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Three Part Question

In [a patient who has IHD presenting with an upper GI bleed] what [is the evidence] for [continuing prophylactic aspirin?]

Clinical Scenario

An 80 year-old man is admitted on the medical take with a three day history of melaena. He is on aspirin 75mg following an MI 18 months ago. He is not on a PPI and from his risk factors he does not seem to have any other risk factors for an upper GI bleed?
DO you continue the aspirin?

Search Strategy

• Pubmed search 1966-2006 using the OVID interface.
Search words: aspirin, prophylactic aspirin, GI bleed, GI haemorrhage, melaena, haematemesis, NSAIDS.
• BMJ search 1995-2006 using the above search words
The literature review focused on the use of aspirin alone and does not apply to the concomitant use of other antiplatelet agents such a clopidogrel.

Search Outcome

Pubmed: 7 of the 72 articles which were found were of sufficient importance.
BMJ : 2/33 articles which were relevant to aspirin use alone, in a patient who is taking it for cardioprophylaxis.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Biskupiak et al, 2006 Canada	3.2 million people whose health records were available in a primary care database	Retrospective review of an electronic Medical Record database	Peptic Ulcer bleed	Odds ratio of a PUB were 3.36 with ibuprofen and aspirin (2.36-4.80 p=<.00001) and 2.07 (1.23-3.49 p=.005) with aspirin and naproxen	They did not measure the prevalence for aspirin use alone and they did not take into consideration other risk factors for so-called PUBs. Furthermore it only gives information on the patients who are on the database and not the general population.
Geyer et al. 2006 Switzerland	7406 hospitalisations	One year prospective study to investigate the epidemiology of GI bleeding.	GI bleed	Mortality of a GI bleed is 3.1%. The frequency of bleeds increases with the patient's age especially with the concomitant use of aspirin	No other risk factors seemed to be taken into account e.g. previous GI bleed.
Collet et al. 2004 France	1358 patients admitted with ACS who were followed up for a thirty day period thereafter.	Cohort study	ACS	Pts with recent withdrawals of oral antiplatelet agents had a 30 day rate of death or MI of 21.9% p=0.04 compared to non-users	No other risk factors for an increase in MI prevalence were discussed.
Quilliam et al. 2001 USA	16939 pts over a 5 year period who had presented with a first GI bleed	Case-control study	GI bleed	The odds ratio of aspirin causing a bleed was 1.07 (95% CI, 0.96-1.18). The number needed to treat to harm one resident is 467.	The population chosen was biased as it only encompassed pts from a nursing home and not the population at large.
Loke et al. 2000 UK	66,000 patients from a medline search 1990-1999	Meta-analysis of 24 random controlled trials	GI haemorrhage	The incidence of a GI haemorrhage in a pt taking aspirin was 2.47 vs 1.42 in a pt taking a placebo.	It was unclear in the analysis if all the patients were on the same dose of aspirin.
Sanmuganathan et al. 2001 UK	Meta-analysis of four randomised controlled trials of aspirin for primary prevention.	Randomised controlled studies	Primary prevention, bleeding	Aspirin for primary prevention significantly reduced all cardiovascular events by 15% (95% CI 6-22%) and MIs by 30%. Bleeding complications were 69% (95% CI 38-107%).Aspirin treatment for primary prevention is safe and worthwhile at a coronary event risk >/= 1.5% per year	The population studied has not been defined nor have any other factors affecting IHD.
Cappelleri et al. 1995 USA	Medline search of pertinent studies between 1966-1992 which look at the efficacy and safety of different aspirin doses at patients at high risk of cardiovascular disease.	36 apt random controlled studies which compared increasing doses of aspirin with a placebo.	Side effects of aspirin	For every 25mg/day increased dose of aspirin the odds ratio of GI sx and withdrawals increased respectively by 0.87% (99% CI. 0.18-1.57%) and 0.94% (99%CI 0.06-1.82%).	Although the study shows that there are no statistical differences between efficacy and side effects, no recommended dose was given and for what reasons.
Weil J, Colin-Jones D. 1995 UK	Case control study with hospital and community controls.	1121 patients who had been admitted with gastric or duodenal ulcers.	Prophylactic aspirin and risk of peptic ulcer bleeding	144 of the bleeds in inpatients 12.8% had been regular users of aspirin whilst 101 (9%) of the community group. From the study it appeared that 900 of the bleeds could be attributed to aspirin use.	These figures may be such that the inclusion criteria for the trial may have excluded pts who would have had GI bleeds caused by other agents. The above figure may be a gross generalisation.
Hawkey et al. 2002 UK	Estimates of ulcer disease from epidemiological studies	Review of current data	Aspirin use, non-aspirin antiplatelet agents and gastroprotection	10% of all GI bleeds can be attributed to aspirin use. PPIs after ulcer bleeds can reduce late ulcer bleeding by 4-6 fold	This study was based on statistics being applied to everyday practice which is not always a reliable predictor of disease

Comment(s)

From the literature review it is evident that the GI side effects of aspirin may be overestimated as the cause and effect cannot always be distinguished. There may be confounding factors that may attribute to a patient presenting with melaena such as increasing age, other NSAIDs, steroids, previous PUD and an underlying undiagnosed haemophilia which may not always be considered. With regard to the clinical question at hand, each case needs to be considered on its own merit. What needs to be taken into account is that in a patient with a considerable IHD risk, even after a GI bleed, it is sensible to continue the aspirin as the risk of a further cardiovascular event increases on the abrupt withdrawal of the aspirin. Those at particular risk, by doubling or more, are those patients who had been users for less than a month in comparison with users of aspirin for more than a month. PPIs offer effective gastroprotection and have a small side effect profile compared to other available regimes. From the above literature review there are no articles which can provide advice on the exact management of a patient on aspirin with a GI bleed however, it can provide the information necessary to take the patient's long term IHD risk in mind and balance the need for it over the long term risk of ulcer bleeding.

Clinical Bottom Line

Abandoning aspirin following an ulcer bleed in a patient with considerable coronary instability would run the risk of precipitating vascular events during hypotension post haemorrhage or as a consequence of the bleeding associated hypercoagulable state. The chances of cardiovascular death are overall many times higher than those of ulcer death.

References

1. Biskupiak JE. Gastrointestinal complications of over-the-counter nonsteroidal antiinflammatory drugs. Journal of Pain Palliative Care Pharmacothererapy 2006;20(3):7-14
2. Geyer M, Stamenic I, Epidemiology of gastrointestinal bleeding in the elderly PubMed 2006 May 10;95(19):757-65
3. Collet JP, Montalescot G, Blanchet B, Tanguy ML, Golmard JL, Choussat R, Beygui F, Payot L, Vignolles N, Metzger JP, Thomas D. Impact of prior use or recent withdrawal of oral antiplatelet agents on acute coronary syndromes. Circulation, PubMed 2004 Oct 19;110(16):2361-7
4. Quilliam BJ, Lapane KL, Eaton CB, Mor V. Effect of antiplatelet and anticoagulant agents on risk of hospitalization for bleeding among a population of elderly nursing home stroke survivors. Stroke, PubMed 2001 Oct;32(10):2299-304
5. Derry S, Loke YK Risk of gastrointestinal haemorrhage with long term use of aspirin:meta-analysis BMJ November 11, 2000: 321 (7220): 1183-1187
6. Sanmuganathan PS, Ghahramani P, Jackson PR, Wallis EJ, Ramsay LE. Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from meta-analysis of randomized trials. Heart, PubMed March 1,2001; 85(3):265-271
7. Cappelleri JC, Lau J, Kupelnick B, Chalmers TC Efficacy and safety of different aspirin dosages on vascular diseases in high-risk patients. A metaregression analysis. Online J Curr Clin Trials, PubMed 1995 Mar 14;Doc No 174
8. Weil J, Colin-Jones D. Prophylactic aspirin and risk of peptic ulcer bleeding BMJ 1995;310-827-830
9. Hawkey CJ, Langman MJS. Non-steroidal anti-inflammatory drugs: overall risks and management. Complementary roles of COX-2 inhibitors and proton pump inhibitors Gut 2003; 52: 600-608