A 67-year-old Caucasian male patient presents to establish cardiology care after recently moving into your area. He has a history that is significant for type 2 diabetes mellitus, systemic hypertension, ischemic cardiomyopathy, and benign prostatic hypertrophy. He was admitted for non-ST-segment elevation myocardial infarction 6 months ago for which he underwent percutaneous coronary intervention with drug-eluting stent placement in the proximal left anterior descending coronary artery. He has remained free of any further anginal symptoms.
Echocardiogram showed global left ventricular dysfunction with an ejection fraction of 35%. Medications include aspirin, clopidogrel, carvedilol, atorvastatin, lisinopril, and eplerenone. He tolerates his medications very well and reports no side effects. As part of his post-myocardial infarction (MI) cardiac rehabilitation, he joined the local YMCA where he met his gym buddie. His gym buddy is a big proponent of "alternative therapies and complementary medicine" and advised the patient to try a new regimen that the gym buddy had read about recently in a medical journal. The journal stated that ethylenediaminetetraacetic acid- (EDTA-) based chelation and high-dose oral vitamins can benefit patients like him greatly. The patient seeks your expert opinion on this issue.
Which of the following choices represents an appropriate response to address the patient's concerns?
The correct answer is: A. A small-scale trial has demonstrated that the combination of high-dose oral vitamins and chelation therapy reduced clinically important cardiovascular events in a statistically significant manner that is of potential clinical relevance.
Despite a lack of strong evidence, medical practitioners have treated atherosclerotic disease with chelation therapy on and off for over 50 years. Chelation therapy was, at a time, relegated to complementary and alternative medicine practitioners who reported good anecdotal results. However, epidemiologic evidence has gradually mounted linking xenobiotic metals with cardiovascular disease and mortality, suggesting a plausible role for chelation therapy. On the basis of the continued use of chelation therapy without an evidence base, the National Institutes of Health released a Request for Applications for a definitive trial of chelation therapy. The TACT (Trial to Assess Chelation Therapy) was a double-blind, placebo-controlled, 2 × 2 factorial multicenter randomized trial of 1,708 post-MI patients ≥50 years of age and with creatinine ≤2.0 mg/dL randomized to receive 40 infusions of disodium EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitamin-multimineral mixture or placebo. In this double-blind 2 × 2 factorial trial, patients were randomized into one of four groups:
Active IV chelation infusions + active oral vitamins
Active IV chelation infusions + placebo oral vitamins
Placebo IV chelation infusions + active oral vitamins
Placebo IV chelation infusions + placebo oral vitamins.
The primary end point was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina.
The 5-year Kaplan-Meier estimate for the primary end point was lower (31.9%) in the chelation + high-dose vitamin group when compared with the other groups: 33.7% in the chelation + placebo vitamin group, 36.6% in the placebo infusion + active vitamin group, and 40.2% in the placebo infusions + placebo vitamin group.
The reduction in primary end point by double active treatment compared with double placebo was significant (hazard ratio 0.74, 95% confidence interval [0.57-0.95], p = .016). In patients with diabetes, the primary end point reduction of double active compared with double placebo was more pronounced (hazard ratio 0.49, 95% confidence interval [0.33-0.75], p = 0.001).
In summary, in stable post-MI patients on evidence-based medical therapy, the combination of high-dose oral vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance.
Lamas GA, Goertz C, Boineau R, et al. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. JAMA 2013;309:1241-50.
Peguero JG, Arenas I, Lamas GA, et al. Chelation therapy and cardiovascular disease: connecting scientific silos to benefit cardiac patients. Trends Cardiovasc Med 2014;24:232-40.