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

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de Mendonca Furtado, Remo Holanda ; Giugliano, Robert Patrick ; Cassaro Strunz, Celia Maria ; Cavalheiro Filho, Cyrillo ; Franchini Ramires, Jose Antonio ; Kalil Filho, Roberto ; Lemos Neto, Pedro Alves ; Pereira, Alexandre Costa ; Rocha, Tania Rubia ; Freire, Beatriz Tonon ; D'Amico, Elbio Antonio ; Nicolau, Jose Carlos

• Document type: Journal article
• Source: American Journal of Cardiovascular Drugs; v. 16, n. 4, p. 275-284, AUG 2016.
• Web of Science Citations: 7

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 (TM) (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. (AU)

• FAPESP's process: 10/16324-1 - Possible drug interaction between clopidogrel and ranitidin or omeprazol in patients with stable coronary artery disease: a comparative study
• Grantee: José Carlos Nicolau
• Support Opportunities: Regular Research Grants