Effect of homocysteine interventions on the risk of cardiocerebrovascular events: a meta-analysis of randomised controlled trials

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To evaluate the effects of homocysteine lowering intervention on the risk of cardiocerebrovascular events and all-cause mortality in randomised controlled trials among people with preexisting cardiocerebrovascular or renal disease. Studies were retrieved by searching MEDLINE and OVID (from January 1966 to December 2008) using the following keywords: homocysteine, hyperhomocysteinaemia, cardiovascular disease, coronary disease, cerebrovascular disease, B vitamins, folic acid, randomised controlled trial. References of all retrieved articles were also searched. Randomised controlled trials which compared folic acid or plus B vitamins supplementation with either placebo or usual care were evaluated with cardiocerebrovascular disease events or all-cause mortality reported as an end-point. Data on study design, characteristics of participants, changes in homocysteine levels, and cardiocerebrovascular events and all-cause mortality were independently abstracted by two investigators using a standardised protocol. Seventeen trials involving 39,107 patients with preexisting cardiocerebrovascular or renal disease were included. Results of meta-analyses showed that no significant differences were identified between the intervention group and the control group. The overall relative risks (95% confidence intervals) of outcomes for patients treated with folic acid or plus B vitamins supplementation compared with controls were 1.01 (0.97-1.05) for cardiovascular events, 1.01 (0.94-1.07) for coronary heart disease, 0.94 (0.85-1.04) for stroke and 1.00 (0.95-1.05) for all-cause mortality. In the exclusion of low-quality trials and seven trials in grain fortification countries respectively, sensitivity analyses did not change the overall results. There is no sufficient evidence to show that homocysteine lowering intervention can reduce the risk of cardiocerebrovascular diseases or all-cause mortality among people with preexisting vascular disease. Folic acid supplementation should not be recommended for the secondary prevention of cardiocerebrovascular diseases. More evidence from large-scale randomised controlled trials is needed to confirm this.