[Note: peripheral arterial disease is a common circulatory problem in which narrowed arteries reduce blood flow to the limbs. Many have it with mild or no symptoms (are asymptomatic), but some experience muscle pain/cramping when walking. The full text of this article is available free.]
Objective: To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease.
Design: Multicenter, randomized, double blind, 2x2 factorial, placebo controlled trial.
Setting: 16 hospital centers in Scotland, supported by 188 primary care groups.
Participants: 1,276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease.
Interventions: Daily, 100 mg aspirin tablet plus antioxidant capsule (n=320), aspirin tablet plus placebo capsule (n=318), placebo tablet plus antioxidant capsule (n=320), or placebo tablet plus placebo capsule (n=318).
Main Outcome Measures: Two hierarchical composite primary end points of death from coronary heart disease or stroke, non-fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke.
• No evidence was found of any interaction between aspirin and antioxidant.
• Overall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups (18.2% v 18.3%): hazard ratio 0.98 (95% confidence interval 0.76 to 1.26).
• 43 deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups (6.7% v 5.5%): 1.23 (0.79 to 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).
• 42 (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).
Conclusion: This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied.
Trial Registration: Current Controlled Trials ISRCTN53295293.
Source: British Medical Journal, Oct 2008:16;337:a1840 PMID: 18927173, Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, Macfarlane P, Morris A, Jung R, Kelly C, Connacher A, Peden N, Jamieson A, Matthews D, Leese G, McKnight J, O'Brien I, Semple C, Petrie J, Gordon D, Pringle S, MacWalter R; Prevention of Progression of Arterial Disease and Diabetes Study Group; Diabetes Registry Group; Royal College of Physicians Edinburgh; Institute of Cardiovascular Research, University of Dundee, Ninewells Hospital, Dundee, Scotland. [E-mail:J.J.F.Belch@dundee.ac.uk]