This is the second of two posts about a study of whether chelation therapy might benefit some patients who have suffered a heart attack. In the first post, I gave health reporters high marks for their coverage.
Early in my career, I covered a story on chelation therapy. It was the first time I’d ever heard of the alternative treatment. I was a broadcast producer, and we needed video, so we visited a chelation clinic. Looking back, I can’t recall what our story was about, but I do remember what it was like to talk to the patients as they sat in recliners that lined the walls of the narrow storefront.
They were all hooked up to IV bags filled with a vivid yellow liquid that was a mixture of B-vitamins and the chemical EDTA that they believed was flushing heavy metals, minerals, and toxins from their bodies.
Many spoke of chelation with fervor. One man, a diabetic, credited the regular three-hour infusions with saving his legs, which were riddled with sores.
Chelation has been around for decades. It is accepted treatment for lead poisoning and other kinds of heavy metal toxicity. But alternative practitioners have greatly expanded its use, with claims that it can treat myriad ills, everything from autism to Alzheimer’s to problems caused by metal hip implants. There’s almost no scientific evidence to back up these claims.
It was against this backdrop – lots of claims, enthusiastic patients, evangelistic providers – that the NIH set out to test the practice.
The Trial to Assess Chelation Therapy, or TACT, has again ignited a heated debate among doctors.
Here’s another voice to add to the discussion. He is lead study author Gervasio A. Lamas, M.D., chairman of medicine at Mount Sinai Medical Center in Miami Beach, Fla., and professor of clinical medicine at Columbia University Division of Cardiology. I asked him to talk about the process of publishing TACT and asked him to respond to a few of the main criticisms of the trial. These are lightly edited questions and answers from our interview:
AHCJ: Why did you do this study?
Lamas: In 1999, a patient asked me if he should receive chelation therapy and I said, “Of course not.”
Then I kind of looked into it, and I realized I couldn’t give that answer because it wasn’t yes and it wasn’t no, because there were not credible data, that I could see. And that started this particular road towards getting the data.
AHCJ: If that same patient came to you today, what would you tell him?
Lamas: I would tell them that chelation therapy, if it’s done carefully, it’s not dangerous. That If it’s done in the right kind of patient… If it’s done for somebody who’s had a heart attack, reasonably normal kidneys, above age 50 and a couple of other criteria, it’s likely to provide modest benefit, but that the most important thing that they can do is the routine, evidence-based care, for sure. Then, you know, I would say that at this point, that chelation therapy in my patients would not be for routine use.
That’s the cautious tone of the conclusion of the abstract and of the paper are really the way that I feel about it. It provides modest benefit. We’re not ready at this point to recommend it for routine use following a heart attack.
AHCJ: Were you happy with the way JAMA presented the study? It’s pretty unusual, I think, for a journal to present so much additional material to try to frame the findings of a study.
Lamas: You have to step back a little bit and understand the history of chelation therapy in order to understand that the fact that JAMA editors chose to publish the paper actually speaks volumes for their assessment of the quality of the study and their assessment of the data and the investigators.
Chelation was initially used in 1955. In 1956, there was a case series of angina that seemed to get better with EDTA [the chemical in the chelation mixture that’s thought to bind and flush metals and minerals]; the theory was that the calcium would be leached out of the arteries and somehow that would improve blood flow.
Sometime in the 1960s, conventional medicine turned away from chelation, and it slid into an alternative medicine treatment, where it remained. We’re talking 58 years before there was a large-scale clinical trial published between the time it was first used and the time the trial came to publication.
There wasn’t anything else – maybe aspirin – that was around for so long before it was tested.
Because of the length of time this treatment has been out there, because of the controversy that’s swirled around it, I think that it is incumbent on us to be enthusiastic because there may be a new way of treating atherosclerosis, but to mute that enthusiasm and to be cautious about applying it.
AHCJ: One of the criticisms of the study was that the benefit was really driven by some of the softer endpoints. Patients had fewer revascularizations and less chest pain that led to hospitalization. But it didn’t really save lives. How do you answer that?
Lamas: Combined endpoints are used a lot of times. We didn’t pull this out of nowhere.
In the accompanying editorial, Dr. Nissen sort of criticizes the endpoint. Well, he’s the steering committee chairman of a trial called ACCELERATE of a new cholesterol drug. The primary endpoint is exactly our primary endpoint. So what gives?
What gives is bias against chelation therapy. We’re starting off with a population of physicians, cardiologists who for years have been taught that this can’t possibly work, that this is dangerous quackery. And now there are data.
AHCJ: Was it hard to get the trial published?
Lamas: I’ve been in sort of major journals before, I would say this one was a little harder than usual, yeah. I think it was appropriate, and I think it was helpful on both sides of the equation, both the editors’ side and the side of the authors because all of us became more convinced about our results.
You saw the letter? That was the initial review from the editors.
AHCJ: I can’t remember another time when the journal has released the editors’ questions and your responses like that.
Lamas: Exactly. I think they did it for a couple of reasons: One was to show their due diligence, because they expected to be heavily criticized for publishing this, and secondly to show that not only did they do their due diligence, but we did our scholarly due diligence, and said listen, you’re asking some tough questions and these are the answers. And that led to publication.
AHCJ: Was JAMA the first journal that you submitted to?
Lamas: I think that needs to remain confidential.
AHCJ: Really, why?
Lamas: Because I think that JAMA would be…. I think that all parties involved would probably be sensitive. You’re not really supposed to talk about what else you’ve done. It’s kind of an unwritten thing.
AHCJ: Your study had a high dropout rate, about 18 percent of people were lost to follow up. More actually withdrew from the placebo group than the chelation group. Why do you think so many dropped out?
Lamas: In TACT, the patients knew they had a 50 percent chance of being on a placebo, and they have to come in every week and receive a three-hour infusion for 30 weeks. If you include the travel time, the time it takes to put a bandage on and make sure the arm is not still bleeding, etc., it’s easily a five-hour commitment once a week. I’m incredibly grateful that our patients gave us the time they did, but I do not wonder at all that there were a larger number than usual that said “I don’t want to do this anymore.”
We’re really grateful to our patients, to say they went an extra mile is a complete understatement.
AHCJ: There have been some questions about the quality of sites that participated in the trial. How do you answer those?
Lamas: About 60 percent of the clinical sites already practiced chelation therapy in their offices. The rest of them were mostly conventional cardiology sites, academic medical centers, etc. Each type of site brought with it some strengths and weaknesses. So if you have a place like Bayview Hopkins or Mayo Clinic, both of which were sites, they brought excellent knowledge of the research process, but they had never done chelation therapy ever before. They didn’t have the infrastructure to set it up. Their coordinator was not used to managing the IVs, they had some problems getting the IVs in, etc. They did not have chelation experience, but they had research experience. You look at the other group of sites and they had extensive chelation experience, but they had little or no research experience. So we handled that to create standardized training two or three times, give online training, and try to create a blended team that could do the study. The proof that that worked is when you look at figure 3, at the subgroup analysis, there’s no interaction so that there’s no difference in the results from site to site.