July 17th, 2014
Clinical Events vs. Quality of Life: An Insider’s View of TACT
On July 1st, two Trial to Assess Chelation Therapy (TACT) articles were published that appear to show contradictory results regarding the effects of chelation therapy on clinical events and the quality of life.
For those who don’t live and breathe TACT (as I do, being one of the investigators), the 10-year trial tested a disodium ethylene diamine tetra acetic acid (EDTA)-based chelation solution versus placebo chelation, and high doses of oral multivitamins and multiminerals versus oral placebo in post-MI patients age 50 or older on OMT including statins and anti-platelets. For this piece, I will focus on the active-active versus placebo-placebo comparison.
The clinical study appears in the American Heart Journal and reports endpoints in the four factorial groups of TACT. In the overall group, there was a 26% reduction in combined cardiovascular events by active chelation plus active oral vitamins (5-year NNT=12; p=0.016). In patients with diabetes, there was a 51% reduction in combined cardiovascular events by active chelation plus active oral vitamins (5-year NNT=5.5, p<0.001). There is simply nothing else like this in diabetes. Safety data were solid. Edetate disodium chelation, as administered in TACT, was safe.
Over one million Americans survive an MI annually and, of these, about half have experienced a recurrent MI; thus, they are potentially TACT-type patients. A total of 68% of patients with diabetes die with heart disease contributing to their deaths. The public health implications of this trial are obvious. Curiously, medical media — Medscape and theheart.org in particular — chose not to cover this paper, and instead covered the second study and its negative quality of life results. Lay media did not even blink. However, this is a subject for another day.
The second study appears online in Circulation:Cardiovascular Quality and Outcomes, and in it we analyze quality of life (QOL) in a randomly selected 911-patient subgroup of TACT. Patients were mostly asymptomatic at baseline. We prospectively collected a battery of QOL instruments at baseline and at 6, 12, and 24 months after randomization. The primary endpoint was the Duke Activity Status Index (DASI). The analyses were intention-to-treat. We found no treatment-related improvement in QOL.
QOL is a complex endpoint in clinical trials and it always has to be viewed in the context of the study population and the overall benefit of the therapy. If a study population is mostly asymptomatic, it is hard to improve the QOL. TACT patients were mostly asymptomatic. Few had severe angina, so an improvement in the QOL should have been difficult to demonstrate, as it was. There are other effective treatments with similar apparent dissociations between clinical events and QOL. For example, aspirin, ICDs, and statins reduce cardiovascular events, but do not improve QOL, like chelation. Nitrates, on the other hand, improve QOL in angina, but do not reduce events. Therefore, clinical events are key.
Finally, we need to put this emerging literature in context for clinicians. It seems clear that the underlying mechanisms for benefit need exploration. But it is also clear that the treatment, as practiced in TACT, is safe and effective. Future studies will likely be performed, but there is no money on the table yet.
However, there is more to what we do than science. I see patients who want to know how to reduce their risk of another cardiac event. I am finding it increasingly difficult, particularly when I see diabetic post-MI patients (43% mortality reduction, 5-year NNT=12) to tell them that aspirin, statins, ACE inhibitors, and an annual stress test are all they have for options.
Share your thoughts on TACT and chelation therapy.