title: Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial.
abstract: OBJECTIVE
  Chelation therapy with disodium EDTA has been used for more than 50 years to treat atherosclerosis without proof of efficacy.
  
  
  OBJECTIVE
  To determine if an EDTA-based chelation regimen reduces cardiovascular events.
  
  
  METHODS
  Double-blind, placebo-controlled, 2 × 2 factorial randomized trial enrolling 1708 patients aged 50 years or older who had experienced a myocardial infarction (MI) at least 6 weeks prior and had serum creatinine levels of 2.0 mg/dL or less. Participants were recruited at 134 US and Canadian sites. Enrollment began in September 2003 and follow-up took place until October 2011 (median, 55 months). Two hundred eighty-nine patients (17% of total; n=115 in the EDTA group and n=174 in the placebo group) withdrew consent during the trial.
  
  
  METHODS
  Patients were randomized to receive 40 infusions of a 500-mL chelation solution (3 g of disodium EDTA, 7 g of ascorbate, B vitamins, electrolytes, procaine, and heparin) (n=839) vs placebo (n=869) and an oral vitamin-mineral regimen vs an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. Fifteen percent discontinued infusions (n=38 [16%] in the chelation group and n=41 [15%] in the placebo group) because of adverse events.
  
  
  METHODS
  The prespecified primary end point was a composite of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. This report describes the intention-to-treat comparison of EDTA chelation vs placebo. To account for multiple interim analyses, the significance threshold required at the final analysis was P = .036.
  
  
  RESULTS
  Qualifying previous MIs occurred a median of 4.6 years before enrollment. Median age was 65 years, 18% were female, 9% were nonwhite, and 31% were diabetic. The primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.99]; P = .035). There was no effect on total mortality (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0.93 [95% CI, 0.70-1.25]; P = .64), but the study was not powered for this comparison. The effect of EDTA chelation on the components of the primary end point other than death was of similar magnitude as its overall effect (MI: chelation, 6%; placebo, 8%; HR, 0.77 [95% CI, 0.54-1.11]; stroke: chelation, 1.2%; placebo, 1.5%; HR, 0.77 [95% CI, 0.34-1.76]; coronary revascularization: chelation, 15%; placebo, 18%; HR, 0.81 [95% CI, 0.64-1.02]; hospitalization for angina: chelation, 1.6%; placebo, 2.1%; HR, 0.72 [95% CI, 0.35-1.47]). Sensitivity analyses examining the effect of patient dropout and treatment adherence did not alter the results.
  
  
  CONCLUSIONS
  Among stable patients with a history of MI, use of an intravenous chelation regimen with disodium EDTA, compared with placebo, modestly reduced the risk of adverse cardiovascular outcomes, many of which were revascularization procedures. These results provide evidence to guide further research but are not sufficient to support the routine use of chelation therapy for treatment of patients who have had an MI.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00044213.
authors.affiliation: Columbia University Division of Cardiology, Mount Sinai Medical Center, 4300 Alton Rd, Miami Beach, FL 33140, USA. gervasio.lamas@msmc.com
authors.forename: Gervasio A
authors.initials: GA
authors.lastname: Lamas
authors.forename: Christine
authors.initials: C
authors.lastname: Goertz
authors.forename: Robin
authors.initials: R
authors.lastname: Boineau
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Mark
authors.forename: Theodore
authors.initials: T
authors.lastname: Rozema
authors.forename: Richard L
authors.initials: RL
authors.lastname: Nahin
authors.forename: Lauren
authors.initials: L
authors.lastname: Lindblad
authors.forename: Eldrin F
authors.initials: EF
authors.lastname: Lewis
authors.forename: Jeanne
authors.initials: J
authors.lastname: Drisko
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Lee
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000517:prevention & control*; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy; D002614:Chelating Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004492:Edetic Acid / Q000627:therapeutic use*; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control*; D062645:Percutaneous Coronary Intervention; D012008:Recurrence; D012306:Risk; D020521:Stroke / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D002614:Chelating Agents; D004492:Edetic Acid