Chelation: Therapy or quackery?
More than 110,000 American adults used chelation in 2007, according to the National Health Interview Survey—a significant increase from the 66,000 patients using this therapy in 2002. Although chelation therapy is indicated for acute poisoning due to lead, iron, and other toxic compounds, much of its use has been by alternative medicine providers, especially for the treatment of cardiovascular disease (CVD).
According to its proponents, chelation therapy works by binding calcium in atherosclerotic plaques. The evidence of its effectiveness remains anecdotal in nature, however, lacking the data from large clinical trials common with CVD therapies such as antiplatelet agents.
The TACT study
In November 2012, preliminary findings from the Trial to Assess Chelation Therapy (TACT) were presented at the annual meeting of the American Heart Association. TACT is the only large double-blind, placebo-controlled study to evaluate the safety and efficacy of chelation therapy in individuals who had a prior myocardial infarction (MI). A total of 134 sites in the United States and Canada were used.
Patients were randomized to a chelation or placebo infusion. The disodium salt of ethylene diamine tetra-acetic acid (EDTA) was used as the chelation agent, and the I.V. solution was similar to that used in practice. The solution also contained vitamin C 7 g, magnesium 2 g, and unfractionated heparin 2,500 units. The therapy was administered once weekly for 30 doses, followed by an additional 10 doses which were given every 2 weeks to 8 weeks.
The primary endpoint was a composite of all-cause mortality, MI, stroke, hospitalization for angina, and coronary revascularization. Secondary endpoints included the individual components of the composite, health-related quality of life, safety, and other outcomes. The mean age of the 1,708 study participants was 65 years, and 82% were men. About one-third of participant had diabetes and two-thirds had hypertension. At least three-quarters of individuals were receiving aspirin, beta-blockers, and statins.
After a follow-up period of 55 months, 26.5% of patients receiving chelation therapy met the primary endpoint, compared with 30% for placebo. The difference between the two groups barely reached statistical significance; the individual components of the primary endpoint were similar in the two groups.
The rate of coronary revascularization appeared to be lower with chelation, but this finding did not achieve statistical significance. The slight difference in this component of the primary endpoint drove the apparent difference in the overall composite. TACT also had a withdrawal rate of 17%, which could have affected the rate of revascularization procedures. The benefit was seen primarily among patients with diabetes. A benefit on physical functioning or psychological well-being was not apparent.
What TACT means
Funded by the National Heart Lung and Blood Institute and the National Center for Complementary and Alternative Medicine (NCCAM), TACT was controversial from its inception. Unlike other studies funded by NCCAM, such as of glucosamine and saw palmetto, little previous evidence was available to justify further exploring the efficacy of chelation.
TACT began enrolling patients in 2003 with the goal of recruiting 2,400 people within 3 years. Recruitment was prolonged and did not reach its intended goal. In addition, the study was stopped temporarily in 2008 to permit investigations into concerns about how the study was conducted at some sites and whether patients were being adequately informed about risks with chelation therapy. Although the study showed a slight benefit, the withdrawal rate was high.
A final consideration is that data presented at conferences may not be what is in the eventual publication. While news media have highlighted this study, it is critical that patients do not view these preliminary, unpublished findings as evidence of an established treatment for coronary heart disease. Significant concerns exist that patients may decide to pursue chelation therapy over well-established therapies, even though the TACT data have not yet been published in a peer-reviewed journal.
What to tell patients
Counsel patients who ask about chelation therapy that the recent TACT findings were unexpected and preliminary. Chelation for CVD remains an unproven therapy. Encourage patients to focus on traditional approaches such as smoking cessation and lifestyle changes for achieving a desirable weight, as well as appropriate management of hypertension, lipid disorders, and diabetes.