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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):1163-70JAMA

Abstract

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 < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/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 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/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.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00032435.

Authors+Show Affiliations

Veterans Affairs Palo Alto Health Care Systems and Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94304, USA. rjamison@stanford.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

17848650

Citation

Jamison, Rex L., et al. "Effect of Homocysteine Lowering On Mortality and Vascular Disease in Advanced Chronic Kidney Disease and End-stage Renal Disease: a Randomized Controlled Trial." JAMA, vol. 298, no. 10, 2007, pp. 1163-70.
Jamison RL, Hartigan P, Kaufman JS, et al. 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):1163-70.
Jamison, R. L., Hartigan, P., Kaufman, J. S., Goldfarb, D. S., Warren, S. R., Guarino, P. D., & Gaziano, J. M. (2007). Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. JAMA, 298(10), pp. 1163-70.
Jamison RL, et al. 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 Sep 12;298(10):1163-70. PubMed PMID: 17848650.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. AU - Jamison,Rex L, AU - Hartigan,Pamela, AU - Kaufman,James S, AU - Goldfarb,David S, AU - Warren,Stuart R, AU - Guarino,Peter D, AU - Gaziano,J Michael, AU - ,, PY - 2007/9/13/pubmed PY - 2007/9/15/medline PY - 2007/9/13/entrez SP - 1163 EP - 70 JF - JAMA JO - JAMA VL - 298 IS - 10 N2 - 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 < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/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 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00032435. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/17848650/Effect_of_homocysteine_lowering_on_mortality_and_vascular_disease_in_advanced_chronic_kidney_disease_and_end_stage_renal_disease:_a_randomized_controlled_trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.298.10.1163 DB - PRIME DP - Unbound Medicine ER -