Are Concerns About Reliability in the Trial to Assess Chelation Therapy Fair Grounds for a Hasty Dismissal?

> Preconceived notions are the locks on the door to wisdom. > > — Merry Browne Trial to Assess Chelation Therapy (TACT) was a prospective, randomized, double-blind, placebo-controlled trial designed to evaluate the effect of ethylenediaminetetraacetic acid-based intravenous chelation therapy on cardiovascular outcomes.1,2 A total of 1708 stable patients >50 years of age with a previous myocardial infarction were enrolled at 134 North American sites and followed for a median of 55 months. The overall results showed that chelation therapy reduced the risk of primary major adverse cardiac events plus end point—a composite of death, myocardial infarction, stroke, coronary revascularization, or hospitalization for angina.2Article see p 15In this report, the TACT investigators present the results of a prespecified subgroup analysis in the diabetic cohort.3 The investigators used an expanded definition of diabetes mellitus compared with what was prespecified in trial design1 or reported previously.2 As a result, the size of the cohort increased from 538 to 633, and the number of primary end point events accrued increased from 169 to 197. The principal finding is that chelation therapy was associated with a reduction in the primary MACE plus and secondary stringent MACE end point—a composite of death, nonfatal myocardial infarction, or stroke. In contrast, chelation failed to yield benefit in patients without diabetes mellitus (nominal P for interaction=0.0037). There was no significant heterogeneity in treatment effect across individual end points. The treatment benefit was observed independent of changes in lipid or glycemic control. Although randomization was not stratified by diabetes mellitus status, there was sufficient overlap and balance between treatment arms to ensure valid causal estimates. The investigators appropriately conclude that although treatment benefit with chelation is suggested, additional studies are warranted to replicate the findings and determine the mechanism of action.Several findings …