Aspirin raises bleeding risk marginally among patients with diabetes

by Bruce Sylvester – taken from The Journal of the American Medical Association (JAMA)

Researchers in a large, retrospective study report that daily use of low-dose aspirin is associated with an increased risk of major gastrointestinal or cerebral bleeding.

The also found patients with diabetes had a high rate of major bleeding, irrespective of aspirin use.

Low-dose aspirin is recommended for certain patients with diabetes

“Any benefit of low-dose aspirin might be offset by the risk of major bleeding,” the authors wrote. “It is known that aspirin is associated with gastrointestinal and intracranial haemorrhagic complications. However, randomised controlled trials have shown that these risks are relatively small.”

The findings were published in the June 6 issue of JAMA.

Giorgia De Berardis M.Sc., of Consorzio Mario Negri Sud, Santa Maria Imbaro, and colleagues and colleagues conducted the study to determine the incidence of major gastrointestinal and intracranial bleeding episodes in individuals with and without diabetes taking aspirin.

They evaluated administrative data from 4.1 million citizens in 12 local health authorities in Puglia, Italy. They identified persons with new prescriptions for low-dose aspirin (<300 mg) during the index period from January 2003 to December 2008. These subjects were matched with individuals who did not take aspirin during this period.

The investigators included 186,425 individuals being treated with low-dose aspirin and 186,425 matched controls who reported no aspirin use in the study period.

During 6 years, they found 6,907 first episodes of major bleeding requiring hospitalization, of which there were 4,487 episodes of gastrointestinal bleeding and 2,464 episodes of intracranial hemorrhage.

Aspirin-use was associated with a 55% increased relative risk of gastrointestinal bleeding and a 54% increased relative risk of intracranial bleeding.

Compared with other estimates of rates of major bleeding, the findings indicated a 5-times higher incidence of major bleeding leading to hospitalization among both aspirin using diabetics and those not using aspirin.

Regarding the use of aspirin being associated with a 55% relative risk increase in major bleeding, the authors wrote, “…this translates to 2 excess cases for 1,000 patients treated per year….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 researchers also found that the use of aspirin was associated with a greater risk of major bleeding in most of the subgroups evaluated, but not in individuals with diabetes.

Diabetes was independently associated with a 36% increased relative risk of major bleeding episodes, irrespective of aspirin use.

Among individuals not taking aspirin, those with diabetes had an increased relative risk of 59% for gastrointestinal bleeding and a 64% increased risk for intracranial bleeding.

“Our study shows, for the first time, to our knowledge, that aspirin therapy only marginally increases the risk of bleeding in individuals with diabetes,” the authors wrote. “These results can represent indirect evidence that the efficacy of aspirin in suppressing platelet function is reduced in this population.”

“In conclusion, weighing the benefits of aspirin therapy against the potential harms is of particular relevance in the primary prevention setting, in which benefits seem to be lower than expected based on results in high-risk populations,” they wrote. “In this population-based cohort, aspirin use was significantly associated with an increased risk of major bleeding, but this association was not observed for patients with diabetes. In this respect, diabetes might represent a different population in terms of both expected benefits and risks associated with antiplatelet therapy.”

In an accompanying editorial, Jolanta M. Siller-Matula, MD, Medical University of Vienna, Vienna, Austria, wrote that, “a decision-making process based on balancing an individual patient’s risk of bleeding and ischemic events is difficult. The study by De Berardis et al underscores that the potential risk of bleeding should be carefully considered in decision making. Assessment of bleeding risk and of net clinical benefit will merit further emphasis as issues inherent to aspirin use also apply to more potent platelet inhibitors and anticoagulants; there is only a thin line between efficacy and safety, and the reduction in ischemic events comes at the cost of increased major bleedings. Therefore, future studies investigating the risks and benefits for individual patients appear to be mandatory to help physicians appropriately make recommendations about aspirin use for primary prevention.”