A Cochrane review [Abstract] 1 included 15 studies with a total of 71 422 subjects. Participants differed somewhat in cardiovascular risk levels (with established cardiovascular disease (CVD) or at high risk of CVD), baseline homocysteine levels, access to foods fortified with folic acid or not. Studies in patients with end-stage renal disease were excluded.The interventions considered were vitamins B6, B9 (folic acid) or B12 given alone or in combination, at any dosage compared with placebo, standard care, homocysteine-lowering interventions at low dose, or antihypertensive medication (enalapril). Length of follow-up ranged from 1 to 7.3 years.
Homocysteine lowering interventions did not reduce the risk of non-fatal or fatal myocardial infarction, or death by any cause, and did not significantly affect serious adverse events (cancer) compared with placebo or conventional care. Results, see table T1. Compared with placebo, homocysteine-lowering interventions were associated with reduced stroke outcome. Compared with low doses, there were uncertain effects of high doses of homocysteine-lowering interventions on stroke (RR 0.90, 95% CI 0.66 to 1.22, I2 = 72%; 2 studies, n=3 929). One study (n=20 702) found a reduced risk of non-fatal or fatal stroke in participants receiving enalapril plus folic acid compared with participants receiving enalapril as monotherapy (RR 0.79, 95% CI 0.68 to 0.93; NNTB 143, 95% CI 85 to 428).
| Outcome | Participants (studies) | Assumed risk (placebo) | Corresponding risk | Relative effect (95% CI) |
|---|---|---|---|---|
| Myocardial infarction (non-fatal or fatal) | 46 699 (12) | 60 per 1000 | 61 per 1000 (57 to 66) | RR 1.02 (0.95 to 1.10) |
| Stroke(non-fatal or fatal) | 44 224 (10) | 51 per 1000 | 46 per 1000 (42 to 50) | RR 0.90 (0.82 to 0.99) |
| Death by any cause | 44 817 (11) | 123 per 1000 | 1241 per 1000 (118 to 130) | RR 1.01 (0.96 to 1.06) |
| Cancer | 35 788 (8) | 85 per 1000 | 91 per 1000 (85 to 97) | RR 1.07 (1.00 to 1.14) |
Primary/Secondary Keywords