Does chelation therapy work?
The National Center for Complementary and Alternative Medicine (NCCAM) is attempting to fulfill its mandate to prove or disprove the value of alternative treatments. A division of the National Institutes of Health, NCCAM has done research on everything from supplements to meditation. This latest study looks at chelation therapy in patients with cardiovascular disease. Chelation therapy with ethylene diamine tetra-acetic acid (EDTA) has been used for decades to treat lead toxicity, and it has also been found to reduce metastatic calcium deposits. Despite the fact that small studies have never shown a benefit for chelation in treating cardiovascular disease, many alternative clinics continue to tout its value in this role. A recently published NCCAM-funded study to evaluate the value of chelation enrolled more than 1700 patients ≥ 50 years of age with a history of myocardial infarction (MI) at least 6 weeks prior. The study was a double-blind, placebo-controlled, 2 × 2 factorial randomized trial from 2003 through 2011. There were 289 patients who withdrew consent from the study, of which 60% were in the placebo group. The study consisted of 40 EDTA/vitamin infusions vs placebo infusions (given weekly for 30 weeks then at 2-8 week intervals). About 15% of patients in both groups dropped out during therapy. The primary outcome was a composite of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. The primary endpoint occurred in 222 (26%) in the chelation group and 261 (30%) in the placebo group (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.69-0.99; P = 0.35). There was no effect on total mortality, but there was slight improvement in other outcomes with chelation. The authors conclude that among stable patients with a history of MI, chelation therapy modestly reduced the risk of adverse cardiovascular outcomes. They conclude that this study provides evidence to guide further research but is not sufficient to support the routine use of chelation therapy in patients with cardiovascular disease (JAMA 2013;309:1241-1250). Editorialists in the same issue of JAMA immediately leveled strong criticisms, ranging from allegations of noncompliance with regulations for the protection of research participants to questioning the professional credentials of the study sites and investigators. The JAMA editorial board did an extensive review of the data, and despite concerns, decided to publish the study with the caveat that "these findings do not support the routine use of chelation therapy as secondary prevention for patients with previous myocardial infarction and established coronary disease." (JAMA 2013;309:1291-1292.) Another editorialist, however, suggests that "limitations in the design and execution" of this trial compromise the findings. For example, the high number of withdrawals of consent in the placebo group suggests that the study was not truly blinded. There is also concern about the use of "softer" endpoints such as coronary revascularization and hospitalization for angina. Also, the trial design was altered midway through the study because of the length of the trial. Given these concerns, "including missing data, potential investigator or patient unmasking, use of subjective endpoints, and intentional unblinding of the sponsor, the results cannot be accepted as reliable and did not demonstrate a benefit of chelation therapy." (JAMA 2013;309:1293-1294.)