General

Clinical Question:
Does reducing homocysteine levels with supplemental folic acid and B vitamins reduce mortality or morbidity in patients with chronic kidney disease?

Bottom Line:
Supplemental folic acid and B vitamins in patients with chronic kidney disease does not reduce mortality or the incidence of cardiovascular events. (LOE = 1b)

Reference:
Jamison RL, Hartigan P, Kaufman JS, et al, for the Veterans Affairs Site Investigators. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease. A randomized controlled trial. JAMA 2007;298(10):1163-1170.  [PMID:17848650]

Study Design:
Randomized controlled trial (double-blinded)

Funding:
Industry + govt

Allocation:
Concealed

Setting:
Outpatient (any)

Synopsis:
Supplemental folic acid and B vitamins is not beneficial in high-risk cardiovascular patients. Whether this is also true for patients with chronic renal disease is unknown. These investigators identified 2056 adults, 21 years or older, with advanced or end-stage chronic kidney disease and elevated homocysteine levels (>= 15 umol/L). Patients randomly received, in double-blind fashion (concealed allocation assignment), a once-daily capsule containing folic acid (40 mg), pyridoxine (100 mg), and cyanocobalamin (2mg), or an identical placebo. Individuals assessing outcomes remained masked to treatment group assignment. Complete follow-up occurred for more than 96% of patients for a median length of 3.2 years. Analyses were by intention to treat. Although plasma homocysteine levels were significantly lower in the intervention group, treatment had no effect on all-cause mortality or the incidence of any secondary outcomes, including myocardial infarction, stroke, or amputation. The study was 80% powered to detect a 17% relative risk reduction in mortality in the intervention group compared with the placebo group.