Association of Aspirin Use With Major Bleeding in Patients With and Without Diabetes

Study Questions:

What is the incidence of major gastrointestinal and intracranial bleeding in individuals with and without diabetes taking aspirin?


This was a population-based cohort study using administrative data from 4.1 million citizens in 12 local health authorities in Puglia, Italy. Individuals with new prescriptions for low-dose aspirin (≤300 mg) were identified during the index period from January 1, 2003 to December 31, 2008, and were propensity matched on a 1:1 basis with individuals who did not take aspirin during this period. The main outcome measure was hospitalization for major gastrointestinal bleeding or cerebral hemorrhage occurring after the initiation of antiplatelet therapy.


There were 186,425 individuals being treated with low-dose aspirin and 186,425 matched controls without aspirin use. During a median follow-up of 5.7 years, the overall incidence rate of hemorrhagic events was 5.58 (95% confidence interval [CI], 5.39-5.77) per 1,000-person years for aspirin users and 3.60 (95% CI, 3.48-3.72) per 1,000-person years for those without aspirin use (incidence rate ratio [IRR], 1.55; 95% CI, 1.48-1.63). The use of aspirin was associated with a greater risk of major bleeding in most of the subgroups investigated, but not in individuals with diabetes (IRR, 1.09; 95% CI, 0.97-1.22). Irrespective of aspirin use, diabetes was independently associated with an increased risk of major bleeding episodes (IRR, 1.36; 95% CI, 1.28-1.44).


The authors concluded that patients with diabetes had a high rate of bleeding that was not independently associated with aspirin use.


This study reports that the use of aspirin was associated with a 55% relative risk increase in major bleeding, which translated into two excess cases for 1,000 patients treated every year. The excess number of major bleeding events associated with aspirin use is of the same magnitude as the number of major adverse cardiovascular events avoided in the primary prevention setting for individuals with a 10-year risk of events between 10-20%. The excess bleeding risk with aspirin was not observed in patients with diabetes, and diabetics might represent a different population in terms of both expected benefits and risks with aspirin use. Given significant limitations of this observational administrative database study, prospective validation is indicated. For now, clinicians should follow the American College of Cardiology/American Diabetes Association recommendations and use aspirin in those diabetics at increased cardiovascular disease risk (10-year risk of cardiovascular disease events over 10%) and who are not at increased risk for bleeding. Aspirin is not recommended for cardiovascular disease prevention for adults with diabetes at low cardiovascular disease risk.

Clinical Topics: Prevention

Keywords: Incidence, Intracranial Hemorrhages, Follow-Up Studies, Cardiology, Cardiovascular Diseases, Gastrointestinal Hemorrhage, Primary Prevention, United States, Italy, Cerebral Hemorrhage

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