Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin

Abstract

heparin (Fragmin) in patients with venous thromboembolism and contraindications to coumarin. Thromb Haemost 1994; 71: 7-11. 13 Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG.Heparin-induced thrombocytopenia in patients treated with lowmolecular-weight heparin or unfractionated heparin. N Engl J Med 1995; 332: 1330-5. 14 Pini M, Aiello S, Manotti C, Pattacini C, Quintavalla R, Poli T, Tagliaferri A, Dettori AG. Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin An association of aspirin with clopidogrel is the reference treatment for prevention of thrombosis secondary to coronary angioplasty [1]. Clopidogrel inhibits platelet activation by blocking the P2Y12 platelet receptor, activation of which is associated with dephosphorylation of intraplatelet vasodilatorstimulated phosphoprotein (VASP). VASP phosphorylation provides an index of platelet reactivity to clopidogrel, which varies between individuals: the greater it is the more frequently thrombosis occurs [2]. Clopidogrel is a prodrug, activated by cytochrome 2C19. We investigated whether interactions with other substances could account for the observed variation in biological response to clopidogrel. The VASP test was performed on 105 consecutive patients (mean age: 63.7 years, 61% male) receiving aspirin + clopidogrel bitherapy in a context of high-risk coronary angioplasty.The mean VASP test result, performed at least 48 h after initiation of treatment, was 52.2 ± 18.7, with a range of 6-89. Platelet response was analyzed by Mann-Whitney U-test according to the different standard accompanying treatments: no significant differences were found for statins, angiotensinconverting enzyme inhibitors, angiotensin II receptor antagonist and beta blockers. Conversely, proton pump inhibitors (PPI) users had significantly higher VASP values than nonusers [61.4 ± 23.2 (n ¼ 24), vs. 49.5 ± 16.3 (n ¼ 81) respectively, P ¼ 0.007].These results are the first to show an association between PPI treatment and diminished biological action of clopidogrel. CYP 2C19, which the 681G>A polymorphism has recently been shown to determine the response to clopidogrel [3], is involved in both clopidogrel activation and PPI metabolism [4]. A competitive effect of PPIs on CYP 2C19 might thus underlie clopidogrel's reduced effectiveness in patients receiving PPIs.Demonstrating an interaction between these two drugs, which are so routinely associated in cardiology, would have major implications for the management of the risk of thrombosis following angioplasty, but will require the results of a randomized study that is currently under way.

Clopidogrel and proton pump inhibitors: can near patient testing help in the tailoring of dual antiplatelet prescription?

“…Gilard et al [7] first highlighted the negative impact of PPIs and, in particular, omeprazole on the pharmacodynamic clopidogrel response, possibly owing to inhibition of CYP2C19, and this group further confirmed this drug-drug interaction by carrying out the randomized and double-blinded Omeprazole CLopidogrel Aspirin study [8]. Since then, however, other groups have shown that this response may not be relevant to all PPIs.…”

Gastrointestinal safety of triflusal solution in healthy volunteers: a proof of concept endoscopic study

“…In an attempt to decrease the incidence of serious gastrointestinal side effects associated to aspirin and clopidogrel, proton pump inhibitors are frequently associated to these antiplatelet drugs and, in this sense, the American College of Cardiology/American Heart Association Guidelines in Unstable Angina/Non-ST Elevation Myocardial Infarction [23] recommends than in patients with a history of gastrointestinal bleeding, when aspirin or clopidogrel are administered alone or in combination, drugs to minimize the risk of recurrent gastrointestinal bleeding (e.g., proton pump inhibitors) should be prescribed concomitantly [24]. Recently there is emerging evidence that concomitant administration of proton pump inhibitors diminishes the antiplatelet effect [25] and the clinical efficacy of clopidogrel [26]. For the above mentioned reasons it is convenient to dispose of alternative antiplatelet agents with a good gastrointestinal safety profile such as triflusal.…”

Efectos adversos a largo plazo de los inhibidores de la bomba de protones. Perspectiva desde la medicina basada en la evidencia

“…Experimentos in vitro reportaron una reducción en la acción biológica del clopidogrel sobre la función plaquetaria, pero estudios posteriores arrojaron respuestas contradictorias sobre la relevancia clínica de la interacción o la variación de resultados entre moléculas de IBP (5). El estudio COGENT (2010) concluyó que el uso de omeprazol con clopidogrel reduce el riesgo de eventos gastrointestinales, comparado con el uso de clopidogrel más placebo, sin incremento en el riesgo de eventos cardiovasculares (muerte, infarto agudo de miocardio no fatal, revascularización o accidente cerebrovascular).…”