How the conflicting results of the ASCEND trial are actually much more determinant than they appear, and critical in the scope of treating comorbidities in patients with diabetes.
Jane Armitage, FRCP, FFPH
Upon completing one of the greatest clinical assessments of aspirin for patients with diabetes mellitus (DM), investigators have come to a conclusion: the jury’s still out.
The results of the randomized Study of Cardiovascular Events in Diabetes (ASCEND) trial, presented at the European Society of Cardiology (ESC) 2018 Congress this weekend, assessed for the efficacy and safety of enteric-coated aspirin for patients with DM. In analyzing 15,480 patients with DM who were administered either once-daily 1 mg aspirin and 1 g n-3 fatty acid tablet or placebo equivalent, investigators from the University of Oxford found conflicting results in its effect on vascular event prevention and rates of major bleeding events.
In their 7.4-year mean follow-up analysis, investigators found that significantly fewer patients treated with aspirin (8.5%) reported serious vascular events than patients treated with placebo (9.6%). They also found that the former group were more likely to experience major bleeding events (4.1%) than the latter group (3.2%).
In an interview with MD Magazine®, investigator Jane Armitage, FRCP, FFPH, professor of Clinical Trials and Epidemiology in the Nuffield Department of Population Health, University of Oxford, explained how the conflicting results of the ASCEND trial are actually much more determinant than they appear, and critical in the scope of treating comorbidities in patients with diabetes.
MD Mag: What was the inspiration for this study?
Armitage: Patients with diabetes are, on average, at increased risk of cardiovascular disease. Aspirin reduces the risk of second cardiovascular events and is recommended for patients who have evidence of cardiovascular disease. However, its role in preventing first events (primary prevention) was less clear because of the increase in bleeding. It was therefore unclear whether aspirin should be recommended for cardiovascular prevention in diabetic patients without existing cardiovascular disease.
What is the significance of these results?
ASCEND is the largest study ever undertaken to investigate whether aspirin should be recommended for cardiovascular prevention in diabetic patients without existing cardiovascular disease. We have shown conclusively that aspirin reduces the risk of vascular events in primary prevention, as it does in people who already have cardiovascular disease, but these benefits are counter-balanced by the number of major bleeds.
This is an important finding with implications for many millions of people who have diabetes but have not yet had cardiovascular events. Current clinical guidelines vary in their recommendations about the use of aspirin for primary prevention because of a previous lack of clear evidence. The results of ASCEND now provide much needed clarity. We have shown that there is no added benefit to taking aspirin.
What are the next steps with this data? Since the benefits and hazards of aspirin treatment for patients with diabetes mellitus are unclear, what work needs to be done to clarify this uncertainty?
The ASCEND trial did provide clarity regarding the use of aspirin to prevent first cardiovascular events.
Previous studies had suggested that aspirin might produce a reduction in cancers in the gut (especially in the bowel), with the effects increasing over time. A large number of cancers were observed during 7.4 years of follow-up in the ASCEND trial. However, no effect of aspirin on incident gastrointestinal cancer was observed, nor was there any apparent effect of aspirin on the overall risk of cancer. Longer-term follow-up is ongoing to see if any effects on cancer emerge later.
We also looked at the use of fish oil supplements to reduce the risk of cardiovascular events in patients with diabetes and found that fish oil supplements do not reduce the risk of cardiovascular events in patients with diabetes. We are analysing these data to see whether any cognitive benefits are derived from taking fish oil supplements.