Patients with end-stage kidney disease treated with high doses of folic acid and B vitamins to lower homocysteine levels did not have improvement in survival or reductions in the incidence of vascular events, according to a study in the September 12 issue of JAMA.
Numerous studies have shown that high plasma levels of homocysteine are associated with vascular disease. Patients with chronic kidney disease or end-stage renal disease (ESRD) have extensive vascular disease, with estimates of an annual rate of death as high as 20 percent, according to background information in the article. Folic acid and B vitamins decrease homocysteine levels in these patients, but whether they lower the rate of death and vascular events is not known.
Rex L. Jamison, M.D., of the Veterans Affairs (VA) Palo Alto Health Care Systems and Stanford University School of Medicine, Stanford, Calif., and colleagues conducted a study to determine whether treatment with a combination of high-dose folic acid and B vitamins can reduce the rate of death and cardiovascular events in patients with advanced chronic kidney disease (ACKD) and ESRD. The randomized controlled trial (2001-2006), involving 36 VA medical centers, included patients with ACKD (n = 1,305) or ESRD (n = 751) and high homocysteine levels. Median (midpoint) follow-up was 3.2 years. Participants received a daily capsule containing folic acid and vitamin B6 and B12 or a placebo.
After three months, patients in the vitamin group had their homocysteine level lowered by about 26 percent, while this level decreased by 1.7 percent in the placebo group. This treatment had no significant effect on the rate of death between the two groups (448 deaths in the vitamin group vs. 436 deaths in the placebo group). Treatment also had no significant effect on other outcomes such as heart attack, stroke and amputation.
"What might account for the failure of the treatment in our study" Possibly the underlying burden of disease was too great for a measurable benefit from lowering homocysteine," the authors write.
"Our findings do not support the administration of folic acid and B vitamin supplements to prevent vascular injury or improve survival in patients with ACKD or ESRD."
(JAMA. 2007;298(10):1163-1170. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: B Vitamins for the Prevention of Vascular Disease - Insufficient Evidence to Justify Treatment
In an accompanying editorial, Colin Baigent, B.M., B.Ch., F.R.C.P., and Robert Clarke, M.D., F.R.C.P., of the University of Oxford, England, speculate on why this and other trials have failed to show B vitamins as an effective treatment for this condition.
"Possible reasons for the failure of the 5 completed trials to demonstrate statistically definite effects on vascular risk include an inadequate number of recorded events or insufficient duration of treatment; an attenuation of the benefit owing to folic acid fortification in North America, where most of the trials have been conducted to date; or a true failure of treatment to reduce vascular risk."
(JAMA. 2007;298(10):1212-1214. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.
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