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. 1993 Mar;35(3):219–226. doi: 10.1111/j.1365-2125.1993.tb05689.x

The gastrointestinal toxicity of aspirin: an overview of randomised controlled trials.

P J Roderick 1, H C Wilkes 1, T W Meade 1
PMCID: PMC1381566  PMID: 8471398

Abstract

The proven benefit of aspirin in the secondary prevention of cardiovascular disease and its possible value in primary prevention must be weighted against its potential hazards. This paper is an overview of the gastrointestinal toxicity of aspirin, its most serious complication after intracerebral haemorrhage. Information on toxicity has been drawn only from randomised trials, thus avoiding the potential biases of observational studies. All randomised placebo controlled trials listed in the Anti-platelet Trialists Collaboration where a direct aspirin-placebo comparison was possible were included. Twenty-one trials were included, all but one of secondary prevention. There were over 75,000 person years of aspirin exposure. The pooled odds ratios for categories of gastrointestinal bleeding (e.g. haematemesis, melaena) were between 1.5-2.0; fatal bleeds were very rare. The risk of peptic ulcers was 1.3 and of upper gastrointestinal symptoms 1.7. These risks were lower than those found in observational studies. Attributable disease rates are also presented. For haematemesis for example they varied from 0.2-1.0 per 1000 person years. Toxicity was dose related. Aspirin does have significant gastrointestinal toxicity, although this is rarely fatal. More recent work has demonstrated the efficacy of low doses of aspirin (75 mg daily) but there is limited information yet available on its toxicity.

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Selected References

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  1. Bousser M. G., Eschwege E., Haguenau M., Lefaucconnier J. M., Thibult N., Touboul D., Touboul P. J. "AICLA" controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. Stroke. 1983 Jan-Feb;14(1):5–14. doi: 10.1161/01.str.14.1.5. [DOI] [PubMed] [Google Scholar]
  2. Boysen G., Sørensen P. S., Juhler M., Andersen A. R., Boas J., Olsen J. S., Joensen P. Danish very-low-dose aspirin after carotid endarterectomy trial. Stroke. 1988 Oct;19(10):1211–1215. doi: 10.1161/01.str.19.10.1211. [DOI] [PubMed] [Google Scholar]
  3. Breddin K., Loew D., Lechner K., Uberla K., Walter E. Secondary prevention of myocardial infarction: a comparison of acetylsalicylic acid, placebo and phenprocoumon. Haemostasis. 1980;9(6):325–344. doi: 10.1159/000214375. [DOI] [PubMed] [Google Scholar]
  4. Cairns J. A., Gent M., Singer J., Finnie K. J., Froggatt G. M., Holder D. A., Jablonsky G., Kostuk W. J., Melendez L. J., Myers M. G. Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial. N Engl J Med. 1985 Nov 28;313(22):1369–1375. doi: 10.1056/NEJM198511283132201. [DOI] [PubMed] [Google Scholar]
  5. Ehresmann U., Alemany J., Loew D. Prophylaxe von Rezidivverschlüssen nach Revaskularisations-eingriffen mit Acetylsalicylsäure. Ergebnisse einer doppeltblinden Langzeitstudie. Med Welt. 1977 Jul 1;28(26):1157–1162. [PubMed] [Google Scholar]
  6. Elwood P. C., Cochrane A. L., Burr M. L., Sweetnam P. M., Williams G., Welsby E., Hughes S. J., Renton R. A randomized controlled trial of acetyl salicylic acid in the secondary prevention of mortality from myocardial infarction. Br Med J. 1974 Mar 9;1(5905):436–440. doi: 10.1136/bmj.1.5905.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Elwood P. C., Sweetnam P. M. Aspirin and secondary mortality after myocardial infarction. Lancet. 1979 Dec 22;2(8156-8157):1313–1315. doi: 10.1016/s0140-6736(79)92808-3. [DOI] [PubMed] [Google Scholar]
  8. Fields W. S., Lemak N. A., Frankowski R. F., Hardy R. J. Controlled trial of aspirin in cerebral ischemia. Stroke. 1977 May-Jun;8(3):301–314. doi: 10.1161/01.str.8.3.301. [DOI] [PubMed] [Google Scholar]
  9. Hawkey C. J. Non-steroidal anti-inflammatory drugs and peptic ulcers. BMJ. 1990 Feb 3;300(6720):278–284. doi: 10.1136/bmj.300.6720.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hess H., Mietaschk A., Deichsel G. Drug-induced inhibition of platelet function delays progression of peripheral occlusive arterial disease. A prospective double-blind arteriographically controlled trial. Lancet. 1985 Feb 23;1(8426):415–419. doi: 10.1016/s0140-6736(85)91144-4. [DOI] [PubMed] [Google Scholar]
  11. High-dose acetylsalicylic acid after cerebral infarction. A Swedish Cooperative Study. Stroke. 1987 Mar-Apr;18(2):325–334. doi: 10.1161/01.str.18.2.325. [DOI] [PubMed] [Google Scholar]
  12. Kurata J. H., Abbey D. E. The effect of chronic aspirin use on duodenal and gastric ulcer hospitalizations. J Clin Gastroenterol. 1990 Jun;12(3):260–266. doi: 10.1097/00004836-199006000-00005. [DOI] [PubMed] [Google Scholar]
  13. Laporte J. R., Carné X., Vidal X., Moreno V., Juan J. Upper gastrointestinal bleeding in relation to previous use of analgesics and non-steroidal anti-inflammatory drugs. Catalan Countries Study on Upper Gastrointestinal Bleeding. Lancet. 1991 Jan 12;337(8733):85–89. doi: 10.1016/0140-6736(91)90744-a. [DOI] [PubMed] [Google Scholar]
  14. McEnany M. T., Salzman E. W., Mundth E. D., DeSanctis R. W., Harthorne J. W., Weintraub R. M., Gates S., Austen W. G. The effect of antithrombotic therapy on patency rates of saphenous vein coronary artery bypass grafts. J Thorac Cardiovasc Surg. 1982 Jan;83(1):81–89. [PubMed] [Google Scholar]
  15. Meade T. W., Roderick P. J., Brennan P. J., Wilkes H. C., Kelleher C. C. Extra-cranial bleeding and other symptoms due to low dose aspirin and low intensity oral anticoagulation. Thromb Haemost. 1992 Jul 6;68(1):1–6. [PubMed] [Google Scholar]
  16. Miller G. J. Antithrombotic therapy in the primary prevention of acute myocardial infarction. Am J Cardiol. 1989 Jul 18;64(4):29B–32B. doi: 10.1016/s0002-9149(89)80007-4. [DOI] [PubMed] [Google Scholar]
  17. Petersen P., Boysen G., Godtfredsen J., Andersen E. D., Andersen B. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet. 1989 Jan 28;1(8631):175–179. doi: 10.1016/s0140-6736(89)91200-2. [DOI] [PubMed] [Google Scholar]
  18. Peto R., Gray R., Collins R., Wheatley K., Hennekens C., Jamrozik K., Warlow C., Hafner B., Thompson E., Norton S. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed) 1988 Jan 30;296(6618):313–316. doi: 10.1136/bmj.296.6618.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sorensen P. S., Pedersen H., Marquardsen J., Petersson H., Heltberg A., Simonsen N., Munck O., Andersen L. A. Acetylsalicylic acid in the prevention of stroke in patients with reversible cerebral ischemic attacks. A Danish cooperative study. Stroke. 1983 Jan-Feb;14(1):15–22. [PubMed] [Google Scholar]
  20. Vogel G., Fischer C., Huyke R. Reinfarktprophylaxe mit Azetylsalizylsäure. Folia Haematol Int Mag Klin Morphol Blutforsch. 1979;106(5-6):797–803. [PubMed] [Google Scholar]
  21. Yusuf S., Peto R., Lewis J., Collins R., Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985 Mar-Apr;27(5):335–371. doi: 10.1016/s0033-0620(85)80003-7. [DOI] [PubMed] [Google Scholar]

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