asymptomatic peripheral arterial disease and antioxidants in patients with diabetes and randomised placebo controlled trial of aspirin factorial disease and diabetes (POPADAD) trial: The prevention of progression of arterial

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. DesignMulticentre, randomised, double blind, 2×2 factorial, placebo controlled trial. Setting16hospital centres in Scotland, supported by 188 primary care groups. Participants 1276 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 primaryendpointsofdeath fromcoronaryheartdiseaseor stroke, non-fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke. ResultsNoevidencewas foundof any interactionbetween 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). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups comparedwith 35 in the no aspirin groups (6.7% v 5.5%): 1.23 (0.79 to 1.93). Among the antioxidant groups117of 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 comparedwith 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 andmortality in thepopulationwith diabetes studied. Trial registration Current Controlled Trials ISRCTN53295293. INTRODUCTION Cardiovascular disease is themajor cause of morbidity and mortality in patients with type 1 or type 2 diabetes mellitus. These patients have been reported to have an overall mortality of 50% within 40 years of diagnosis comparedwith only 10% in a control population. This increased mortality is mainly from ischaemic heart disease and cerebrovascular disease, the incidence of which is reported to be twofold to fivefold greater 5 than the general population without diabetes. Peripheral arterial disease is another powerful indicator of systemic atheroma. Regardless of whether symptoms are evident, patients with peripheral Institute of Cardiovascular Research, University of Dundee, Ninewells Hospital, Dundee DD1 9SY Diabetes Centre, Glasgow Royal Infirmary Department of Medicine, Royal Victoria Hospital, Kirkcaldy British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow Royal Victoria Infirmary, Newcastle upon Tyne Department of Biochemistry, Glasgow Royal Infirmary Department of Medical Cardiology, Glasgow Royal Infirmary Medical Statistics Unit, University of Edinburgh Diabetes Research Centre, Ninewells Hospital Diabetes and Endocrinology, Ninewells Hospital Diabetes Centre, Stirling Royal Infirmary Diabetes Centre, Perth Royal Infirmary Diabetes Centre, Falkirk and District Royal Infirmary, Falkirk Diabetes Centre, Queen Margaret Hospital, Dunfermline BMJ | ONLINE FIRST | bmj.com page 1 of 10 on 17 October 2008 bmj.com Downloaded from