EDTA Chelation Not Associated With Reduced CV Events in Patients With MI and Diabetes

Edetate disodium (EDTA) chelation is not effective for decreasing cardiovascular events in stable patients with coronary artery disease who have diabetes and a history of myocardial infarction (MI), although blood lead levels are reduced, according to a study in JAMA.

The multicenter TACT2 (Trial to Assess Chelation Therapy 2; ClinicalTrials.gov Identifier: NCT02733185) trial compared the effect of 40 weekly infusions of an EDTA-based solution with placebo infusions and the effect of high doses of oral multivitamins and minerals with oral placebo.

Participants were aged 50 years or older with diabetes and had an MI at least 6 weeks before recruitment. The randomized oral vitamin regimen, including high-dose oral multivitamins and minerals or matching placebo, was given during the 60-month follow-up.

Clinical events were assessed at 6 and 12 months postrandomization and every 4 months for 5 years or until the study’s end. The primary endpoint was a composite of death from any cause, MI, stroke, coronary revascularization, or hospitalization for unstable angina.

A total of 1000 individuals were assigned randomly to EDTA-based chelation (n=499) or to placebo (n=501) from October 27, 2016, to December 31, 2021. Their median age was 67 years (IQR, 60-72 years), 27% were women, and 78% were White. The primary analysis included 483 patients in the EDTA group and 476 in the placebo group.

The primary composite cardiovascular disease (CVD) outcome occurred in 172 patients (35.6%) in the chelation group and 170 (35.7%) in the placebo group (adjusted hazard ratio [HR], 0.93; 95% CI, 0.76-1.16; P =.53). Kaplan-Meier 5-year cumulative incidence estimates were 45.8% (95% CI, 39.9%-51.5%) in the chelation group and 46.5% (95% CI, 39.7%-53.0%) in the placebo group for the primary endpoint.

CV death, MI, or stroke events were reported in 89 patients (18.4%) in the chelation group and 94 (19.7%) in the placebo group (adjusted HR, 0.89; 95% CI, 0.66-1.19). In the chelation group, 84 patients (17.4%) died from any cause compared with 84 (17.6%) in the placebo group (adjusted HR, 0.96; 95% CI, 0.71-1.30).

The chelation group had a decrease in median blood lead levels from 9.0 μg/L (IQR 6.1-13.6 μg/L) preinfusion to 3.5 μg/L (IQR 2.3-5.5 μg/L; P <.001) at the 40th infusion, which was a 61% decrease. No clinically relevant reduction in blood lead levels was found in the placebo group, which decreased from a median of 9.3 μg/L (IQR 6.4-14.0 μg/L) to 8.7 μg/L (IQR 6.0-12.0 μg/L).

Among several study limitations, the primary analyses were performed only in a modified intention-to-treat population, and treatment adherence was imperfect.

“The findings herein do not support the clinical use of chelation to reduce CVD risk in US and Canadian participants with diabetes and a prior MI,” wrote the study authors.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on The Cardiology Advisor