Graded Benefit of EDTA Chelation in Post-MI Patients with Diabetes Treated with Different Hypoglycemic Strategies

Introduction: The NIH-funded Trial to Assess Chelation Therapy (TACT) reported a clinical benefit of EDTA-based chelation on cardiovascular (CV) outcomes in post-MI patients with diabetes (DM). We assessed the benefit of therapy by severity of diabetes. Methods: TACT, a multi-center, double-blind, placebo-controlled, 2 X 2 factorial trial of EDTA chelation and high-dose vitamins, enrolled pts age > 50 years with an MI at least 6 weeks prior and creatinine < 2.0. Median duration of follow-up was 55 months. The primary endpoint was death from any cause, MI, stroke, coronary revascularization, or hospitalization for angina. The major secondary clinical endpoint was cardiovascular death, MI, or stroke. The type of hypoglycemic therapy (insulin, oral, or none) was used as a surrogate for severity of diabetes. The log rank test and Cox model were used for treatment comparisons. This is a non-prespecified subgroup comparison. Results: TACT enrolled 1708 pts. Among the 633 (37%)with diabetes, 162 (26%) were on insulin, 301 (48%) not on insulin, but on oral hypoglycemic, and 170 (27%) on neither. For the overall subgroup of 633 pts with diabetes EDTA chelation significantly reduced the primary endpoint (HR 0.59 95% confidence intervals (CI) 0.44-0.79, p<0.001). For pts on insulin, the benefit was qualitatively greatest (HR 0.42 95% CI 0.25-0.74, p=0.002), compared with the effect on patients receiving oral hypoglycemic therapy (HR 0.66 95% CI 0.43-1.01, p=0.053), or none (HR 0.69 95% CI (0.39-1.20), p=0.19). For the key secondary endpoint, the best results were in the patients on insulin (HR 0.53) or on oral drugs (HR 0.54), whereas the smallest effect was seen in the patients on neither type of medication (HR 0.82). Conclusions: In post-MI pts with DM treated with standard therapies, the clinical benefit of EDTA-based chelation therapy was most pronounced among the patients with the most severe diabetes, those on insulin therapy. Additional work to understand mechanisms will be necessary.