Lamas GA, Anstrom KJ, Navas-Acien A, et al.
TACT2 was designed as a follow-up to the original TACT trial. In TACT, investigators reported an 18% relative reduction in cardiovascular events in the overall study population of 1,708 patients with prior myocardial infarction. A prespecified subgroup analysis suggested a substantially larger benefit in participants with diabetes, which led researchers to test that finding directly in TACT2.
Between 2016 and 2023, TACT2 enrolled 1,000 patients with diabetes and prior myocardial infarction at 88 sites in the United States and Canada. Participants were randomized to receive edetate disodium-based chelation infusions or placebo in a double-masked trial.
TACT2 confirmed that the chelation regimen substantially lowered blood lead levels. However, it did not show a significant reduction in the primary cardiovascular composite endpoint compared with placebo. In other words, TACT2 did not replicate the cardiovascular benefit suggested by the diabetes subgroup in the original TACT trial.
TACT2 is an important trial because it tested the population thought most likely to benefit based on TACT. Its findings make the cardiovascular evidence for EDTA chelation more uncertain — the original trial suggested benefit, while the dedicated replication trial in diabetic post-MI patients was neutral on clinical outcomes, despite clear blood lead reduction.
Bottom line — TACT2 confirmed that edetate disodium–based chelation lowers blood lead levels, but it did not reproduce the cardiovascular event reduction suggested in the diabetes subgroup of the original TACT trial. Taken together, TACT and TACT2 leave the cardiovascular evidence mixed rather than confirmatory.