Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: A meta-analysis of phase III multicenter randomized trials

Derek P. Chew, Deepak L. Bhatt, Shelly Sapp, Eric J. Topol

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Abstract

Background - Numerous clinical trials have established the benefits of intravenous glycoprotein IIb/IIIa inhibition in the management of coronary artery disease. In contrast, the recent large-scale, placebo-controlled, randomized trials of the oral glycoprotein IIb/IIIa antagonists have failed to provide commensurate reductions in late composite ischemic end points despite potent inhibition of platelet aggregation. Methods and Results - The ORs for death, myocardial infarction, urgent revascularization, and major bleeding from the 4 large-scale, placebo-controlled, randomized trials with oral glycoprotein IIb/IIIa inhibitors were calculated and combined. Stratification by low-dose or high-dose therapy and the use of concurrent aspirin was also undertaken. In 33 326 patients followed for >30 days, a consistent and statistically significant increase in mortality was observed with oral glycoprotein IIb/IIIa therapy (OR, 1.37; 95% CI, 1.13 to 1.66; P=0.001). This effect was evident regardless of aspirin coadministration and treatment with either low-dose or high-dose therapy. Although a reduction in urgent revascularization was observed with oral glycoprotein IIb/IIIa inhibition, pooled analysis favored an increase in myocardial infarction that did not demonstrate statistical significance. Conclusions - Although we found a highly significant excess in mortality consistent across 4 trials with 3 different oral glycoprotein IIb/IIIa inhibitor agents, this was associated with a reduction in the need for urgent revascularization and no increase in myocardial infarction. These findings suggest the potential for a direct toxic effect with these agents and argue against a prothrombotic mechanism. Further investigation to elucidate the cause of this increased fatality risk is warranted.

Original languageEnglish
Pages (from-to)201-206
Number of pages6
JournalCirculation
Volume103
Issue number2
DOIs
Publication statusPublished or Issued - 16 Jan 2001
Externally publishedYes

Keywords

  • Glycoproteins
  • Mortality
  • Trials

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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