EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: The factorial group results of the Trial to Assess Chelation Therapy

Abstract

Background Disodium ethylene diamine tetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. Objective This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes. Methods Double-blind placebo-controlled 2 × 2 factorial multicenter randomized trial of 1708 post-MI patients ≥ 50 years and creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitaminmultimineral mixture or placebo. Primary endpoint was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina. Results Median age was 65 years, 18% female, 94% Caucasian, 37% diabetic, 83% prior coronary revascularization, and 73% on statins. Five-year Kaplan-Meier estimates for the primary endpoint in the chelation + high-dose vitamin group was 31.9%, in the chelation + placebo vitamin group 33.7%, in the placebo infusion + active vitamin group 36.6%, and in the placebo infusions + placebo vitamin group 40.2 %. The reduction in primary endpoint by double active treatment compared with double placebo was significant (HR 0.74, 95% CI (0.57,0.95); p=0.016). In patients with diabetes, the primary endpoint reduction of double active compared with double placebo was more pronounced (HR 0.49, 95% CI (0.33,0.75), p<0.001). Conclusions In stable post- MI patients on evidence-based medical therapy, the combination of oral high-dose vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance.

Association of Multivitamin and Mineral Supplementation and Risk of Cardiovascular Disease

“…Among these, 6 studies did not meet the inclusion criteria and were excluded. 23,30,[41][42][43][44] One study met the inclusion criteria, but the population was duplicated in another study; therefore, the study with the longer follow-up data was selected for final analysis. 45 As a result, 18 studies were included in the final analysis.…”

EDTA Chelation Therapy to Reduce Cardiovascular Events in Persons with Diabetes

“…The analysis comparing chelation (with or without oral highdose vitamin-mineral supplement) versus placebo infusion showed significant reduction in cardiovascular risk [1•]. The factorial group results [5] show that the 5-year Kaplan-Meier estimate for the composite primary outcome for the active chelation+active vitamins was significantly different from the placebo-placebo group (p=0.016) ( Table 1). The other groups with a single active therapy (either chelation or highdose vitamins) had an intermediate number of events but were not statistically different from the placebo-placebo group.…”

“…The TACT trial was a 2×2 factorial trial with chelation as one factor and high-dose vitamins as the second factor [5]. The analysis comparing chelation (with or without oral highdose vitamin-mineral supplement) versus placebo infusion showed significant reduction in cardiovascular risk [1•].…”

Chelation therapy and cardiovascular disease: Connecting scientific silos to benefit cardiac patients

“…Overall, there was a stepwise reduction with the addition to double placebo of oral MVM, or chelation, or both. The 5-year Kaplan-Meier event rate estimate for the primary endpoint in the chelation + high-dose vitamin group was 31.9%, in the chelation + placebo vitamin group 33.7%, in the placebo infusion + active vitamin group 36.6%, and in the placebo infusions + placebo vitamin group 40.2 % (Figure 2) (36). The primary endpoint by treatment group occurred in 139 (32%) of the placebo infusion + placebo vitamin group, and 108 (26%) of patients in the chelation + high-dose vitamin group.…”

“…Patients with diabetes mellitus randomized to EDTA chelation had a significant reduction in recurrent MI (HR, 0.48; 95% CI, 0.26–0.88; P=0.015), in all-cause mortality (HR, 0.57; 95% CI, 0.36–0.88; P=0.011; Figure 4; 5-year NNT= 12; Table 2), and in coronary revascularizations (HR, 0.68; 95% CI, 0.47–0.99; P=0.042). Furthermore, when the factorial analyses comparing chelation + active vitamins with placebo infusions + placebo oral vitamins, the primary endpoint occurred in 56 (38%) of the placebo infusion + placebo vitamin group, and 36 (23%) of patients in the chelation + high-dose vitamin group (HR 0.49, 95% CI (0.33, 0.75) p<0.001, Figure 5), with a 5-year NNT=5.5 (Table 2) (36). …”