Although daily low-dose aspirin may provide high-risk individuals with protection from cardiovascular events, a considerable number of people run a serious risk of major bleeding, researchers from Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy, reported in JAMA (Journal of the American Medical Association). The authors found that almost 200,000 people in their study on low-dose daily aspirin had a greater likelihood of major cerebral or gastrointestinal bleeding.
The researchers wrote that a significant number of patients with diabetes, irrespective of aspirin usage, have a high rate of major bleeding.
The authors wrote as background information in their report:
“Therapy with low-dose aspirin is used for the treatment of cardiovascular disease. It is recommended as a secondary prevention measure for individuals with moderate to high risk of cardiovascular events (i.e., for patients with multiple risk factors such as hypertension, dyslipidemia, obesity, diabetes, and family history of ischemic heart disease).
Any benefit of low-dose aspirin might be offset by the risk of major bleeding. It is known that aspirin is associated with gastrointestinal and intracranial hemorrhagic complications. However, randomized controlled trials have shown that these risks are relatively small.”
The investigators explained that most randomized controlled human studies focus on selected patient groups; their participants are not usually representative of the entire population.
Some diabetes patients should receive low-dose aspirin, according to guidelines. However, meta-analysis findings appear to indicate that people with diabetes have a significantly higher chance of developing extracranial hemorrhages. An extracranial hemorrhage is a collection of blood (hematoma) outside the skull.
They write that the risk-to-benefit ratio of low-dosage aspirin usage for patients with diabetes mellitus is unclear, because previous study estimates involved a small number of events within randomized trials.
Giorgia De Berardis, M.Sc., and team set out to find out what the rates of major intracranial and gastrointestinal bleeding might be among patients with and without diabetes who take low-dose aspirin.
They gathered administrative data from 12 local health authorities in Puglia, Italy, involving 4.1 million people. They focused on low-dose (max 300mg) aspirin patients between January 2003 and December 2008. That sample population was then matched with people who were not on low-dose aspirin during the same period.
186,425 patients on low-dose aspirin were identified, and data on 186,425 others (not on aspirin) were gathered as well. 6,907 first episodes of major bleeding that required admittance to hospital were registered – 2,464 cases of intracranial hemorrhage and 4,487 of gastrointestinal bleeding during the six-year period.
They found that low-dose aspirin usage was linked to:
- a 55% higher risk of gastrointestinal bleeding
- a 54% higher risk of intracranial bleeding.
In comparison with estimates from other studies on major bleedings, these findings indicate a fivefold higher rate of major bleeding requiring hospitalization among both non-aspirin and aspirin users.
With reference to low-dose aspirin usage being linked to a 55% relative risk rise 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 percent and 20 percent.”
It appears that low-dose aspirin use is linked to a higher risk of major bleeding in the majority of the subgroups the investigators evaluated, but not in those with diabetes. Diabetes itself was independently linked to a 36% higher relative risk of major bleeding episodes, regardless of aspirin usage. Among those not on aspirin, diabetes patients had a higher relative risk of 64% for intracranial bleeding and 59% for gastrointestinal bleeding.
The researchers wrote:
“Our study shows, for the first time, to our knowledge, that aspirin therapy only marginally increases the risk of bleeding in individuals with diabetes. 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. 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 Editorial in the same journal, Jolanta M. Siller-Matula, M.D., Ph.D., of the Medical University of Vienna, Austria, wrote:
“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.”
Written by Christian Nordqvist