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Randomized Controlled Trial
. 2011 Apr 26;123(16):1763-70.
doi: 10.1161/CIRCULATIONAHA.110.000588. Epub 2011 Apr 11.

Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial

Andrew G Bostom  1 , Myra A Carpenter, John W Kusek, Andrew S Levey, Lawrence Hunsicker, Marc A Pfeffer, Jacob Selhub, Paul F Jacques, Edward Cole, Lisa Gravens-Mueller, Andrew A House, Clifton Kew, Joyce L McKenney, Alvaro Pacheco-Silva, Todd Pesavento, John Pirsch, Stephen Smith, Scott Solomon, Matthew Weir
Affiliations
Randomized Controlled Trial

Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial

Andrew G Bostom et al. Circulation. .

Abstract

Background: Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease. The impact of lowering total homocysteine levels in kidney transplant recipients is unknown.

Methods and results: In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome (myocardial infarction, stroke, cardiovascular disease death, resuscitated sudden death, coronary artery or renal artery revascularization, lower-extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high-dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n=547 total events; hazards ratio [95 confidence interval]=0.99 [0.84 to 1.17]), secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86 to 1.26]), or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93 to 1.43]) compared to the low-dose multivitamin.

Conclusions: Treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level.

Trial registration: ClinicalTrials.gov NCT00064753.

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Figures

Figure 1
Figure 1
Enrollment, follow-up and analysis diagram
Figure 2
Figure 2
Kaplan-Meier analyses for (A) Primary CVD, (B) All-cause mortality, and (C) Dialysis-dependent kidney failure outcomes
Figure 3
Figure 3
Hazard ratios for treatment group comparisons from primary and secondary outcome subgroup analyses
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