The initial TACT report showed a significant interaction of EDTA therapy and the diagnosis of diabetes mellitus…. Ethylene diamine tetraacetic acid (EDTA)-based chelation therapy has been used by practitioners to treat complications of atherosclerosis. The Trial to Assess Chelation Therapy (TACT), was designed as a pivotal trial of disodium EDTA chelation therapy for patients who had a myocardial infarction (MI). The initial TACT report showed a significant interaction of EDTA therapy and the diagnosis of diabetes mellitus. This initial TACT report along with present research demonstrated the role of EDTA in the development of advanced glycation end-products which are mediators of complications of diabetes mellitus. In this report, the authors provide greater detail on the effect of

EDTA-based chelation therapy on patients with diabetes mellitus who have had a prior MI.

A total of 1708 patients aged ≥50 years with a history of MI ≥6 weeks before enrollment were selected for this study. The patients came from 134 different sites across the United States and Canada. The median duration of follow-up was 55 months. This analysis broadened the definition of diabetes mellitus from the original trial to include patients with self-reported diabetes mellitus, those taking oral or insulin treatment for diabetes mellitus, or those who had a fasting blood glucose of ≥6.99 mmol/L (126 mg/dL) at the time of enrollment in the study. A total of 633 (37%) patients had diabetes mellitus (322 EDTA and 311 placebo) according to the broadened definition. Patients received 40 infusions of EDTA chelation or placebo. The primary end point was a composite of death from any cause, reinfarction, stroke, coronary revascularization or hospitalization for angina. The principal secondary end point consisted of a composite of cardiovascular death, reinfarction, or stroke.

In the results, the authors found a 41% (P<0.001) relative reduction in the risk of a combined cardiovascular end point. There was also a reduction in risk of the composite of cardiovascular mortality, nonfatal stroke, or nonfatal MI of 40% (P=0.017); a 52% reduction in recurrent MI (P=0.015); and a reduction in death from any cause of 43% (P=0.011). The result remained significant after Bonferroni adjustment for multiple subgroups. The number needed to treat to reduce 1 primary end point over 5 years was 6.5 (95% CI, 4.4–12.7). There was no reduction in events in non-diabetes mellitus (n=1075; P=0.877), resulting in a treatment by diabetes mellitus interaction.

Based on the results of this study, the authors conclude that post-myocardial infarction patients with diabetes mellitus aged ≥50 demonstrated a marked reduction in cardiovascular events with EDTA chelation. Further studies are needed to replicate these findings and to define the mechanisms of benefit.

Practice Pearls:

• The initial TACT report showed a significant interaction of EDTA therapy and the diagnosis of diabetes mellitus.
• The authors found a 41% (P<0.001) relative reduction in the risk of a combined cardiovascular end point.
• There was also a reduction in risk of the composite of cardiovascular mortality, nonfatal stroke, or nonfatal MI of 40% (P=0.017); a 52% reduction in recurrent MI (P=0.015); and a reduction in death from any cause of 43% (P=0.011).

Circulation Cardiovascular Quality and Outcomes, November 2013