Results of TACT
Overall, those receiving chelation had an 18% reduced risk of subsequent cardiovascular events, such as heart attack, stroke, hospitalization for angina, or coronary revascularization or death from any cause. A cardiovascular event occurred in 222 patients (26%) in the chelation group and 261 patients (30%) in the placebo group. This advantage achieved statistical significance.
Of particular note was a subgroup analysis that revealed that two cohorts of participants enjoyed an exceptional reduction in risk for cardiovascular events. Those with diabetes had a 39% reduction in risk, and those who had experienced a specific type of heart attack (an anterior MI) had a 37% reduction in risk.
An NIH-appointed Data and Safety Monitoring Board oversaw the trial throughout its entirety, providing ongoing review of patient safety. Roughly comparable numbers of chelation and control patients cited “adverse reactions” as a reason for leaving the study. There were two severe unanticipated adverse reactions in each group, one of which resulted in death in each group.
One patient in the active chelation group required hospitalization for transient hypocalcemia, but the much-feared side effect of renal failure did not emerge in chelation patients, despite thousands of infusions. The rate of heart failure was not increased by chelation.
Although cardiac endpoints were impacted by chelation therapy, no overall enhancement of quality of life was found. Patients’ daily functioning and sense of mental well being remained unchanged while receiving chelation therapy.
Reactions to TACT
There was no shortage of editorials written in the aftermath of TACT. Steven Nissen, MD, a cardiologist at the Cleveland Clinic, wrote, “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.” Dr. Nissen concluded, “The findings of TACT should not be used as a justification for increased use of this controversial therapy.”8
In an unprecedented step, the editors of The Journal of the American Medical Association (JAMA) wrote a letter defending their decision to publish the TACT study, highlighting the fact that their review went above and beyond the routine due diligence accorded to studies that appear in the journal.
“Because articles published in journals like JAMA can influence the practice of medicine, this level of scrutiny of TACT reflects our commitment to fulfilling the responsibility to try to ensure that every article published in JAMA is valid and is reported accurately,” the editors wrote in a letter accompanying the published trial.9 In the end, the editor conceded that TACT was, “a positive, if perplexing, study [that] suggested that chelation therapy may modestly improve clinical outcomes in patients after an acute MI.”
Even TACT researchers did not recommend the routine use of chelation therapy in post-MI patients. These researchers believed that the study results should only be used to guide future research. Eric Topol, MD, a cardiologist with the Scripps Translational Science Institute in San Diego, struck a conciliatory note.
“Back in 2003, when this trial was announced, I thought it was a crazy notion,” said Topol. “At the end of the day, after all this work of all these investigators, I give them credit, and I give the JAMA editors credit for publishing it.”10
However, the most recently published analysis of the TACT data uncovered an even more robust protective effect of chelation, specifically for post-MI patients with diabetes.11 Researchers reported a 51% reduction in cardiovascular risk in the subgroup of persons with diabetes in the treatment arm that received chelation plus vitamins vs. persons with diabetes treated with placebo.
According to the study authors, “These findings, if replicable, would have an impact on the health of patients with diabetes. We emphasize, however, that these results are based on a subgroup of the overall trial, albeit prespecified, and therefore must be interpreted with caution.”
Multivitamins and Heart Disease
While TACT was not empowered to properly address the question of whether multivitamins impact CAD, the study did deliver provocative data on supplement usage. Owing to its two-by-two factorial design, half of the TACT participants received multivitamins (with or without active chelation).
In the vitamin arm of TACT, treatment with high-dose vitamin therapy resulted in a statistically nonsignificant 11% relative reduction in the risk of death, MI, stroke, coronary revascularization and hospitalization for angina when compared with patients who received placebo vitamins. However, the addition of high-dose multivitamins was found to boost the efficacy of chelation, suggesting synergy between chelation and supplements in conferring protection from adverse cardiovascular endpoints. This contrasts with previous studies that suggested an adverse effect of certain supplement regimens on circulatory disease.
The Future of Chelation Therapy
It is still unclear whether the benefits of chelation therapy are derived from EDTA or some of the other components of the IV cocktail, such as magnesium, vitamin B, vitamin C, or procaine. TACT was not designed to determine chelation therapy’s mechanism of action.
Dr. Lamas hypothesizes that chelation therapy eliminates heavy metals associated with damage to systems in the blood that combat reactive oxygen species. Dr. Lamas points out that lead and cadmium are associated with higher incidences of such vascular events as stroke, heart attack, and renal insufficiency.
Could chelation therapy join the armamentarium of treatments offered by conventional cardiologists? Dr. Lamas does not see this happening any time soon. “Receiving IV chelation is such a time-consuming and expensive treatment for patients,” he said. “The ideal would be for a pharmaceutical company to research and develop an oral version of this therapy for patients who have had a heart attack and those with diabetes.” (See “Can oral chelation therapy be trusted.”)
More extensive analysis of the TACT data will allow researchers to tease out potential relationships between chelation and such surrogate markers as cholesterol and cholesterol subfractions, homocysteine, and C-reactive protein. This analysis might provide clues to chelation’s benefits.
Because of federal budgetary constraints and the chorus of criticism that “soft” research into alternative therapies incites, it is unlikely that another government-sponsored study of chelation will be undertaken in the near future.
Industry funding, along the lines of conventional pharmaceutical research, is unlikely to materialize due to the vague proprietorship and regulatory status of disodium EDTA, whose marketability may lie only in the niche realm of a small number of alternative practitioners treating a relatively small population of patients.
Ronald L. Hoffman, MD, the founder and medical director of the Hoffman Center in New York City.
- Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report. 2008;12:1-23.
- Lamas GA, Goertz C, Boineau R, et al. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. JAMA. 2013;309:1241-1250.
- Rozema TC. The protocol for the safe and effective administration of EDTA and other chelating agents for vascular disease, degenerative disease, and metal toxicity. J Advancement Med. 1997;10:5-100.
- National Center for Complementary and Alternative Medicine. NIH launches large clinical trial on EDTA chelation therapy for coronary artery disease.
- Atwood KC, Woeckner E, Baratz RS, Sampson WI. Why the NIH Trial to Assess Chelation Therapy (TACT) should be abandoned. Medscape J Med. 2008;10:115.
- Clay B. Study of chelation therapy should not be abandoned. J Am Physicians Surg. 2009;14:51-57.
- Brown MJ, Willis T, Omalu B, Leiker R. Deaths resulting from hypocalcemia after administration of edetate disodium: 2003-2005. Pediatrics. 2006;118:e534-6.
- Nissen SE. Concerns about reliability in the Trial to Assess Chelation Therapy (TACT). JAMA. 2013;309:1293-1294.
- Bauchner H, Fontanarosa PB, Golub RM. Evaluation of the Trial to Assess Chelation Therapy (TACT): the scientific process, peer review, and editorial scrutiny. JAMA. 2013;309:1291-1292.
- Medscape. Chelation therapy in TACT: Daring to challenge dogma (and suspend disbelief). Available at www.medscape.com/viewarticle/802786.
- Escolar E, Lamas GA, Mark DB, et al. The Effect of an EDTA-based chelation regimen on patients with diabetes mellitus and prior myocardial infarction in the trial to assess chelation therapy (TACT). Circ Cardiovasc Qual Outcomes. 2013 Nov 19.
All electronic documents accessed January 7, 2014.
This article originally appeared on Clinical Advisor