No Sign of QoL Benefits With Chelation in TACT

Shelley Wood

July 01, 2014

NEW YORK, NY — Quality of life (QoL) over two years was no better, but no worse, among patients who underwent chelation therapy in the controversial Trial to Assess Chelation Therapy (TACT), according to research published online July 1, 2014 in Circulation: Cardiovascular Quality and Outcomes[1].

In the study, Dr Daniel Mark (Duke University Medical Center, Durham, NC) and colleagues report that there were no differences between patients treated with disodium EDTA chelation and patients treated with a placebo infusion on either the Duke Activity Status Index or the Medical Outcomes Study Short-Form 36 Mental Health Inventory, designed to assess cardiac-related functional status and psychological well-being, respectively.

Speaking with heartwire , Mark pointed out that it was back in the late '50s and early '60s when physicians using chelation to treat metal toxicity first heard from patients that their angina symptoms had improved.

"When we designed the [TACT] study, the design wasn't focused on symptom relief but on changing outcomes. In a big trial you have to show you are moving the ball down the field to justify that kind of expenditure. But we did want to look at QoL. We didn't really know at the outset of the study what proportion of patients would have symptoms and whether we would be able to demonstrate an effect on QoL."

As previously reported by heartwire , the National Institutes of Health–sponsored study surprised almost everyone when it showed an 18% drop in a composite end point of all-cause mortality, MI, stroke, coronary revascularization, and hospitalization for angina with chelation therapy compared with placebo. That difference, however, only barely reached the prespecified threshold for statistical significance, and while all components of the end point moved in the same direction, the difference was largely driven by the "softer" components of the composite primary end point: coronary revascularization and hospitalization for angina.

At the study outset in 2002 it was "uncertain" whether chelation would have any QoL benefits in the stable post-MI patients in whom the trial was conducted, the authors write. The most plausible, if chelation worked, would be less angina and better functional status.

Given the primary trial findings and in particular the effects on coronary revascularization and hospitalization for angina, the lack of an effect on QoL is notable.

"Although both of those end points would be expected to have a symptomatic element, it is possible that the duration of symptoms was truncated by application of effective therapies, and no long-term decrements in QoL were produced," Mark et al write. "Another possible explanation for our negative findings is that TACT selected a population in which there was little opportunity for a QoL benefit to be produced because of the low level of cardiac symptoms present at the time of enrollment."

 
One study, no matter how well-designed and conducted . . . is rarely going to definitively establish the efficacy of a therapy."
 

Of note, the prespecified QoL analysis was done in just 50% of the trial participants, based on budgetary restrictions in what ultimately proved to be a more than $31-million trial. Still, say the authors, the number of patients was sufficient to provide enough power to detect small but clinically important differences.

To heartwire , Mark noted that there was a suggestion that people with angina at baseline had "more movement" in their QoL scores, "but there were really too few of them to even suggest that that was something definitive. To have any confidence that that was true you'd have to replicate the study with a larger cohort of patients with angina."

That's increasingly difficult in the modern practice of medicine, he continued, because there are fewer patients with angina that isn't already being managed medically or, in certain cases, through PCI. "That's not to say that people don't have chest pain any more, but the kind of chronic typical angina that we used to see when I first trained has really become much less frequent" in cardiology practices, specifically the kind of pain that drives patients to seek hospital-based care.

According to Mark, there is ongoing "discussion" about prospects for another chelation trial, especially one that would zero in on diabetic patients, in whom the effects of chelation were particularly marked. "We would like to see a follow-up study," he said. "One study, no matter how well-designed and conducted [and in the case of TACT, that was a topic of some debate] is rarely going to definitively establish the efficacy of a therapy."

So far "no one has any money on the table" to fund such a study, at least that Mark is aware of. But if one were to move forward, he said, it would make sense to include a QoL component, particularly if the study’s design produced a more symptomatic cohort at baseline.

Mark disclosed received grant funding from Eli Lilly (significant), AstraZeneca (significant), Medtronic (significant), and Gilead (significant) and has served as a consultant for Janssen. Disclosures for the coauthors are listed in the article.

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