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Intravenous infusions based on disodium EDTA have previously reduced cardiovascular events in a clinical trial. The TACT2 study has been planned similarly to the initial study design.

The aim of the research was to determine the potential clinical benefit of the chelation agent disodium EDTA in elderly adults with a history of myocardial infarction (MI) and diabetes.

TACT2 is a multicenter clinical trial supported by the National Institutes of Health, focusing on patients with diabetes and a history of myocardial infarction. It employs a randomized, 2x2 factorial design with double-blind, placebo-controlled methodology. In the study, a 40-week multi-component chelation solution based on disodium EDTA (disodium ethylenediaminetetraacetic acid or Na2EDTA) and high-dose oral multivitamin and mineral supplements taken twice daily are being tested. The enrollment of 1000 patients was completed in December 2020, and infusions were completed by December 2021. Patients were followed for a duration of 2.5 to 5 years. The primary endpoint is the time to the first occurrence of all-cause death, myocardial infarction, stroke, coronary revascularization, or hospitalization due to unstable angina. The study also includes a Trace Metals and Biological Sample Core Laboratory to test whether the benefits of treatment are derived from chelation of lead and cadmium from patients. The design of TACT2 has been adjusted based on the design of the previous TACT study. The initial TACT study demonstrated a significant reduction in cardiovascular outcomes between the EDTA chelation arm and placebo in patients with prior myocardial infarction, with the most significant effect observed in diabetic patients.

For the primary endpoint of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization due to unstable angina, the hazard ratio was determined to be 0.93 (95% CI 0.76-1.16, p = 0.53) for EDTA compared to placebo. EDTA chelation resulted in >60% reduction in blood lead levels. When primary and secondary endpoints were examined individually, there was no statistically significant difference found between the two groups.

In conclusion, EDTA chelation did not reduce adverse endpoints in patients with diabetes who had previously experienced myocardial infarction.

The original TACT study showed a modest reduction in death and cardiovascular events associated with EDTA, thought to be largely due to the low rates of coronary revascularization. TACT2 was designed to replicate the findings of the previous study, which showed the greatest benefit compared to placebo in diabetic patients. Surprisingly, despite similar follow-up durations and cohorts, no difference in clinical outcomes was observed in this cohort. The authors suggest that this could reflect a smaller potential treatment effect size, possibly due to declining blood lead levels in the study cohort compared to contemporary population data, with levels even lower than those observed in the TACT cohort. Furthermore, a significant portion of patients in TACT2 were not only receiving statins or antiplatelet therapies but also agents with proven cardiovascular benefits, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. Therefore, the current findings do not support chelation therapy for post-MI diabetic patients.