Randomized, double-blind comparison of effects of abiciximab bolus only vs. on-label regimen on ex vivo inhibition of platelet aggregation in responders to clopidogrel undergoing coronary stenting

J Thromb Haemost. 2010 Sep;8(9):1903-11. doi: 10.1111/j.1538-7836.2010.03972.x.

Abstract

Background: On top of aspirin, an abciximab bolus-only regimen results in a 30% drop in platelet inhibition at 6 h as compared with the on-label regimen. The concomitant administration of high loading dose clopidogrel, by bridging with abciximab bolus, may sustain suppression of platelet activity over time.

Objectives: To investigate the non-inferiority of abciximab bolus-only and concomitant high loading dose clopidogrel vs. abciximab bolus + infusion with respect to the inhibition of platelet aggregation (IPA) as determined by light transmission aggregometry.

Patients/methods: Seventy-three patients with non-ST segment elevation acute coronary syndromes underwent double-blind randomization to abciximab bolus followed by a 12-h placebo infusion and concomitant 600-mg clopidogrel vs. abciximab bolus + a 12-h infusion and 300 mg of clopidogrel. IPA was determined by light transmission aggregometry throughout 24 h. Clopidogrel poor responsiveness was defined as ≥ 50% 5 μmol L⁻¹ ADP-induced maximum platelet aggregation.

Results: In clopidogrel responders (n = 68), IPA after 20 μmol L⁻¹ ADP at 4 h was 89% ± 13% in the bolus-only arm vs. 92% ± 14% in the bolus + infusion arm (P = 0.011 for non-inferiority). IPA after 5 or 20 μmol L⁻¹ ADP and 5 or 15 μmol L⁻¹ TRAP and the proportion of patients showing ≥ 80% IPA did not differ at any time point, irrespective of clopidogrel responsiveness status. Thirty-day outcomes were similar, whereas hemoglobin (0.91 ± 0.8 vs. 0.5 ± 0.7 g dL⁻¹ ; P = 0.01) and platelet count mean drop (41.7 ± 57 vs. 18.6 ± 34 10⁹ L⁻¹; P = 0.042) were significantly reduced in the bolus-only arm.

Conclusions: Withholding abciximab post-bolus infusion in patients receiving high loading dose clopidogrel does not impair platelet inhibition throughout 24 h, and has the potential to improve the safety profile of the drug at reduced costs.

Trial registration: ClinicalTrials.gov NCT00929279.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abciximab
  • Aged
  • Angiography / methods
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / therapeutic use*
  • Blood Platelets / drug effects*
  • Clopidogrel
  • Double-Blind Method
  • Female
  • Humans
  • Immunoglobulin Fab Fragments / administration & dosage*
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Platelet Function Tests
  • Stents
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin Fab Fragments
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Abciximab

Associated data

  • ClinicalTrials.gov/NCT00929279