The ASCEND Study – Aspirin for Prevention of Cardiovascular Events

The ASCEND study findings demonstrate a balance between cardiovascular protection and major bleeding. 

Aspirin is known to reduce the risk of cardiovascular events and increase the risk of bleeding. It is beneficial for patients with cardiovascular disease, but what is not clear is the balance of benefits and hazards for the prevention of primary cardiovascular events in patients with diabetes who have not had a cardiovascular event. Previous studies conducted failed to report clear data on whether the benefits for using aspirin among people with diabetes outweigh the risks. Past retrospective meta-analyses have suggested that low-dose aspirin can reduce the incidence of gastrointestinal cancers, with the effects appearing after long exposure and long follow up to 20 years.

The ASCEND study, (A Study of Cardiovascular Events in Diabetes), was conducted to assess the efficacy and safety of aspirin EC 100mg daily, compared with placebo, in people with diabetes without cardiovascular disease at the start of the trial. 15,480 participants were enrolled and underwent randomization with a mean follow-up of 7.4 years. Participants were also randomly assigned to receive either n-3 fatty acids (1g capsules) or placebo. 

The study included participants of age ≥40 years, with any type of diabetes, and no known cardiovascular disease at trial initiation, whom it is unknown whether they would benefit from antiplatelet therapy. Participants were not to be included in the trial if they had a clear indication for aspirin or a contraindication to aspirin or any clinical conditions that might limit adherence to the trial for at least 5 years.

The primary efficacy outcome was the first serious vascular event (composite of nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, or death from any vascular cause). The primary safety outcome was the first occurrence of any major bleeding. Secondary outcomes were gastrointestinal tract cancer and the composite of any serious vascular event or arterial revascularization procedure.

The primary efficacy outcome of first serious vascular event was reported to be lower in the aspirin group (8.5%) vs placebo (9.6%) (rate ratio, 0.88; 95% [CI], 0.79-0.97; P=0.01) with the risk difference seen mainly in the first 5 years, with the absolute difference of 1.1%: i.e., approximately 91 patients would need to be treated to avoid a serious vascular event over a period of 7.4 years. The primary safety outcome (occurrence of any major bleeding) was higher in the aspirin group (4.1%) compared with placebo (3.2%) (rate ratio, 1.29; 95% [CI], 1.09-1.52; P=0.003), with the absolute difference of 0.9%: i.e., approximately 112 patients need to be treated to cause a major bleeding event over a period of 7.4 years. 41.3% of first major bleeding events in the study were gastrointestinal. The incidence of hemorrhagic stroke was similar between groups. There was also no difference in the risk of gastrointestinal tract cancer between groups or risk of fatal and nonfatal cancer overall.

In conclusion, this trial showed that the use of enteric coated aspirin 100mg for people with diabetes results in a risk that is 12% lower of serious vascular events compared with placebo, but also results in a risk of occurrence of any major bleeding that is 29% higher compared with placebo. The lower risk of serious vascular events reported by the ASCEND trial is similar to those of the previous Antithrombotic Trialists’ Collaboration meta-analysis of primary prevention trials. The main difference is that the ASCEND trial possibly provides a balance of the benefits and hazards of aspirin use and entertains a decent external validity because there were higher rates of the use of cardioprotective treatments (statins and blood pressure lowering medications) among participants.

Practice Pearls:

• The use of enteric coated aspirin 100mg for people with diabetes and no evident cardiovascular disease led to a lower risk of serious vascular events compared with placebo, but also led to higher rates of major bleeding over a period of 7.4 years.
• The use of aspirin did not decrease the risk of gastrointestinal tract cancer or any other cancer over a period of 7.4 years, but follow-up is still required and being continued to assess effects on a longer-term.
• The benefits of lower risk of serious vascular events were offset and balanced by the higher rates of major bleeding as they were almost of similar magnitude.

Bowman L, Mafham M, Wallendszus K, et al. The ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018;379:1529-39. DOI: 10.1056/NEJMoa1804988

Marian Ayad, BSPharm, PharmD candidate, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences