Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial

Background Excess cardiovascular mortality has been documented in chronic haemodialysis patients. Oxidative stress is greater in haemodialysis patients with prevalent cardiovascular disease than in those without, suggesting a role for oxidative stress in excess cardiovascular disease in haemodialysis. We investigated the effect of high-dose vitamin E supplementation on cardiovascular disease outcomes in haemodialysis patients with pre-existing cardiovascular disease. Methods Haemodialysis patients with pre-existing cardiovascular disease (n=196) aged 40–75 years at baseline from six dialysis centres were enrolled and randomised to receive 800 IU/day vitamin E or matching placebo. Patients were followed for a median 519 days. The primary endpoint was a composite variable consisting of: myocardial infarction (fatal and non-fatal), ischaemic stroke, peripheral vascular disease (excluding the arteriovenous fistula), and unstable angina. Secondary outcomes included each of the component outcomes, total mortality, and cardiovascular-disease mortality. Findings A total of 15 (16%) of the 97 patients assigned to vitamin E and 33 (33%) of the 99 patients assigned to placebo had a primary endpoint (relative risk 0·46 [95% CI 0·27–0·78], p=0·014). Five (5·1%) patients assigned to vitamin E and 17 (17·2%) patients assigned to placebo had myocardial infarction (0·3 [0·11–0·78], p=0·016). No significant differences in other secondary endpoints, cardiovascular disease, or total mortality were detected. Interpretation In haemodialysis patients with prevalent cardiovascular disease, supplementation with 800 IU/day vitamin E reduces composite cardiovascular disease endpoints and myocardial infarction.