Edetate Disodium-Based Chelation for Patients With a Previous Myocardial Infarction and Diabetes: TACT2 Randomized Clinical Trial.
Level 2 - randomized trial
Multicenter, double-blind, placebo-controlled randomized clinical trial
PubMed 39141382 · doi:10.1001/jama.2024.11463
What was done
A 2 × 2 factorial, double-blind, placebo-controlled trial across 88 sites in the US and Canada evaluated 959 adults (median age 67 years; 27% female) aged 50 or older with diabetes and a history of myocardial infarction (MI) at least 6 weeks prior. Participants were randomized to 40 weekly infusions of an edetate disodium (EDTA)-based chelation solution (483 received at least 1 infusion) or matching placebo infusions (476 received at least 1 infusion). The primary composite endpoint was all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina over a median follow-up of 48 months.
What was found
The primary endpoint occurred in 172 participants (35.6%) in the chelation group and 170 (35.7%) in the placebo group (adjusted HR 0.93; 95% CI, 0.76–1.16; P = .53). The 5-year cumulative incidence of primary events was 45.8% with chelation vs 46.5% with placebo. CV death, MI, or stroke occurred in 18.4% (89/483) of the chelation group vs 19.7% (94/476) of the placebo group (adjusted HR 0.89; 95% CI, 0.66–1.19). All-cause death occurred in 17.4% (84/483) vs 17.6% (84/476), respectively (adjusted HR 0.96; 95% CI, 0.71–1.30). Chelation reduced median blood lead levels from 9.03 μg/L to 3.46 μg/L at infusion 40 (P < .001), compared to a change from 9.3 μg/L to 8.7 μg/L with placebo.
Why it matters
This trial failed to replicate the cardiovascular event reduction previously reported in subgroup analyses of the earlier TACT trial. EDTA chelation does not reduce secondary cardiovascular events in diabetic patients with prior MI despite successfully lowering blood lead levels.
Limits
The study was restricted to stable patients aged 50 and older with diabetes and established post-MI status; findings do not address populations with higher baseline environmental lead or toxic metal exposure, non-diabetic coronary disease, or alternative chelation regimens. Abstract analyses focus on patients receiving at least one infusion rather than full intention-to-treat, and outcomes for the oral multivitamin factorial arm are not reported.
Cited by
- contradicts The NIH funded a $30 million trial called TACT evaluating IV EDTA chelation, which found it to be effective in preventing heart disease and heart attacks.