Clopidogrel and PPI interaction: Clinically relevant or not?

Current Cardiology Reports

Volumn 14, Issue 1, 2012, Pages 49-58

  Harrison, Robert W ^a   Mahaffey, Kenneth W ^a  

^a DUKE CLINICAL RESEARCH INSTITUTE   (United States)

Author keywords

Acute coronary syndromes; Clopidogrel; Clopidogrel PPI interaction; Proton pump inhibitors

Indexed keywords

ACETYLSALICYLIC ACID; CLOPIDOGREL; CYTOCHROME P450 2C19; ESOMEPRAZOLE; LANSOPRAZOLE; OMEPRAZOLE; PANTOPRAZOLE; PRASUGREL; PROTON PUMP INHIBITOR; RABEPRAZOLE; TICAGRELOR;

ACUTE CORONARY SYNDROME; ARTICLE; BLEEDING; BLOOD CLOTTING PARAMETERS; CONSENSUS DEVELOPMENT; DRUG EFFICACY; DRUG INHIBITION; DRUG LABELING; FOOD AND DRUG ADMINISTRATION; GASTROINTESTINAL HEMORRHAGE; HUMAN; IN VITRO STUDY; LOADING DRUG DOSE; MEDICAL LITERATURE; META ANALYSIS (TOPIC); OBSERVATIONAL STUDY; PRESCRIPTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RETROSPECTIVE STUDY; SINGLE DRUG DOSE; THROMBOCYTE AGGREGATION INHIBITION; UNITED STATES;

ACUTE CORONARY SYNDROME; ASPIRIN; DRUG INTERACTIONS; DRUG THERAPY, COMBINATION; FEMALE; GASTROINTESTINAL HEMORRHAGE; HUMANS; MALE; OMEPRAZOLE; PLATELET AGGREGATION INHIBITORS; PROTON PUMP INHIBITORS; THIENOPYRIDINES; TICLOPIDINE;

EID: 84857632980     PISSN: 15233782     EISSN: 15343170     Source Type: Journal    
DOI: 10.1007/s11886-011-0233-y     Document Type: Article

References (63)

1. Sanofi-Aventis. Plavix Prescribing Information. http://products.sanofi. us/plavix/plavix.html#S1.2. http://products.sanofi.us/plavix/plavix.html#S1.2. Accessed 10/18/2011.
2. CAPRIE Steering Committee 1996 A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) Lancet 348 9038 1329 39 10.1016/S0140-6736(96)09457-3 (Pubitemid 26383772)
3. IMS Institute for Healthcare Informatics. The Use of Medicines in the United States: Review of 2010. http://www.imshealth.com/deployedfiles/imshealth/ Global/Content/IMS%20Institute/Static%20File/IHII-UseOfMed-report.pdf. Accessed September 11, 2011.
4. SR Mehta S Yusuf RJ Peters ME Bertrand BS Lewis MK Natarajan, et al. 2001 Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study Lancet 358 9281 527 33 11520521 10.1016/S0140-6736(01)05701-4 1:CAS:528:DC%2BD3MXmtV2ht7g%3D (Pubitemid 32772726)
5. S Yusuf F Zhao SR Mehta S Chrolavicius G Tognoni KK Fox 2001 Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation N Engl J Med 345 7 494 502 11519503 10.1056/NEJMoa010746 1:CAS:528:DC%2BD3MXms1arsrY%3D (Pubitemid 32758501)
6. SR Steinhubl PB Berger JT Mann 3rd ET Fry A DeLago C Wilmer, et al. 2002 Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial JAMA 288 19 2411 20 12435254 10.1001/jama.288.19.2411 1:CAS:528:DC%2BD38XoslOksL0%3D (Pubitemid 35340537)
7. MS Sabatine CP Cannon CM Gibson JL Lopez-Sendon G Montalescot P Theroux, et al. 2005 Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation N Engl J Med 352 12 1179 89 15758000 10.1056/NEJMoa050522 1:CAS:528:DC%2BD2MXisFShsbY%3D (Pubitemid 40397259)
8. ZM Chen LX Jiang YP Chen JX Xie HC Pan R Peto, et al. 2005 Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial Lancet 366 9497 1607 21 16271642 10.1016/S0140-6736(05)67660-X 1:STN:280:DC%2BD2MrptlKmtQ%3D%3D (Pubitemid 41552416)
9. SJ Connolly J Pogue RG Hart SH Hohnloser M Pfeffer S Chrolavicius, et al. 2009 Effect of clopidogrel added to aspirin in patients with atrial fibrillation N Engl J Med 360 20 2066 78 19336502 10.1056/NEJMoa0901301
10. SD Wiviott E Braunwald CH McCabe G Montalescot W Ruzyllo S Gottlieb, et al. 2007 Prasugrel versus clopidogrel in patients with acute coronary syndromes N Engl J Med 357 20 2001 15 17982182 10.1056/NEJMoa0706482 1:CAS:528: DC%2BD2sXhtlWis7rN (Pubitemid 350106708)
11. L Wallentin RC Becker A Budaj CP Cannon H Emanuelsson C Held, et al. 2009 Ticagrelor versus clopidogrel in patients with acute coronary syndromes N Engl J Med 361 11 1045 57 19717846 10.1056/NEJMoa0904327 1:CAS:528: DC%2BD1MXhtFaltL%2FJ
12. L Bonello US Tantry R Marcucci R Blindt DJ Angiolillo R Becker, et al. 2010 Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate J Am Coll Cardiol 56 12 919 33 20828644 10.1016/j.jacc.2010.04.047 1:CAS:528:DC%2BC3cXhtlWjt7jJ
13. •• Abraham NS, Hlatky MA, Antman EM, Bhatt DL, Bjorkman DJ, Clark CB et al. ACCF/ACG/AHA 2010 Expert Consensus Document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Circulation. 2010;122(24):2619-33. This reference represents the consensus recommendations from the American College of Cardiology Foundation, American Heart Association, and the American College of Gastroenterology on the concomitant use of PPIs and clopidogrel. The article thoroughly reviews the relevant literature.
14. DL Bhatt J Scheiman NS Abraham EM Antman FK Chan CD Furberg, et al. 2008 ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents J Am Coll Cardiol 52 18 1502 17 19017521 10.1016/j.jacc.2008.08.002
15. T Simon C Verstuyft M Mary-Krause L Quteineh E Drouet N Meneveau, et al. 2009 Genetic determinants of response to clopidogrel and cardiovascular events N Engl J Med 360 4 363 75 19106083 10.1056/NEJMoa0808227 1:CAS:528: DC%2BD1MXhtVSlsbY%3D
16. JL Mega SL Close SD Wiviott L Shen RD Hockett JT Brandt, et al. 2009 Cytochrome p-450 polymorphisms and response to clopidogrel N Engl J Med 360 4 354 62 19106084 10.1056/NEJMoa0809171 1:CAS:528:DC%2BD1MXhtVSlsbs%3D
17. M Gilard B Arnaud G Le Gal JF Abgrall J Boschat 2006 Influence of omeprazole on the antiplatelet action of clopidogrel associated to aspirin JTH 4 11 2508 9 16898956 1:CAS:528:DC%2BD28Xht1yjtbfJ (Pubitemid 44575451)
18. Food and Drug Administration. Early Communication about an Ongoing Safety Review of clopidogrel bisulfate (marketed as Plavix). 2009. http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/ucm079520.htm. Accessed August 31, 2011.
19. Food and Drug Administration. Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC). 2009. http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/ucm190787.htm. Accessed August 31, 2011.
20. HC Diener J Bogousslavsky LM Brass C Cimminiello L Csiba M Kaste, et al. 2004 Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial Lancet 364 9431 331 7 15276392 10.1016/S0140-6736(04)16721-4 1:CAS:528:DC%2BD2cXmtVSktbs%3D (Pubitemid 38970009)
21. PB Berger DL Bhatt V Fuster PG Steg KA Fox M Shao, et al. 2010 Bleeding complications with dual antiplatelet therapy among patients with stable vascular disease or risk factors for vascular disease: results from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial Circulation 121 23 2575 83 20516378 10.1161/CIRCULATIONAHA. 109.895342 1:CAS:528:DC%2BC3cXns1yltLc%3D
22. WA Ray KT Murray MR Griffin CP Chung WE Smalley K Hall, et al. 2010 Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study Ann Intern Med 152 6 337 45 20231564
23. FK Chan JY Ching LC Hung VW Wong VK Leung NN Kung, et al. 2005 Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding N Engl J Med 352 3 238 44 15659723 10.1056/NEJMoa042087 1:CAS:528: DC%2BD2MXmslShtA%3D%3D (Pubitemid 40110812)
24. KC Lai KM Chu WM Hui BC Wong WK Hung CK Loo, et al. 2006 Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association. 4 7 860 5 1:CAS:528:DC%2BD28XotFarsrk%3D (Pubitemid 43994542)
25. FH Ng KF Lam SY Wong CM Chang YK Lau WC Yuen, et al. 2008 Upper gastrointestinal bleeding in patients with aspirin and clopidogrel co-therapy Digestion. 77 3-4 173 7 18577887 10.1159/000141264 1:CAS:528:DC%2BD1cXhtVejtrbJ
26. •• Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363(20):1909-17. The COGENT trial is the only prospective randomized clinical trial to investigate the concomitant use of omeprazole and clopidogrel. Omeprazole use resulted in fewer GI bleeding events with no increase in ischemic events.
27. CS Kwok RS Nijjar YK Loke 2011 Effects of proton pump inhibitors on adverse gastrointestinal events in patients receiving clopidogrel: systematic review and meta-analysis Drug safety: an international journal of medical toxicology and drug experience. 34 1 47 57 10.2165/11584750-000000000-00000 1:CAS:528:DC%2BC3MXhvVGhsrc%3D
28. A Lanas LA Garcia-Rodriguez MT Arroyo L Bujanda F Gomollon M Forne, et al. 2007 Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants Am J Gastroenterol 102 3 507 15 17338735 10.1111/j.1572-0241.2006.01062.x 1:CAS:528:DC%2BD2sXkt12nt74%3D (Pubitemid 46328156)
29. PM Ho TM Maddox L Wang SD Fihn RL Jesse ED Peterson, et al. 2009 Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome JAMA. 301 9 937 44 19258584 10.1001/jama.2009.261 1:CAS:528:DC%2BD1MXivFejt7g%3D
30. K Shrestha JD Hughes YP Lee R Parsons 2011 The prevalence of co-administration of clopidogrel and proton pump inhibitors Qual Prim Care 19 1 35 42 21703110
31. S Siriswangvat N Sansanayudh S Nathisuwan D Panomvana 2010 Comparison between the effect of omeprazole and rabeprazole on the antiplatelet action of clopidogrel Circulation journal: official journal of the Japanese Circulation Society. 74 10 2187 92 10.1253/circj.CJ-09-0913 1:CAS:528:DC%2BC3cXhtlWjt7zE
32. JP Pham M Ueno A Tello-Montoliu JL Ferreiro SD Tomasello K Dharmashankar, et al. 2011 Impact of gastric Acid-suppressing therapies on platelet reactivity in patients with coronary artery disease treated with clopidogrel results of a pharmacodynamic study J Am Coll Cardiol. 58 13 1396 8 21920272 10.1016/j.jacc.2011.06.031 1:CAS:528:DC%2BC3MXhtlCgsrnE
33. M Gilard B Arnaud JC Cornily G Le Gal K Lacut G Le Calvez, et al. 2008 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. 51 3 256 60 18206732 10.1016/j.jacc.2007.06.064 1:CAS:528:DC%2BD1cXpt1Gksg%3D%3D
34. T Furuta T Iwaki K Umemura 2010 Influences of different proton pump inhibitors on the anti-platelet function of clopidogrel in relation to CYP2C19 genotypes Br J Clin Pharmacol 70 3 383 92 20716239 10.1111/j.1365-2125.2010. 03717.x 1:CAS:528:DC%2BC3cXhtFOkurrK
35. R Fontes-Carvalho A Albuquerque C Araujo P Pimentel-Nunes VG Ribeiro 2011 Omeprazole, but not pantoprazole, reduces the antiplatelet effect of clopidogrel: a randomized clinical crossover trial in patients after myocardial infarction evaluating the clopidogrel-PPIs drug interaction Eur J Gastroenterol Hepatol 23 5 396 404 21464720 10.1097/MEG.0b013e3283460110 1:CAS:528: DC%2BC3MXks1Whs74%3D
36. JL Ferreiro M Ueno D Capodanno B Desai K Dharmashankar A Darlington, et al. 2010 Pharmacodynamic effects of concomitant versus staggered clopidogrel and omeprazole intake: results of a prospective randomized crossover study Circ Cardiovasc Interv. 3 5 436 41 20858862 10.1161/CIRCINTERVENTIONS.110.957829 1:CAS:528:DC%2BC3cXhsFaiurzM
37. T Cuisset C Frere J Quilici R Poyet B Gaborit L Bali, et al. 2009 Comparison of omeprazole and pantoprazole influence on a high 150-mg clopidogrel maintenance dose the PACA (Proton Pump Inhibitors And Clopidogrel Association) prospective randomized study J Am Coll Cardiol. 54 13 1149 53 19761935 10.1016/j.jacc.2009.05.050 1:CAS:528:DC%2BD1MXht1GntbbK
38. DJ Angiolillo CM Gibson S Cheng C Ollier O Nicolas L Bergougnan, et al. 2011 Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmacokinetics of clopidogrel in healthy subjects: randomized, placebo-controlled, crossover comparison studies Clin Pharmacol Therapeut 89 1 65 74 10.1038/clpt.2010.219 1:CAS:528:DC%2BC3cXhsFylt7zP
39. P Moceri D Doyen P Cerboni E Ferrari 2011 Doubling the dose of Clopidogrel restores the loss of antiplatelet effect induced by esomeprazole Thromb Res 128 5 458 462 21777954 10.1016/j.thromres.2011.06.029 1:CAS:528:DC%2BC3MXhtl2ntrjI
40. JL Ferreiro M Ueno SD Tomasello D Capodanno B Desai K Dharmashankar, et al. 2011 Pharmacodynamic evaluation of pantoprazole therapy on clopidogrel effects: results of a prospective, randomized, crossover study Circ Cardiovasc Interv. 4 3 273 9 21521834 10.1161/CIRCINTERVENTIONS.110.960997 1:CAS:528:DC%2BC3MXpsVGksbs%3D
41. JS Hulot G Wuerzner C Bachelot-Loza M Azizi A Blanchard S Peyrard, et al. 2010 Effect of an increased clopidogrel maintenance dose or lansoprazole co-administration on the antiplatelet response to clopidogrel in CYP2C19-genotyped healthy subjects JTH 8 3 610 3 20040040 1:CAS:528: DC%2BC3cXktF2hsb4%3D
42. DS Small NA Farid CD Payne GJ Weerakkody YG Li JT Brandt, et al. 2008 Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel J Clin Pharmacol 48 4 475 84 18303127 10.1177/0091270008315310 1:CAS:528:DC%2BD1cXkslKntLk%3D (Pubitemid 351389118)
43. ML O'Donoghue E Braunwald EM Antman SA Murphy ER Bates Y Rozenman, et al. 2009 Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials Lancet. 374 9694 989 97 19726078 10.1016/S0140-6736(09)61525-7
44. RF Storey DJ Angiolillo SB Patil B Desai R Ecob S Husted, et al. 2010 Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes: the PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy J Am Coll Cardiol. 56 18 1456 62 20832963 10.1016/j.jacc.2010.03.100 1:CAS:528:DC%2BC3cXhsFyhur%2FO
45. • Kwok CS, Loke YK. Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel. Alimentary pharmacology & therapeutics. 2010;31(8):810-23. This reference contains a meta-analysis of 23 studies investigating the clinical impact of a clopidogrel-PPI interaction. Concomitant use of PPIs and clopidogrel is not associated with increased cardiovascular risk in studies that either employ propensity matching or use data from randomized clinical trials, whereas there is increased risk in other observational studies.
46. JM Siller-Matula B Jilma K Schror G Christ K Huber 2010 Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and meta-analysis JTH 8 12 2624 41 20831618 1:STN:280:DC%2BC3M%2FitlGlug%3D%3D
47. • Banerjee S, Weideman RA, Weideman MW, Little BB, Kelly KC, Gunter JT et al. Effect of concomitant use of clopidogrel and proton pump inhibitors after percutaneous coronary intervention. Am J Cardiol. 2011;107(6):871-8. This observational study of 23,200 patients employs propensity matching and accounts for whether or not subjects continuously took PPIs and/or clopidogrel. After propensity matching, there was no associated increase in cardiovascular risk with concomitant use of PPIs and clopidogrel.
48. D Grady SM Rubin DB Petitti CS Fox D Black B Ettinger, et al. 1992 Hormone therapy to prevent disease and prolong life in postmenopausal women Ann Intern Med. 117 12 1016 37 1443971 1:STN:280:DyaK3s%2FntlensQ%3D%3D
49. DM Herrington 2003 Hormone replacement therapy and heart disease: replacing dogma with data Circulation. 107 1 2 4 12515732 10.1161/01.CIR. 0000048891.81129.2D (Pubitemid 36070922)
50. Dunn SP, Macaulay TE, Brennan DM, Campbell CL, Charnigo R, Smyth S et al. Baseline proton pump inhibitor use is associated with increased cardiovascular events with and without the use of clopidogrel in the CREDO trial. Circulation. 2008;118:S-815.
51. • Goodman S, Clare R, Pieper K, James S, Nicolau JC, Storey RF et al. Proton Pump Inhibitor Use is Likely a Marker for, Rather than a Cause of, a Higher Risk of Cardiovascular Events: Insights from PLATO Circulation. 2010;122:A12092. This authors of this abstract used data from the PLATO trial to demonstrate that PPI use is associated with increased cardiovascular risk regardless of whether patients were taking clopidogrel or ticagrelor. Knowledge that ticagrelor does require activiation by the cytochrome P450 system, and thus should not be affected by PPI use, allows the authors to conclude that PPI use is not a cause of cardiovascular events in patients taking clopidogrel or ticagrelor.
52. Garcia Rodriguez LA, ed. Concomitant use of clopidogrel and proton pump inhibitors is not associated with an increased risk of coronary events. European Society of Cardiology Congress; 2011; Paris, France.
53. A Gaspar S Ribeiro S Nabais S Rocha P Azevedo MA Pereira, et al. 2010 Proton pump inhibitors in patients treated with aspirin and clopidogrel after acute coronary syndrome Portuguese journal of cardiology: an official journal of the Portuguese Society of Cardiology. 29 10 1511 20
54. DN Juurlink T Gomes MM Mamdani DJ Gladstone MK Kapral 2011 The safety of proton pump inhibitors and clopidogrel in patients after stroke Stroke. 42 1 128 32 21164123 10.1161/STROKEAHA.110.596643 1:CAS:528:DC%2BC3MXhtlOitL4%3D
55. JF Munoz-Torrero D Escudero C Suarez C Sanclemente MT Pascual J Zamorano, et al. 2011 Concomitant use of proton pump inhibitors and clopidogrel in patients with coronary, cerebrovascular, or peripheral artery disease in the factores de Riesgo y ENfermedad Arterial (FRENA) registry J Cardiovasc Pharmacol. 57 1 13 9 21164357 10.1097/FJC.0b013e3181fc65e5 1:CAS:528: DC%2BC3MXlsFSjsQ%3D%3D
56. Ortolani P, Marino M, Marzocchi A, De Palma R, Branzi A. One-year clinical outcome in patients with acute coronary syndrome treated with concomitant use of clopidogrel and proton pump inhibitors: results from a regional cohort study. Journal of cardiovascular medicine (Hagerstown, Md). Jan 19, 2011.
57. R Rossini D Capodanno G Musumeci C Lettieri N Lortkipanidze M Romano, et al. 2011 Safety of clopidogrel and proton pump inhibitors in patients undergoing drug-eluting stent implantation Coron Artery Dis. 22 3 199 205 21358542 10.1097/MCA.0b013e328343b03a
58. OS van Boxel MG van Oijen MP Hagenaars AJ Smout PD Siersema 2010 Cardiovascular and gastrointestinal outcomes in clopidogrel users on proton pump inhibitors: results of a large Dutch cohort study Am J Gastroenterol 105 11 2430 6 20736935 10.1038/ajg.2010.334
59. M Charlot O Ahlehoff ML Norgaard CH Jorgensen R Sorensen SZ Abildstrom, et al. 2010 Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study Ann Intern Med. 153 6 378 86 20855802
60. KJ Harjai C Shenoy P Orshaw S Usmani J Boura RH Mehta 2011 Clinical outcomes in patients with the concomitant use of clopidogrel and proton pump inhibitors after percutaneous coronary intervention: an analysis from the Guthrie Health Off-Label Stent (GHOST) investigators Circ Cardiovasc Interv. 4 2 162 70 21386091 10.1161/CIRCINTERVENTIONS.110.958884 1:CAS:528: DC%2BC3MXnsVSksrY%3D
61. Hsiao FY, Mullins CD, Wen YW, Huang WF, Chen PF, Tsai YW. Relationship between cardiovascular outcomes and proton pump inhibitor use in patients receiving dual antiplatelet therapy after acute coronary syndrome. Pharmacoepidemiology and drug safety. 2011.
62. T Simon PG Steg M Gilard D Blanchard L Bonello M Hanssen, et al. 2011 Clinical events as a function of proton pump inhibitor use, clopidogrel use, and cytochrome P450 2 C19 genotype in a large nationwide cohort of acute myocardial infarction: results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) registry Circulation. 123 5 474 82 21262992 10.1161/CIRCULATIONAHA.110.965640 1:CAS:528:DC%2BC3MXhs1Sgs7Y%3D
63. I Tentzeris R Jarai S Farhan I Brozovic P Smetana A Geppert, et al. 2010 Impact of concomitant treatment with proton pump inhibitors and clopidogrel on clinical outcome in patients after coronary stent implantation Thromb haemostasis. 104 6 1211 8 10.1160/TH10-04-0218 1:CAS:528:DC%2BC3MXht1aks7Y%3D