A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary artery stents

J Am Coll Cardiol. 2003 Mar 19;41(6):969-73. doi: 10.1016/s0735-1097(02)02974-1.

Abstract

Objectives: The aim of the present study was to compare clopidogrel and ticlopidine after coronary stenting with regard to cardiovascular death during long-term follow-up.

Background: Randomized trials comparing clopidogrel and ticlopidine with a restricted use of intravenous glycoprotein IIb/IIIa inhibition have reported a trend toward a higher incidence of thrombotic stent occlusion with clopidogrel at 30 days.

Methods: After successful coronary stent implantation, 700 patients with 899 lesions were randomly assigned to receive a four-week course of either 500 mg ticlopidine (n = 345) or 75 mg clopidogrel (n = 355) in addition to 100 mg aspirin. Cardiovascular death was the primary end point and was recorded during a median follow-up period of 28 months.

Results: Cardiovascular death occurred in eight patients with ticlopidine versus 26 patients with clopidogrel (hazard ratio with ticlopidine compared with clopidogrel, 0.30; 95% confidence interval [CI], 0.14 to 0.66; p = 0.003). After adjustment for co-variables, ticlopidine reduced the risk of cardiovascular death by 63% compared with clopidogrel. The combined end point of cardiovascular death or nonfatal myocardial infarction was present in 19 patients assigned ticlopidine, compared with 40 patients assigned clopidogrel (hazard ratio, 0.45; p = 0.005). The hazard ratio for all-cause mortality with ticlopidine as compared with clopidogrel was 0.30 (95% CI, 0.14 to 0.64; p = 0.002).

Conclusions: After the placement of coronary artery stents in unselected patients, ticlopidine was associated with a significantly lower mortality than clopidogrel. This raises concern about the current practice of substituting clopidogrel for ticlopidine after stenting and highlights the need for further long-term studies.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aspirin / administration & dosage*
  • Aspirin / therapeutic use*
  • Blood Vessel Prosthesis Implantation / adverse effects*
  • Clopidogrel
  • Coronary Artery Disease / mortality*
  • Coronary Artery Disease / surgery*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Graft Occlusion, Vascular / etiology*
  • Graft Occlusion, Vascular / mortality
  • Graft Occlusion, Vascular / prevention & control*
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Postoperative Complications
  • Stents / adverse effects*
  • Survival Rate
  • Ticlopidine / administration & dosage*
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use*
  • Time Factors

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Aspirin