Edetate Disodium–Based Chelation for Patients With a Previous Myocardial Infarction and Diabetes
Authors: Lamas Gervasio A. , Anstrom Kevin J. , Navas-Acien Ana , Boineau Robin , Nemeth Hayley , Huang Zhen , Wen Jun , Rosenberg Yves , Stylianou Mario , Jones Teresa L. Z. , Joubert Bonnie R. , Yu Qilu , Santella Regina M. , Mon Ana C. , Ujueta Francisco , Escolar Esteban , Nathan David M. , Fonseca Vivian A. , Aude Y. Wady , Ehrman Jonathan K. , Elliott Thomas , Prashad Rakesh , Lewis Eldrin F. , Lopes Renato D. , Farkouh Michael E. , Elliott Anne-Marie , Newman Jonathan D. , Mark Daniel B. ,   TACT2 Investigators, Bear Philip , Prouty Donna , Baxter Jodi , Ehrman Jonathan , Golden Heather , Katoch Vikrant , Krikorian Raffi , Paixao Andre , Anazawa Fujiko , Ramirez-Kelly Leybi , Nolen Abby , Barney Venus , Natzke Gerald , Pop-Busui Rodica , Plunkett Cindy , Meyer Laura , Roberts James , Rollins Scott , Hollis Tamra , Vijay Nampalli , Washam Melinda , Zidar David , Semenec Terence , Huntington Lauren , Klumpp Amanda , Doughty Matthew Scott , Baker Jeffrey , Allen Joseph , Cortez Rebecca , Purushottam Bhaskar , Stauffacher Kirstin , Airey Kelly , Christofides Elena , Conway Jordyn , Hoffman David , Schuler Patty , Solbrig Ronald , Chacon Loni , Levy Phillip , Gojcevic Linda , Collins Roy , McClure II John Miles , Mook Ellen , DeFilippi Christopher , Sheaffer Wendy , Bonaccorso Antoinette , Donovan Daniel , Hartwell Julee , Garner Andrew , Kalbfliesh Dawn , Hsi David , Ducey Maryanne , Trump Paula , Leuenberger Urs , Loffredo Katie , Persico Betty , Magaziner Allan , Goodman Dennis , Garabedian Michela , Coates Jane , Wingo Jeanne , Gottlieb Sheldon , Schachter Michael , Minniefield Sally , Akinboboye Olakunle , Ullah Kazi , Wolske Karen , Friedman Dennis , Lorber Daniel , Tsovian Mari , Druz Regina , Hodnett Patricia , Meller Stephanie , Bartolome Maria , Cortez Vargas Giselle , Ergui Ian , Ujueta Francisco , Valls Priscilla , Lozada Marnie , Blanco Raul , Arenas Ivan , Escolar Esteban , Pan Xiaoou , Seidel Ilana , Corado-Williams Melisa , Lamas Ana , Viera-Navarro Mariana , Trevino Miguel , Mai Kimberly , Eidelman Rachel , Reyes Gabriela , Brown Kelly , Yaryura Ricardo , Little Amy , Varela Heber , Bienes Malu , Jeanfreau Robert , Neff Paul , Thompson Mark , Lineberger-Moore Melody , Miller Donna , Prashad Rakesh , Schmedtje Jr John , Shelton Melissa , Treasure II Charles , Freel Ashley , Rojas Gerardo , Bruceles Damaris , Uwaifo Gabriel , Hixon- Calliet Veronica , Passini Amber , Melton Stacey , Moreno Denise , Blanco Antonio , Otero Anisia , Rodriguez Mayra , Sogade Felix , Oludare Simisola , Fonseca Vivian , Moreau Cynthia , Marquez Sofia , Duncan Phillip , Davis Unice , Tang Steven , DeMuth Bonnie , Christie Donovan , Roberts Lorin , Martin Amanda , Luo Lan , Waddle Summer , Brown Shameka , Bianco Salvatore , Steinberg Helmut , Bell Amy , Patel Dharmendra , Bailey Alison , Rice Michelle , Herrington David , Blinson Karen , Doomy Lynda , Smith David , Norton Jenny , Gross Suvi , Mouhaffel Assad , Guillory Clinton , Korn Samantha , Aude Yamil Wady , Esparza Yirsa , Leal Sonia , Abreu Leidy , Auerbach Eric , Huff Cindy , Brooks Miriam , Johnson Marina , Allen Tammy , Berkson Arthur , McAuliffe Krystal , Little Holly , Little Raymond , Abbas Jalal , Collard Christina , Foreman Jamie , Richardson Shelby , Desire Andre , Shneker Ayham , Cordero Omar , Kunik Piotr , Kiesz Radoslav , Sasser Kathy , Golden Patrick , Garden Renee , Green Allen , Fung Gordon , Uyemura Keith , Hamal Sajad , Budoff Matthew , Dinh Dinh , Nguyen Jenny , Erande Ashwini , Brink Kelly , Malik Shaista , Chronos Nicolas , Maslanka Nicole , O'Donnell Philip , Bittorf Margaret Ann , Garg Rajesh , Matheson Della , Martinez Aldo , Hernandez Yasiel , Haught Walter Herbert , Eskridge Lisa , Jaffrani Naseem , Trimble Melissa , Powell James (Jamie) , Bryant Winifred , Bryant Nakeydia , Bergman Shmuel , Libuit Rezelle , Bringas Angelica , Visentin Diana , Murphy Lori , Junek Adrienne , Nahas Shadi , Berlingieri Joseph , Urso Caroline , Moshiri Alireza , Elliott Thomas , Inducil Marla , Parker Wanda , Stults Ryan , Kim Hwasoon , Acevedo Beatriz 
Published: August 2024

ImportanceIn 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).ObjectiveTo replicate the finding of TACT in individuals with diabetes and previous MI.Design, Setting, and ParticipantsA 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.InterventionsEligible 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 MeasuresThe 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.ResultsOf 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 &amp;lt; .001). Corresponding levels in the placebo group were 9.3 μg/L and 8.7 μg/L, respectively.Conclusions and RelevanceDespite 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 RegistrationClinicalTrials.gov Identifier: NCT02733185