TACT: Routine use of chelation therapy unsupported

Chelation therapy can reduce risk for adverse CV events in patients with previous MI, according to data from the TACT trial, but evidence does not support routine clinical use, researchers said.

“In stable patients with a history of MI, the use of an intravenous chelation regimen with disodium EDTA, compared with placebo, modestly reduced the risk of a composite of adverse CV outcomes, many of which were revascularization procedures,” study researcher Gervasio A. Lamas, MD, of the Columbia University and Mount Sinai Medical Center, and colleagues wrote. “These results provide evidence to guide further research but are not sufficient to support the routine use of chelation therapy for treatment of patients who have had an MI.”

Gervasio A. Lamas

The trial

The double blind, placebo-controlled TACT trial included 1,708 participants aged 50 years or older who had an MI at least 6 weeks before enrollment and serum creatinine levels ≤2 mg/dL. The chelation group (n=839) received 40 infusions of a 500-mL chelation solution (3 g disodium EDTA, 7 g ascorbate, B vitamins, electrolytes, procaine and heparin) for 30 weeks followed by 10 infusions 2 to 8 weeks apart.

Researchers found that the primary endpoint (a composite of death from any cause, reinfarction, stroke, coronary revascularization or hospitalization for angina) occurred in 26% of the chelation group and 30% of the placebo group (HR=0.82; 95% CI, 0.69-0.99). Results indicated no effect on total mortality, but researchers said the study was not powered to detect a difference.

Researchers also found similar effects for the chelation and placebo groups for components of the primary endpoint other than death, including MI (6% vs. 8%; HR=0.77; 95% CI, 0.54-1.11), stroke (1.2% vs. 1.5%; HR=0.77; 95% CI, 0.34-1.76), coronary revascularization (15% vs. 18%; HR=0.81; 95% CI, 0.64-1.02) and hospitalization for angina (1.6% vs. 2.1%; HR=0.72; 95% CI, 0.35-1.47).

Major concerns

At follow-up, a large number of participants had withdrawn consent, leading to controversy.

In an editorial that accompanied the study’s recent publication in JAMA, Cardiology Today Editorial Board member Steven E. Nissen, MD, said in most randomized controlled trials, participants in the intervention group leave the study due to adverse effects or toxicity, but in TACT, participants also were withdrawing from the placebo group.

Steven E. Nissen

“A logical explanation [for withdrawals in both groups] is unmasking of treatment assignments. If either the investigators or patients knew who was receiving chelation, patients assigned to the placebo group would likely be influenced to withdraw or stop study treatment, particularly when some investigators were advocates for chelation therapy,” Nissen said.

Nissen cited other concerns, including missing data, use of subjective endpoints and intentional unmasking of the sponsor, but added that all randomized controlled trials should be published because they provide useful information to the medical community, even when they fail.

“TACT provides useful insights into the overwhelming challenges faced when trying to determine the effectiveness of an unusual and controversial therapy,” he said.

Decision to publish

JAMA Editor-in-Chief Howard Bauchner, MD, and colleagues said in a second editorial that publication of TACT in the journal was warranted after editorial assessment, peer reviews, revisions by authors and detailed methodological evaluation.

“Clinical decision making is complex, reflecting a synthesis of evidence, physician experience, and patient preference, bound together by social norms,” Bauchner and colleagues wrote. “Based on full consideration of the strengths and limitations of TACT, the conclusion is clear and should influence practice — these findings do not support the routine use of chelation therapy as secondary prevention for patients with previous MI and established coronary disease. Whether chelation therapy may have a role in the prevention of CVD remains to be determined.”

For more information:

Lamas GA. JAMA. 2013;309:1241-1250.

Nissen SE. JAMA. 2013;309:1293-1294.

Disclosure: Lamas reports that from 2000 to 2003 he served as consultant to OmniComm.