Modest benefit from aspirin as primary prevention therapy in diabetics

Although several large trials of aspirin for primary prevention have included diabetic subgroups, no trial has been specifically dedicated to looking at the effects of aspirin in this patient group.

Ogawa et al. conducted a multicentre, prospective, randomized, blinded trial at 163 Hospitals in Japan.  2539 patients with type 2 diabetes were assigned to either 81mg or 100mg of aspirin a day or to the nonaspirin group.  The primary end point was any atherosclerotic event; the secondary endpoints included combinations of the primary endpoints and death from any cause.

Overall 154 atherosclerotic events occurred: 68 in the aspirin group (13.6 per 1000 person-years) and 86 in the nonaspirin group (17.0 per 1000 person-years) (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.58-1.10; log-rank test, P = .16). The combined end point of fatal coronary events and fatal cerebrovascular events occurred in 1 patient (stroke) in the aspirin group and 10 patients (5 fatal myocardial infarctions and 5 fatal strokes) in the nonaspirin group (HR, 0.10; 95% CI, 0.01-0.79; P = .0037). A total of 34 patients in the aspirin group and 38 patients in the nonaspirin group died from any cause (HR, 0.90; 95% CI, 0.57-1.14; log-rank test, P = .67). The composite of hemorrhagic stroke and significant gastrointestinal bleeding was not significantly different between the aspirin and nonaspirin groups.

The presence of diabetes mellitus and peripheral arterial disease (PAD) increase future cardiovascular mortality by two and six-fold respectively, as compared to healthy populations. Guidelines currently recommend the use of aspirin for the primary prevention of cardiovascular disease among subjects with diabetes or PAD, despite there being a lack of evidential support. Additionally, among high-risk patients the role of anti-oxidant therapy, which may reduce oxidative stress and decrease platelet aggregation, remains unclear.

In a multicentre, randomised, double blind, 2 x 2 factorial, placebo controlled trial, Belch and colleagues investigated the effects of aspirin and / or antioxidant therapy in 1,276 patients with diabetes and asymptomatic PAD.  Overall, 116 of 638 (18.2%) primary events occurred in patients taking aspirin compared with 117 of 638 (18.3%) in the no aspirin group (hazard ratio 0.98; 95% confidence interval 0.76-1.26). 43 deaths from coronary heart disease or stroke (6.7%) occurred in the aspirin groups compared with 35 in the no aspirin groups(5.5%) (hazard ratio 1.23; 95% confidence interval 0.79-1.93). Among the antioxidant groups 117 of 640 (18.3%) primary events occurred compared with 116 of 636 (18.2%) in the no antioxidant groups (1.03, 0.79 to 1.33). Forty two (6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 (5.7%) in the no antioxidant groups (1.21, 0.78 to 1.89).

Therefore the first trial demonstrated a significant reduction in cardiovascular endpoints with aspirin use, but limited overall benefit.  This contrasts the second trial published in the BMJ. Current guidelines recommend daily aspirin for diabetics in order to reduce cardiovascular risk, however firm evidence for this recommendation is lacking.  Two upcoming trials aim to provide further information on the role of aspirin as primary prevention therapy: A Study of Cardiovascular Events in Diabetes (ASCEND) and Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D).

  • Ogawa H, Nakayama M, Morimoto T, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA 2008; 300:2180-2181.
  • Nicolucci A. Aspirin for primary prevention of cardiovascular events in diabetes. Still an open question. JAMA 2008; 300:2134-2141.
  • Belch J, MacCuish A, Campbell I, et al. The prevention and progression of arterial disease and diabetes (POPADAD) trial: factorial randomized placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease.BMJ 2008;337:a1840