Trial DesignHomocysteine-lowering trials for prevention of cardiovascular events: A review of the design and power of the large randomized trials
Section snippets
Data from ongoing or completed trials
We aimed to identify all randomized trials involving >1000 participants that were assessing the effects of folic acid supplements (with or without the addition of vitamins B12 or B6) versus control without such supplementation on the incidence of vascular events.13, 14, 15, 16, 17, 18, 19 Trials were identified by MEDLINE searches and by personal contact with relevant investigators. Investigators were asked to provide information about the number of people to be randomized, the details of the
Trials in patients with prior CHD
Table I provides selected details of the number randomized, treatment duration, vitamin regimen, plasma homocysteine reductions, and vascular event rates in each trial involving >1000 people. Among the 7 large randomized trials in people with prior CHD, 5 involve 22 694 people in European populations without systematic fortification of food with folic acid and 2 involve 11 022 people predominantly recruited in North America with mandatory folic acid fortification. All trials use daily doses of
Discussion
Combined analyses of previous observational epidemiologic studies suggest that a 25% lowering in homocysteine levels is associated with about 10% lower risk of CHD and 20% lower risk of stroke.4 If these epidemiologically predicted differences in risk of 10% to 20% are reversible at least within a few years, then the implications for public health of decreasing population homocysteine concentrations could be substantial. Several large-scale randomized trials are assessing whether lowering
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Cited by (0)
The study was supported in part by grants from the British Heart Foundation, London, England, and the Medical Research Council, London, England, and the European Union BIOMED Program (BMH4-98-3549), Brussels, Belgium.
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Authors members and collaborators are listed at Appendix A.
Reprint requests: Robert Joseph Clarke, MD, MRCP, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, OX2 6HE Oxford, UK. E-mail: [email protected]