Trial to Assess Chelation Therapy 2 - TACT2

Contribution To Literature:

The TACT2 trial showed that in patients with prior MI and diabetes, intravenous chelation therapy with EDTA was not associated with a reduced risk of death or cardiovascular events compared with placebo.


The goal of the trial was to determine the potential clinical benefit of the chelating agent edetate disodium (EDTA) in older adults with a history of myocardial infarction (MI) and diabetes mellitus (DM).

Study Design

  • Randomized
  • Double-blind
  • Multicenter (USA/Canada)
  • Factorial

Patients with a history of MI and DM were randomized in a 1:1 fashion to receive 40 weekly intravenous infusions of 500 mL EDTA (n = 483) or saline/1.2% dextrose placebo (n = 476). The EDTA infusion included up to 3 grams of EDTA based on renal function. Each arm was also randomized in a 1:1 fashion to receive an oral high-dose vitamin and mineral supplement or placebo (results not reported here).

  • Total number of enrollees: 1,000
  • Median follow-up duration: 48 months
  • Median patient age: 67 years
  • Percentage female: 27%

Inclusion criteria:

  • Men or postmenopausal women age ≥50 years
  • MI >6 weeks prior
  • DM history, defined by use of insulin or oral diabetes therapy, fasting blood glucose >125 mg/dL, or glycated hemoglobin (HbA1c) ≥6.5%

Exclusion criteria:

  • Serum creatinine >2.0 mg/dL
  • HbA1c >11.0%
  • Coronary or peripheral revascularization <6 months prior
  • Intravenous or oral chelation therapy <5 or <2 years prior, respectively
  • Aminotransferase levels >2 times upper limit of normal
  • Active tobacco smoking

Other salient features/characteristics:

  • Median time since qualifying MI: 5 years
  • Mean HbA1c: 7.5%
  • Mean low-density lipoprotein cholesterol (LDL-C): 80 mg/dL
  • Median blood lead level: 9.22 µg/L
  • Mean urine cadmium level: 0.30 µg/g creatinine

Principal Findings:

The primary outcome, composite of time to all-cause death, MI, stroke, coronary revascularization, or hospitalization for unstable angina, for EDTA vs. placebo, was: hazard ratio (HR) 0.93 (95% confidence interval [CI]  0.76-1.16), p = 0.53

Secondary outcomes for EDTA vs. placebo:

  • All-cause death: HR 0.96 (95% CI 0.71-1.30)
  • Change in median blood lead level from baseline: -5.5 vs. -0.6 µg/L, p < 0.001
  • Change in median urine cadmium level from baseline: -0.04 vs. 0 µg/g creatinine, p = 0.15

Compliance with all 40 infusions, EDTA vs. placebo, was: 68% vs. 67%.


The original TACT trial demonstrated a modest reduction in death and cardiovascular events associated with EDTA, driven largely by lower rates of coronary revascularization. Given the historically contested reception to chelation therapy for atherosclerotic disease, TACT2 was designed to replicate its predecessor’s findings in patients with DM, who derived the greatest benefit compared with placebo in the original study. Surprisingly, no difference in clinical outcomes was observed in this cohort despite similar adherence over a similar follow-up period.

The authors note that this may reflect a smaller potential treatment effect size as blood lead levels in the US and Canada have continued to decrease since the TACT cohort was studied and were even lower in the study cohort compared with contemporary population data. Moreover, a greater proportion of patients in TACT2 were not only taking statins or antiplatelet therapies but also sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, agents with proven cardiovascular benefits that were not available during TACT. The current findings therefore do not support chelation therapy for post-MI patients with DM. Given the outsized benefit originally seen with TACT in this subset further implies that chelation therapy is not indicated regardless of DM status after MI.


Presented by Dr. Gervasio A. Lamas at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 7, 2024.

Clinical Topics: Atherosclerotic Disease (CAD/PAD), Acute Coronary Syndromes, Diabetes and Cardiometabolic Disease

Keywords: ACC24, ACC Annual Scientific Session, Coronary Artery Disease, Diabetes Mellitus

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