LOS ANGELES – Chelation therapy resulted in a slight reduction in cardiovascular events in patients with coronary artery disease and a prior myocardial infarction, according to a randomized, government-funded trial, but the findings are far from practice changing.
Experts at the annual scientific sessions of the American Heart Association, including the study’s authors, were quick to point out that the results yielded more questions than answers, and called for additional research to confirm or refute the findings.
Dr. Elliott Antman
"Intriguing as the results are, they are unexpected and should not be interpreted as an indication to adopt chelation therapy into clinical practice," said Dr. Elliott Antman, chair of the AHA Scientific Sessions Program Committee, and a cardiologist at Brigham and Women’s Hospital in Boston.
The therapy did not reduce mortality, and a substudy showed that patients did not have any sustained improvement in their quality of life.
Dr. Gervasio A. Lamas, the study’s lead author and a cardiologist at Mount Sinai Medical Center in Miami Beach, said that the trial "does not constitute evidence to recommend the clinical application of chelation therapy."
Chelation, which is not approved by the Food and Drug Administration (FDA), is an intravenous therapy in which the synthetic amino acid ethylenediaminetetraacetic acid (EDTA) binds to and extracts metals. The controversial treatment has been around since the 1950s, and research findings have been inconsistent.
In the case of heart disease, the idea is that EDTA binds to the calcium in the arterial plaques.
"But there are no data that show that it happens," said Dr. Sidney Goldstein, professor of medicine at Wayne State University in Detroit, who was not involved in the study. "I wouldn’t put much value on the [trial], because the science is thin or nonexistent," he said about the $30 million NIH-funded study.
TACT (Trial to Assess Chelation Therapy) was a randomized, double-blind, placebo-controlled study that was 20 times larger than previous studies conducted on the controversial treatment (Am. Heart J. 2012;163:7-12).
The trial has had its share of turbulence since it enrolled the first patient in 2003. It was once stopped after the FDA raised concerns about its process and conduct. After taking corrective steps, the investigators had to scale down the study population from nearly 2,400 to 1,700 owing to difficulty enrolling patients.
Researchers randomized and followed the 1,708 post-MI patients for an average of 4 years at 134 sites in the United States and Canada from September 2003 to October 2010. Their goal was to test the benefits and risks of 40 infusions of a 500-mL multicomponent disodium EDTA chelation solution compared with placebo, which was a solution of normal saline and 1.2% dextrose.
A total of 55,222 EDTA and placebo infusions were administered during the trial, each patient receiving 30 weekly infusions followed by 10 maintenance infusions 2-8 weeks apart. Each infusion lasted for about 3 hours.
The primary composite end point was death, MI, stroke, coronary revascularization, and hospitalization for angina. The composite secondary end point was irreversible ischemic events, including cardiovascular death, nonfatal MI, and nonfatal stroke.
Patients were at least 50 years old (mean age, 65 years). The average body mass index for both groups was 30 kg/m2, and roughly 30% of each group had diabetes.
Sixty-five percent of the patients completed all 40 infusions, and 76% completed at least 30. Meanwhile, 30% discontinued infusions for several reasons, and 17% percent withdrew consent.
The results showed that 39 fewer patients in the chelation therapy group had a cardiovascular event compared with the placebo group, a nonsignificant difference that was driven largely by coronary revascularization, where there was a 3% difference between the two groups (15% vs. 18%), a "soft end point," according to Dr. Goldstein.
There were no significant benefits for angina (1.5% in the EDTA chelation group vs. 2.1% in the placebo group), mortality (10.4% vs. 10.7%, respectively), MI (6.2% vs. 7.7%), or stroke (1.2% vs. 1.5%).
Seventy-nine patients (12%) discontinued infusions due to adverse events or side effects. Of those, 17 reached an end point, 11 had heart failure, and 7 had cardiac issues, among other reasons.
There were four unexpected severe adverse events, including two deaths, one in each group.
A surprising effect was found in the diabetes subgroup, for which researchers did not have a biological explanation. Diabetes patients had 35 fewer events than the placebo group (P = .002). The difference was minimal in the subgroup with no diabetes.
"Although there were some aspects of the trial that suggested chelation may be beneficial, too many questions remain to recommend chelation as standard therapy at this time," said Dr. David. O. Williams, a cardiologist at Brigham and Women’s Hospital, who was not involved in the study. He pointed out that many patients didn’t receive complete study therapy, and a substantial number dropped out of the trial, which meant that their outcomes didn’t contribute to the follow-up data.