Sammendrag
European Heart Journal 2009: 30 (Abstract Supplement), 184. P 1274. Objectives: Observational studies have reported associations between circulating total homocysteine (tHcy) concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B12 can lower plasma tHcy levels. Our purpose was to assess the effects of homocysteine-lowering treatment in the Norwegian Vitamin Trial (NORVIT) and the Western Norway B-vitamin Intervention Trial (WENBIT) by combined analyses of trial results and long-time follow-up of the two study populations.
Methods: A total of 6837 patients, 76.5% male, mean (SD) age 62.3 (11.0) years, with acute myocardial infarction (AMI) or angiographically verified coronary artery disease, were included between December, 1998 and April, 2004. They were randomly assigned to four groups receiving daily oral treatment with 1) folic acid (0.8 mg)/vitamin B12 (0.4 mg)/vitamin B6 (40 mg), 2) folic acid/vitamin B12, 3) vitamin B6 alone or 4) placebo. Otherwise, they were given conventional medical treatment. The primary end point during the intervention was a composite of AMI, thromboembolic stroke or cardiovascular death. The end point during long-time follow-up was cardiovascular death. Estimates of the hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox proportional hazard regression with adjustment for trial.
Results: By 1 to 2 months after randomization, plasma tHcy concentration was lowered by median 25% in the groups receiving folic acid/vitamin B12. During in-trial follow-up of median 39 months, the primary end point was experienced by 533 (15.6%) of participants receiving folic acid/vitamin B12 versus 503 (14.7%) of those not receiving such treatment (HR, 1.07; 95% CI, 0.95 to 1.21; P=0.25). The incidence of the separate end points of AMI and thromboembolic stroke did not differ among the groups. During extended long-time follow-up of median 74 months from randomization until September, 2007, a total of 571 (8.4%) of participants died from cardiovascular disease. There was no difference in cardiovascular mortality between groups that had received folic acid/vitamin B12 or not (HR, 1.10; 95% CI, 0.94 to 1.3; P=0.24).
Conclusions: The combined results and long-time follow-up in two large randomized clinical trials with coronary artery disease patients in Norway, are consistent with no beneficial effects of treatment with folic acid/vitamin B12 on major cardiovascular events during intervention or on cardiovascular death during long-time follow-up. Use of homocysteine-lowering B-vitamin supplements as secondary prevention in such patients is not justified.
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