Impact of clopidogrel resistance on thrombotic events after percutaneous coronary intervention with drug-eluting stent

Thromb Res. 2009 May;124(1):46-51. doi: 10.1016/j.thromres.2008.10.007. Epub 2008 Nov 28.

Abstract

Objectives: This study examines whether patient resistance to clopidogrel is associated with long-term thrombotic events after elective coronary drug-eluting stent (DES) implantation.

Methods: We prospectively enrolled 386 patients with stable angina who received elective percutaneous coronary intervention (PCI) with DES. Before the procedure, platelet reactivity was measured by light transmittance aggregometry (LTA) at baseline and approximately 24 h after the 300 mg loading dose of clopidogrel. Clopidogrel resistance was conservatively defined as < or = 10% absolute difference between baseline and post-treatment platelet aggregation. All patients received chronic dual antiplatelet treatment (aspirin 300 mg and clopidogrel 75 mg daily) for 12 months. Patients were followed for 1 year after coronary stenting for the occurrence of composite thrombotic events, including cardiovascular death, non-fatal myocardial infarction (MI), stent thrombosis or cerebrovascular ischemic accident (CVA).

Results: Clopidogrel resistance was present in 65 patients (16.8%). During follow-up, composite thrombotic events occurred in 16.9% of clopidogrel resistant patients, yet in only 6.2% of non-resistant patients (p = 0.010). The incidence of definite or probable stent thrombosis was 9.2% in clopidogrel resistant patients and 2.5% in non-resistant patients (p = 0.018). After adjustment for other factors that affect cardiovascular outcome, clopidogrel resistance, diabetes, and left ventricular (LV) dysfunction were independently associated with 1-year composite thrombotic events. The hazard ratio (HR) for clopidogrel resistance was 2.44 (95% CI = 1.09 to 5.45; p = 0.031).

Conclusion: This study demonstrates the natural history of clopidogrel resistance among patients with stable cardiovascular disease, and shows that this resistance is an independent predictor of thrombotic events in patients undergoing PCI with DES.

MeSH terms

  • Aged
  • Angina Pectoris / drug therapy
  • Angioplasty, Balloon, Coronary / adverse effects
  • Angioplasty, Balloon, Coronary / methods*
  • Clopidogrel
  • Coronary Thrombosis / drug therapy*
  • Coronary Thrombosis / etiology
  • Drug Resistance*
  • Drug Therapy, Combination
  • Drug-Eluting Stents*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Practice Guidelines as Topic / standards
  • Sirolimus / therapeutic use
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Sirolimus