The VISP (Vitamin Intervention for Stroke Prevention) trial randomized patients with prior nondisabling stroke to varying doses of folic acid, B6, and B12. Despite a reduction in homocysteine that was 2 mmol/L greater in the group allocated to the high dose of supplementation, there were no differences in the incidence of recurrent stroke, IHD, or death.822 Similarly, the HOPE 2 (Heart Outcome in Preven- tion) trial found no benefit of folate and vitamins B6 and B12 in patients with vascular disease or diabetes mellitus.821 The NORVIT (Norwegian Vitamin Trial) examined 3 combina- tions of folate and B vitamins in patients who had an AMI and observed no decrease in the risk of cardiovascular events.820 A meta-analysis of these and 9 other smaller trials also found no reduction in cardiovascular events or mortality with folate supplementation.819 These studies indicate that routine use of folate and B vitamins for the prevention or treatment of cardiovascular disease should not be recommended. 4.4.2.5.4. Chelation Therapy. Chelation therapy, which con- sists of a series of intravenous infusions of disodium ethylene diamine tetraacetic acid (EDTA) in combination with other substances, has been promoted as a noninvasive means of Fihn et al Stable Ischemic Heart Disease: Full Text e407 improving blood flow in atherosclerotic vessels. EDTA combines with polyvalent cations, such as calcium ions, to form soluble complexes that can be excreted. Advocates maintain that this process can result in regression of athero- sclerotic plaques and relief of angina and that EDTA reduces oxidative stress in the vascular wall. Anecdotal reports have suggested that EDTA chelation therapy can result in relief of angina in patients with SIHD. In general, however, the efficacy of chelation therapy in athero- sclerotic disease is not supported by clinical trials. 