1. Drug Interaction Between Clopidogrel and Ranitidine or Omeprazole in Stable Coronary Artery Disease: A Double-Blind, Double Dummy, Randomized Study.
- Author
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Furtado, Remo, Giugliano, Robert, Strunz, Celia, Filho, Cyrillo, Ramires, José, Filho, Roberto, Neto, Pedro, Pereira, Alexandre, Rocha, Tânia, Freire, Beatriz, D'Amico, Elbio, and Nicolau, José
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ANALYSIS of variance , *BLOOD coagulation tests , *BLOOD platelet aggregation , *COMBINATION drug therapy , *CHI-squared test , *CONFIDENCE intervals , *DRUG interactions , *FACTOR analysis , *FISHER exact test , *LONGITUDINAL method , *OMEPRAZOLE , *POLYMERASE chain reaction , *PROBABILITY theory , *RANITIDINE , *STATISTICS , *T-test (Statistics) , *COMORBIDITY , *DATA analysis , *STATISTICAL significance , *RANDOMIZED controlled trials , *REPEATED measures design , *BLIND experiment , *CLOPIDOGREL , *DATA analysis software , *DESCRIPTIVE statistics , *MANN Whitney U Test , *GENOTYPES , *PHARMACODYNAMICS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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