Aspirin and omeprazole for secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers

References

• World Health Organization. 2016. http://www.who.int/
   Google Scholar
• Patrono C, García Rodríguez LA, Landolfi R, et al. Low dose aspirin for the prevention of atherothrombosis. N Engl J Med. 2005;353:49–59.
   Web of Science ®Google Scholar
• Casado-Arroyo R, Bayrak F, Sarkozy A, et al. Role of ASA in the primary and secondary prevention of cardiovascular events. Best Pract Res Clin Gastroenterol. 2012;26(2):113–123.
   PubMed Web of Science ®Google Scholar
• Sostres C, Lanas A. Epidemiology of low dose aspirin damage in the lower gastrointestinal tract. Curr Pharm Des. 2015;21(35):5094–5100.
   PubMed Web of Science ®Google Scholar
• Sostres C, Lanas A. Gastrointestinal effects of aspirin. Nat Rev Gastroenterol Hepatol. 2011;8(7):385–394.
   PubMed Web of Science ®Google Scholar
• Bhatt DL, Scheiman J, Abraham NS, et al. American College of Cardiology Foundation Task Force on clinical expert consensus documents. 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. Circulation. 2008;118(18):1894–1909.
   PubMed Web of Science ®Google Scholar
• Casado-Arroyo R, Sostres C, Lanas A. Optimizing the use of aspirin for cardiovascular prevention. Drugs. 2013;73(8):803–814.
   PubMed Web of Science ®Google Scholar
• Baigent C, Blackwell L, Collins R, et al. Antithrombotic trialists’ (ATT) collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849.
   PubMed Web of Science ®Google Scholar
• Bibbins-Domingo K. U.S. Preventive services task force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive services task force recommendation statement. Ann Intern Med. 2016;164(12):836–845.
   PubMed Web of Science ®Google Scholar
• Mora S, Ames JM, Manson JE. Low-dose aspirin in the primary prevention of cardiovascular disease: shared decision making in clinical practice. Jama. 2016;316(7):709–710.
   PubMed Web of Science ®Google Scholar
• Casado-Arroyo R, Lanas A, Brugada P. A balanced view of efficacy and safety of aspirin in cardiovascular diseases. Curr Pharm Des. 2015;21(35):5101–5107.
   PubMed Web of Science ®Google Scholar
• Antithrombotic Trialists Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high-risk patients. Bmj. 2002;324:71–86.
   PubMed Web of Science ®Google Scholar
• Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124:2458–2473.
   PubMed Web of Science ®Google Scholar
• Kernan WN, Ovbiagele B, Black HR, et al. American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160–2236.
   PubMed Web of Science ®Google Scholar
• Berger JS, Brown DL, Becker RC. Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis. Am J Med. 2008;121:43–49.
   PubMed Web of Science ®Google Scholar
• British Cardiac S, British Hypertension S, Diabetes UK, et al. Primary care cardiovascular S, Stroke A. JBS 2: Joint British Societies’ guidelines on prevention of cardiovascular disease in clinical practice. Heart. 2005;91(Suppl 5):v1–52.
   PubMedGoogle Scholar
• Perk J, De Backer G, Gohlke H, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012): the Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Atherosclerosis. 2012;223(1):1–68.
   PubMed Web of Science ®Google Scholar
• Weisman SM, Graham DY. Evaluation of the benefits and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events. Arch Intern Med. 2002;162(19):2197–2202.
   PubMedGoogle Scholar
• Peters RJG, Mehta SR, Fox KAA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes. Observations from the clopidogrel in unstable angina to prevent recurrent events (CURE) study. Circulation. 2003;108:1682–1687.
   PubMed Web of Science ®Google Scholar
• Held C, Asenblad N, Bassand JP, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery bypass surgery: results from the PLATO (Platelet Inhibition and patient outcomes) trial. J Am Coll Cardiol. 2011;57:672–684.
   PubMed Web of Science ®Google Scholar
• Wiviott SD, Braunwald E, McCabe CH, et al. TRITON-TIMI 38 investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–2015.
   PubMed Web of Science ®Google Scholar
• Gibler KB, Huskamp HA, Sabatine MS, et al. Cost-effectiveness analysis of short-term clopidogrel therapy for ST elevation myocardial infarction. Crit Pathw Cardiol. 2010;9(1):14–18.
   PubMedGoogle Scholar
• Rainsford KD. Profile and mechanisms of gastrointestinal and other side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Am J Med. 1999;107(6A):27S–35S. discussion 35S-36S.
   PubMedGoogle Scholar
• Sørensen HT, Mellemkjaer L, Blot WJ, et al. Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin. Am J Gastroenterol. 2000;95(9):2218–2224.
   PubMed Web of Science ®Google Scholar
• Kelly JP, Kaufman DW, Jurgelon JM, et al. Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product. Lancet. 1996;348(9039):1413–1416.
   PubMed Web of Science ®Google Scholar
• Darling RL, Romero JJ, Dial EJ, et al. The effects of aspirin on gastric mucosal integrity, surface hydrophobicity, and prostaglandin metabolism in cyclooxygenase knockout mice. Gastroenterology. 2004;127(1):94–104.
   PubMed Web of Science ®Google Scholar
• Cryer B, Feldman M. Effects of very low dose daily, long-term aspirin therapy on gastric, duodenal, and rectal prostaglandin levels and on mucosal injury in healthy humans. Gastroenterology. 1999;117(1):17–25.
   PubMed Web of Science ®Google Scholar
• Patrignani P, Tacconelli S, Piazuelo E, et al. Reappraisal of the clinical pharmacology of low-dose aspirin by comparing novel direct and traditional indirect biomarkers of drug action. J Thromb Haemost. 2014;12(8):1320–1330.
   PubMed Web of Science ®Google Scholar
• Smecuol E, Pinto Sanchez MI, Suarez A, et al. Low-dose aspirin affects the small bowel mucosa: results of a pilot study with a multidimensional assessment. Clin Gastroenterol Hepatol. 2009;7(5):524–529.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Cayla G, Collet JP, Silvain J, et al. Prevalence and clinical impact of upper gastrointestinal symptoms in subjects treated with low dose aspirin: the UGLA survey. Int J Cardiol. 2012;156(1):69–75.
   PubMed Web of Science ®Google Scholar
• Sostres C, Gargallo CJ. Gastrointestinal lesions and complications of low-dose aspirin in the gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2012;26(2):141–151.
   PubMed Web of Science ®Google Scholar
• Biondi-Zoccai GG, Lotrionte M, Agostoni P, et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J. 2006;27:2667–2674.
   PubMed Web of Science ®Google Scholar
• Muller P, Fuchs W, Simon B. Studies on protective effect of lansoprazole on human gastric mucosa against low-dose acetylsalicylic. An endoscopic controlled double-blind study. Arzneimittelforshung. 1997;47:758–760.
   PubMed Web of Science ®Google Scholar
• McQuaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med. 2006;119(8):624–638.
   PubMed Web of Science ®Google Scholar
• Lanas A, Wu P, Medin J, et al. Low doses of acetylsalicylic acid increase risk of gastrointestinal bleeding in a meta-analysis. Clin Gastroenterol Hepatol. 2011;9(9):762–768.
   PubMed Web of Science ®Google Scholar
• Thorat MA, Cuzick J. Prophylactic use of aspirin: systematic review of harms and approaches to mitigation in the general population. Eur J Epidemiol. 2015;30(1):5–18.
   PubMed Web of Science ®Google Scholar
• García Rodríguez LA, Martín-Pérez M, Hennekens CH, et al. Bleeding risk with long-term low-dose aspirin: a systematic review of observational studies. PLoS One. 2016;11(8):e0160046.
   PubMed Web of Science ®Google Scholar
• Elwood PC, Morgan G, Galante J, et al. Systematic review and meta-analysis of randomised trials to ascertain fatal gastrointestinal bleeding events attributable to preventive low-dose aspirin: no evidence of increased risk. PLoS One. 2016;11(11):e0166166.
   PubMed Web of Science ®Google Scholar
• Moore RA, Derry S, McQuay HJ. Faecal blood loss with aspirin, nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 selective inhibitors: systematic review of randomized trials using autologous chromium-labelled erythrocytes. Arthritis Res Ther. 2008;10:R7.
   PubMed Web of Science ®Google Scholar
• Fortun PJ, Hawkey CJ. Nonsteroidal antiinflammatory drugs and the small intestine. Curr Opin Gastroenterol. 2005;21:169–175.
   PubMed Web of Science ®Google Scholar
• Endo H, Hosono K, Inamori M, et al. Incidence of small bowel injury induced by low-dose aspirin: a crossover study using capsule endoscopy in healthy volunteers. Digestion. 2009;79(1):44–51.
   PubMed Web of Science ®Google Scholar
• Endo H, Hosono K, Inamori M, et al. Characteristics of small bowel injury in symptomatic chronic low-dose aspirin users: the experience of two medical centers in capsule endoscopy. J Gastroenterol. 2009;44(6):544–549.
   PubMed Web of Science ®Google Scholar
• Shiotani A, Honda K, Murao T, et al. Combination of low-dose aspirin and thienopyridine exacerbates small bowel injury. Scand J Gastroenterol. 2011;46(3):281–286.
   PubMed Web of Science ®Google Scholar
• Endo H, Sakai E, Kato T, et al. Small bowel injury in low-dose aspirin users. J Gastroenterol. 2015;50(4):378–386.
   PubMed Web of Science ®Google Scholar
• Lanas A, Carrera-Lasfuentes P, Arguedas Y, et al. Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants. Clin Gastroenterol Hepatol. 2015;13(5):906–12 e2.
   PubMed Web of Science ®Google Scholar
• Strate LL, Liu YL, Huang ES, et al. Use of aspirin or nonsteroidal anti-inflammatory drugs increases risk for diverticulitis and diverticular bleeding. Gastroenterology. 2011;140:1427–1433.
   PubMed Web of Science ®Google Scholar
• Yuhara H, Corley DA, Nakahara F, et al. Aspirin and non-aspirin NSAIDs increase risk of colonic diverticular bleeding: a systematic review and meta-analysis. J Gastroenterol. 2014;49(6):992–1000.
   PubMed Web of Science ®Google Scholar
• Lanas A, Scheiman J. Low-dose aspirin and upper gastrointestinal damage: epidemiology, prevention and treatment. Curr Med Res Opin. 2007;23(1):163–173.
   PubMed Web of Science ®Google Scholar
• Valkhoff VE, Sturkenboom MC, Kuipers EJ. Risk factors for gastrointestinal bleeding associated with low-dose aspirin. Best Pract Res Clin Gastroenterol. 2012;26(2):125–140.
   PubMed Web of Science ®Google Scholar
• Leung KEL, Chan FK. Interaction of Helicobacter pylori infection and low-dose aspirin in the upper gastrointestinal tract: implications for clinical practice. Best Pract Res Clin Gastroenterol. 2012;26(2):163–172.
   PubMed Web of Science ®Google Scholar
• Lanas A, Bajador E, Serrano P, et al. Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding. N Engl J Med. 2000;343:834–839.
   PubMed Web of Science ®Google Scholar
• Serrano P, Lanas A, Arroyo MT, et al. Risk of upper gastrointestinal bleeding in patients taking low-dose aspirin for the prevention of cardiovascular diseases. Aliment Pharmacol Ther. 2002;16:1945–1953.
   PubMed Web of Science ®Google Scholar
• Lanas A, García-Rodríguez LA, Polo-Tomás M, et al. The changing face of hospitalization due to gastrointestinal bleeding and perforation. Aliment Pharmacol Ther. 2011;33(5):585–591.
   PubMed Web of Science ®Google Scholar
• Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib long-term arthritis safety study. Jama. 2000;284(10):1247–1255.
   PubMed Web of Science ®Google Scholar
• García Rodríguez LA, Lin KJ, Hernández-Díaz S, et al. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation. 2011;123(10):1108–1115.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002;347:969–974.
   PubMed Web of Science ®Google Scholar
• Johnson WC, Williford WO. Benefits, morbidity, and mortality associated with long-term administration of oral anticoagulant therapy to patients with peripheral arterial bypass procedures: a prospective randomized study. J Vasc Surg. 2002;35:413–421.
   PubMed Web of Science ®Google Scholar
• Chan FK, Ching JY, Suen BY, et al. Effects of Helicobacter pylori infection on long-term risk of peptic ulcer bleeding in low-dose aspirin users. Gastroenterology. 2013;144(3):528–535.
   PubMed Web of Science ®Google Scholar
• Newton JL, Johns CE, May F. 2004 review article: the ageing bowel and intolerance to aspirin. Aliment Pharmacol Ther. 2004;19:39–45.
   PubMed Web of Science ®Google Scholar
• Garcia Rodriguez LA, Hernandez-Diaz S, De Abajo FJ. Association between aspirin and upper gastrointestinal complications: systematic review of epidemiologic studies. Br J Clin Pharmacol. 2001;52:563–571.
   PubMed Web of Science ®Google Scholar
• Ng W, Wong WM, Chen WH, et al. Incidence and predictors of upper gastrointestinal bleeding in patients receiving low-dose aspirin for secondary prevention of cardiovascular events in patients with coronary artery disease. World J Gastroenterol. 2006;12:2923–2927.
   PubMed Web of Science ®Google Scholar
• Serebruany VL, Steinhubl SR, Berger PB, et al. Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials. Am J Cardiol. 2005;95:1218–1222.
   PubMed Web of Science ®Google Scholar
• Lanas A, Garcia-Rodriguez LA, Arroyo MT, et al. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut. 2006;55:1731–1738.
   PubMed Web of Science ®Google Scholar
• De Abajo FJ, Garcia Rodriguez LA. Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations. BMC Clin Pharmacol. 2001;1:1.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Fletcher EH, Johnston DE, Fisher CR, et al. Systematic review: helicobacter pylori and the risk of upper gastrointestinal bleeding risk in patients taking aspirin. Aliment Pharmacol Ther. 2010;32(7):831–839.
   PubMed Web of Science ®Google Scholar
• Sostres C, Carrera-Lasfuentes P, Benito R, et al. Peptic ulcer bleeding risk. The role of helicobacter pylori infection in NSAID/low-dose aspirin users. Am J Gastroenterol. 2015;110(5):684–689.
   PubMed Web of Science ®Google Scholar
• Chan FK, Chung SC, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med. 2001;344:967–973.
   PubMed Web of Science ®Google Scholar
• Giral A, Ozdogan O, Celikel CA, et al. Effect of Helicobacter pylori eradication on anti-thrombotic dose aspirin-induced gastroduodenal mucosal injury. J Gastroenterol Hepatol. 2004;19:773–777.
   PubMed Web of Science ®Google Scholar
• Hart J, Hawkey CJ, Lanas A, et al. Predictors of gastroduodenal erosions in patients taking low-dose aspirin. Aliment Pharmacol Ther. 2010;31:143–149.
   PubMed Web of Science ®Google Scholar
• Sostres C, Gargallo CJ, Lanas A. Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: old question new insights. World J Gastroenterol. 2014;20(28):9439–9450.
   PubMed Web of Science ®Google Scholar
• Helicobacter Eradication Aspirin Trial (HEAT). Available: https://clinicaltrials.gov/ct2/show/NCT01506986.
   Google Scholar
• Donnelly MT, Goddard AF, Filipowicz B, et al. Low-dose misoprostol for the prevention of low-dose aspirin-induced gastroduodenal injury. Aliment Pharmacol Ther. 2000;14:529–534.
   PubMed Web of Science ®Google Scholar
• Mo C, Sun G, Lu ML, et al. Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries. World J Gastroenterol. 2015;21(17):5382–5392.
   PubMed Web of Science ®Google Scholar
• Tamura A, Murakami K, Kadota J. OITA-GF study investigators. Prevalence and independent factors for gastroduodenal ulcers/erosions in asymptomatic patients taking low-dose aspirin and gastroprotective agents: the OITA-GF study. Qjm. 2011;104(2):133–139.
   PubMed Web of Science ®Google Scholar
• Lanas A, García-Rodríguez 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(3):507–515.
   PubMed Web of Science ®Google Scholar
• Chin MW, Yong G, Bulsara MK, et al. Predictive and protective factors associated with upper gastrointestinal bleeding after percutaneous coronary intervention: a case-control study. Am J Gastroenterol. 2007;102(11):2411–2416.
   PubMed Web of Science ®Google Scholar
• Luinstra M, Naunton M, Peterson GM, et al. PPI use in patients commenced on clopidogrel: a retrospective cross-sectional evaluation. J Clin Pharm Ther. 2010;35(2):213–217.
   PubMed Web of Science ®Google Scholar
• Ng FH, Lam KF, Wong SY, et al. Upper gastrointestinal bleeding in patients with aspirin and clopidogrel co-therapy. Digestion. 2008;77(3–4):173–177.
   PubMed Web of Science ®Google Scholar
• 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(4):865–871.
   PubMed Web of Science ®Google Scholar
• Bhatt DL, Cryer BL, Contant CF, et al. COGENT Investigators. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363:1909–1917.
   PubMed Web of Science ®Google Scholar
• Lanas A, Rodrigo L, Márquez JL, et al. Low frequency of upper gastrointestinal complications in a cohort of high-risk patients taking low-dose aspirin or NSAIDS and omeprazole. Scand J Gastroenterol. 2003;38(7):693–700.
   PubMed Web of Science ®Google Scholar
• Sugano K, Choi MG, Lin JT, et al. LAVENDER Study Group. Multinational, double-blind, randomised, placebo-controlled, prospective study of esomeprazole in the prevention of recurrent peptic ulcer in low-dose acetylsalicylic acid users: the LAVENDER study. Gut. 2014;63(7):1061–1068.
   PubMed Web of Science ®Google Scholar
• Ng FH, Tunggal P, Chu WM, et al. Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction. Am J Gastroenterol. 2012;107:389–396.
   PubMed Web of Science ®Google Scholar
• Scheiman JM, Devereaux PJ, Herlitz J, et al. Prevention of peptic ulcers with esomeprazole in patients at risk of ulcer development treated with low-dose acetylsalicylic acid: a randomised, controlled trial (OBERON). Heart. 2011;97:797–802.
   PubMed Web of Science ®Google Scholar
• Yeomans N, Lanas A, Labenz J, et al. Efficacy of esomeprazole (20 mg once daily) for reducing the risk of gastroduodenal ulcers associated with continuous use of low-dose aspirin. Am J Gastroenterol. 2008;103:2465–2473.
   PubMed Web of Science ®Google Scholar
• Chan FK, Kyaw M, Tanigawa T, et al. Similar efficacy of proton-pump inhibitors vs h2-receptor antagonists in reducing risk of upper gastrointestinal bleeding or ulcers in high-risk users of low-dose aspirin. Gastroenterology. 2016;S0016-5085(16):35031–35034.
   Google Scholar
• Iwakiri R, Higuchi K, Kato M, et al. Randomised clinical trial: prevention of recurrence of peptic ulcers by rabeprazole in patients taking low-dose aspirin. Aliment Pharmacol Ther. 2014;40(7):780–795.
   PubMed Web of Science ®Google Scholar
• Sanuki T, Fujita T, Kutsumi H, et al. Rabeprazole reduces the recurrence risk of peptic ulcers associated with low-dose aspirin in patients with cardiovascular or cerebrovascular disease: a prospective randomized active-controlled trial. J Gastroenterol. 2012;47:1186–1197.
   PubMed Web of Science ®Google Scholar
• Sugano K, Matsumoto Y, Itabashi T, et al. Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term low-dose aspirin therapy: results of a prospective, multicenter, double blind, randomized, double-dummy, active-controlled trial. J Gastroenterol. 2011;46:724–735.
   PubMed Web of Science ®Google Scholar
• Lai KC, Lam SK, Chu KM, et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med. 2002;346:2033–2038.
   PubMed Web of Science ®Google Scholar
• Nema H, Kato M. Comparative study of therapeutic effects of PPI and H2RA on ulcers during continuous aspirin therapy. World J Gastroenterol. 2010;16(42):5342–5346.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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(9684):119–125.
   PubMed Web of Science ®Google Scholar
• Tricco AC, Alateeq A, Tashkandi M, et al. Histamine H2 receptor antagonists for decreasing gastrointestinal harms in adults using acetylsalicylic acid: systematic review and meta-analysis. Open Med. 2012;6(3):e109–17.
   PubMedGoogle Scholar
• Hsu PI. The efficacy and safety of proton pump inhibitor versus histamine-2 receptor antagonist in the prevention of upper gastrointestinal events among ADP receptor antagonist users with a history of ulcer bleeding - a randomized, comparison trial. Gastroenterology. 2016;150(Suppl 1):685.
   Google Scholar
• 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. Circulation. 2010;122:2619–2633.
   PubMed Web of Science ®Google Scholar
• Mössner J. The indications, applications, and risks of proton pump inhibitors. Dtsch Arztebl Int. 2016;113(27–28):477–483.
   PubMed Web of Science ®Google Scholar
• Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706–715.
   PubMed Web of Science ®Google Scholar
• Filion KB, Chateau D, Targownik LE, et al. CNODES Investigators. Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis. Gut. 2014;63(4):552–558.
   PubMed Web of Science ®Google Scholar
• Kwok CS, Arthur AK, Anibueze CI, et al. Risk of clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107(7):1011–1019.
   PubMed Web of Science ®Google Scholar
• Tleyjeh IM, Bin Abdulhak AA, Riaz M, et al. Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis. PLoS One. 2012;7(12):e50836.
   PubMed Web of Science ®Google Scholar
• Deshpande A, Pasupuleti V, Thota P, et al. Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. J Gastroenterol Hepatol. 2013;28(2):235–242.
   PubMed Web of Science ®Google Scholar
• Lam JR, Schneider JL, Zhao W, et al. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. Jama. 2013;310(22):2435–2442.
   PubMed Web of Science ®Google Scholar
• Corley DA, Kubo A, Zhao W, et al. Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology. 2010;139(1):93–101.
   PubMed Web of Science ®Google Scholar
• Gomm W, Von Holt K, Thomé F, et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410–416.
   PubMed Web of Science ®Google Scholar
• Johnson DA. The possible association between proton pump inhibitors and dementia. Gastroenterol Hepatol (N Y). 2016;12(10):644–646.
   PubMedGoogle Scholar
• Ghebremariam YT, LePendu P, Lee JC, et al. Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation. 2013;128(8):845–853.
   PubMed Web of Science ®Google Scholar
• Wallace JL, Syer S, Denou E, et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology. 2011;141(4):1314–1322.
   PubMed Web of Science ®Google Scholar
• Jackson MA, Goodrich JK, Maxan ME, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016;65(5):749–756.
   PubMed Web of Science ®Google Scholar
• Clooney AG, Bernstein CN, Leslie WD, et al. A comparison of the gut microbiome between long-term users and non-users of proton pump inhibitors. Aliment Pharmacol Ther. 2016;43(9):974–984.
   PubMed Web of Science ®Google Scholar
• Lué A, Lanas A. Protons pump inhibitor treatment and lower gastrointestinal bleeding: balancing risks and benefits. World J Gastroenterol. 2016;22(48):10477–10481.
   PubMed Web of Science ®Google Scholar
• Endo H, Sakai E, Taniguchi L, et al. Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users: data from a prospective multicenter capsule endoscopy registry. Gastrointest Endosc. 2014;80(5):826–834.
   PubMed Web of Science ®Google Scholar
• Nagata N, Niikura R, Yamada A, et al. Acute middle gastrointestinal bleeding risk associated with NSAIDs, antithrombotic drugs, and PPIs: a multicenter case-control study. PLoS One. 2016;11(3):e0151332.
   PubMed Web of Science ®Google Scholar