ASCEND Results Confirm Aspirin Prevents Primary Vascular Events in Diabetes

Serious vascular events in patients with diabetes can be prevented with aspirin use, according to results of the ASCEND (A Study of Cardiovascular Events iN Diabetes) trial, which were presented at the ongoing ESC Congress in Munich, Germany.

The results were simultaneously published in The New England Journal of Medicine.¹

A substantial amount of evidence exists linking diabetes with heart disease, and The Framingham Heart Study was the first to show that patients with type 2 diabetes are more susceptible to heart disease. Aspirin use has, of course, been found to benefit patients with cardiovascular (CV) disease, and joint guidelines² developed by the American Heart Association and the American College of Cardiology Foundation recommend a 75- to 162-mg daily dose of aspirin in all patients with coronary artery disease.

However, the value of this antiinflammatory agent in preventing the first CV event in patients undergoing treatment for diabetes remains unknown.

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The ASCEND trial was designed to randomly assign 15,480 adults with diabetes to receive 100 mg of aspirin daily, or a matching placebo. Trial participants did not have any hint of CV disease. Efficacy and safety were monitored and measured as the first serious vascular event (myocardial infarction, stroke, or transient ischemic attack; or death from any vascular cause, excluding any confirmed intracranial hemorrhage) and the first major bleeding event (intracranial hemorrhage, sight-threatening bleeding event in the eye, gastrointestinal bleeding, or other serious bleeding), respectively. Gastrointestinal (GI) tract cancers were monitored as secondary outcomes.

Following a mean follow-up period of 7.4 years, significantly lower serious vascular events were observed in the aspirin group compared to the placebo group (658 [8.5%] vs 743 [9.6%]; relative risk [RR], 0.88; 95% confidence interval [CI], 0.79-0.97; P = .01). Bleeding events, however, were observed at a much higher rate in the aspirin-treated group (n = 314, 4.1%) compared to the placebo group (n = 245, 3.2%) (RR, 1.29; 95% CI, 1.09-1.52; P = .003).

While the trial continues to monitor long-term outcomes for GI cancers, at the time of the current analysis, the incidence rate was comparable between the treatment and placebo groups (157 [2.0%] and 158 [2.0%], respectively).

“Even though we showed clearly that aspirin reduces the risk of vascular events, including heart attacks, strokes, and mini-strokes, it also increased the risk of major bleeds, mainly from the gastrointestinal tract, so overall there was no clear benefit,” said Jane Armitage, FRCP, FFPH, principal investigator, Nuffield Department of Population Health, University of Oxford, United Kingdom, in a statement. “It had been suggested that low-dose aspirin might protect against cancer, but we saw no reduction in any cancers; we are continuing to follow the participants to see whether any benefits appear later.”

According to Armitage, their study results provide “much needed clarity” to existing guidelines, which vary in their recommendations of using aspirin for the primary prevention of CV events in patients with diabetes.

References

1. The ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus [published online August 26, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1804988.
2. Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association. J Am Coll Cardiol. 2011;58(23):2432-2446. doi: 10.1016/j.jacc.2011.10.824. Erratum in: J Am Coll Cardiol. 2015;65(14):1495. Dosage error in article text.