The aim of ASCEND is to determine whether 100mg daily aspirin and/or supplementation with 1 gram capsules containing 90% omega-3 fatty acids (0.4g EPA, 0.3g DHA) daily prevents cardiovascular events in patients with diabetes who do not already have clinically manifest arterial disease (without leading to significant bleeding or other adverse events). In order to do this reliably, over 15,000 patients with diabetes and no clinical evidence of occlusive arterial disease have been randomly allocated to receive 100mg aspirin or matching placebo tablets and 1g omega-3 fatty acids or matching placebo capsules daily for about 5-7 years. A study of this size should have good power to detect a 10-15% proportional reduction in the cardiovascular event rate among such patients.
Aspirin therapy: The primary comparison will involve "logrank" analyses of "serious vascular events" (defined as the combination of non-fatal myocardial infarction, non-fatal stroke or vascular death excluding confirmed cerebral haemorrhage [ICD I00-I52 and I63-99 in the 10th International Classification of Diseases]) during the scheduled treatment period among all those allocated aspirin tablets versus all those allocated placebo tablets (i.e. "intention-to-treat" comparisons).
Omega-3 fatty acid supplementation: The primary comparison will involve "logrank" analyses of "serious vascular events" during the scheduled treatment period among all those allocated omega-3 fatty acid capsules versus all those allocated placebo capsules.
The principal subsidiary comparisons will be of the effect of allocation to aspirin versus allocation to placebo tablets and, separately, of allocation to omega-3 FA versus allocation to placebo capsules on:
- The incidence of serious vascular events, and the combined endpoint of "serious vascular events or revascularisations" (i.e. serious vascular event, or coronary or non-coronary revascularisation) in various prognostic subgroups (e.g. older versus younger, men versus women, longer versus shorter duration diabetes); and in the presence and absence of the other study treatments.
- The incidence of confirmed cerebral haemorrhage and, separately of other "major haemorrhage" (defined as any other bleeding episode that requires hospitalisation or transfusion, or is fatal or disabling).
The reliable assessment of the important questions that ASCEND is addressing requires the randomisation of a very large number of people with diabetes, and their long-term treatment and follow-up. In order to be able to study 15,000 people with diabetes for about 5-7 years at low cost, ASCEND is streamlined and being undertaken predominantly by mail (supplemented by central records). If it can reliably demonstrate that aspirin and/or omega-3 fatty acids safely reduces the risk of cardiovascular events and deaths in patients with diabetes who do not have pre-existing occlusive arterial disease, then this would be relevant to some tens of millions of people world-wide (who are currently not receiving such therapy) and could save tens of thousands of lives each year.
- Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. Part I: Introduction and design. Br J Cancer 1976;34:585-612