Daily aspirin use was significantly linked to an increased risk for major gastrointestinal or cerebral bleeding episodes in patients with or without diabetes, based on data from a cohort study.

Low-dose aspirin regimens are often used for the secondary prevention of cardiovascular disease. Previous observational studies have suggested one or two major bleeding episodes annually for every 1,000 patients administered low doses of aspirin. Therefore, Giorgia De Berardis, MSc, and colleagues designed a population-based cohort study to determine the incidence of major gastrointestinal and cerebral bleeding episodes in patients with or without diabetes.

“In line with existing evidence, the use of aspirin was associated with a 55% relative risk increase in major bleeding; this translates to 2 excess cases for 1,000 patients treated per year,” researchers wrote. “In other words, the excess number of major bleeding events associated with the use of aspirin is of the same magnitude of the number of major cardiovascular events avoided in the primary prevention setting for individuals with a 10-year risk of between 10% and 20%.”

The study included administrative data from 4.1 million residents in 12 local health facilities in Puglia, Italy. Patients with new prescriptions for low-dose aspirin (≤300 mg) were identified from 2003 to 2008. They were then matched on a 1:1 basis with patients who did not take aspirin in that time.

Of the 241,844 patients from the initial cohort, 186,425 patients treated with low-dose aspirin had an overall incidence rate of bleeding events of 5.58 (95% CI, 5.39-5.77) per 1,000-person years, during a median follow-up of 5.7 years. The rate was 3.6 (95% CI, 3.48-3.72) for those without aspirin use.

The average age of the patients was 69 years — 53% female, 57% affected by hypertension, 15% treated with hypoglycemic medication, 2% experienced previous hospitalization for CV event and 0.9% experienced hospitalization for gastrointestinal complications.

Patients who used aspirin were associated with a greater risk for major bleeding in most subgroups analyzed, but not in patients with diabetes (incidence rate ratio [IRR]=1.09; 95% CI, 0.97-1.22), researchers wrote.

However, patients with diabetes had a high rate of bleeding that was not independently linked to aspirin use (IRR=1.36; 95% CI, 1.28-1.44), they concluded.

“The study by De Berardis et al underscores that the potential risk of bleeding should be carefully considered in decision making,” Jolanta M. Siller-Matula, MD, PhD, of the Medical University of Vienna, Austria, said in an accompanying editorial.

“Aspirin is widely used for primary and secondary prevention of cardiovascular events,” Siller-Matula said. “Substantial scientific evidence supports the beneficial role of aspirin in reducing the risk of cardiovascular events in secondary prevention.”

She wrote that future studies investigating the risks and benefits for individual patients should be developed to help physicians make appropriate recommendations about aspirin use as primary prevention for CV events.

For More Information:
De Berardis G. JAMA. 2012;307:2286-2294.
Siller-Matula JM. JAMA. 2012:307:2318-2320.

Disclosure: Three of the study researchers report financial ties with Bayer and Bristol-Myers Squibb. Dr. Siller-Matula reports receiving speakers’ fees from AstraZeneca and Eli Lilly.