Edetate Disodium–Based Chelation for Patients With a Previous Myocardial Infarction and Diabetes
Gervasio A. Lamas, Kevin J. Anstrom, Ana Navas‐Acién, Robin Boineau, Hayley Nemeth, Zhen Huang, Jun Wen, Yves Rosenberg, Mario Stylianou, Teresa L.Z. Jones, Bonnie R. Joubert, Qilu Yu, Regina M. Santella, Ana C. Mon, Francisco Ujueta, Esteban Escolar, David M. Nathan, Vivian Fonseca, Y. Wady Aude, Jonathan K. Ehrman, T.S.J. Elliott, Rakesh Prashad, Eldrin F. Lewis, Renato D. Lopes, Michael E. Farkouh, Anne-Marie Elliott, Jonathan Newman, Daniel B. Mark, TACT2 Investigators, Philip Bear, Donna Prouty, Jodi Baxter, Jonathan K. Ehrman, Heather Golden, Vikrant Katoch, Raffi K. Krikorian, André Paixão, Fujiko Anazawa, Leybi Ramirez-Kelly, Abby Nolen, Venus Barney, Gerald Natzke, Rodica Pop‐Busui, Cindy Plunkett, Laura Meyer, J. Kirk Roberts, Scott A. Rollins, Tamra Hollis, Nampalli Vijay, Melinda Washam, David Zidar, Terence Semenec, Lauren Huntington, Amanda Klumpp, Matthew S. Doughty, Jeffrey Baker, Joseph P. Allen, Rebecca Cortez, Bhaskar Purushottam, Kirstin Stauffacher, Kelly J. Airey, Elena Christofides, Jordyn Conway, David Hoffman, Patty Schuler, Ronald M Solbrig, Loni Chacon, Phillip D. Levy, Linda Gojcevic, R. Eric Collins, John Miles McClure, Ellen Mook, Christopher R. deFilippi, Wendy Sheaffer, Antoinette Bonaccorso, Daniel Donovan, Julee Hartwell, Andrew P. Garner, Dawn Kalbfliesh, David H. Hsi, Maryanne Ducey, Paula Trump, Urs A. Leuenberger, Katie Loffredo, Betty Persico, Allan Magaziner, Dennis Goodman, Michela L. Garabedian, J. Coates, Jeanne P. Wingo, Sheldon H. Gottlieb, Michael Schächter, Sally Minniefield, Olakunle Akinboboye, Kazi Masel Ullah, Karen Wolske, Dennis Friedman, Daniel Lorber, M. Tsovian, Regina Druz
Abstract
Importance: In 2013, the Trial to Assess Chelation Therapy (TACT) reported that edetate disodium (EDTA)-based chelation significantly reduced cardiovascular disease (CVD) events by 18% in 1708 patients with a prior myocardial infarction (MI). Objective: To replicate the finding of TACT in individuals with diabetes and previous MI. Design, Setting, and Participants: A 2 × 2 factorial, double-masked, placebo-controlled, multicenter trial at 88 sites in the US and Canada, involving participants who were 50 years or older, had diabetes, and had experienced an MI at least 6 weeks before recruitment compared the effect of EDTA-based chelation vs placebo infusions on CVD events and compared the effect of high doses of oral multivitamins and minerals with oral placebo. This article reports on the chelation vs placebo infusion comparisons. Interventions: Eligible participants were randomly assigned to 40 weekly infusions of an EDTA-based chelation solution or matching placebo and to twice daily oral, high-dose multivitamin and mineral supplements or matching placebo for 60 months. This article addresses the chelation study. Main Outcomes and Measures: The primary end point was the composite of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina. Median follow-up was 48 months. Primary comparisons were made from patients who received at least 1 assigned infusion. Results: Of the 959 participants (median age, 67 years [IQR, 60-72 years]; 27% females; 78% White, 10% Black, and 20% Hispanic), 483 received at least 1 chelation infusion and 476 at least 1 placebo infusion. A primary end point event occurred in 172 participants (35.6%) in the chelation group and in 170 (35.7%) in the placebo group (adjusted hazard ratio [HR], 0.93; 95% CI, 0.76-1.16; P = .53). The 5-year primary event cumulative incidence rates were 45.8% for the chelation group and 46.5% for the placebo group. CV death, MI, or stroke events occurred in 89 participants (18.4%) in the chelation group and in 94 (19.7%) in the placebo group (adjusted HR, 0.89; 95% CI, 0.66-1.19). Death from any cause occurred in 84 participants (17.4%) in the chelation group and in 84 (17.6%) in the placebo group (adjusted HR, 0.96; 95% CI, 0.71-1.30). Chelation reduced median blood lead levels from 9.03 μg/L at baseline to 3.46 μg/L at infusion 40 (P < .001). Corresponding levels in the placebo group were 9.3 μg/L and 8.7 μg/L, respectively. Conclusions and Relevance: Despite effectively reducing blood lead levels, EDTA chelation was not effective in reducing cardiovascular events in stable patients with coronary artery disease who have diabetes and a history of MI. Trial Registration: ClinicalTrials.gov Identifier: NCT02733185.