Chelation therapy in TACT: Daring to challenge dogma (and suspend disbelief)

Reposted from www.theheart.org.  Video can be seen at http://www.theheart.org/columns/topolog/chelation-therapy-in-tact-daring-to-challenge-dogma-and-suspend-disbelief.do.

Transcript:

I’d like to review with you one of the most controversial trials in cardiovascular medicine that has been published in a long time: the TACT trial of over 1700 patients who had a prior myocardial infarction and then were getting chelation therapy.

The chelation therapy was given over 30 weeks, every week. It wasn’t just EDTA but also a mixture of various vitamins, potentially what you could consider antioxidants, that were added to the solution. It was given for 30 weeks consecutively, with another series of infusions given several weeks after that. And this was conducted at various sites. It took from 2003 to 2011—eight years—before it was completed.

The trial has a lot of warts and a lot of strengths. The warts are many, but they include the fact that 18% of the patients are lost to follow-up. There were also problems with 11 interim analyses. There was an imbalance in the loss of follow-up, and it suggested concerns regarding the blinding in the trial and the fact that many of the sites were very into “alternative,” “complementary” medicine. There are a lot of things that are of concern.

But what is notable about this trial is the consistent directionality of the end points. There was overall an 18% reduction of a composite end point, which included—and I’ll just review with you, of the various end points that you see in table 2 of the manuscript—death, heart attack, stroke, coronary revascularization, and hospitalization for angina. Each of these was reduced. Death was reduced 7%, MI by 23%, stroke by 23%, coronary vascularization by 19%, hospitalization for angina by 8%.

The biggest absolute difference was in coronary vascularization, but the directionality and the magnitude were pretty similar across the board. In fact, the weakest was for the end point that’s most subjective: hospitalization for angina.

The other thing that’s interesting is that overall this significant reduction in the end points is 18%, but the subgroup analysis revealed that it wasn’t necessarily consistent across all the subgroups. There were two—diabetes and anterior MI—that had particular benefit (and that is summarized in figure 4 of the manuscript).

This paper, because it’s so controversial—since we don’t really understand the biology of how chelation therapy or the solution with all these antioxidants could be playing a role—this is, of course, tricky. And the fact that JAMA published this: I applaud the editor, Dr Howard Bauchner, and the associate editor, Dr Phil Fontanarosa, and their colleagues for having published this trial even though it’s controversial because it makes a big statement about challenging dogma.

When the NIH and the complementary-medicine NIH divisions got behind this trial and supported it with $31 million—despite all of its fits and starts—it did get completed. It had some problems, but it challenged the dogma about whether chelation would be helpful. Overall, when you look at the data it looks like there is something going on—whether it’s the chelation, whether it’s the very careful selection of patients, whether it was where it was conducted, whether it was other stuff in the solution . . . who knows? But it does raise some questions, and it’s good because it challenged the notion that chelation is bad. It didn’t certainly show that.

In fact, in my practice in cardiology in California I have so many patients that come to me on chelation, and all this time I actually thought it could be harmful. At least I feel perhaps that is not the case. I certainly wouldn’t recommend it based on this trial, but it’s very provocative.

Whether it was worth $31 million? I don’t know. Back in 2003 when this trial was announced, I thought it was a crazy notion. But at the end of the day, after all this work of all these investigators, I give them credit and I give the JAMAeditors credit for publishing it. It will be controversial, it will be provocative, but that’s a good thing for clinical trials.

Thanks a lot for your attention.