TACT: Chelation therapy reduced adverse events in post-MI patients
LOS ANGELES — Patients with a prior MI given weekly infusions of chelation therapy experienced fewer CV events than patients who received placebo infusions, according to new results from the TACT trial.
The randomized, double blind, placebo-controlled, 2x2 factorial trial examined a multicomponent disodium ethylene diamine tetra-acetic (EDTA) chelation solution as compared with placebo, and of an oral high-dose multivitamin and mineral supplement as compared with placebo.
At a late-breaking clinical trials session, Gervasio A. Lamas, MD, presented data on 1,708 post-MI patients aged 50 years and older, for a total of 55,222 infusions overall.
The primary endpoint was a composite of total mortality, recurrent MI, stroke, coronary revascularization or hospitalization for angina.
“The 10-component disodium EDTA chelation and ascorbate regimen reduced adverse cardiac events in post-MI patients, meeting prespecified significance criteria,” Lamas, of the Columbia University division of cardiology and Mount Sinai Medical Center in Miami Beach, Fla., said at a press conference.
Serious CV events occurred in 26% of patients assigned chelation vs. 30% of patients assigned placebo (HR=0.82; 95% CI, 0.69-0.99). The regimen reduced clinical events early after treatment onset and effects persisted for at least 5 years. The overall effect size (18% relative reduction in the primary endpoint) was not dominated by one single component, although there was no evidence of an effect on mortality, according to Lamas.
Analysis of two prespecified subgroups revealed particular benefit of chelation: presence of diabetes and MI location. With chelation, patients with diabetes had a 39% reduction in risk and patients with anterior MI had a 37% reduction in risk. Thirty-two percent of patients in the TACT trial had diabetes.
“We have to look carefully at these unexpected results,” Lamas stated in a press release. “Although not approved by the FDA for treating heart disease, chelation therapy has been used for over 50 years and has generally been believed by conventional medical practitioners and cardiologists to be without value. A definitive answer on chelation therapy will take much additional research.”
Daniel B. Mark, MD, MPH, presented data from a quality of life substudy of the TACT trial.
Daniel B. Mark
“In a population of stable, predominantly asymptomatic CAD patients with a history of prior MI, the use of EDTA chelation therapy did not produce a consistent sustained improvement in any domain of health-related QOL,” Mark, of Duke University Medical Center and Duke Clinical Research Institute, said at a press conference.
The QOL study included 911 randomly selected patients from the main TACT trial (53%). QOL was assessed by structured QOL interviews at baseline, 6, 12 and 24 months. Follow-up was conducted via telephone.
One of the tools used to measure QOL was the Duke Activity Status Index (DASI), an assessment of ability to complete daily tasks. Lower scores indicate less ability to complete tasks. Patients assigned chelation had a score that was about 2 points higher than placebo at 6 months, 3 points higher at 12 months and 2 points higher at 24 months (not significant).
Results were similar when researchers used the Short Form Health Survey (SF-36), an assessment of mental well-being or stress. After 24 months of chelation or placebo, patients reported similar scores.
The chelation therapy used in the TACT trial included infusions of a 500 mL chelation solution containing 3 g of disodium EDTA; 7 g ascorbic acid; 2 mg magnesium chloride; 100 mg procaine hydrochloride; 2,500 U unfractionated heparin; 2 mEq potassium chloride; 840 mg sodium bicarbonate; 250 mg pantothenic acid and 100 mg thiamine; 100 mg pyridoxine; and sterile water to make up 500 mL of solution. The placebo infusion was 500 mL of normal saline. Patients received 40 infusions, each lasting at least 3 hours.
The study was conducted at 134 sites in the United States and Canada. Mean follow-up was 55 months.
The investigators’ original plan was to randomly assign 2,372 patients with follow-up of at least 1 year. In 2009, blinded investigators asked the Data and Safety Monitoring Board to reduce the total sample size to 1,700, with a compensatory increase in follow-up to maintain the same power. – by Katie Kalvaitis
For more information:
Lamas GA. Late-breaking clinical trials: Practice implications for CAD and VTE.
Mark DB. Late-breaking clinical trials: Health economics and quality of life in contemporary trials. Both presented at: the American Heart Association Scientific Sessions; Nov. 3-7, 2012; Los Angeles.
Disclosure: Lamas reports no relevant financial disclosure. Mark reports consulting for Janssen and research grants from AstraZeneca, Eli Lilly, Gilead and Medtronic.