Drug Interaction Between Clopidogrel and Ranitidine or Omeprazole in Stable Coronary Artery Disease: A Double-Blind, Double Dummy, Randomized Study

Am J Cardiovasc Drugs. 2016 Aug;16(4):275-284. doi: 10.1007/s40256-016-0172-5.

Abstract

Background: Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine.

Objectives: Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine.

Methods: We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12™ (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA).

Results: We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] -1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04).

Conclusions: Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel.

Clinical trial registration: NCT01896557.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Blood Platelets / drug effects
  • Clopidogrel
  • Coronary Artery Disease / drug therapy*
  • Double-Blind Method
  • Drug Interactions*
  • Drug Therapy, Combination / methods
  • Female
  • Humans
  • Male
  • Middle Aged
  • Omeprazole / therapeutic use*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use
  • Platelet Function Tests / methods
  • Prospective Studies
  • Proton Pump Inhibitors / therapeutic use
  • Ranitidine / therapeutic use*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Ranitidine
  • Clopidogrel
  • Omeprazole
  • Ticlopidine

Associated data

  • ClinicalTrials.gov/NCT01896557