The failure of orally administered glycoprotein IIb/IIIa inhibitors to prevent recurrent cardiac events

Am J Med. 2002 Jun 1;112(8):647-58. doi: 10.1016/s0002-9343(02)01106-3.


Purpose: Despite the success of intravenous glycoprotein IIb/IIIa antagonists, oral formulations have failed to show benefit and have been associated with increased mortality. To understand these findings, we performed a meta-analysis of results from four phase 3 trials.

Subjects and methods: Trials were identified by MEDLINE search; review of abstracts from American College of Cardiology, European Society of Cardiology, and American Heart Association scientific sessions; or querying investigators in the field. Published, phase 3, randomized, placebo-controlled trials involving more than 1000 patients with coronary artery disease that compared an oral glycoprotein IIb/IIIa antagonist with or without background aspirin versus aspirin, and that had a planned follow-up of > or =30 days, were included. Four trials met these criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were generated from results, and combined using an empirical Bayes random-effects model.

Results: Among 33,326 patients, oral glycoprotein IIb/IIIa agents were associated with 31% increased mortality (OR = 1.31; 95% CI: 1.12 to 1.53; P= 0.0001). Results were similar whether the agent was added to (OR = 1.38; 95% CI: 1.15 to 1.67) or substituted for (OR = 1.37; 95% CI: 1.00 to 1.86) aspirin. Ischemic events or sudden death (OR = 1.22; 95% CI: 0.91 to 1.63) were also more common. Among patients with acute coronary syndromes, the incidence of myocardial infarction was increased (OR = 1.16; 95% CI: 1.03 to 1.29).

Conclusion: Oral glycoprotein IIb/IIIa inhibitor therapy is associated with increased mortality and myocardial infarction. No single explanation for these findings is satisfactory; the problem is likely to be multifactorial.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Coronary Disease / complications
  • Coronary Disease / mortality
  • Coronary Disease / prevention & control*
  • Death, Sudden, Cardiac
  • Humans
  • Myocardial Infarction / etiology
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Randomized Controlled Trials as Topic
  • Treatment Failure


  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Aspirin