In a Large Multicenter Trial, Chelation Therapy Did Not Reduce Cardiovascular Disease Events in Patients With Diabetes and a History of Heart Attack

Chelation therapy does not reduce the occurrence of major adverse cardiovascular events in patients with diabetes who have had a myocardial infarction even though it effectively reduces blood lead levels, according to a multicenter clinical trial funded by the National Institutes of Health (NIH). The results, which did not replicate those of an earlier trial, were published in the Journal of the American Medical Association.

Chelation therapy is a process in which a substance is delivered intravenously (through the veins) to bind metals or minerals and hold them so they can be removed from the body via urination. It has been used as a complementary therapy for cardiovascular disease (CVD), although it has not been proven beneficial for this purpose. 

An NIH-supported study published in 2013, the Trial to Assess Chelation Therapy (TACT), found that EDTA chelation reduced the risk of further CVD events by 18 percent in people who had already had a heart attack. Further analysis of the study results showed a marked reduction (41 percent) in CVD events in participants with diabetes but no significant benefit in those who did not have diabetes. Because the finding that this intervention reduced CVD events was unexpected, a second trial was conducted to see whether the TACT findings could be replicated in the subgroup that showed the largest benefit—people with diabetes and a history of heart attack. This second study, called Trial to Assess Chelation Therapy 2 (TACT2), also assessed the effect of EDTA chelation on levels of heavy metals, particularly lead and cadmium, associated with CVD, to see whether removal of these metals from the body was associated with reduced CVD risk.

In TACT2, which was conducted at 88 sites, 1,000 participants aged 50 or older who had diabetes and a history of myocardial infarction were randomly assigned to receive 40 weekly EDTA chelation treatments or placebo; 959 participants actually received at least one infusion (483 assigned to EDTA chelation and 476 assigned to placebo). The study was conducted in a double-blind fashion, meaning that neither the participants nor the study staff knew the participants’ treatment assignments; the research team was not able to review data until the study was completed. Participants were followed for an average of 48 months. 

More than one-third of the study participants had a CVD event (death, heart attack, stroke, a coronary revascularization procedure, or hospitalization for unstable angina) during the follow-up period. There was no significant difference between the chelation and placebo groups in the occurrence of these events. However, changes in blood lead levels did differ between the groups; those who received chelation therapy showed a 61 percent drop in blood lead levels after the series of chelation treatments, while those who received placebo did not show a significant decrease. Urine cadmium levels increased immediately after each chelation infusion. Thus, EDTA therapy was effective in chelating both lead and cadmium and promoting their excretion.

These findings from TACT2 did not reproduce the results of TACT and do not support the use of chelation to reduce CVD risk in patients with diabetes and a prior heart attack. The researchers suggested that differences between the TACT and TACT2 study participants might have contributed to the difference in the results between the two studies. The TACT2 participants had more advanced disease and higher CVD event rates than those in TACT and may have been exposed to lower levels of lead. It is also possible that TACT2 was underpowered; the number of participants might have been too small to allow more modest effects to be detected.

The TACT2 study was funded by the National Center for Complementary and Integrative Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; and National Institute of Environmental Health Sciences, all part of the National Institutes of Health.