Long-term clinical outcome based on aspirin and clopidogrel responsiveness status after elective percutaneous coronary intervention: a 3T/2R (tailoring treatment with tirofiban in patients showing resistance to aspirin and/or resistance to clopidogrel) trial substudy

J Am Coll Cardiol. 2010 Oct 26;56(18):1447-55. doi: 10.1016/j.jacc.2010.03.103.

Abstract

Objectives: The purpose of this study was to investigate the long-term outcome after elective percutaneous coronary intervention in low-risk patients screened for aspirin and/or clopidogrel responsiveness in the 3T/2R (Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel) trial.

Background: The impact of aspirin and/or clopidogrel poor response on long-term outcome is debated.

Methods: Aspirin and clopidogrel response was measured with the VerifyNow system aspirin and P2Y12 assays. After percutaneous coronary intervention (PCI), death, stroke, and myocardial infarction were assessed up to 1 year.

Results: Overall, 1,277 patients were screened, and 826 (65%) were treated with PCI. In all, 124 patients were found to be aspirin poor responders, and there were 179 clopidogrel poor responders (totally, 278 poor responders). The 1-year end point was significantly higher in poor responders as compared to full responders (15.8% vs. 8.6%, p=0.002), which is principally due to more myocardial infarction occurrence. At multivariable analysis, clopidogrel poor response emerged as an independent predictor (hazard ratio: 1.15, 95% confidence interval: 1.03 to 1.28). Receiver-operator characteristic analysis identifies≤23 of percentage of platelet inhibition and ≥208 of P2Y12 reactivity units as optimal cut offs to predict 1-year end point. Excluding periprocedural events, also peri-PCI myocardial infarction, which is strongly related to aspirin/clopidogrel poor response, was an independent predictor (hazard ratio: 1.25, 95% confidence interval: 1.14 to 1.37). Glycoprotein IIb/IIIa inhibitor administration reduces this risk in poor responders (21.2% vs. 34.7%, p=0.02), but not in full responders (6.3% vs. 6.5%, p=0.8).

Conclusions: Poor response to clopidogrel is an independent predictor of periprocedural myocardial infarction and worse 1-year outcome in low-risk patients undergoing PCI, whereas poor response to aspirin failed to predict a worse outcome. Contrary to what was observed in poor responders, glycoprotein IIb/IIa inhibitor therapy failed to provide a benefit in aspirin and/or clopidogrel full responders.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angioplasty, Balloon, Coronary / trends*
  • Aspirin / therapeutic use*
  • Clopidogrel
  • Drug Resistance*
  • Elective Surgical Procedures / trends*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / mortality
  • Myocardial Infarction / prevention & control
  • Predictive Value of Tests
  • Prospective Studies
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors
  • Tirofiban
  • Treatment Outcome
  • Tyrosine / analogs & derivatives*
  • Tyrosine / therapeutic use

Substances

  • Tyrosine
  • Clopidogrel
  • Tirofiban
  • Ticlopidine
  • Aspirin