Chelation therapy on hold for cardiac patients
medwireNews: The findings of the controversial Trial to Assess Chelation Therapy (TACT) have been published in JAMA.
Although the results suggest modest benefits from intravenous chelation treatment in patients with myocardial infarction (MI), the limitations of the trial mean its findings "should not be used as a justification for increased use of this controversial therapy," according to editorialist Steven Nissen (Cleveland Clinic Foundation, Ohio, USA).
There are, in fact, two editorials accompanying the study; the huge controversy attached to the trial prompted the journal editors to set out the rationale for accepting the study for publication. Also, some of the authors' responses to the editors' concerns during assessment of the study are available on the JAMA website.
The study's primary endpoint was a composite of mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. During a median follow up of 55 months, 26% of the 839 patients receiving disodium EDTA infusions (30 weekly, then 10 every 2-8 weeks) had an endpoint event, as did 30% of 869 patients receiving placebo infusions.
This equated to a significant 18% reduction in risk; however, about half of the endpoint events were coronary revascularizations, which Nissen describes as a "softer" endpoint than mortality, MI, or stroke and therefore more open to bias.
This is compounded by the very high dropout rate in the trial, with 18% of patients withdrawing. Of these 311 patients, 289 withdrew their consent, and the number was significantly higher in the placebo than the chelation group, at 174 versus 115. Nissen says this implies unblinding of treatment allocation, a particular concern given that 60% of the study centers specialized in complementary and alternative medicine, suggesting that some investigators were "advocates for chelation therapy."
The findings did tend to favor chelation therapy for all endpoints, but the benefit was not significant for any individual endpoint and some of the "hard" endpoints occurred in very few patients. The overall difference was only just significant (p=0.035) and there were 11 interim analyses, which Nissen says is "is highly unusual and increases the risk that the study was stopped exactly at the point when marginal 'significance' was reached."
There were no safety concerns, however, with similar numbers of patients dropping out of the chelation and placebo groups because of adverse effect, report Gervasio Lamas (Mount Sinai Medical Center, Miami Beach, Florida, USA) and team. Patients in the chelation group received 500 mL infusions of disodium EDTA 3 g, ascorbate 7 g, B vitamins, electrolytes, procaine, and heparin, along with oral vitamins and minerals; those in the placebo group received saline with 1.2% dextrose and an oral placebo.
Finally, Nissen notes that the study sponsors - the National Heart, Lung, and Blood Institute and the National Center for Complementary and Alternative Medicine - were unblinded, which "represents a serious deviation from acceptable standards of conduct for supervision of clinical trials."
He says: "TACT provides useful insights into the overwhelming challenges faced when trying to determine the effectiveness of an unusual and controversial therapy."
By Eleanor McDermid, Senior medwireNews Reporter