Prescribing proton pump inhibitor and clopidogrel together: Current state of recommendations

Current Opinion in Gastroenterology

Volumn 27, Issue 6, 2011, Pages 558-564

  Abraham, Neena S ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

antiplatelets; cardiac patients; clinical practice recommendations; consensus statement documents; gastrointestinal bleeding risk prevention; proton pump inhibitors; thienopyridine

Indexed keywords

ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; CARDIOVASCULAR AGENT; CLOPIDOGREL; OMEPRAZOLE; WARFARIN;

ACUTE CORONARY SYNDROME; ANTIPHOSPHOLIPID SYNDROME; BARE METAL STENT; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG METABOLISM; GASTROINTESTINAL HEMORRHAGE; GENETIC VARIABILITY; HEART ATRIUM FIBRILLATION; HEART INFARCTION; HIGH RISK PATIENT; HUMAN; INTRACARDIAC THROMBOSIS; MONOTHERAPY; MORTALITY; PHARMACOGENOMICS; POINT OF CARE TESTING; PRESCRIPTION; REVIEW; RISK; THROMBOEMBOLISM; UNSTABLE ANGINA PECTORIS;

DRUG INTERACTIONS; DRUG PRESCRIPTIONS; DRUG THERAPY, COMBINATION; GASTROINTESTINAL HEMORRHAGE; HUMANS; OMEPRAZOLE; PLATELET AGGREGATION INHIBITORS; PRACTICE GUIDELINES AS TOPIC; PROTON PUMP INHIBITORS; RISK ASSESSMENT; RISK FACTORS; TICLOPIDINE;

EID: 80054690540     PISSN: 02671379     EISSN: 15317056     Source Type: Journal    
DOI: 10.1097/MOG.0b013e32834a382e     Document Type: Review

References (68)

1. Bhatt DL, Steg PG, Ohman EM, et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006;295:180-189. (Pubitemid 43076437)
2. Cannon CP, Rhee KE, Califf RM, et al. Current use of aspirin and antithrombotic agents in the United States among outpatients with atherothrombotic disease (from the REduction of Atherothrombosis for Continued Health [REACH] Registry). Am J Cardiol 2010;105:445-452.
3. Abraham NS, Hlatky MA, Antman EM, 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. J Am Coll Cardiol 2010;56:2051-2066. This multidisciplinary consensus document provides physicians with the expert opinions of the ACCF, ACG and AHA on this evolving area of clinical practice. This document critically reviews the science and provides pragmatic guidance for clinical management.
4. Weil J, Colin-Jones D, Langman M, et al. Prophylactic aspirin and risk of peptic ulcer bleeding. BMJ 1995;310:827-830.
5. Current OASIS 7 Investigators, Mehta SR, Bassand JP, et al. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med 2010;363:930-942. This study provides evidence that doubling dose of clopidogrel improves cardiac outcomes in post-PCI group, but at the cost of increasing major bleeding.
6. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 2004;110:e82-e292.
7. Boersma E, Mercado N, Poldermans D, et al. Acute myocardial infarction. Lancet 2003;361:847-858. (Pubitemid 36331851)
8. Hirsh J, Fuster V, Ansell J, Halperin JL American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation 2003;107:1692-1711. (Pubitemid 36397341)
9. Andreotti F, Testa L, Biondi-Zoccai GG, Crea F. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25 307 patients. Eur Heart J 2006;27:519-526.
10. Becker RC, Scheiman J, Dauerman HL, et al. Management of platelet-directed pharmacotherapy in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal procedures. J Am Coll Cardiol 2009;54:2261-2276. This study provides a thorough review of dual-antiplatelet therapy and the risk associated with elective gastrointestinal procedures, discussing the benefit of antiplatelet therapy, thrombotic risk associated with antiplatelet therapy cessation and gastrointestinal procedural bleeding risk. This document also provides a practical approach to management.
11. Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction. A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol 2011;57:e215-e367.
12. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502. (Pubitemid 32758501)
13. Connolly SJ, Pogue J, Hart RG, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009;360:2066-2078.
14. Berger PB, Bhatt DL, Fuster V, et al. 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 2010;121:2575-2583. This study highlights the increased risk of gastrointestinal bleeding associated with dual-antiplatelet therapy.
15. Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med 2005;352:238-244. (Pubitemid 40110812)
16. Hsiao FY, Tsai YW, Huang WF, et al. A comparison of aspirin and clopidogrel with or without proton pump inhibitors for the secondary prevention of cardiovascular events in patients at high risk for gastrointestinal bleeding. Clin Ther 2009;31:2038-2047.
17. Lanas A, Garcia-Rodriguez LA, Arroyo MT, et al. Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal antiinflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol 2007;102:507-515. (Pubitemid 46328156)
18. Ng FH, Wong SY, Lam KF, et al. Gastrointestinal bleeding in patients receiving a combination of aspirin, clopidogrel, and enoxaparin in acute coronary syndrome. Am J Gastroenterol 2008;103:865-871.
19. Bhatt DL, Scheiman J, Abraham NS, et al. 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 2008;52:1502-1517.
20. Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009;180:713-718.
21. Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009;301:937-944.
22. Gupta E, Bansal D, Sotos J, Olden K. Risk of adverse clinical outcomes with concomitant use of clopidogrel and proton pump inhibitors following percutaneous coronary intervention. Dig Dis Sci 2010;55:1964-1968.
23. Gaglia MA Jr, Torguson R, Hanna N, et al. Relation of proton pump inhibitor use after percutaneous coronary intervention with drug-eluting stents to outcomes. Am J Cardiol 2010;105:833-838.
24. Stockl KM, Le L, Zakharyan A, et al. Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor. Arch Intern Med 2010;170:704-710.
25. 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;51:256-260.
26. Siller-Matula JM, Spiel AO, Lang IM, et al. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J 2009;157:148-155.
27. Dunn SP, Macaulay TE, Brennan DM, 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:S815.
28. Gilard M, Arnaud B, Le GG, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated to aspirin. J Thromb Haemost 2006;4:2508-2509. (Pubitemid 44575451)
29. U. S. Food and Drug Administration. Information on Clopidogrel Bisulfate (marketed as Plavix). 2010. http://www.fda.gov/Drugs/DrugSafety/Postmar ketDrugSafetyInformationforPatientsandProviders/ucm190836.htm. [Accessed 27 October 2010]
30. Tantry US, Kereiakes DJ, Gurbel PA. Clopidogrel and proton pump inhibitors: influence of pharmacological interactions on clinical outcomes and mechanistic explanations. JACC Cardiovasc Interv 2011;4:365-380. This study provides an excellent overview of the evidence regarding a potential PPI-clopidogrel interaction.
31. Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C1 9 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet 2009;373:309-317.
32. Pezalla E, Day D, Pulliadath I. Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors. J Am Coll Cardiol 2008;52:1038-1039.
33. Ray WA, Murray KT, Griffin MR, et al. Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. Ann Intern Med 2010;152:337-345.
34. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009;360:363-375.
35. Kwok CS, Loke YK. Meta-analysis: effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel. Aliment Pharmacol Ther 2010;31:810-823.
36. Siller-Matula JM, Jilma B, Schror K, et al. Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and meta-analysis. J Thromb Haemost 2010;8:2624-2641.
37. van Boxel OS, van Oijen MG, Hagenaars MP, et al. Cardiovascular and gastrointestinal outcomes in clopidogrel users on proton pump inhibitors: results of a large Dutch cohort study. Am J Gastroenterol 2010;105:2430-2436.
38. Rassen JA, Choudhry NK, Avorn J, Schneeweiss S. Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome. Circulation 2009;120:2322-2329.
39. Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010;363:1909-1917. This is the only published randomized controlled trial (to date) specifically designed to assess the clinical occurrence of gastrointestinal bleeding and cardiovascular events associated with the concomitant prescription of clopidogrel and PPIs in patients prescribed dual-antiplatelet therapy. Study results suggest no clinically significant harmful interaction between omeprazole and clopidogrel on cardiovascular outcomes. Findings also quantify the reduction in gastrointestinal bleeding risk associated with PPI co-prescription.
40. Brandt JT, Close SL, Iturria SJ, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost 2007;5:2429-2436. (Pubitemid 350154353)
41. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354-362.
42. Shuldiner AR, O'Connell JR, Bliden KP, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 2009;302:849-857.
43. Luo HR, Poland RE, Lin KM, Wan YJ. Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: a cross-ethnic comparative study. Clin Pharmacol Ther 2006;80:33-40. (Pubitemid 43946839)
44. Xiao ZS, Goldstein JA, Xie HG, et al. Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele. J Pharmacol Exp Ther 1997;281:604-609. (Pubitemid 27203121)
45. Takakubo F, Kuwano A, Kondo I. Evidence that poor metabolizers of (S) - mephenytoin could be identified by haplotypes of CYP2C19 in Japanese. Pharmacogenetics 1996;6:265-267. (Pubitemid 26226321)
46. Breet NJ, van Werkum JW, Bouman HJ, et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA 2010;303:754-762.
47. Price MJ, Berger PB, Teirstein PS, et al. Standard-vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011;305:1097-1105.
48. Patti G, Pasceri V, Vizzi V, et al. Usefulness of platelet response to clopidogrel by point-of-care testing to predict bleeding outcomes in patients undergoing percutaneous coronary intervention (from the Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Bleeding Study). Am J Cardiol 2011;107:995-1000.
49. Sibbing D, Morath T, Stegherr J, et al. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost 2009;101:714-719.
50. Furuta T, Iwaki T, Umemura K. Influences of different proton pump inhibitors on the antiplatelet function of clopidogrel in relation to CYP2C19 genotypes. Br J Clin Pharmacol 2010;70:383-392.
51. Cuisset T, Frere C, Quilici J, et al. 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 2009;54:1149-1153.
52. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-1057.
53. Steinhubl SR, Berger PB, Mann JT III, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;288:2411-2420. (Pubitemid 35340537)
54. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-2015. (Pubitemid 350106708)
55. Hernandez-Diaz S, Rodriguez LA. Association between nonsteroidal antiinflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s. Arch Intern Med 2000;160:2093-2099. (Pubitemid 30482713)
56. Abraham NS, Hartman C, Castillo D, et al. Effectiveness of national provider prescription of PPI gastroprotection among elderly NSAID users. Am J Gastroenterol 2008;103:323-332. (Pubitemid 351248716)
57. Hansen JM, Hallas J, Lauritsen JM, Bytzer P. Nonsteroidal anti-inflammatory drugs and ulcer complications: a risk factor analysis for clinical decisionmaking. Scand J Gastroenterol 1996;31:126-130. (Pubitemid 26047042)
58. Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A metaanalysis. Ann Intern Med 1991;115:787-796.
59. Nikolsky E, Mehran R, Dangas G, et al. Development and validation of a prognostic risk score for major bleeding in patients undergoing percutaneous coronary intervention via the femoral approach. Eur Heart J 2007;28:1936-1945. (Pubitemid 47579535)
60. Lanas A, Fuentes J, Benito R, et al. Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. Aliment Pharmacol Ther 2002;16:779-786. (Pubitemid 34407526)
61. Stack WA, Atherton JC, Hawkey GM, et al. Interactions between Helicobacter pylori and other risk factors for peptic ulcer bleeding. Aliment Pharmacol Ther 2002;16:497-506. (Pubitemid 34214529)
62. Yeomans ND, Lanas AI, Talley NJ, et al. Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin. Aliment Pharmacol Ther 2005;22:795-801. (Pubitemid 41564359)
63. Dall M, Schaffalitzky de Muckadell OB, Lassen AT, et al. An association between selective serotonin reuptake inhibitor use and serious upper gastrointestinal bleeding. Clin Gastroenterol Hepatol 2009;7:1314-1321.
64. Ng FH, Chan P, Kwanching CP, et al. Management and outcome of peptic ulcers or erosions in patients receiving a combination of aspirin plus clopidogrel. J Gastroenterol 2008;43:679-686.
65. Ng FH, Lam KF, Wong SY, et al. Upper gastrointestinal bleeding in patients with aspirin and clopidogrel co-therapy. Digestion 2008;77:173-177.
66. Barada K, Karrowni W, Abdallah M, et al. Upper gastrointestinal bleeding in patients with acute coronary syndromes: clinical predictors and prophylactic role of proton pump inhibitors. J Clin Gastroenterol 2008;42:368-372. (Pubitemid 351450621)
67. Taha AS, McCloskey C, Prasad R, Bezlyak V. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): a phase III, randomised, double-blind, placebo-controlled trial. Lancet 2009;374:119-125.
68. Ng FH, Wong SY, Lam KF, et al. Famotidine is inferior to pantoprazole in preventing recurrence of aspirin-related peptic ulcers or erosions. Gastroenterology 2010;138:82-88.