BACKGROUND: Homocysteine is a risk factor for cardiovascular disease. Folic acid, with vitamins B6 and B12, is effective lowering the blood homocysteine levels. The aim of this study is to determine the effect of folic acid-based supplementation in the secondary prevention of clinical events in subjects with intermediate- and high intermediate- and high-risk unstable angina, and non-ST segment elevation myocardial infarction (NSTEMI).
METHODS: The study is a randomized placebo-controlled trial. Two hundred and forty subjects with either unstable angina or NSTEMI in the previous 2 weeks were recruited and randomized into the active group (n=116) or placebo (n=124). The active group received a daily supplement of 1 mg folic acid, 400 ug vitamin B12, and 10 mg vitamin B6. The subjects were followed up for 6 months.
RESULTS: The composite endpoints of death, nonfatal acute coronary syndrome (ACS) and serious rehospitalization is significantly increased in the active treatment (p=0.444, RR=1.20 (1.00-1.44). There is a trend of increasing death and nonfatal ACS. Serious rehospitalizations are significantly higher in the active group (p=0.0161, RR=5.11 (1.14-23.00). Folic acid supplementation is significantly harmful in subjects with advance age (>44 in male;>55 in females) for the composite outcome (p=0.0388), with a strong trend for serious non-ACS rehospitalization (p=0.0606). Folic acid supplementation is significantly harmful to diabetics for composite outcomes (p=0.0275) with a strong trend for nonfatal ACS (p=0.0694). Previous history of stroke significantly predict a lower chance for the active group (p=0.0318).
CONCLUSION: Folic acid with vitamin B12 and B6, is not beneficial and could be harmful in the secondary prevention of death, ACS and serious rehospitalization in patients with unstable angina and NSTEMI. Further studies on the safety of the supplement are suggested before large-scale human use is contemplated.