A randomized trial of 15,480 adults in the UK who had diabetes but no evidence of cardiovascular disease showed mixed results for aspirin use and no benefit for use of omega-3 fatty acids in preventing serious vascular events at 7.4 years follow-up, according to findings presented Sunday at the European Society of Cardiology (ESC) Congress 2018 in Munich, Germany.
The ASCEND (A Study of Cardiovascular Events in Diabetes) trial did find a significant reduction of serious vascular events with the daily use of a small dose of aspirin, but that benefit was largely canceled out by increased bleeding risk, results show.
ASCEND ‑ A randomized trial of aspirin versus placebo for primary cardiovascular prevention in 15,480 people with diabetes
The trial randomized diabetic adults with no evidence of cardiovascular disease to receive a daily dose of 100 mg of aspirin or matching placebo.
Jane Armitage, FRCP, FFPH, a professor of clinical trials and epidemiology at the University of Oxford, presented the findings at ESC on behalf of the ASCEND Study Collaborative Group.
The primary efficacy outcome was the first serious vascular event, which was defined as myocardial infarction, stroke or transient ischemic attack, or death from any vascular cause, excluding any confirmed intracranial hemorrhage. The primary safety outcome was the first major bleeding event, defined as intracranial hemorrhage, sight-threatening bleeding in the eye, gastrointestinal bleeding or other serious bleeding. Secondary outcomes included gastrointestinal tract cancer.
During a mean follow-up of 7.4 years, serious vascular events occurred in a significantly lower percentage of participants in the aspirin group than in the placebo group (658 participants [8.5%] vs. 743 [9.6%]; rate ratio 0.88; 95% CI 0.79-0.97). However, major bleeding events occurred in 314 participants (4.1%) in the aspirin group vs. 245 (3.2%) in the placebo group (rate ratio 1.29; 95% CI 1.09-1.52), according to a manuscript simultaneously published in the New England Journal of Medicine.
There was no significant difference between the aspirin group and the placebo group in the incidence of gastrointestinal tract cancer (157 participants [2.0%] and 158 [2.0%], respectively) or all cancers (897 [11.6%] and 887 [11.5%]).
The investigators concluded that aspirin use significantly reduced the risk of serious vascular events but also significantly increased the risk of major bleeding. The absolute benefits were largely canceled out by the bleeding hazard.
“There was no group in which the benefits (of aspirin use) clearly outweighed the risks,” Armitage said in concluding her presentation at ESC.
ASCEND ‑ A randomized trial of omega‑3 fatty acids (fish oil) versus placebo for primary cardiovascular prevention in 15,480 people with diabetes
A separate portion of the trial randomized the patients to receive 1 g capsules containing either 840 mg of marine omega-3 fatty acids (460 mg of eicosapentaenoic acid and 380 mg of docosahexaenoic acid), known as the fatty acid group, or a matching placebo capsule (olive oil) to be taken once daily.
Louise Bowman, MD, a professor of clinical trials and epidemiology at the University of Oxford, presented the findings at ESC on behalf of the ASCEND Study Collaborative Group.
The primary outcome was the first serious vascular event, which was defined as nonfatal myocardial infarction or stroke, transient ischemic attack, or vascular death, excluding confirmed intracranial hemorrhage. The secondary outcome was a first serious vascular event or any arterial revascularization.
During a mean follow-up of 7.4 years, in which rate of patient adherence to the regimen was 76%, a serious vascular event occurred in 689 patients (8.9%) in the fatty acid group and in 712 (9.2%) in the placebo group (rate ratio 0.97; 95% CI, 0.87-1.08). The composite outcome of a serious vascular event or revascularization occurred in 882 patients (11.4%) in the fatty acid group and 887 patients (11.5%) in the placebo group (rate ratio 1.00; 95% CI 0.91-1.09). Death from any cause occurred in 752 patients (9.7%) in the fatty acid group and in 788 (10.2%) in the placebo group (RR 0.95; 95% CI 0.86-1.05), according to a manuscript simultaneously published in the New England Journal of Medicine.
The investigators concluded that among patients with diabetes without evidence of cardiovascular disease, there was no significant difference in the risk of serious vascular events between those who were assigned to receive omega-3 fatty acid supplementation and those who were assigned to receive placebo.
“These findings, together with results of earlier randomized trials involving patients with and those without diabetes, do not support the current recommendations for routine dietary supplementation with n−3 (omega-3) fatty acids to prevent vascular events,” Bowman and colleagues wrote.
The ASCEND trial was sponsored by the University of Oxford and funded by the British Heart Foundation and UK Medical Research, with support from Abbott, Bayer, Mylan and Solvay.