Impact of Platelet Reactivity After Clopidogrel Administration on Drug-Eluting Stent Thrombosis

J Am Coll Cardiol. 2007 Jun 19;49(24):2312-7. doi: 10.1016/j.jacc.2007.01.094. Epub 2007 Jun 4.

Abstract

Objectives: We sought to determine whether nonresponsiveness to clopidogrel as revealed by high in vitro post-treatment platelet reactivity is predictive of drug-eluting stent (DES) thrombosis.

Background: No data exist about the impact of nonresponsiveness to clopidogrel on the risk of DES thrombosis.

Methods: We conducted a prospective observational cohort study from July 2005 to August 2006 in an academic hospital. A total of 804 patients who had successful sirolimus- or paclitaxel-eluting stent implantation were assessed for post-treatment platelet reactivity after a loading dose of 600 mg of clopidogrel. Patients with platelet aggregation by 10 mumol adenosine 5'-diphosphate > or =70% were defined as nonresponders. All patients received chronic dual antiplatelet treatment (aspirin 325 mg and clopidogrel 75 mg daily) for 6 months. The primary end point was the incidence of definite/probable early, subacute, and late stent thrombosis at 6-month follow-up.

Results: The incidence of 6-month definite/probable stent thrombosis was 3.1%. All stent thromboses were subacute or late. Of 804 patients, 105 (13%) were not responsive to clopidogrel. The incidence of stent thrombosis was 8.6% in nonresponders and 2.3% in responders (p < 0.001). By multivariate analysis, the predictors of stent thrombosis were as follows: nonresponsiveness to clopidogrel (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.32 to 7.16; p = 0.009), left ventricular ejection fraction (HR 0.95, 95% CI 0.92 to 0.98; p = 0.001), total stent length (HR 1.01, 95% CI 1.00 to 1.02; p = 0.010), and ST-segment elevation acute myocardial infarction (HR 2.41, 95% CI 1.04 to 5.63; p = 0.041).

Conclusions: Nonresponsiveness to clopidogrel is a strong independent predictor of stent thrombosis in patients receiving sirolimus- or paclitaxel-eluting stents.

MeSH terms

  • Adult
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Blood Platelets / drug effects*
  • Clopidogrel
  • Comorbidity
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Male
  • Multivariate Analysis
  • Myocardial Ischemia / epidemiology
  • Myocardial Ischemia / therapy
  • Paclitaxel / administration & dosage
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Function Tests
  • Prospective Studies
  • Sirolimus / administration & dosage
  • Stents / adverse effects*
  • Thrombosis / physiopathology
  • Thrombosis / prevention & control*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology

Substances

  • Antineoplastic Agents, Phytogenic
  • Immunosuppressive Agents
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Paclitaxel
  • Sirolimus