Brief History and Overview
Chelation is the administration of chelating agents to remove heavy metals from the body. Chelation treatment was first reported to have clinical benefits in patients with symptomatic coronary artery disease (CAD) through a serendipitous set of observations starting in 1956. Subsequent clinical investigations of chelation, however, were mixed and serious research in this area stopped in the early 1960s.
Alternative medicine practitioners continued to use chelation for prevention of complications of atherosclerosis based on their anecdotal experiences. Because of the lack of proof of benefit and the implausibility of the proposed mechanism of benefit (removal of calcium from complex atherosclerotic plaques), most major mainstream medical organizations during the 1980s to 1990s made policy statements against chelation.
The first Trial to Assess Chelation Therapy (TACT1) was developed in response to a Request for Applications from the National Center for Complementary and Alternative Medicine (NCCAM) and the National Heart Lung and Blood Institute (NHLBI). At the time, members of the U.S. Congress expressed concern that chelation use was widespread but there were no reliable data on either safety or efficacy. Our research team, led by Drs. Gervasio Lamas, Kerry Lee, and Daniel Mark, was awarded the TACT1 grant in 2002.
TACT1 was completed in 2012 (enrolling 1708 patients) and showed that a combination of up to 40 infusions with intravenous (IV) disodium EDTA plus oral multivitamins and multiminerals (OMVM) compared with intravenous and oral placebo led to a significant reduction in the time to first recurrent cardiovascular event in patients with prior myocardial infarction, age 50 or older, already treated with standard evidence-based medical therapies.
In the subgroup with diabetes (633 patients), the results were dramatic: the chelation-based strategy reduced cardiac events by 51% and reduced total mortality by 43%.
In response to the data from TACT1, the American College of Cardiology/American Heart Association granted chelation a 2b indication for treatment of chronic ischemic heart disease.
As a result of the TACT1 findings, and because of the public health impacts of cardiovascular disease and of diabetes, we were encouraged by the National Institutes of Health (NIH) and the FDA to confirm the results of TACT1. After key discussions with the NIH, FDA, and leaders in the field of cardiology, we elected to perform TACT2 in patients with diabetes, representing the patients in TACT1 with the greatest benefit. This refinement will reduce the size, duration, and cost of the clinical trial relative to TACT1.
In TACT1, a factorial design examined the two major components of the chelation strategy in common use by alternative medicine practitioners, EDTA chelation and oral multivitamins and multiminerals (OMVM). Because our analyses found those two therapies provided additive benefits, both the NIH and FDA supported the decision to test the strongest strategy in TACT2, chelation plus OMVM, to promote the most efficient trial possible.
TACT2 will enroll 1200 patients with diabetes who are 50 years of age or older, have had a heart attack (prior myocardial infarction [MI]), and have good kidney function (serum creatinine 2.0 mg/dL or less). Patients will be randomly allocated to receive either chelation plus OMVM, or placebo (inactive substance). All patients will be followed for ~ 5 years.
The specific aims of TACT2 are:
- To determine if the chelation-based strategy in patients with diabetes and prior MI improves event-free survival;
- To determine if the chelation-based strategy in patients with diabetes and prior MI reduces mortality;
- To perform an economic analysis of the TACT2 chelation strategy.