Cited by 520Folate and B Vitamins ResearchLipoproteins and Cardiovascular HealthMetabolism and Genetic Disorders

Homocysteine lowering interventions for preventing cardiovascular events

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Martí-Carvajal, Arturo J, Solà, Ivan, Lathyris, Dimitrios, Salanti, Georgia·2009·Cochrane Database of Systematic Reviews

Abstract

BACKGROUND: Cardiovascular disease such as coronary artery disease, stroke and congestive heart failure, is a leading cause of death worldwide. A postulated risk factor is elevated circulating total homocysteine (tHcy) levels which is influenced mainly by blood levels of cyanocobalamin (vitamin B12), folic acid (vitamin B9) and pyridoxine (vitamin B6). There is uncertainty regarding the strength of association between tHcy and the risk of cardiovascular disease. OBJECTIVES: To assess the clinical effectiveness of homocysteine-lowering interventions (HLI) in people with or without pre-existing cardiovascular disease. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (issue 3 2008), MEDLINE (1950 to August 2008), EMBASE (1988 to August 2008), and LILACS (1982 to September 2, 2008). We also searched in Allied and Complementary Medicine (AMED; 1985 to August 2008), ISI Web of Science (1993 to August 2008), and the Cochrane Stroke Group Specialised Register (April 2007). We hand searched pertinent journals and the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. SELECTION CRITERIA: We included randomised clinical trials (RCTs) assessing the effects of HLI for preventing cardiovascular events with a follow-up period of 1 year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. DATA COLLECTION AND ANALYSIS: We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model to synthesise the findings. MAIN RESULTS: We included eight RCTs involving 24,210 participants with a low risk of bias in general terms. HLI did not reduce the risk of non-fatal or fatal myocardial infarction, stroke, or death by any cause (pooled RR 1.03, 95% CI 0.94 to 1.13, I(2) = 0%; pooled RR 0.89, 95% CI 0.73 to 1.08, I(2) = 15%); and pooled RR 1.00 (95% CI 0.92 to 1.09, I(2): 0%), respectively. AUTHORS' CONCLUSIONS: Results from available published trials suggest that there is no evidence to support the use of HLI to prevent cardiovascular events.

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  • A Cochrane meta-analysis of eight RCTs found homocysteine-lowering interventions did not reduce risk of fatal/non-fatal MI (RR 1.03, 95% CI 0.94-1.13), stroke (RR 0.89, 95% CI 0.73-1.08), or death by any cause (RR 1.00, 95% CI 0.92-1.09).

    “The Cochrane Collaboration concluded in a recent meta-analysis of eight RCTs that homocysteine-lowering interventions did not reduce the risk of fatal/non-fatal myocardial infarction (RR 1.03, 95% CI 0.94-1.13),stroke (RR 0.89, 95% CI 0.73 -1.08), or death by any cause (RR 1.00, 95% CI 0.92-1.09).290”

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Research works printed but not linked: 3

  1. International Committee on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use 1997 Code of Federal Regulations & International Conference on Harmonisation Guidelines Philadelphia, US Barnett International/PAREXEL
  2. Spence JD Bang H Chambless LE Stampfer MJ Vitamin Intervention For Stroke Prevention trial: an efficacy analysis Stroke 2005 36 2404 09 16239629
  3. Wang X Qin X Demirtas H Li J Mao G Huo Y Efficacy of folic acid supplementation in stroke prevention: a meta-analysis The Lancet 2007 369 1876 82 17544768

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Authors
Martí-Carvajal, A. J., Solà, I., Lathyris, D., & Salanti, G.
Affiliations
  • G. Papanikolaou General Hospital (GR)
  • University of Ioannina (GR)
Venue
Cochrane Database of Systematic Reviews
Published
2009-10-07
Volume
8
Issue
4
Pages
CD006612-CD006612
ISSN
1361-6137 (ISSN-L)
OpenAlex
W2144717748
Cited by
520
References
311
Citations by year
2025: 16 · 2024: 18 · 2023: 32 · 2022: 30 · 2021: 48 · 2020: 47 · 2019: 41 · 2018: 31 · 2017: 33 · 2016: 45 · 2015: 42 · 2014: 34 · 2013: 31 · 2012: 26
Type
reference entry
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
total homocysteine, cardiovascular disease prevention, myocardial infarction, stroke, vitamin B12, folic acid, pyridoxine, cardiovascular risk factors, cardiovascular mortality, congestive heart failure, coronary artery disease, stroke prevention, myocardial infarction prevention, vitamin supplementation, randomized controlled trials, meta-analysis of trials
MeSH terms
Angina Pectoris, Cardiovascular Diseases, Humans, Myocardial Infarction, Vitamin B Complex, Randomized Controlled Trials as Topic, Hyperhomocysteinemia, Stroke

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