Incidence and clinical impact of dual nonresponsiveness to aspirin and clopidogrel in patients with drug-eluting stents

J Am Coll Cardiol. 2008 Aug 26;52(9):734-9. doi: 10.1016/j.jacc.2008.05.032.


Objectives: This study sought to determine the incidence of aspirin nonresponsiveness in addition to clopidogrel nonresponsiveness and whether this association identifies patients at an increased risk of drug-eluting stent (DES) thrombosis.

Background: Nonresponsiveness to clopidogrel is a predictor of DES thrombosis. No prospective data exist about the possible association of dual nonresponsiveness to clopidogrel and aspirin with DES thrombosis.

Methods: Platelet function was assessed after a loading dose of 600 mg clopidogrel in 746 patients who had successful DES implantation followed by 6-month dual-antiplatelet therapy. Platelet reactivity was assessed by light transmittance aggregometry using adenosine 5'-diphosphate, arachidonic acid, and collagen. The primary end point was definite/probable DES thrombosis at 6 months. The secondary end point was the composite of cardiac mortality and DES thrombosis.

Results: The incidence of dual nonresponsiveness to aspirin and clopidogrel was 6%. Definite/probable DES thrombosis was significantly higher in dual aspirin and clopidogrel nonresponders (11.1%) than in clopidogrel and aspirin responders (2.1%, p < 0.001), isolated clopidogrel nonresponders (2.2%, p < 0.05), or aspirin nonresponders (2.3%, p < 0.05). The incidence of the secondary end point was 4.4% in isolated clopidogrel nonresponders, 2.3% in isolated aspirin nonresponders, and 13.3% in dual aspirin and clopidogrel nonresponders. Dual clopidogrel and aspirin nonresponsiveness was an independent predictor of DES thrombosis (hazard ratio: 3.18, 95% confidence interval: 1.14 to 8.83, p = 0.027) and the composite of cardiac mortality and DES thrombosis (hazard ratio: 2.94, 95% confidence interval: 1.16 to 7.41, p = 0.022).

Conclusions: Dual nonresponsiveness to aspirin and clopidogrel is a relatively infrequent condition that identifies patients at a very high risk of DES thrombosis or death.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aspirin / pharmacology*
  • Clopidogrel
  • Cohort Studies
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / therapy
  • Drug Resistance, Multiple*
  • Drug-Eluting Stents*
  • Female
  • Graft Occlusion, Vascular / diagnosis
  • Graft Occlusion, Vascular / epidemiology*
  • Graft Occlusion, Vascular / prevention & control
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Radiography
  • Risk Factors
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Aspirin