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 h aemodialysis patients. Oxidative stress is greater in haemodialysis patient s with prevalent cardiovascular disease than in those without, suggesting a role for oxidative stress in excess cardiovascular disease in haemodialysi s. We investigated the effect of high-dose vitamin E supplementation on car diovascular disease outcomes in haemodialysis patients with pre-existing ca rdiovascular disease. Methods Haemodialysis patients with pre-existing cardiovascular disease (n= 196) aged 40-75 years at baseline from six dialysis centres were enrolled a nd 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), ischae mic stroke, peripheral vascular disease (excluding the arteriovenous fistul a), 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 3 3 (33%) of the 99 patients assigned to placebo had a primary endpoint (rela tive 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 inf arction (0.3 [0.11-0.78], p=0.016). No significant differences in other sec ondary endpoints, cardiovascular disease, or total mortality were detected. Interpretation In haemodialysis patients with prevalent cardiovascular dise ase, supplementation with 800 IU/day vitamin E reduces composite cardiovasc ular diesease endpoints and myocardial infarction.