciximab/UFH group vs. 290 in bivalirudin group) were enrolled in this study. Presence or absence of HPR following clopidogrel loading was determined by platelet function testing on a Multiplate analyzer (Verum Diagnostica, Munich, Germany). Per study group and stratified in HPR and no-HPR patients, the 30-day incidence of a combined efficacy endpoint (death, myocardial infarction, urgent target vessel revascularization) was determined.

Results: For abciximab with UFH, the incidence of the efficacy endpoint was similar in HPR versus no-HPR patients (9.4% vs. 6.7%; odds ratio: 1.4; 95% confidence interval: 0.6 to 3.5; p = 0.43). For bivalirudin, the incidence of the efficacy endpoint was significantly higher in HPR versus no-HPR patients (22.0% vs. 5.0%; odds ratio: 5.4; 95% confidence interval: 2.4 to 12.1; p < 0.0001).

Conclusions: For patients with a risk profile similar to the subjects enrolled in this platelet substudy, the impact of HPR on clinical outcomes may depend on the type of adjunctive antithrombotic therapy used during PCI. Further investigations are warranted to clarify whether assessment of platelet function may help tailoring antithrombotic therapy during PCI.

Trial registration: ClinicalTrials.gov NCT00373451.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abciximab
  • Aged
  • Angioplasty, Balloon, Coronary*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Antithrombins / adverse effects
  • Antithrombins / therapeutic use*
  • Clopidogrel
  • Cohort Studies
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Electrocardiography / drug effects
  • Female
  • Heparin / adverse effects
  • Heparin / therapeutic use*
  • Hirudins / adverse effects
  • Humans
  • Immunoglobulin Fab Fragments / adverse effects
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / mortality
  • Myocardial Infarction / therapy*
  • Peptide Fragments / adverse effects
  • Peptide Fragments / therapeutic use*
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Prognosis
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Signal Processing, Computer-Assisted
  • Stents*
  • Survival Analysis
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Anticoagulants
  • Antithrombins
  • Hirudins
  • Immunoglobulin Fab Fragments
  • Peptide Fragments
  • Platelet Aggregation Inhibitors
  • Recombinant Proteins
  • Heparin
  • Clopidogrel
  • Ticlopidine
  • bivalirudin
  • Abciximab

Associated data

  • ClinicalTrials.gov/NCT00373451