Effects of Pantoprazole and Esomeprazole on Platelet Inhibition by Clopidogrel

El artículo anterior, publicado en este mismo blog, trata de la interacción entre el clopidogrel y la inhibidores de la bomba de protones ( IBP ) y como era de esperar , por el diseño del trabajo, no se habló de cuáles podían usarse y cuáles no, sin embargo por la observación hecha en los comentarios del blog, por nuestro colega el Dr. Edgar Hernández Paz, Internista y Cardiólogo del Hospital General San Juna de Dios de la Ciudad de Guatemala, es importante aclarar que en el caso del paciente con Síndrome coronario agudo SCA y uso de la combinación de clopidogrel y IBP, podemos usar con seguridad Pantoprazole y esomeprazole y por ello transcribo el resumen aparecido en Medscape Internal Medicine al respecto, acompañado de sus autores y las referencia bibliográficas más importantes del mismo.


Jolanta M. Siller-Matula, MD; Alexander O. Spiel, MD; Irene M. Lang, MD; Gerhard Kreiner, MD; Guenter Christ, MD; Bernd Jilma, MD. Effects of Pantoprazole and Esomeprazole on Platelet Inhibition by Clopidogrel Systematic review and meta-analysis. Am Heart J 2007;154:221-31. Siller-Matula J, Schror K, Wojta J, et al. Thienopyridines in cardiovascular ...
Journal Article, Am Heart J, January 2009

Abstract
Background: Clopidogrel is activated by CYP2C19, which also metabolizes proton pump inhibitors (PPI). As proton pump inhibitors are metabolized to varying degrees by CYP2C19, we hypothesized that the reported negative omeprazole clopidogrel drug interaction may not be a class effect.Methods: Responsiveness to clopidogrel was assessed by the vasodilator-stimulated phosphoprotein phosphorylation (VASP) assay and aggregometry (Multiplate Analyzer) in 300 patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).
Results: The mean platelet reactivity index (PRI, assessed by the VASP assay) was nearly the same in patients with (n = 226; PRI = 51%) or without PPI treatment (n = 74; PRI = 49%; P = .724). Likewise, the adenosine diphosphate-induced platelet aggregation did not differ significantly between patients with or without PPI treatment (45 vs. 41 U; P = .619). Similarly, there was no difference in the PRI or the adenosine diphosphate-induced platelet aggregation between patients with pantoprazole (n = 152; PRI = 50%; aggregation = 47 U), esomeprazole (n = 74; PRI = 54%; aggregation = 42 U), or without PPI (n = 74; PRI = 49%; aggregation = 41 U; P = .382).
Conclusion: In contrast to the reported negative omeprazole-clopidogrel drug interaction, the intake of pantoprazole or esomeprazole is not associated with impaired response to clopidogrel.
Bibliografia:
1. Snoep JD, Hovens MM, Eikenboom JC, et al. Clopidogrel non-responsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis. Am Heart J 2007;154:221-31.
2. Siller-Matula J, Schror K, Wojta J, et al. Thienopyridines in cardiovascular disease: focus on clopidogrel resistance. Thromb Haemost 2007;97:385-93.
3. Angiolillo DJ, Guzman LA, Bass TA. Current antiplatelet therapies: benefits and limitations. Am Heart J 2008;156:S3-9.
4. Gladding P, Webster M, Ormiston J, et al. Antiplatelet drug nonresponsiveness. Am Heart J 2008;155:591-9.
5. Savi P, Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 2000;84:891-6.
6. Pereillo JM, Maftouh M, Andrieu A, et al. Structure and stereo-chemistry of the active metabolite of clopidogrel. Drug Metab Dispos 2002;30:1288-95.
7. Small DS, Farid NA, Payne CD, et al. Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. J Clin Pharmacol 2008;48: 475-84.
8. Lotfi A, Schweiger MJ, Giugliano GR, et al. High-dose atorvastatin does not negatively influence clinical outcomes among clopidogrel treated acute coronary syndrome patients—a Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) analysis. Am Heart J 2008; 155:954-8.
9. Li XQ, Andersson TB, Ahlstrom M, et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 2004;32: 821-7.
10. Gilard M, Arnaud B, Cornily JC, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol 2008;51:256-60.
11. Gilard M, Arnaud B, Le Gal G, et al. Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin. J Thromb Haemost 2006;4:2508-9.
12. Ishizaki T, Horai Y. Review article: cytochrome P450 and the metabolism of proton pump inhibitors—emphasis on rabeprazole. Aliment Pharmacol Ther 1999;13(Suppl 3): 27-36.
13. Cairns JA, Eikelboom J. Clopidogrel resistance: more grist for the mill. J Am Coll Cardiol 2008;51:1935-7.
14. Gurbel PA, Becker RC, Mann KG, et al. Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol 2007;50: 1822-34.
15. Manolopoulos P, Glenn JR, Fox SC, et al. Acyl derivatives of coenzyme A inhibit platelet function via antagonism at P2Y1 and P2Y12 receptors: a new finding that may influence the design of anti-thrombotic agents. Platelets 2008;19:134-45.
16. Sudo T, Ito H, Kimura Y. Phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) by the anti-platelet drug, cilostazol, in platelets. Platelets 2003;14:381-90.
17. Judge HM, Buckland RJ, Sugidachi A, et al. The active metabolite of prasugrel effectively blocks the platelet P2Y12 receptor and inhibits procoagulant and pro-inflammatory platelet responses. Platelets 2008;19:125-33.
18. Bonello L, Paganelli F, Arpin-Bornet M, et al. Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. J Thromb Haemost 2007;5:1630-6.
19. Bonello L, Camoin-Jau L, Arques S, et al. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study. J Am Coll Cardiol 2008; 51:1404-11.
20. Kleiman NS. Will measuring vasodilator-stimulated phosphoprotein phosphorylation help us optimize the loading dose of clopidogrel? J Am Coll Cardiol 2008;51:1412-4.
21. Siller-Matula J, Lang I, Christ G, et al. Calcium channel blockers reduce the antiplatelet effect of clopidogrel. J Am Coll Cardiol 2008; 52:1557-63.
22. Siller-Matula JM, Panzer S, Jilma B. Reproducibility and standardised reporting of the vasodilator-stimulated phosphoprotein phosphor-ylation assay. Platelets 2008;19:551-4.
23. Morel O, Faure A, Ohlmann P, et al. Impaired platelet responsiveness to clopidogrel identified by flow cytometric vasodilator-stimulated phosphoprotein (VASP) phosphorylation in patients with subacute stent thrombosis. Thromb Haemost 2007;98:896-9.
24. Seyfert UT, Haubelt H, Vogt A, et al. Variables influencing Multiplate (TM) whole blood impedance platelet aggregometry and turbidi-metric platelet aggregation in healthy individuals. Platelets 2007;18: 199-206.
25. Sibbing D, Braun S, Jawansky S, et al. Assessment of ADP-induced platelet aggregation with light transmission aggregometry and multiple electrode platelet aggregometry before and after clopidogrel treatment. Thromb Haemost 2008;99:121-6.
26. Toth O, Calatzis A, Penz S, et al. Multiple electrode aggregometry: a new device to measure platelet aggregation in whole blood. Thromb Haemost 2006;96:781-8.
27. Penz SM, Reininger AJ, Toth O, et al. Glycoprotein Ibalpha inhibition and ADP receptor antagonists, but not aspirin, reduce platelet thrombus formation in flowing blood exposed to atherosclerotic plaques. Thromb Haemost 2007;97:435-43.
28. Mueller T, Dieplinger B, Poelz W, et al. Utility of whole blood impedance aggregometry for the assessment of clopidogrel action using the novel Multiplate(R) analyzer-comparison with two flow cytometric methods. Thromb Res 2007;121:249-58.
29. Abelo A, Andersson TB, Antonsson M, Naudot AK, Skanberg I, Weidolf L. Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab Dispos 2000;28:966-72.
30. Lau WC, Waskell LA, Watkins PB, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 2003;107:32-7.
31. Saw J, Brennan DM, Steinhubl SR, et al. Lack of evidence of a clopidogrel-statin interaction in the CHARISMA trial. J Am Coll Cardiol 2007;50:291-5.
32. Angiolillo DJ, Alfonso F. Clopidogrel-statin interaction: myth or reality? J Am Coll Cardiol 2007;50:296-8.