Objectives

To evaluate whether edetate disodium-based chelation therapy reduces cardiovascular events in patients with diabetes and prior myocardial infarction.

Background

In 2013, the Trial to Assess Chelation Therapy (TACT) reported that edetate disodium (EDTA)–based chelation significantly reduced cardiovascular disease (CVD) events by 18% in patients with a prior myocardial infarction (MI). EDTA binds to heavy metals and eliminates them from the body via urinary excretion. Epidemiological studies have linked chronic exposure to heavy metals, especially lead and cadmium, in patients with CVD.

TACT2 was designed to replicate its predecessor study but involving patients with diabetes and prior MI to assess the relationship between the expected prognostic benefits and the depletion of body stores of lead with repeated EDTA infusions.

Participants

Eligible participants were 50 years of age or older, had diabetes, and had experienced an MI at least 6 weeks before recruitment. Exclusion criteria included individuals with baseline serum creatinine >2.0 mg/dL, HbA1C >11%, blood pressure greater than 160/100 mm Hg, or heart failure hospitalization within 6 months.

A total of 1,000 participants were enrolled. 499 patients were randomized to receive active EDTA chelation infusions and 501 were randomized to receive placebo infusions.

Design

TACT2 was a multicenter, double-masked 2 × 2 factorial trial. Participants were randomized to receive either 40 weekly infusions of EDTA or placebo. EDTA infusions consisted of up to 3 g of disodium EDTA, adjusted based on estimated creatinine clearance; 7 g of ascorbic acid; 2 g of magnesium chloride; 100 mg of procaine hydrochloride; 2500 U of unfractionated heparin; 2 mEq of potassium chloride; 840 mg of sodium bicarbonate; 250 mg of pantothenic acid; 100 mg of thiamine; 100 mg of pyridoxine; and sterile water to make up 500 mL of solution. The identical-appearing placebo solution consisted of 500 mL of normal saline and 1.2% dextrose (2.5 g total). During the infusion phase of the trial, all study participants received a daily low-dose vitamin regimen. The randomized oral vitamin regimen, composed of high-dose oral multivitamins and minerals or matching placebo caplets, was administered throughout the 60-month follow-up.

During the infusion period, participants completed physical exams. Participants were contacted to assess interval clinical events at 6 months and 12 months after randomization and continuing every 4 months for 5 years or until the end of the study.

The primary endpoint was a composite of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina.

Conclusions

Despite effectively reducing blood lead levels, EDTA chelation was not effective in reducing cardiovascular events in stable patients with coronary artery disease who have diabetes and a history of myocardial infarction.

Lamas GA, Anstrom KJ, Navas-Acien A, et al. Edetate Disodium-Based Chelation for Patients With a Previous Myocardial Infarction and Diabetes: TACT2 Randomized Clinical Trial. JAMA. 2024;332(10):794-803. doi:10.1001/jama.2024.11463

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