Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction
Open accessAbstract
BACKGROUND: Homocysteine is a risk factor for cardiovascular disease. We evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients who had had an acute myocardial infarction. METHODS: The trial included 3749 men and women who had had an acute myocardial infarction within seven days before randomization. Patients were randomly assigned, in a two-by-two factorial design, to receive one of the following four daily treatments: 0.8 mg of folic acid, 0.4 mg of vitamin B12, and 40 mg of vitamin B6; 0.8 mg of folic acid and 0.4 mg of vitamin B12; 40 mg of vitamin B6; or placebo. The primary end point during a median follow-up of 40 months was a composite of recurrent myocardial infarction, stroke, and sudden death attributed to coronary artery disease. RESULTS: The mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12, but such treatment had no significant effect on the primary end point (risk ratio, 1.08; 95 percent confidence interval, 0.93 to 1.25; P=0.31). Also, treatment with vitamin B6 was not associated with any significant benefit with regard to the primary end point (relative risk of the primary end point, 1.14; 95 percent confidence interval, 0.98 to 1.32; P=0.09). In the group given folic acid, vitamin B12, and vitamin B6, there was a trend toward an increased risk (relative risk, 1.22; 95 percent confidence interval, 1.00 to 1.50; P=0.05). CONCLUSIONS: Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested. Such treatment should therefore not be recommended. (ClinicalTrials.gov number, NCT00266487.).
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- Authors
- Bønaa, K. H., Njølstad, I., Ueland, P. M., Schirmer, H., Tverdal, A., Steigen, T., Wang, H., Nordrehaug, J. E., Arnesen, E., & Rasmussen, K.
- Affiliations
- UiT The Arctic University of Norway (NO)
- University of Bergen (NO)
- Norwegian Institute of Public Health (NO)
- University Hospital of North Norway (NO)
- Haukeland University Hospital (NO)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-04-13
- Volume
- 354
- Issue
- 15
- Pages
- 1578-1588
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2115135910
- Cited by
- 1,442
- References
- 41
- Citations by year
- 2026: 22 · 2025: 25 · 2024: 27 · 2023: 29 · 2022: 17 · 2021: 25 · 2020: 28 · 2019: 26 · 2018: 33 · 2017: 49 · 2016: 48 · 2015: 52 · 2014: 61 · 2013: 68 · 2012: 97
- FWCI
- 134.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universitetet i Tromsø
- European Society of Cardiology
- Norges Forskningsråd
- Helse Nord RHF
- Topics
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- homocysteine, acute myocardial infarction, B vitamins, folic acid, vitamin B12, vitamin B6, secondary prevention, cardiovascular events, reinfarction, stroke, sudden cardiac death, hyperhomocysteinemia
- MeSH terms
- Adult, Aged, Aged, 80 and over, Double-Blind Method, Drug Therapy, Combination, Female, Folic Acid, Humans, Male, Middle Aged, Myocardial Infarction, Vitamin B 12, Proportional Hazards Models, Death, Sudden, Cardiac, Hyperhomocysteinemia, Stroke, Vitamin B 6, Secondary Prevention
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