Cited by 1,442Folate and B Vitamins ResearchAcute Myocardial Infarction ResearchLipoproteins and Cardiovascular Health

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Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction

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Bønaa, Kaare Harald, Njølstad, Inger, Ueland, Per Magne, Schirmer, Henrik, Tverdal, Aage, Steigen, Terje, Wang, Harald, Nordrehaug, Jan Erik, Arnesen, Egil, Rasmussen, Knut·2006·New England Journal of Medicine

DOI 10.1056/nejmoa055227

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Abstract

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: Bønaa, Kaare Harald
Njølstad, Inger
Ueland, Per Magne
Schirmer, Henrik
Tverdal, Aage
Steigen, Terje
Nordrehaug, Jan Erik
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
DOI: 10.1056/nejmoa055227
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 › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › 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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Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction

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