New discovery also raises risks of the preventative heart disease measure,
Heart Health: Aspirin
Taking a daily low-dose aspirin to prevent heart disease may actually increase the risk of major gastrointestinal (GI) or cerebral bleeding, Italian researchers found.
In a large population study, daily prescribed aspirin was associated with a 55 percent relative increase in the risk of major bleeding — an excess of two bleeding cases per 1,000 patients treated each year, Antonio Nicolucci, MD, of Consorzio Mario Negri Sud in Maria Imbaro, Italy, and colleagues reported in the June 6 issue of the Journal of the American Medical Association.
That’s of the same magnitude as 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,” the researchers wrote.
“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 patients,” they wrote.
They also found that diabetic patients had a high rate of major bleeding, regardless of aspirin use.
“Diabetes might represent a different population in terms of both expected benefits and risks associated with antiplatelet therapy,” they added. Some research has shown that diabetes itself carries an increased risk of hemorrhage.
Aspirin has long been proven in secondary prevention for patients with moderate to high risk of cardiovascular events, but its benefit in primary prevention of heart disease has been controversial.
So to clarify these issues, Nicolucci and colleagues looked at data from patients in 12 local health authorities in Puglia, Italy, who had new prescriptions for low-dose aspirin (less than 300 mg) between Jan. 1, 2003 and Dec. 31, 2008.
They matched the 186,425 patients treated with aspirin with patients who didn’t take the drug during that time.
Over a median follow-up of 5.7 years, the researchers found that the overall incidence rate of hemorrhagic events was 5.58 per 1,000 person-years for aspirin users, compared with 3.60 per 1,000 person-years for those who didn’t use aspirin, which translated to a 55 percent higher risk of bleeding in those on aspirin.
The researchers observed an excess risk of both gastrointestinal and brain, or intracranial, bleeding.
In addition to aspirin use, the risk of bleeding increased with age and was higher in men; individuals treated with high blood pressure drugs; patients taking prescription nonsteroidal anti-inflammatory drugs (NSAIDs); and patients taking other antiplatelet and antithrombotic agents.
However, diabetes was independently associated with an increased risk for major bleeding regardless of aspirin use, a finding that “deserves additional consideration,” the researchers wrote.
“Our study shows … that aspirin therapy only marginally increases the risk of bleeding in individuals with diabetes,” they wrote, which suggests that the aspirin therapy isn’t as effective in patients with diabetes.
That may have something to do with the accelerated platelet turnover seen with diabetes, the researchers said.
They also noted that the use of statins was associated with a significant reduction in both GI and intracranial bleeding, which could be due to simultaneous use of proton pump inhibitors (PPIs) in this population.
In an accompanying editorial, Jolanta Siller-Matula, MD, PhD, of the Medical University of Vienna in Austria, wrote that the study “underscores that the potential risk of bleeding should be carefully considered in decision making.”
“There is only a thin line between efficacy and safety, and the reduction in ischemic events comes at the cost of increased major bleedings,” she wrote, adding that future studies assessing individual risk-versus-benefits will be “mandatory to help physicians appropriately make recommendations about aspirin use for primary prevention.”
The study was limited because it wasn’t possible to consider variables that aren’t routinely captured in claims databases, including lifestyle factors such as obesity, smoking, alcohol consumption, or the use of over-the-counter NSAIDS or over-the-counter aspirin.
Suzanne Steinbaum, MD, of Lenox Hill Hospital in New York City, who was not involved in the study, said it “remains clear that aspirin should be used in intermediate- and high-risk patients.” She noted that it’s important to know an individual patient’s risk factors before prescribing aspirin, “as [aspirin] may be more dangerous than it is protective.”
Co-authors reported relationships with Bristol-Myers Squibb and Bayer.
Siller-Matula reported relationships with Eli Lilly and AstraZeneca.