Comparative effect on platelet function of a fixed-dose aspirin and clopidogrel combination versus separate formulations in patients with coronary artery disease: A phase IV, multicenter, prospective, 4-week non-inferiority trial

Int J Cardiol. 2016 Jan 1:202:331-5. doi: 10.1016/j.ijcard.2015.09.024. Epub 2015 Sep 21.

Abstract

Background/objectives: The effect of aspirin and clopidogrel in a fixed-dose combination (FDC) on platelet function was compared with separate formulations in patients that had undergone percutaneous coronary intervention (PCI) with drug-eluting stent (DES).

Methods: This was a phase IV, prospective, multicenter, single-arm, non-inferiority study. Patients that had taken aspirin 100 mg and clopidogrel 75 mg once daily as separate formulations for >6 months after PCI with DES were enrolled, and then switched to an aspirin/clopidogrel FDC once-daily for 4 weeks. Platelet reactivity was determined using the VerifyNow® P2Y12 assay at baseline (immediately prior to switching) and 4 weeks later.

Results: A total of 648 patients (the full-analysis population; age, 63.6±9.0 years; male, 76.5%) finished the study, and 565 (the per-protocol population) completed without protocol violations. In the per-protocol population, the % inhibitions of P2Y12 and ARU were not significantly different between baseline and after 4 weeks of FDC treatment (29.2±20.0% to 29.0±19.9%, P=0.708; 445.1±69.2 to 446.2±63.0, P=0.799, respectively) and the difference in P2Y12 inhibition observed did not exceed the predetermined limit of non-inferiority (95% CI, -0.9 to 1.3). In the full-analysis population, the % inhibitions of P2Y12, PRU, and ARU were not significantly changed after 4 weeks of FDC treatment.

Conclusions: This study demonstrates that the efficacy of platelet inhibition by an aspirin/clopidogrel FDC was not inferior to that of separate aspirin and clopidogrel formulations in patients that had undergone PCI with DES.

Keywords: Aspirin; Clopidogrel; Fixed-dose combination; Platelet function.

Publication types

  • Clinical Trial, Phase IV
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin / administration & dosage*
  • Clopidogrel
  • Coronary Artery Disease / drug therapy*
  • Drug Combinations
  • Drug-Eluting Stents
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Function Tests
  • Prospective Studies
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Treatment Outcome

Substances

  • Drug Combinations
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Aspirin