Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) should be used with caution, especially in people aged over 60 years and those who are taking corticosteroids, bisphosphonates, or other antithrombotic drugs.[24]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 Mar 15;123(10):1108-15.
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.110.973008
http://www.ncbi.nlm.nih.gov/pubmed/21357821?tool=bestpractice.com
[25]Knopp-Sihota JA, Cummings GG, Homik J, et al. The association between serious upper gastrointestinal bleeding and incident bisphosphonate use: a population-based nested cohort study. BMC Geriatr. 2013 Apr 20;13:36.
https://bmcgeriatr.biomedcentral.com/articles/10.1186/1471-2318-13-36
http://www.ncbi.nlm.nih.gov/pubmed/23602075?tool=bestpractice.com
Concurrent use of a proton-pump inhibitor (PPI) has been shown to reduce the risk of gastrointestinal complications in patients taking long-term aspirin and/or oral anticoagulants.[36]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 May;97(10):797-802.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088470/?tool=pubmed
http://www.ncbi.nlm.nih.gov/pubmed/21415072?tool=bestpractice.com
[37]Kurlander JE, Barnes GD, Fisher A, et al. Association of Antisecretory Drugs with Upper Gastrointestinal Bleeding in Patients Using Oral Anticoagulants: A Systematic Review and Meta-Analysis. Am J Med. 2022 Oct;135(10):1231-1243.e8.
https://www.doi.org/10.1016/j.amjmed.2022.05.031
http://www.ncbi.nlm.nih.gov/pubmed/35679879?tool=bestpractice.com
[38]Ahn HJ, Lee SR, Choi EK, et al. Protective effect of proton-pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: a systematic review and meta-analysis. Br J Clin Pharmacol. 2022 Nov;88(11):4676-87.
http://www.ncbi.nlm.nih.gov/pubmed/35921204?tool=bestpractice.com
PPIs prevent peptic ulcers and complications in people who require NSAID therapy.[39]Yang M, He M, Zhao M, et al. Proton pump inhibitors for preventing non-steroidal anti-inflammatory drug induced gastrointestinal toxicity: a systematic review. Curr Med Res Opin. 2017 Jan 25;33(6):973-80.
http://www.ncbi.nlm.nih.gov/pubmed/28076696?tool=bestpractice.com
However, guidelines suggest considering a test and treat strategy for Helicobacter pylori before starting long-term NSAID therapy, as H pylori eradication has been shown to protect against aspirin-associated peptic ulcer bleeding.[40]Lanza FL, Chan FK, Quigley EM; Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009 Mar;104(3):728-38.
http://www.ncbi.nlm.nih.gov/pubmed/19240698?tool=bestpractice.com
[41]Hawkey C, Avery A, Coupland CAC, et al. Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial. Lancet. 2022 Nov 5;400(10363):1597-606.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01843-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36335970?tool=bestpractice.com
Prophylactic use of a PPI is appropriate for patients in intensive care, especially those who require mechanical ventilation, those who are deemed at high risk of gastrointestinal bleeding due to comorbidities such as chronic liver disease, or those who have co-existing conditions such as coagulopathy, sepsis, or acute kidney injury.[33]Cash BD. Evidence-based medicine as it applies to acid suppression in the hospitalized patient. Crit Care Med. 2002 Jun;30(suppl 6):S373-8.
http://www.ncbi.nlm.nih.gov/pubmed/12072665?tool=bestpractice.com
[34]Ye Z, Reintam Blaser A, Lytvyn L, et al. Gastrointestinal bleeding prophylaxis for critically ill patients: a clinical practice guideline. BMJ. 2020 Jan 6;368:l6722.
https://www.bmj.com/content/368/bmj.l6722.long
http://www.ncbi.nlm.nih.gov/pubmed/31907223?tool=bestpractice.com
PPIs are generally accepted to be superior to H2 antagonists at preventing clinically important gastrointestinal bleeding in critically ill patients.[34]Ye Z, Reintam Blaser A, Lytvyn L, et al. Gastrointestinal bleeding prophylaxis for critically ill patients: a clinical practice guideline. BMJ. 2020 Jan 6;368:l6722.
https://www.bmj.com/content/368/bmj.l6722.long
http://www.ncbi.nlm.nih.gov/pubmed/31907223?tool=bestpractice.com
[42]Alshamsi F, Belley-Cote E, Cook D, et al. Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care. 2016 May 4;20(1):120.
https://www.doi.org/10.1186/s13054-016-1305-6
http://www.ncbi.nlm.nih.gov/pubmed/27142116?tool=bestpractice.com
[43]Alhazzani W, Alshamsi F, Belley-Cote E, et al. Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials. Intensive Care Med. 2017 Dec 4;44(1):1-11.
https://www.doi.org/10.1007/s00134-017-5005-8
http://www.ncbi.nlm.nih.gov/pubmed/29199388?tool=bestpractice.com
Evidence from one double-blind randomised trial suggests that PPIs and H2 antagonists have similar efficacy in reducing the risk of upper gastrointestinal bleeding or ulcers in people taking low-dose aspirin.[44]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 Sep 15;152(1):105-10.e1.
http://www.ncbi.nlm.nih.gov/pubmed/27641510?tool=bestpractice.com
A meta-analysis that evaluated H2 antagonists, PPIs, and prostaglandin analogues found that PPIs were more effective in preventing bleeding from ulcers than H2 antagonists and prostaglandin analogues.[45]Scally B, Emberson JR, Spata E, et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol. 2018 Apr;3(4):231-41.
https://www.doi.org/10.1016/S2468-1253(18)30037-2
http://www.ncbi.nlm.nih.gov/pubmed/29475806?tool=bestpractice.com
PPIs were also more effective in healing ulcers and preventing recurrent bleeding and the need for blood transfusion.[45]Scally B, Emberson JR, Spata E, et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol. 2018 Apr;3(4):231-41.
https://www.doi.org/10.1016/S2468-1253(18)30037-2
http://www.ncbi.nlm.nih.gov/pubmed/29475806?tool=bestpractice.com