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J Am Coll Cardiol, 2003; 41:2105-2113, doi:10.1016/S0735-1097(03)00485-6 © 2003 by the American College of Cardiology Foundation |



* Department of Cardiology, Oosterschelde Ziekenhuizen, Goes, The Netherlands
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Leiden University Medical Center, Leiden, The Netherlands
University Hospital, Groningen, The Netherlands
* Reprint requests and correspondence: Dr. Anho Liem, Department of Cardiology, Oosterschelde Ziekenhuizen, Postbus 106, 4460BB Goes, The Netherlands.
anho{at}zeelandnet.nl
OBJECTIVES: We sought to conduct a randomized trial with folic acid 0.5 mg/day in a patient population with stable coronary artery disease (CAD).
BACKGROUND: Folic acid has favorable effects on vascular endothelium and lowers plasma homocysteine levels. In addition, homocysteine appears to be an independent risk factor for atherosclerotic disease. However, the value of folic acid in secondary prevention had seldom been tested.
METHODS: In this open-label study, 593 patients were included; 300 were randomized to folic acid and 293 served as controls. Mean follow-up time was 24 months. At baseline all patients had been on statin therapy for a mean of 3.2 years.
RESULTS: In patients treated with folic acid, plasma homocysteine levels decreased by 18%, from 12.0 ± 4.8 to 9.4 ± 3.5 µmol/l, whereas these levels remained unaffected in the control group (p < 0.001 between groups). The primary end point (all-cause mortality and a composite of vascular events) was encountered in 31 (10.3%) patients in the folic acid group and in 28 (9.6%) patients in the control group (relative risk 1.05; 95% confidence interval: 0.63 to 1.75). In a multifactorial survival model with adjustments for clinical factors, the most predictive laboratory parameters were, in order of significance, levels of creatinine clearance, plasma fibrinogen, and homocysteine.
CONCLUSIONS: Within two years, folic acid does not seem to reduce clinical end points in patients with stable coronary artery disease (CAD) while on statin treatment. Homocysteine might therefore merely be a modifiable marker of disease. Thus, low-dose folic acid supplementation should be treated with reservation, until more trial outcomes become available.
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