Low-dose aspirin may not reduce cardiovascular events in diabetic patients
The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes trial included 2,539 patients with type 2 diabetes and without pre-existing cardiovascular disease, randomized to receive aspirin (81 mg or 100 mg daily) or no aspirin.
In patients with type 2 diabetes, low-dose aspirin for primary prevention did not affect the risk for cardiovascular events but increased risk for gastrointestinal bleeding, a Japanese study found.
The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes trial was an open-label trial that included 2,539 Japanese patients with type 2 diabetes and without pre-existing cardiovascular disease. Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily) or no aspirin. The trial ended in 2008, and researchers followed patients until 2015, with a median follow-up period of 10.3 years and with no attempt to change therapy. Primary end points were cardiovascular events, including sudden death, fatal or nonfatal coronary artery disease, fatal or nonfatal stroke, and peripheral vascular disease. Researchers also looked at hemorrhagic events for safety, including gastrointestinal bleeding, hemorrhagic stroke, and bleeding from any other sites. Results were published Nov. 15 by Circulation.
Low-dose aspirin did not reduce cardiovascular events when the study was analyzed per protocol (hazard ratio [HR], 1.14; 95% CI, 0.91 to 1.42). Models adjusted for age, sex, glycemic control, kidney function, smoking status, hypertension, and dyslipidemia showed similar results (HR, 1.04; 95% CI, 0.83 to 1.30), with no heterogeneity of efficacy in subgroup analyses stratified by each of these factors. Sensitivity analyses on the intention-to-treat cohort yielded consistent results (HR, 1.01; 95% CI, 0.82 to 1.25).
Gastrointestinal bleeding occurred in 25 (2%) patients in the aspirin group and 12 (0.9%) in the no-aspirin group (P=0.03), though the incidence of hemorrhagic stroke was not different between the groups. Based on the results, low-dose aspirin is not recommended for Japanese patients with diabetes and without cardiovascular disease, the researchers concluded.
They noted that international trials are underway and that, while recommendations for aspirin for primary prevention exist in the general population, studies have reported that aspirin has a smaller benefit for primary prevention among diabetics.
“It seems there are differential effects of low-dose aspirin therapy on preventing cardiovascular events in patients with and without diabetes,” the researchers wrote. “Platelet dysfunction, increased platelet turnover, or aspirin resistance in diabetes might diminish aspirin's benefit, although the precise mechanism is not clear at present.” Other aspirin dosing strategies could potentially mitigate these issues, but randomized trials would be needed to assess the effects, they said.