Aspirin fails to reduce cardiovascular events in diabetes
Aspirin and antioxidants appear to be of little benefit in primary prevention in patients with diabetes, the results of a recent trial suggest.
The POPADAD trial enrolled 1,276 patients aged over 40 with diabetes and evidence of asymptomatic peripheral arterial disease (PAD). Participants were randomised to aspirin 100mg or placebo with an antioxidant or placebo in a 2x2 factorial fashion, and followed up for a median of 6.7 years.
The primary endpoints were a composite of death from CHD or stroke, nonfatal MI or stroke, or amputation above the ankle for critical limb ischaemia; and death from CHD or stroke.
There were 116 primary events in patients in the aspirin groups compared with 117 in the no aspirin groups (HR 0.98, 95% CI 0.76-1.26, P=0.86), and 43 deaths from CHD or stroke in the aspirin groups compared with 35 in the no aspirin groups (HR 1.23, 95% CI 0.79-1.93, P=0.36).
Similar results were seen with antioxidants, with 117 events in the treatment groups compared with 116 in the control groups (HR 1.03, 95% CI 0.79-1.33, P=0.85) and 42 deaths from CHD or stroke in the antioxidant groups compared with 36 in the no antioxidant groups (HR 1.21, 95% CI 0.78-1.89, P=0.40).
Although there appeared to be no significant difference in the primary outcomes, the trial was relatively small and the confidence intervals were wide.
However, patients with diabetes and evidence of PAD are at high risk of CVD and therefore this trial would tend to support the theory that aspirin is best avoided for primary prevention of CVD and should be reserved for patients with a history of a major coronary or cerebral ischaemic event. This is in contrast to the evidence for statins and antihypertensives, where benefit extends across all CVD risk groups, including those without manifest CVD.
This study suggests that aspirin is of no benefit in the primary prevention of cardiovascular events in patients with diabetes. However, I wouldn't give up on aspirin for primary prevention just yet. Clearly, more evidence is required before firm conclusions are drawn.
The ASCEND trial, comprising 10,000 patients, is now underway to try and answer this question.
This trial has added further weight to the evidence already available that antioxidants are unlikely to be of benefit in reducing cardiovascular events.
Belch J, MacCuish A, Campbell I et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 2008;337:1840-50Reviewer
Dr Peter Savill
GPwSI Cardiology, Southampton