Mortality and Cardiovascular Events in Patients Treated With Homocysteine-Lowering B Vitamins After Coronary Angiography

Abstract

Context Observational studies have reported associations between circulating total homocysteine concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B 12 can lower plasma total homocysteine levels.Objective To assess the effect of treatment with folic acid and vitamin B 12 and the effect of treatment with vitamin B 6 as secondary prevention in patients with coronary artery disease or aortic valve stenosis.Design, Setting, and Participants Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double-or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes.Interventions Using a 2ϫ2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B 12 , 0.4 mg, plus vitamin B 6 , 40 mg (n=772); folic acid plus vitamin B 12 (n=772); vitamin B 6 alone (n=772); or placebo (n=780). Main Outcome MeasuresThe primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke. ResultsMean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B 12 . The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B 12 vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P=.36) and 200 participants (13.0%) receiving vitamin B 6 vs 222 (14.3%) not receiving vitamin B 6 (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P=.28).Conclusions This trial did not find an effect of treatment with folic acid/vitamin B 12 or vitamin B 6 on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease.

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

“…Of these, 4164 patients with suspected stable angina pectoris were selected for the current study. About two‐thirds of these patients were included in WENBIT (the Western Norway B‐vitamin Intervention Trial), a randomized clinical trial investigating the effect of B‐vitamin treatment on CVD and mortality 15. NORVIT was a randomized clinical trial including 3749 patients hospitalized with acute myocardial infarction in the period 1998‐2002 and randomized to identical treatment protocols as in WENBIT 16.…”

Plasma Cystathionine and Risk of Incident Stroke in Patients With Suspected Stable Angina Pectoris

“…In brief, 4164 patients who underwent coronary angiography for suspected stable angina pectoris at Haukeland and Stavanger University Hospitals in Western Norway during 2000–2004 were included. Of these, 2573 (61.8%) were subsequently enrolled in the WENBIT (Western Norway B‐vitamin Intervention Trial; NCT00354081) and received either (1) folic acid, vitamin B12 and vitamin B6 (n=642), (2) folic acid and vitamin B12 (n=642), (3) vitamin B6 (n=643), or (4) placebo (n=646) 14. Because B‐vitamin supplementation has been reported to lower the risk of stroke in some studies,15, 16 we excluded patients who received supplementation with B‐vitamins in the WENBIT.…”

“…Information on patients’ lifestyle and medical history were obtained through a self‐administered questionnaire and was validated against hospital records, as previously reported 14. Obesity was identified as having body mass index ≥30 kg/m 2 .…”

C1 metabolism and CVD outcomes in older adults

“…Since 2004, the results of a number of much-awaited secondary prevention trials in at-risk patients began to appear in high-profile medical journals (9)(10)(11)(12)(13)(14)(15) . All these failed to demonstrate a benefit of homocysteine-lowering therapy on CVD events generally (Table 1).…”

“…The B-vitamins folate, vitamins B 12 and B 6 and riboflavin are the source of coenzymes which participate in C 1 metabolism. This metabolic process involves the transfer and utilisation of C 1 units for DNA and RNA biosynthesis, methylation reactions and the metabolism of amino acids including methionine.…”