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Effect of Disodium EDTA Chelation Regimen on Cardiovascular Events in Patients With Previous Myocardial Infarction: The TACT Randomized Trial
Study Questions:
Does a disodium EDTA-based chelation regimen reduce cardiovascular events in persons with a previous myocardial infarction (MI)?
Methods:
TACT (The Trial to Assess Chelation Therapy) was a double-blind, placebo-controlled, 2 x 2 factorial, randomized trial conducted in 1,708 patients ages ≥50 years who had experienced an MI at least 6 weeks prior and had serum creatinine levels of ≤2.0 mg/dl. Participants were recruited at 134 US and Canadian sites. 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) versus placebo (n = 869), and an oral vitamin-mineral regimen versus an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2-8 weeks apart. The prespecified primary endpoint 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 versus placebo. To account for multiple interim analyses, the significance threshold required at the final analysis was p = 0.036.
Results:
Median age was 65 years, 18% were female, 9% were nonwhite, and 31% were diabetic; 83% had undergone coronary artery bypass grafting or percutaneous coronary intervention, 84% were taking aspirin, 26% clopidogrel, 72% a beta-adrenergic blocker, and 73% statins, with a median low-density lipoprotein cholesterol level of 89 (interquartile range, 67-115) mg/dl. 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; 15% discontinued infusions in the chelation and placebo groups because of adverse events. Qualifying previous MIs occurred a median of 4.6 years before enrollment. The primary endpoint occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.69-0.99; p = 0.035). 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 = 0.64), but the study was not powered for this comparison. The effect of EDTA chelation on the components of the primary endpoint 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). Two prespecified subgroups appeared to receive particular benefit of therapy. Patients with diabetes had a reduction in risk (HR, 0.61; 95% CI, 0.45-0.83), and patients with anterior MI had a reduction in risk of cardiovascular events (HR, 0.63; 95% CI, 0.47-0.86). 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.
Perspective:
In 2007, at least 111,000 adults were treated with chelation therapy. Mainstream cardiology and the general medical community have been skeptical of chelation. Among the major reasons is the lack of biologic plausibility. The 18% relative treatment effect is within the range of effects that have been considered clinically important in prior trials. The findings will undoubtedly convince enthusiasts to promote chelation therapy, now with some evidence of benefit.
Keywords: Electrolytes, Chelating Agents, Stroke, Myocardial Infarction, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Procaine, Heparin, Adrenergic Antagonists, Percutaneous Coronary Intervention, Cholesterol, Vitamin B Complex, Coronary Artery Bypass
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