Ms. Sabina A. Murphy
Cardiosource. 2006; ©2006 American College of Cardiology
Posted 09/01/2006
Year Published: 2006
Description: The goal of the study was to evaluate the effect of folic acid compared with placebo on cardiovascular (CV) disease and atheroma progression among patients with end-stage renal disease.Drugs/Procedures Used: Patients were randomized to folic acid (15 mg per day; n = 156) or placebo (n = 159). Carotid intima-media thickness (IMT) measurements were obtained annually.
Principal Findings: At study entry, 65.4% of the folic acid group and 56.6% of the placebo group were on hemodialysis. Total plasma homocysteine was 27 µmol/l in both groups at baseline. Folic acid supplements were used at entry in 35% of patients. Total plasma homocysteine was reduced in the folic acid group by 19%. At baseline, mean maximum carotid IMT was 1.06 mm in the folic acid group and 1.08 mm in the placebo group. There was no difference in change in IMT from baseline between treatment groups (-0.020 for folic acid and 0.030 for placebo; p=NS). For the clinical primary endpoint of first CV death, myocardial infarction (MI), or stroke, there was also no difference between treatment groups (6.7 per 100 patient-years for the folic acid group vs. 8.2 per 100 patient-years for the placebo group, p = 0.75). Likewise, there was no difference in the secondary endpoint of first CV event or CV death (9.6 per 100 patient-years for the folic acid group vs. 11.7 per 100 patient-years for the placebo group, p = 0.52). Adverse events leading to study drug discontinuation occurred in 25% of the folic acid group and 18% of the placebo group.
Interpretation: Among patients with chronic renal disease, treatment with folic acid supplements was not associated with a difference in atheroma progression or CV events compared with placebo at a mean follow-up of 3.6 years. Prior observation studies suggested a link between hyperhomocysteinemia and CV disease in patients with chronic renal failure, which led the authors to evaluate whether using folic acid to lower plasma homocysteine levels would reduce atheroma progression and CV events. Despite a reduction in plasma homocysteine levels, there was no difference in IMT thickness or CV events, suggesting the link between lower plasma homocysteine levels and outcomes may not be causal in this population. Other studies in patients with coronary heart disease have also shown no reduction in CV events with folic acid, despite reductions in homocysteine levels.
Conditions: • Prevention
Study Design
Placebo controlled. Randomized. Blinded.
Patients Enrolled: 315
Mean Follow-Up: Median 3.6 years
Mean Patient Age: Mean age 57 years
% Female: 32
Primary Endpoints: Change in the rate of progression of mean maximum carotid artery IMT; composite of MI, stroke, or death from CV cause
Secondary Endpoints: MI, stroke, unstable angina, revascularization, and peripheral vascular disease
Patient Population: Age >18 years with chronic renal failure of any cause, serum creatinine =0.40 mmol/l (creatinine clearance <25 ml/min), and either awaiting dialysis or already treated with continuous ambulatory peritoneal dialysis, intermittent peritoneal dialysis, or hemodialysis
Related Trials: Folic Acid for Secondary Prevention: Effects on Clinical Outcomes (Folic Acid for Secondary Prevention: Effects on Clinical Outcomes) http://www.cardiosource.com/pops/trialsum.asp?trialID=846 Folic Acid Improves Endothelial Function in Coronary Artery Disease via Mechanisms Largely Independent of Homocysteine Lowering (Folic Acid Improves Endothelial Function in Coronary Artery Disease via Mechanisms Largely Independent of Homocysteine Lowering) http://www.cardiosource.com/pops/trialsum.asp?trialID=509