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Aspirin and cardiovascular disease

The role of antiplatelet therapy (chiefly aspirin) for the secondary prevention of cardiovascular disease is firmly established for many high-risk groups with diagnosed occlusive arterial disease, and the proportional reductions in heart attacks and strokes appear to be similar whether or not these patients have diabetes.

In patients with occlusive arterial disease the figure shows that the proportional benefits of antiplatelet therapy are similar in people with or without diabetes.

But, most younger and middle-aged people with diabetes do not have manifest arterial disease - although they are still at significant cardiovascular risk - and yet the available randomised evidence for the use of antiplatelet therapy in such individuals is sparse. As a result, there is major uncertainty about the role of antiplatelet therapy for the primary prevention of cardiovascular events among people with diabetes, and only a small minority receives it. Surveys from around the world indicate that in general less than 20% of patients with diabetes and no vascular disease take regular aspirin.

The main randomised evidence currently available on the effects of antiplatelet therapy in such patients with diabetes comes from 9 trials involving a total of about 5000 patients, and a meta-analysis of their results indicates a much smaller proportional reduction in cardiovascular events than has been found in the secondary prevention setting (just 7% compared with about 20-25%).[2] Even in aggregate, however, those studies in diabetics involved relatively few events, and the confidence interval for the estimated effect is wide, ranging from a 23% risk reduction to an 8% hazard.

Given the consistency of the beneficial effect in other high-risk settings (including patients with diabetes and arterial disease), it seems likely that the true effect of antiplatelet therapy in people with diabetes alone is similar to the reduction of about one-quarter seen overall in high-risk patients as, for example, has been shown with cholesterol-lowering[3] and anti-hypertensive therapies[4].

Higher intake of omega-3 fatty acids is associated with less cardiovascular disease

There is consistent evidence from observational studies of lower rates of cardiovascular disease (particularly cardiac and sudden death) in people with higher intakes, or higher blood levels, of omega-3 fatty acids (FA). For example, in a recent meta-anaysis of cohort studies examining the relationship of fish consumption and coronary heart disease, the pooled estimate suggests that consumption of fish once a week versus less than once a month is associated with 15% (95% CI 4-24%) lower risk of coronary mortality.

At the time ASCEND was designed, randomised evidence from 11,000 patients who had survived a myocardial infarction suggested modest (but potentially worthwhile), 15-20% proportional reductions in coronary events.[5] However, since ASCEND started, several other large randomized trials of omega-3 FA supplementation have reported results. In 2012, a meta-analysis of published data including around 8000 vascular events in about 60,000 participants, showed that allocation to omega-3 FA supplements had no significant effect on reported vascular events (RR=0.96; 95% CI, 0.90–1.03; P=0.24).[6] Hence these recent data do not support the earlier hypothesis that omega-3 fatty supplementation might reduce coronary and other occlusive vascular events by 15-20%. However, many of these trials did not include substantial numbers of people with diabetes and therefore the results of ASCEND will contribute to the reliable assessment of the effects of omega-3 FA in this group. 


  1. Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatelet therapy. I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994;308:81-106
  2. Antithrombotic Trialists' Collaborative Group. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction and stroke in high risk patients. BMJ 2002;324:71-86
  3. MRC/BHF Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals. Lancet 2002;360:7-22
  4. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703-13
  5. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999;354:447-55
  6. Kotwal S, Jun M, Sullivan D, Perkovic V, Neal B. Omega 3 Fatty acids and cardiovascular outcomes: systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2012;5(6):808-18