ATLANTA — Chelation to remove lead and other heavy metals did not improve outcomes in patients with type 2 diabetes after myocardial infarction (MI), the TACT2 trial showed.

The cumulative incidence of first event (myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or death from any cause) was not different from that for placebo infusions (HR 0.93, 95% CI 0.76-1.16).

All-cause mortality also showed no effect of chelation (HR 0.96, 95%), despite the fact that edetate disodium (EDTA) chelation reduced serum lead concentrations by more than 60%. CI 0.71-1.30), Gervasio A. Lamas, MD, researchers at Mount Sinai Medical Center in New York City, reported at the annual meeting of the American College of Cardiology (ACC).

These findings were in contrast to the results of the original TACT trial, which showed that EDTA chelation and oral vitamin administration significantly reduced overall cardiac events by 26% in a 2×2 factorial design study. In patients with diabetes, chelation reduced those events by 41% and all-cause mortality by 43% over five years.

This was what Lamas previously called a “black swan event,” a demonstration of unlikely efficacy that left many clinicians disappointed.

TACT2 is a confirmatory study requested by the FDA that will “test the most effective drug combination (chelation + oral vitamins) with demonstrated greatest efficacy in the population (post-myocardial infarction diabetic patients).” he wrote. today’s med page.

The time has come, he suggested, to make this concept a regular part of American practice. Still, the “take home message” [should not] Instead of “chelation doesn’t work,” the take-home message should be “If you’re using a toxin-specific treatment, make sure that toxin is present in the group.” ”

ACC session research discussant Richard A. Chazal, MD, of Lee Memorial, said the 2023 guidelines for chronic coronary artery disease “express a degree of ambiguity” and that “people are asking about this. “It has become an issue that patients sometimes find confusing.” Health System in Fort Myers, Florida.

So why were the results of the two trials so different?

”[National Health and Nutrition Examination Survey data] The data showed that serum lead levels fell by at least 35% midway between the two trials, and Lamas said public health attention focused on the issue after the crisis in Flint, Michigan. was cited as the reason. .

“If I had to do it all over again, lead level would be the entry criteria,” he said during the session. There are still places in the world where that can be a valuable approach, he suggested. Lead levels in the United States average 11 mcg/L, while the average in poor countries is 66 mcg/L.

When asked at the session about the next direction for chelation research, Lamas said it took a long time to get to this point. He said, “I’m happy to get started, but I need someone with less gray hair to finish it off.”

The TACT2 study included 1,000 non-smoking patients aged 50 and older who had had a myocardial infarction for at least 6 weeks, had diabetes with a creatinine level of 2.0 mg/dL or less.

They received 500 mL of EDTA with vitamins (up to 3 g based on renal function, 7 g of ascorbic acid and 2 g of magnesium chloride), or saline and 1.2% dextrose plus an oral low-dose vitamin and mineral supplement 40 were randomly assigned to injections. . The trial also included factorial randomization to vitamin supplementation, but that comparison was not included in the presentation.

Patients had at least 2.5 years of follow-up, with a median of 4 years. Of these, 27% were women and 61.5% were non-Hispanic white. Although lead was detected in the blood of all patients, the median level was relatively low at 9.22 mcg/L.

EDTA is also expected to chelate cadmium, which was detected in 97% of participants, but the median urinary creatinine of 0.30 mcg/g was not significantly reduced in either group (P=0.15).

At the same time, Lamas noted that no safety issues were observed.

Adherence was about 68%, “which was pretty good considering it was 40 infusions,” he said.

“We probably needed a complete treatment plan to see an effect,” suggested study discussant at the ACC press conference, Dr. Suzanne Baron of Massachusetts General Hospital in Boston.

At the same time, she noted, great strides have been made in treatments, and additional treatments may overcome the benefits that chelation can provide.