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

American Journal of Gastroenterology

Volumn 105, Issue 12, 2010, Pages 2533-2549

  Abraham, Neena S ^a   Hlatky, Mark A ^a   Antman, Elliott M ^a   Bhatt, Deepak L ^a   Bjorkman, David J ^a   Clark, Craig B ^a   Furberg, Curt D ^a   Johnson, David A ^a   Kahi, Charles J ^a   Laine, Loren ^a   Mahaffey, Kenneth W ^a   Quigley, Eamonn M ^a   Scheiman, James ^a   Sperling, Laurence S ^a   Tomaselli, Gordon F ^a  

^a NONE

Author keywords

ACCF Expert Consensus Document antiplatelet drugs; aspirin; gastrointestinal hemorrhage; platelet aggregation inhibitors; proton pump inhibitors; thienopyridine

Indexed keywords

ACETYLSALICYLIC ACID; CLOPIDOGREL; HISTAMINE H2 RECEPTOR ANTAGONIST; PLACEBO; PRASUGREL; PROTON PUMP INHIBITOR; THIENOPYRIDINE DERIVATIVE; TICAGRELOR;

CARDIOVASCULAR DISEASE; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; EXPERT SYSTEM; GASTROINTESTINAL HEMORRHAGE; GENETIC POLYMORPHISM; HUMAN; MEDICAL SOCIETY; MORTALITY; OUTCOME ASSESSMENT; PRIORITY JOURNAL; REVIEW; RISK BENEFIT ANALYSIS; RISK REDUCTION;

ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ARYL HYDROCARBON HYDROXYLASES; ASPIRIN; CARDIOVASCULAR DISEASES; DRUG INTERACTIONS; DRUG THERAPY, COMBINATION; GASTROINTESTINAL HEMORRHAGE; HISTAMINE H2 ANTAGONISTS; HUMANS; PIPERAZINES; PLATELET AGGREGATION INHIBITORS; PROTON PUMP INHIBITORS; PURINERGIC P2Y RECEPTOR ANTAGONISTS; RISK FACTORS; THIENOPYRIDINES; THIOPHENES; TICLOPIDINE;

EID: 78649823909     PISSN: 00029270     EISSN: 15720241     Source Type: Journal    
DOI: 10.1038/ajg.2010.445     Document Type: Review

References (97)

1. 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;52:1502-17.
2. Public Health Advisory: Updated safety information about a drug interaction between Clopidogrel Bisulfate (marketed as Plavix) and Omeprazole (marketed as Prilosec and Prilosec OTC) http://www.fda.gov/Drugs/Drug- Safety/PublicHealthAdvisories/ucm190825.htm Accessed May 28, 2010.
3. 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.
4. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005;352:1179-89.
5. Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebocontrolled trial. Lancet 2005;366:1607-21.
6. King SB III, Smith SC Jr., Hirshfeld JW Jr. et al. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice guidelines. J Am Coll Cardiol 2008;51:172-209.
7. Connolly SJ, Pogue J, Hart RG, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009;360:2066-78.
8. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-39.
9. Smith SC Jr., Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update. J Am Coll Cardiol 2006;47:2130-9.
10. Anderson JL, Adams CD, Antman EM, et al. 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/ American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction). J Am Coll Cardiol 2007;50:e1-157.
11. Fraker TD Jr., Fihn SD, Gibbons RJ, et al. 2007 chronic angina focused update of the ACC/AHA 2002 guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Group to Develop the Focused Update of the 2002 Guidelines for the Management of Patients With Chronic Stable Angina). J Am Coll Cardiol 2007;50:2264-74.
12. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary: a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease). J Am Coll Cardiol 2006;47:1239-312.
13. Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006;354:1706-17.
14. Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, doubleblind, placebo-controlled trial. Lancet 2004;364:331-7.
15. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-15.
16. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-57.
17. Adams RJ, Albers G, Alberts MJ, et al. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke 2008;39:1647-52.
18. Taha AS, McCloskey C, Prasad R, et al. 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;374:119-25.
19. Van HA, Depre M, Wynants K, et al. Effect of clopidogrel on naproxen-induced gastrointestinal blood loss in healthy volunteers. Drug Metabol Drug Interact 1998;14:193-205.
20. Wysota BA, Gorard DA. Colonic carcinoma unmasked by dual antiplatelet therapy. Eur J Intern Med 2008;19:558
21. Spaziani E, Stagnitti F, Iozzino M, et al. [Massive lower gastrointestinal bleeding due to diverticular disease during antiplatelet therapy. Case report]. G Chir 2007;28:428-31.
22. De Palma GD, Salvatori F, Masone S, et al. Acute gastrointestinal bleeding following aortic valve replacement in a patient with Heyde's sindrome. Case report. Minerva Gastroenterol Dietol 2007;53:291-3.
23. Caruana JA, McCabe MN, Smith AD, et al. Risk of massive upper gastrointestinal bleeding in gastric bypass patients taking clopidogrel. Surg Obes Relat Dis 2007;3:443-5.
24. Nelson RS, Thorson AG. Risk of bleeding following hemorrhoidal banding in patients on antithrombotic therapy. Gastroenterol Clin Biol 2009;33:463-5.
25. Nelson RS, Ewing BM, Ternent C, et al. Risk of late bleeding following hemorrhoidal banding in patients on antithrombotic prophylaxis. Am J Surg 2008;196:994-9.
26. Hui AJ, Wong RM, Ching JY, et al. Risk of colonoscopic polypectomy bleeding with anticoagulants and antiplatelet agents: analysis of 1657 cases. Gastrointest Endosc 2004;59:44-8.
27. Singh M, Mehta N, Murthy UK, et al. Postpolypectomy bleeding in patients undergoing colonoscopy on uninterrupted clopidogrel therapy. Gastrointest Endosc 2010;71:998-1005.
28. 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;160:2093-9.
29. 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;43:679-86.
30. Ng FH, Lam KF, Wong SY, et al. Upper gastrointestinal bleeding in patients with aspirin and clopidogrel co-therapy. Digestion 2008;77:173-7.
31. 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;103:865-71.
32. 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;42:368-72.
33. 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;28:1936-45.
34. Nikolsky E, Mehran R, Turcot D, et al. Impact of chronic kidney disease on prognosis of patients with diabetes mellitus treated with percutaneous coronary intervention. Am J Cardiol 2004;94:300-5.
35. Nikolsky E, Mehran R. Understanding the consequences of contrastinduced nephropathy. Rev Cardiovasc Med 2003;5:S10-8.
36. 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;152:337-45.
37. Moukarbel GV, Signorovitch JE, Pfeffer MA, et al. Gastrointestinal bleeding in high risk survivors of myocardial infarction: the VALIANT Trial. Eur Heart J 2009;30:2226-32.
38. Abbas AE, Brodie B, Dixon S, et al. Incidence and prognostic impact of gastrointestinal bleeding after percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2005;96:173-6.
39. Fork FT, Lafolie P, Toth E, et al. Gastroduodenal tolerance of 75 mg clopidogrel versus 325 mg aspirin in healthy volunteers. A gastroscopic study. Scand J Gastroenterol 2000;35:464-9.
40. Abraham NS, Graham DY. NSAIDs and gastrointestinal complications: new clinical challenges. Expert Opin Pharmacother 2005;6:2681-9.
41. Ma L, Elliott SN, Cirino G, et al. Platelets modulate gastric ulcer healing: role of endostatin and vascular endothelial growth factor release. Proc Natl Acad Sci USA 2001;98:6470-5.
42. Jones DB, Howden CW, Burget DW, et al. Acid suppression in duodenal ulcer: a meta-analysis to define optimal dosing with antisecretory drugs. Gut 1987;28:1120-7.
43. Howden CW, Hunt RH. The relationship between suppression of acidity and gastric ulcer healing rates. Aliment Pharmacol Ther 1990;4:25-33.
44. Lanas A, Garcia-Rodriguez LA, Arroyo MT, et al. 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 2007;102:507-15.
45. Laine L, Hennekens C. Proton pump inhibitor and clopidogrel interaction: fact or fiction?. Am J Gastroenterol 2010;105:34-41.
46. Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010;.
47. Gurbel PA, Antonino MJ, Tantry US. Recent developments in clopidogrel pharmacology and their relation to clinical outcomes. Expert Opin Drug Metab Toxicol 2009;5:989-1004.
48. Kazui M, Nishiya Y, Ishizuka T, et al. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 2010;38:92-9.
49. Farid NA, Payne CD, Small DS, et al. Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin Pharmacol Ther 2007;81:735-41.
50. Hagihara K, Nishiya Y, Kurihara A, et al. Comparison of human cytochrome P450 inhibition by the thienopyridines prasugrel, clopidogrel, and ticlopidine. Drug Metab Pharmacokinet 2008;23:412-20.
51. Farid NA, Kurihara A, Wrighton SA. Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans. J Clin Pharmacol 2010;50:126-42.
52. Ma TK, Lam YY, Tan VP, et al. Impact of genetic and acquired alteration in cytochrome P450 system on pharmacologic and clinical response to clopidogrel. Pharmacol Ther 2010;125:249-59.
53. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354-62.
54. Mega JL, Close SL, Wiviott SD, et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 2009;119:2553-60.
55. Husted S, van Giezen JJ. Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist. Cardiovasc Ther 2009;27:259-74.
56. Capodanno D, Dharmashankar K, Angiolillo DJ. Mechanism of action and clinical development of ticagrelor, a novel platelet ADP P2Y12 receptor antagonist. Expert Rev Cardiovasc Ther 2010;8:151-8.
57. Chen XP, Tan ZR, Huang SL, et al. Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects. Clin Pharmacol Ther 2003;73:264-71.
58. Feldman M, Burton ME. Histamine2-receptor antagonists. Standard therapy for acid-peptic diseases. N Engl J Med 1990;323:1672-80.
59. Rendic S. Drug interactions of H2-receptor antagonists involving cytochrome P450 (CYPs) enzymes: from the laboratory to the clinic. Croat Med J 1999;40:357-67.
60. Welage LS. Overview of pharmacologic agents for acid suppression in critically ill patients. Am J Health Syst Pharm 2005;62:S4-S10.
61. Martinez C, Albet C, Agundez JA, et al. Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2- receptor antagonists. Clin Pharmacol Ther 1999;65:369-76.
62. Wolfe MM, Sachs G. Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology 2000;118:S9-31.
63. Small DS, Farid NA, Li YG, et al. Effect of ranitidine on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. Curr Med Res Opin 2008;24:2251-7.
64. Shi S, Klotz U. Proton pump inhibitors: an update of their clinical use and pharmacokinetics. Eur J Clin Pharmacol 2008;64:935-51.
65. Ishizaki T, Horai Y. Review article: cytochrome P450 and the metabolism of proton pump inhibitors-emphasis on rabeprazole. Aliment Pharmacol Ther 1999;3:27-36.
66. Roden DM, Stein CM. Clopidogrel and the concept of high-risk pharmacokinetics. Circulation 2009;119:2127-30.
67. Nguyen T, Frishman WH, Nawarskas J, et al. Variability of response to clopidogrel: possible mechanisms and clinical implications. Cardiol Rev 2006;14:136-42.
68. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009;360:363-75.
69. Gladding P, Webster M, Zeng I, et al. The pharmacogenetics and pharmacodynamics of clopidogrel response: an analysis from the PRINC (Plavix Response in Coronary Intervention) trial. J Am Coll Cardiol Intv 2008;1:620-7.
70. Mehta SR, Bassand JP, Chrolavicius S, et al. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med 2010;363:930-42.
71. Luo HR, Poland RE, Lin KM, et al. Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: a cross-ethnic comparative study. Clin Pharmacol Ther 2006;80:33-40.
72. 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;302:849-57.
73. Bhatt DL. Tailoring antiplatelet therapy based on pharmacogenomics: how well do the data fit?. JAMA 2009;302:896-7.
74. 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;281:604-9.
75. Takakubo F, Kuwano A, Kondo I. Evidence that poor metabolizers of (S)- mephenytoin could be identified by haplotypes of CYP2C19 in Japanese. Pharmacogenetics 1996;6:265-7.
76. Bhatt DL. What makes platelets angry: diabetes, fibrinogen, obesity, and impaired response to antiplatelet therapy?. J Am Coll Cardiol 2008;52:1060-1.
77. Hochholzer W, Trenk D, Fromm MF, et al. Impact of cytochrome P450 2C19 loss-of-function polymorphism and of major demographic characteristics on residual platelet function after loading and maintenance treatment with clopidogrel in patients undergoing elective coronary stent placement. J Am Coll Cardiol 2010;55:2427-34.
78. 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.
79. 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;54:1149-53.
80. O'Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a protonpump inhibitor: an analysis of two randomised trials. Lancet 2009;374:989-97.
81. Siller-Matula JM, Spiel AO, Lang IM, et al. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J 2009;157:148-5.
82. Evaluation of the influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects (SPICE) http://clinicaltrials.gov/ct2/show/ NCT00930670 Accessed March 31, 2010.
83. Dunn SP, Macaulay TE, Brennan DM, et al. Baseline proton pump inhibitor use is associated with increased cardiovascular events with and without use of clopidogrel in the CREDO trial. Circulation 2008;118:S815 Abstract
84. Sibbing D, Morath T, Stegherr J, et al. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost 2009;101:714-9.
85. 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.
86. Stockl KM, Le L, Zakharyan A, et al. Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor. Arch Intern Med 2010;170:704-10.
87. 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;301:937-44.
88. Rassen JA, Choudhry NK, Avorn J, et al. Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome. Circulation 2009;120:2322-9.
89. NDA 20-839 S-044. Plavix label http://www.accessdata.fda.gov/drugsatfda- docs/label/2009/020839s044lbl.pdf Accessed May 28, 2010 .
90. Hill AB. The environment and disease: association or causation?. Proc R Soc Med 1965;58:295-300.
91. Sung JJ, Lau JY, Ching JY, et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Ann Intern Med 2010;152:1-9.
92. Rostom A, Dube C, Wells G, et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev 2002;.
93. Lanas A, Garcia-Rodriguez LA, Arroyo MT, et al. 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 2007;102:507-15.
94. 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;138:82-8.
95. Yeomans ND, Tulassay Z, Juhasz L, et al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAIDassociated Ulcer Treatment (ASTRONAUT) Study Group. N Engl J Med 1998;338:719-26.
96. Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med 2005;352:238-44.
97. Lai KC, Chu KM, Hui WM, et al. Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications. Clin Gastroenterol Hepatol 2006;4:860-5.