Chelation therapy after the trial to assess chelation therapy: results of a unique trial

Abstract

Purpose of review: EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment.

Recent findings: The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P=0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P=0.0002) and a 43% reduction in total mortality (P=0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action.

Summary: Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients.

Box 1

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FIGURE 1

TACT – Kaplan–Meier estimates of the primary composite endpoint chelation therapy vs. placebo. The primary endpoint was a composite of death from any cause, reinfarction, stroke, coronary revascularization, or hospitalization for angina. Reproduced with permission [11], previously published in [5^▪▪]. CI, confidence interval; HR, hazard ratio.

FIGURE 2

The factorial group results of TACT – Kaplan–Meier estimates of the primary endpoint per group. (a) Kaplan–Meier curves (four factorial groups, primary endpoint); (b) Kaplan–Meier curves placebo/placebo vs. active/active (primary endpoint). Reproduced with permission [15^▪].

FIGURE 3

TACT – Kaplan–Meier estimates of the primary composite endpoint EDTA chelation therapy vs. placebo subgroup of patients with diabetes mellitus. The primary endpoint was a composite of death from any cause, reinfarction, stroke, coronary revascularization, or hospitalization for angina. Reproduced with permission [16^▪▪]. CI, confidence interval; HR, hazard ratio.