ASCEND Unable to Discern Reward or Risk in Aspirin for Diabetes Mellitus

Louise Bowman, MD

Aspirin has been long heralded for its occlusive vascular preventive properties, but its increased bleeding risk is no secret. For diabetes mellitus patients who face a greater risk of vascular events, aspirin’s benefits for cardiovascular function may seem attractive, but its risks may not outweigh its rewards.

A recent study led by Louise Bowman, MD, associate professor at the Clinical Trial Service Unit of the University of Oxford, further investigated the efficacy and safety of enteric-coated aspirin for patients with diabetes mellitus. The results, presented at the European Society of Cardiology (ESC) 2018 Congress this weekend, procured more unclear outcomes.

Through conductance of the randomized A Study of Cardiovascular Events in Diabetes (ASCEND) trial, investigators weighed the pros and cons of aspirin in adult patients with diabetes and evident cardiovascular disease. A total of 15,480 patients were administered 100 mg of aspirin once daily or matching placebo, as well as the former group receiving 1 g capsules containing n-3 fatty acid once daily and the latter receiving a matching placebo capsule.

Investigators sought the first diagnosed serious vascular event as the primary efficacy outcome, while the first major bleeding event served as the primary safety outcome. Incidence of gastrointestinal tract cancer served as a secondary outcome.

There was also question at baseline as to whether the therapy’s effects would be distinguishable. Retrospective analyses of previous trials involving low-dose aspirin have led investigators to believe that diabetes may even be associated with a reduced efficacy of aspirin’s antiplatelet effects.

Upon data collection from a 7.4-year mean follow-up of the 15,480 participants from June 2005 to July 2011, serious vascular events occurred in a significantly lower percentage of participants in the aspirin group (8.5%) compared to the placebo group (9.6%).

Adversely, major bleeding events occurred in a higher percentage of individuals treated with aspirin (4.1%) compared to those treated with placebo (3.2%).

The incidence of gastrointestinal tract cancer and all cancers, however, showed no significant difference between the aspirin group and the placebo, with it being reported 2.0% of patients in both groups.

Overall, the study authors concluded that the assessment of the balance between the benefit and harm of aspirin use, in the context of primary prevention, is “complicated by the difficulty of comparing the severity of the vascular events avoided and the bleeding events caused.”

“These results of intention-to-treat analyses tend to underestimate the effect of actual aspirin use, both with respect to events avoided and bleeding events caused owing to a lack of full adherence to the regimen during the trial,” investigators wrote.

While aspirin treatment decreased the number of serious vascular events experienced by diabetes mellitus patients, the benefit was closely balanced by the number of bleeds caused with aspirin treatment—even among patients with a five-year vascular risk of 10% or more.

Although only approximately one-fourth of participants were receiving proton-pump inhibitors (PPIs) towards the end of the trial in 2016, PPIs were noted to possibly have the ability to reduce bleeding rates among aspirin users. However, investigators noted that long-term trials are needed to assess their efficacy and long-term safety.

In addition, aspirin treatment was not observed to encourage a low risk of gastrointestinal tract cancer or other cancers. However, a long-term assessment is also needed to further investigate on this point.

The study, "Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus," was published online in New England Journal of Medicine on Sunday.