DALLAS – An EDTA-based chelation regimen for secondary prevention of cardiovascular events in patients with a history of myocardial infarction got a boost from a new TACT trial analysis showing additive benefit when chelation was accompanied by high-dose oral multivitamins.
"The benefit of chelation plus vitamins compared to placebo plus placebo is statistically significant and of a magnitude sufficient to be clinically important, with a number needed to treat of 12 to prevent one primary event over 5 years," Dr. Gervasio A. Lamas said in presenting the latest TACT (Trial to Assess Chelation Therapy) results at the American Heart Association scientific sessions.
Moreover, the benefit of chelation plus multivitamins was magnified in the more than 600 TACT participants with diabetes. The number needed to treat in that group was an impressively low 5.5, added Dr. Lamas, chairman of medicine at Mount Sinai Medical Center, Miami Beach, and chief of the Columbia University division of cardiology at Mount Sinai Medical Center.
Since 1956, EDTA (ethylenediaminetetraacetic acid) chelation has been utilized in complementary and alternative medical (CAM) practice to treat atherosclerotic disease, despite an absence of any supporting evidence. The TACT trial, sponsored by the National Institutes of Health, was conducted in order to put the CAM regimen to the test.
TACT was a rigorously conducted, randomized, double-blind, two-by-two factorial design trial in which 1,708 stable patients with a previous MI at 134 North American sites were placed on the intravenous chelation regimen or placebo and high-dose oral multivitamins or placebo. It was an arduous regimen designed to replicate what’s being used in CAM practice. The chelation regimen consisted of 30 weekly 500-cc intravenous infusions followed by another 10 infusions at 2- to 8-week intervals. Patients randomized to the multivitamin arm took 6 capsules per day.
"The capsules are large. They’re a bear to take," according to the cardiologist.
Nevertheless, 77% of patients completed 30 infusions and 65% completed all 40. And more than three-quarters of patients took the vitamins for at least a year, and half of participants did so for at least 3 years. All participants had high rates of guideline-recommended preventive medications usage.
The primary composite endpoint was the 5-year rate of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for angina. As previously reported, chelation therapy resulted in a statistically significant 18% reduction in the primary endpoint relative to placebo (JAMA 2013;309:1241-50), while high-dose multivitamin therapy led to a nonsignificant 11% reduction (Ann. Intern. Med., in press).
At the Dallas AHA meeting, Dr. Lamas focused on the results in the 421 subjects randomized to both chelation and multivitamins as compared to the 437 patients on double placebo. The primary composite endpoint occurred in 26% of patients on double active therapy and 32% on double placebo, representing a 26% reduction in relative risk. Thus, the addition of multivitamin therapy increased the magnitude of risk reduction in patients on chelation therapy from 18% to 26%.
The prespecified secondary ‘hard’ endpoint, a composite of cardiovascular death, recurrent MI, or stroke, occurred in 9% of participants on chelation plus multivitamins versus 13% of those on dual placebo, for a 34% reduction in risk.
The results of active therapy were even more impressive in patients with diabetes. They had a 41% reduction in risk of the primary composite endpoint with chelation alone compared with placebo, with a 5-year incidence of 25%, compared with 38% in controls. Notably, diabetic patients’ all-cause mortality with chelation therapy was 10%, compared with 16% with placebo, a 43% reduction in relative risk, while their rate of the secondary composite hard endpoint was 11%, versus 17% in controls.
The diabetic subgroup assigned to dual active therapy with both chelation and multivitamins fared even better, with a 51% decrease in the primary composite endpoint compared with controls on double placebo.
"A lot more work needs to be done on this before we can bring it to the bedside, but this is certainly suggestive data," Dr. Lamas said in summary.
Specific details on the chelation and multivitamin components of the regimen are available in an earlier publication (Am. Heart J. 2012;163:7-12).
Asked about the proposed mechanism of benefit of this CAM therapy, the cardiologist was quick to reply, "The simple answer is we do not really know what is happening."
Plausible hypotheses abound, though. One of the leading ones has to do with the fact that EDTA is a superb metal chelator.
"Heavy metals are associated very well in epidemiologic data with cardiovascular events; in particular, lead, cadmium, arsenic, sometimes mercury, and others that have less evidence, like tungsten and antimony. They’re all in our environment. Any of us who are of an age to have been exposed to leaded gasoline have lead in our bones. If we get an infusion of EDTA, we’ll have lead in our urine. It’s just the way it is. And as you get older and become osteoporotic, that lead starts getting released," Dr. Lamas explained.