Association of aspirin use with major bleeding in patients with and without diabetes.


The potential benefits of aspirin use in prevention of cardiovascular disease must be weighed against the risk of bleeding complications. This study analyzed a large Italian population to quantify the risk of aspirin for gastrointestinal bleeding and bleeding within the brain. They also sought to identify specific populations (i.e., patients with or without diabetes) where these aspirin complications might be more or less likely to increase.


The authors studied the population of Puglia, Italy from 2003-2008 using administrative data (comprehensive National Health Service data). From prescription records, they identified 186,425 people who received prescriptions for low-dose aspirin (≤ 300 mg daily). They then compared these individuals to a matched control population who did not take aspirin. Then, using hospital records they determined who in these groups had been hospitalized in the following 5.7 years for gastrointestinal bleeding or cerebral hemorrhage. They also examined these outcomes in different categories of patients, including patients with and without diabetes.


  • Patients who were prescribed aspirin were 55% more likely to develop a bleeding complication (0.56% per year) than those patients who were not prescribed aspirin (0.36% per year). The magnitude of excess risk for aspirin users was the same for gastrointestinal bleeding and cerebral hemorrhage.

  • The bleeding risk associated with aspirin use applied to most patient subgroups, including across age-groups, gender and whether or not high blood pressure was being treated.

  • Diabetes itself was associated with a 36% increased risk of major bleeding, but aspirin did not increase this risk among those with diabetes.

  • Aspirin did not increase the risk of major bleeding when patients were also taking a proton pump inhibitor that reduces the stomach’s acidity level.


  • Aspirin increases the risk of major bleeding. Aspirin was associated with a large increase in the chance of major gastrointestinal bleeding or bleeding within the brain. These risks should be taken into account when considering aspirin as a preventive therapy for cardiovascular disease.

  • Aspirin did not increase the risk of major bleeding in patients with diabetes. While this suggests that aspirin may be safer in diabetic patients, the study design cannot exclude other indirect explanations for this apparent finding.

  • Proton pump inhibitors appear to protect patients against the bleeding complications of aspirin use. These medications may protect against gastrointestinal bleeding by reducing the stomach’s acidity.