More trials are urgently needed into the use of aspirin for the primary prevention of cardiovascular disease (CVD) in patients with diabetes, say researchers, after finding that the drug may be less effective in these patients than others.
The team from Italy suggests that aspirin's antiplatelet effects may be overwhelmed by aspirin-insensitive mechanisms of platelet activation and thrombus formation, creating an unfavorable risk-to-benefit profile for diabetic patients.
The findings come from a sub-group analysis of the Primary Prevention Project (PPP) trial, a randomized open-label study of the effect of aspirin or vitamin E on CV events in 4495 high-risk individuals, including 1031 with diabetes.
The trial was prematurely stopped after 3.7 years by the data and safety monitoring board, after a consistent benefit with aspirin was seen in reducing the composite endpoint of CV deaths, stroke, or myocardial infarction compared with no aspirin.
In the current study, Michele Sacco (Consorzio Mario Negri Sud Via Nazionale, Maria Imbaro) and colleagues compared the results from diabetic patients with nondiabetic patients with other CV risk factors.
They found that, in diabetics, aspirin treatment was associated with a 10% nonsignificant reduction in the primary endpoint compared with a significant 41% reduction in nondiabetic subjects. Aspirin use was associated with a nonsignificant reduction in total CV events of 11% among patients with diabetes, compared with a significant 31% reduction in those without the condition.
Of concern, use of aspirin was linked with a nonsignificant 23% increase in CV deaths among diabetic subjects, although the drug reduced this risk by 68% in those without diabetes. Vitamin E treatment did not appear to reduce the risk of these endpoints for either of the groups.
Sacco et al emphasize, in the journal Diabetes Care, that although the use of low-dose aspirin is recommended for diabetic patients in existing guidelines, evidence supporting the use of aspirin in the prevention of diabetic CVD is "surprisingly scant."
They conclude: "Further large-scale trials investigating the role of aspirin in the primary prevention of CVD in diabetic patients are urgently needed, together with studies aimed at identifying the mechanisms by which diabetic patients may fail aspirin therapy."
In an editorial accompanying the article, John Colwell (Medical University at South Carolina in Charleston, USA) writes: "It is important to note that the substudy in diabetic patients was not adequately powered."
Nevertheless, he adds: "In this study, a question of "aspirin resistance" in diabetic patients is raised. More research on this issue is needed, including a precise definition and clinical trials."
Free abstract
