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.


RESULTS
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.


CONCLUSIONS
In haemodialysis patients with prevalent cardiovascular disease, supplementation with 800 IU/day vitamin E reduces composite cardiovascular disease endpoints and myocardial infarction.
Boaz
M
M
Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, Tel Aviv University, Israel. mboaz8@yahoo.com
Smetana
S
S
Weinstein
T
T
Matas
Z
Z
Gafter
U
U
Iaina
A
A
Knecht
A
A
Weissgarten
Y
Y
Brunner
D
D
Fainaru
M
M
Green
M S
MS
D000368:Aged; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000517:prevention & control*; D003679:Deglutition / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011537:Pruritus / Q000139:chemically induced; D006435:Renal Dialysis; D016019:Survival Analysis; D016896:Treatment Outcome; D014810:Vitamin E / Q000009:adverse effects / Q000627:therapeutic use*
D000975:Antioxidants; D014810:Vitamin E