Chelation With Multivitamins for Coronary Disease
Chelation With Multivitamins for Coronary Disease
Background Disodium ethylenediaminetetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes.
Methods This was a double-blind, placebo-controlled, 2 × 2 factorial multicenter randomized trial of 1,708 post–myocardial infarction (MI) patients ≥50 years of age and with creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitamin-multimineral mixture or placebo. The primary end point was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina.
Results Median age was 65 years, 18% were female, 94% were Caucasian, 37% were diabetic, 83% had prior coronary revascularization, and 73% were on statins. Five-year Kaplan-Meier estimates for the primary end point was 31.9% in the chelation + high-dose vitamin group, 33.7% in the chelation + placebo vitamin group, 36.6% in the placebo infusion + active vitamin group, and 40.2% in the placebo infusions + placebo vitamin group. The reduction in primary end point by double active treatment compared with double placebo was significant (hazard ratio 0.74, 95% CI 0.57–0.95, P = .016). In patients with diabetes, the primary end point reduction of double active compared with double placebo was more pronounced (hazard ratio 0.49, 95% CI 0.33–0.75, P < .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.
Chelation therapy with ethylenediaminetetraacetic acid (EDTA) has long been used to treat atherosclerotic coronary and peripheral artery disease. The Trial to Assess Chelation Therapy (TACT) found that this treatment reduced clinical events in post–myocardial infarction (MI) patients, particularly in patients with diabetes. Chelation therapy is often administered in conjunction with a regimen of oral high-dose vitamins and minerals, notwithstanding that the results of clinical trials of lower-dose vitamin therapy have generally been negative. Nonetheless, chelation practitioners argued forcefully during the design phase of TACT for the inclusion of an adjunctive high-dose vitamin and mineral regimen. Thus, a 2 × 2 factorial design (intravenous (IV) chelation vs placebo plus oral vitamins vs placebo) was selected to control for the use of vitamins, study the effects of chelation with versus without high-dose vitamins, and thereby eliminate potential confounding due to uncontrolled vitamin use by study participants.
The clinical safety and efficacy of the TACT vitamin regimen have been reported. These analyses demonstrated a nonsignificant 11% reduction in the risk of the primary combined end point. The purpose of this paper is to describe the results across the 4 factorial groups in the 1,708 randomized patients and among the 633 with diabetes.
Abstract and Introduction
Abstract
Background Disodium ethylenediaminetetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes.
Methods This was a double-blind, placebo-controlled, 2 × 2 factorial multicenter randomized trial of 1,708 post–myocardial infarction (MI) patients ≥50 years of age and with creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitamin-multimineral mixture or placebo. The primary end point was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina.
Results Median age was 65 years, 18% were female, 94% were Caucasian, 37% were diabetic, 83% had prior coronary revascularization, and 73% were on statins. Five-year Kaplan-Meier estimates for the primary end point was 31.9% in the chelation + high-dose vitamin group, 33.7% in the chelation + placebo vitamin group, 36.6% in the placebo infusion + active vitamin group, and 40.2% in the placebo infusions + placebo vitamin group. The reduction in primary end point by double active treatment compared with double placebo was significant (hazard ratio 0.74, 95% CI 0.57–0.95, P = .016). In patients with diabetes, the primary end point reduction of double active compared with double placebo was more pronounced (hazard ratio 0.49, 95% CI 0.33–0.75, P < .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.
Introduction
Chelation therapy with ethylenediaminetetraacetic acid (EDTA) has long been used to treat atherosclerotic coronary and peripheral artery disease. The Trial to Assess Chelation Therapy (TACT) found that this treatment reduced clinical events in post–myocardial infarction (MI) patients, particularly in patients with diabetes. Chelation therapy is often administered in conjunction with a regimen of oral high-dose vitamins and minerals, notwithstanding that the results of clinical trials of lower-dose vitamin therapy have generally been negative. Nonetheless, chelation practitioners argued forcefully during the design phase of TACT for the inclusion of an adjunctive high-dose vitamin and mineral regimen. Thus, a 2 × 2 factorial design (intravenous (IV) chelation vs placebo plus oral vitamins vs placebo) was selected to control for the use of vitamins, study the effects of chelation with versus without high-dose vitamins, and thereby eliminate potential confounding due to uncontrolled vitamin use by study participants.
The clinical safety and efficacy of the TACT vitamin regimen have been reported. These analyses demonstrated a nonsignificant 11% reduction in the risk of the primary combined end point. The purpose of this paper is to describe the results across the 4 factorial groups in the 1,708 randomized patients and among the 633 with diabetes.
