Randomized controlled trial of antioxidants in intermittent claudication

Abstract

Epidemiological evidence suggests that antioxidants protect against the development of atherosclerosis. To determine the effectiveness of antioxidant therapy in patients with lower limb atherosclerosis, a randomized placebo- controlled trial was performed in 120 men and women with intermittent claudication and an ankle/brachial pressure index (ABPI) ≤0.9. The study was analysed on an intention-to-treat basis. After 2 years, there were no significant differences between antioxidant and placebo groups in plasma cholesterol, lipoproteins, haemostatic or rheological factors. However, after 6 months, low density lipoprotein cholesterol was significantly lower in those taking antioxidant (108.0 mg/dl compared with 120.1 mg/dl, p<0.05). There were no differences in the ABPI or walking distance, although both groups improved slightly with time. The incidence of cardiovascular events and death was nonsignificantly lower in the antioxidant compared with the placebo group: event rates per year were 5.5% (95% CI 2.4-8.6) in the first year and 9.6% (95% CI 6.8-12.4) in the second year for those on antioxidants; and 7.7% (95% CI 5.1-10.3) and 13.3% (95% CI 8.9-17.7) respectively for those on placebo. Significantly fewer serious adverse events occurred in the antioxidant than the placebo group: 21.8% (95% CI 16.2-27.4) compared with 40.0% (95% CI 33.9-46.1). This study therefore suggests that although antioxidants may prevent cardiovascular events in patients with peripheral atherosclerosis, they do not improve lower limb function.