Chelation Therapy Fails to Improve Outcome in Heart Disease: The TACT2 Trial

Chelation therapy is an intravenous (and occasionally oral or rectal) therapy to remove toxic levels of heavy metals like mercury, lead, arsenic, and cadmium from the body and is approved for that purpose. Over many decades there has been the thought that it could serve as a therapy for heart disease and possibly improve outcomes and reduce plaque burden.

A trial published in 2012 known as the TACT trial did find some clinical benefits mainly in patients with diabetes and prior anterior heart attacks (myocardial infarctions or MI).

A follow-up trial was designed exclusively in diabetic patients with prior heart attacks to maximize the chance of finding benefit from chelation therapy, known as the TACT 2 trial. The results were recently reported.

STUDY AND RESULTS

TACT2 was conducted from 2015 to 2020. The trial involved 1,000 patients with type 2 diabetes (> 90%) and a prior MI at 88 sites in the U.S. and Canada. Patients were randomly assigned to 40 weekly infusions of edetate disodium or placebo.

The mean age of participants was 67 years, 27% were women and 61.5% were non-Hispanic white. The median time from MI to randomization was 5 years. Mean HbA1c was 7.5%. Nearly half of the patients were on insulin and one-quarter were on a GLP-1 or SGLT2 inhibitor. Use of aspirin, warfarin, P2Y12 inhibitors, beta-blockers, and statins was high.

During a median follow-up of 48 months, there was no significant difference between chelation therapy and placebo for the primary endpoint of time to first occurrence of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina, which occurred in about 35% of patients in both groups (adjusted HR = 0.93; 95% CI, 0.76-1.16; P = .53).

There were no significant differences in secondary endpoints including recurrent events of the primary composite endpoint, all-cause mortality, and a composite of CV mortality, MI, or stroke.

Subgroup analyses did not identify any subgroup that would be likely to have greater effects from chelation therapy compared with placebo.

CONCLUSIONS

The TACT2 trial was disappointing after the hopeful findings in the original TACT trial. The full data awaits publication, and it is not known why the results failed to show benefit in a high-risk population. For now, it appears that avoiding chelation therapy for heart disease outcomes is wise. Chelation therapy may still have a role for those with documented heavy metal toxicities.