A randomised study comparing the antiplatelet and antiinflammatory effect of clopidogrel 150 mg/day versus 75 mg/day in patients with ST-segment elevation acute myocardial infarction and poor responsiveness to clopidogrel: results from the DOUBLE study

Thromb Res. 2010 Apr;125(4):309-14. doi: 10.1016/j.thromres.2009.06.016. Epub 2009 Jul 14.

Abstract

Introduction: The antiplatelet effect of standard or increased clopidogrel doses in patients with ST- segment elevation acute myocardial infarction (STEMI) has never been studied. In this study we compared the antiplatelet effect of a 75 mg daily maintenance dose of clopidogrel with 150 mg in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).

Materials and methods: Fifty-four patients with STEMI undergoing PCI were randomly allocated to receive either 75 mg/day clopidogrel (group 1) or 150 mg/day (group 2) for 1 month. Platelet function, measured by 5 different assays, was determined at 3 time points: 38+/-8 hours after the procedure, 1 week and 1 month after randomization.

Results: In group 1, mean +/- SD platelet reactivity index (PRI) measured with the VASP assay was 57.7+/-15.7% and 46.9+/-15.7% at 1 week and 1 month, respectively, compared to 38.8+/-15.7% and 34.9+/-12.6% in group 2 (p=0.0001). Same results were observed for light transmittance aggregometry, whole blood aggregometry and VerifyNow, but not for thromboelastometry. In contrast to what may be expected, the 75 mg daily maintenance dose took longer than 1-week to provide the full clopidogrel antiplatelet effect. Furthermore, patients in group 2 had a nearly 50% reduction in C-reactive protein levels both at 1 week and 1 month.

Conclusion: In patients with STEMI and poor responsiveness to clopidogrel a 150 mg daily maintenance dose of clopidogrel is associated with a significant reduction of platelet aggregation and a trend towards reduced inflammation.

Publication types

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

MeSH terms

  • Anterior Wall Myocardial Infarction
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • C-Reactive Protein / pharmacology
  • C-Reactive Protein / therapeutic use
  • Cell Adhesion Molecules / metabolism
  • Clopidogrel
  • Humans
  • Microfilament Proteins / metabolism
  • Myocardial Infarction / blood
  • Myocardial Infarction / drug therapy*
  • Phosphoproteins / metabolism
  • Platelet Aggregation / drug effects*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Cell Adhesion Molecules
  • Microfilament Proteins
  • Phosphoproteins
  • vasodilator-stimulated phosphoprotein
  • C-Reactive Protein
  • Clopidogrel
  • Ticlopidine