Homocysteine-lowering interventions for preventing cardiovascular events.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 28816346 · doi:10.1002/14651858.CD006612.pub5
What was done
This Cochrane systematic review update searched multiple databases through June 2017 for randomized controlled trials evaluating homocysteine-lowering interventions (vitamins B6, B9/folic acid, or B12 alone or combined) with at least one year of follow-up for preventing cardiovascular events in individuals with or without pre-existing cardiovascular disease. Studies of patients with end-stage renal disease were excluded. Primary outcomes included myocardial infarction and stroke; secondary outcomes included all-cause mortality and serious adverse events. Data were pooled using random-effects meta-analyses and trial sequential analysis.
What was found
Across 15 RCTs (71,422 participants; follow-up 1 to 7.3 years; 9 trials at low risk of bias): - Myocardial infarction: No difference versus placebo (7.1% vs 6.0%; RR 1.02, 95% CI 0.95 to 1.10; 12 trials, n = 46,699; high-quality evidence). - All-cause mortality: No difference versus placebo (11.7% vs 12.3%; RR 1.01, 95% CI 0.96 to 1.06; 11 trials, n = 44,817; high-quality evidence). - Serious adverse events: No difference versus comparator (8.3% vs 8.5%; RR 1.07, 95% CI 1.00 to 1.14; 8 trials, n = 35,788; high-quality evidence). - Stroke: Reduced risk versus placebo (4.3% vs 5.1%; RR 0.90, 95% CI 0.82 to 0.99; 10 trials, n = 44,224; high-quality evidence). - High versus low dose on stroke showed uncertain effects (10.8% vs 11.2%; RR 0.90, 95% CI 0.66 to 1.22; 2 trials, n = 3,929; I² = 72%; very low-quality evidence).
Why it matters
High-certainty evidence demonstrates that lowering homocysteine with B vitamins does not prevent heart attacks or extend survival, though it confers a modest protective effect against stroke.
Limits
Patients with end-stage renal disease were excluded. Six of the 15 included trials (40%) carried unclear or high risk of bias. Dose-comparison analyses were limited to two trials with high heterogeneity and very low certainty, and evidence for specific drug-vitamin combinations (such as enalapril plus folic acid) derived from a single trial.
Cited by
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