Edetate disodium-based chelation does not lead to improved outcomes in patients with diabetes who had previously suffered a myocardial infarction (MI), according to the results of the TACT2 study, presented during a Late-Breaking Clinical Trial session at ACC.24.

The double-blind factorial trial, conducted at 88 sites across the U.S. and Canada, randomized 959 patients (median age 67, 26.9% women, 61.5% Non-Hispanic White) with diabetes (>90% with type 2) and prior MI to either weekly edetate disodium infusions or a placebo for 40 weeks. In the treatment group, 68% of participants received all 40 infusions; 78% received at least 20.

Results showed that at a median follow-up of 48 months, there was no significant difference between the two groups in terms of the primary composite endpoint: death from any cause, MI, stroke, coronary revascularization or hospitalization for unstable angina occurred in 35% of patients in both groups (hazard ratio, 0.93; 95% CI, 0.76-1.16; p=0.53).

Researchers noted that over the same time period, serum levels of lead dropped by an average of 61% in the treatment group compared with the placebo group. Results also indicated that chelation therapy had a good safety profile. There was no increased risk of serious adverse or unexpected serious adverse events in the treatment group.

Notably, the results of the present study differ from the TACT trial, which ran from 2003 to 2012 and suggested that there were modest benefits from edetate disodium-based infusions in reducing cardiovascular events after MI over a median follow-up of 55 months, especially in patients with diabetes. Researchers speculated the reason for the differences between the two studies, which were overseen by the same study team and involved the same medications and study protocols, was the 30% lower baseline lead levels in the participants in TACT2. Furthermore, TACT2 participants may have had more advanced diabetes and severe associated health impacts than the participants of the original TACT study.

"At the present time, in a contemporary population with low lead levels, edetate disodium-based chelation is not effective as a therapy for post-heart attack patients," concluded Gervasio A. Lamas, MD, FACC, the study's lead author.

However, "Our method of treatment was effective at reducing lead, even in patients starting with low lead levels, and it was safe," Lamas added. "In most countries outside of North America and western Europe, lead remains a serious cardiovascular and neurological problem. This study may be more relevant to those areas of the world, but this is a hypothesis that requires further study."