Methods	Design: randomised, open-label, controlled trial. Single centre study. Follow-up period: 1 year.
Participants	N: 593 randomised patients (folic acid: 300 versus standard care: 293). Sex (% males): folic acid: 76% versus standard care: 80%. Age (mean±SD): folic acid: 64.9± 9.9 versus standard care: 65.5± 9.7 Homocysteine levels at baseline: not reported Inclusion criteria: Myocardial infarction, Coronary artery lesions (>60%) on coronary angiography, Percutaneous coronary intervention (PCI), Coronary artery bypass graft surgery (CABG), Patients had to be stable, with no invasive vascular procedures scheduled, Statin therapy for at least three months, Taking any form of vitamin B-containing medication, regularly or sporadic Exclusion criteria: Age < 18 years, History of low vitamin B12 levels, Therapy for hyperhomocysteinemia, Severe renal failure, or any other treatment for renal disease, Hepatic disease, Severe heart failure (New York Heart Association functional class IV), Serious illness that would exclude follow-up time of at least three years
Interventions	Intervention:folic acid: 0.5 mg per day. Control group: Standard care Intensive follow-up and treatment of risk factors, with counselling provided by a qualified nurse. Statin dosage was increased when necessary. Dietary counselling was provided, and smoking discouraged Treatment duration: not reported.
Outcomes	Primary outcome (composite): Composite: vascular death (sudden death, fatal recurrent MI, fatal stroke, and other cardiovascular deaths), Non cardiovascular death, Recurrent MI; Invasive coronary procedures (PCI, CABG); Cerebrovascular accident or transient ischemic attack; Any other vascular surgery (carotid endarterectomy, abdominal aneurysmectomy, or peripheral vascular surgery including limb amputation for vascular reasons) Secondary: Hospitalization for unstable angina
Notes	Study phase: III Sample size calculation a priori: Sample size calculation (80% power and 5% significance level) to detect a 50% reduction in clinical events in that kind of patients, assuming a two-years event rate of 15%. These numbers resulted in an estimation of 300 patients per group. Analyses conducted in ITT basis Sponsors: Trial with public funding (Stichting Paracard). Other: The trial allowed the entry of patients taking vitamin B supplementation. These patients showed higher levels of serum folate and lower levels of homocysteine
Risk of bias
Item	Authors’ judgement	Description
Adequate sequence generation?	Yes	Quote: ‘A computer program randomly allocated patients […] to treatment’
Allocation concealment?	Unclear	No information reported about this domain.
Blinding? All outcomes	No	‘… treatment with open label folic acid […] or standard care’
Incomplete outcome data addressed? All outcomes	Yes	After randomization, 12 patients per group withdrew the study but were followed and included in the final analysis