Chelation with intravenous EDTA (disodium ethylene diamine tetra-acetic acid) has long been used for heavy metal poisoning. It binds the metal ions and facilitates their excretion from the body. In recent years it has been used for many other indications that are not evidence-based, such as autism and coronary heart disease.
The Trial to Assess Chelation Therapy (TACT) was done to assess the effectiveness and safety of EDTA plus high-dose oral vitamins for preventing second heart attacks in patients who had already had one. An article on The People’s Pharmacy website portrays the study as strongly positive. The Graedons, authors of the website, claim that science supports the use of chelation. They report that for every 12 patients undergoing chelation, one heart attack will be prevented over a five-year period. They cite a 5-year NNT (number needed to treat) of 16 for statin therapy and they conclude that:
EDTA chelation outperformed statins because fewer people needed to receive treatment to achieve a desirable outcome.
That’s just wrong. It compares oranges to apples (truckloads of statin oranges to one wormy, rotten chelation apple). The benefits of statins have been established in multiple studies; the alleged benefits of chelation are based on a single fatally-flawed study. You can’t say chelation outperforms statins unless you have done a controlled study comparing the two. In fact, in the TACT study the subjects were all on standard therapy after a heart attack; most of them were taking statins. The Graedons don’t seem to understand the actual results of the study. The Graedons downplay the known risks of chelation and the serious flaws that make the study unreliable, and they provide anecdotes, saying that in combination with the TACT results, those anecdotes mean that some people do get benefit from EDTA chelation therapy. No, they don’t mean that at all, and the Graedons should know better.
In 2008, while the trial was in progress, SBM’s own Kimball Atwood and Wallace Sampson, along with two other authors, wrote an exhaustive evaluation of TACT’s rationale, methodology, and ethics. They said:
We present our findings in 4 parts: history, origin and nature of the TACT, state of the evidence, and risks. We present evidence that chelationists and their organization, the American College for Advancement in Medicine, used political connections to pressure the NIH to fund the TACT. The TACT protocols justified the trial by misrepresenting case series and by ignoring evidence of risks. The trial employs nearly 100 unfit co-investigators. It conflates disodium EDTA and another, somewhat safer drug. It lacks precautions necessary to minimize risks. The consent form reflects those shortcomings and fails to disclose apparent proprietary interests. The trial’s outcome will be unreliable and almost certainly equivocal, thus defeating its stated purpose.
We conclude that the TACT is unethical, dangerous, pointless, and wasteful. It should be abandoned.
Results and criticisms of the completed trial
It wasn’t abandoned. When the results were announced, David Gorski wrote a masterful analysis pointing out its many flaws, including a high drop-out rate and missing data. The results were essentially negative. They reported it as positive, because the primary endpoint (an aggregation of serious cardiovascular events plus softer criteria) showed a modest difference (30% for placebo vs. 26.5% for chelation) that was just barely statistically significant. But there was no significant difference in the individual endpoints of death, heart attack, stroke, coronary revascularization, and hospitalization for angina. Only the subgroup of patients with diabetes appeared to benefit from chelation. For non-diabetics, there was no statistically significant difference in any of the outcome measures. A separate investigation of quality of life showed no difference between placebo and chelation. Even the study investigators concluded that TACT “does not constitute evidence to recommend the clinical application of chelation therapy” and as usual, they recommended further studies.
When the TACT study was published in the Journal of the American Medical Association (JAMA), it was accompanied by an editorial written by cardiologist Steven Nissen. He said:
many important limitations in the design and execution of a clinical trial compromise the reliability of the study and render the results difficult to interpret. Unfortunately, the efforts of these investigators fell short of the minimum level of quality necessary to adequately answer the question they sought to investigate.
He goes on to elaborate some of TACT’s deviations from the scientific principles of a good trial. And he concludes:
Given the numerous concerns with this expensive, federally funded clinical trial, including missing data, potential investigator or patient unmasking, use of subjective end points, and intentional unblinding of the sponsor, the results cannot be accepted as reliable and do not demonstrate a benefit of chelation therapy. The findings of TACT should not be used as a justification for increased use of this controversial therapy.
Kimball Atwood covered the equivocal results and went even further. He argued that it was unethical for journals to publish the study.
Lessons to be learned
This trial was a good example of why we established this blog promoting science-based medicine over evidence-based medicine. We had good evidence from preliminary studies that chelation didn’t work and was dangerous. There was no underlying rationale for why it should work. There had been no laboratory, animal, or human phase 1 or 2 studies; so doing such a trial would fail to meet the Declaration of Helsinki guidelines for ethical research. But evidence-based medicine looks only at what it classifies as evidence, and it fails to consider how human foibles and flawed experimental design make some of that evidence unreliable. It values the results of any randomized controlled trial even if it is Tooth Fairy science done for a treatment that basic science tells us couldn’t possibly work, like homeopathy or therapeutic touch. An article in the American Heart Journal argued that we couldn’t say chelation didn’t work because there hadn’t been any large scale randomized controlled studies. NCCAM was happy to oblige. Evidence-based medicine embraced the study; science-based medicine didn’t.
Conclusion: TACT was a journey to nowhere
The TACT study should never have been done. It accomplished nothing. The published results allow chelationists to claim that it works, just as they did before the study. They allow science-based doctors to claim that it doesn’t work, just as they did before the study. So after spending $31.6 million of taxpayer money, we are right back where we started.