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Titolo Effect of Homocysteine Lowering on Mortality and Vascular Disease in Advanced Chronic Kidney Disease and End-stage Renal Disease
Autore R.L. Jamison, P. Hartigan, J.S. Kaufman, D.S. Goldfarb, S.R. Warren, P.D. Guarino, J.M. Gaziano
Referenza JAMA 2007; 298 (10): 1163-1170
Contenuto Context High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown. Objective To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease. Design, Setting, and Participants Double-blind randomized controlled trial (2001- 2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance _30 mL/min) (n=1305) or end-stage renal disease (n=751) and high homocysteine levels (_15 µmol/L). Intervention Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo. Main Outcome Measures The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients. Results Mean baseline homocysteine level was 24.0 µmol/L in the vitamin group and 24.2 µmol/L in the placebo group. It was lowered 6.3 µmol/L (25.8%; P_.001) in the vitamin group and 0.4 µmol/L (1.7%; P=.14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90;95%CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P=.85), time to dialysis (P=.38), and time to thrombosis in hemodialysis patients (P=.97) did not differ between the vitamin and placebo groups. Conclusion Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease.
Data 14.09.2007
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