Homocysteine-lowering interventions for preventing cardiovascular events

Cardiovascular disease (including coronary artery disease, stroke and congestive heart failure), is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor is elevated circulating total homocysteine levels, which are associated with cardiovascular events. This is an update of a review previously published in 2009.

To assess the clinical effectiveness of homocysteine-lowering interventions in people with or without pre-existing cardiovascular disease.

We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (2012, Issue 2), MEDLINE (1950 to Feb week 2 2012), EMBASE (1980 to 2012 week 07), and LILACS (1986 to February 2012). We also searched ISI Web of Science (1970 to February 2012). We handsearched the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search.

We included randomised controlled trials assessing the effects of homocysteine-lowering interventions for preventing cardiovascular events with a follow-up period of one year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease.

We performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model.

In this updated systematic review, we identified four new randomised trials, resulting in a total of 12 randomised controlled trials involving 47,429 participants. In general terms, the trials had a low risk of bias. Homocysteine-lowering interventions compared with placebo did not significantly affect non-fatal or fatal myocardial infarction (pooled RR 1.02, 95% CI 0.95 to 1.10, I(2) = 0%), stroke (pooled RR 0.91, 95% CI 0.82 to 1.0, I(2) = 11%) or death by any cause (pooled RR 1.01 (95% CI 0.96 to 1.07, I(2): 6%)). Homocysteine-lowering interventions compared with placebo did not significantly affect serious adverse events (cancer) (1 RR 1.06, 95% CI 0.98 to 1.13; I(2) = 0%).

This updated Cochrane review found no evidence to suggest that homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination should be used for preventing cardiovascular events. Furthermore, there is no evidence suggesting that homocysteine-lowering interventions are associated with an increased risk of cancer.