April 8, 2024 — Diabetic patients who have had a heart attack may be treated with edetate disodium-based chelation therapy, a treatment that rids the body of lead and other toxic metals linked to increased risk of heart disease and stroke. The report found no clinical benefit. The study was presented at the American College of Cardiology’s Annual Scientific Sessions.

The TACT2 study was designed to replicate the results of a previous trial, TACT, which reported in 2012 that chelation reduced cardiovascular events after a heart attack. However, TACT2 results showed that those who received weekly edetate disodium-based infusions and those who received a placebo were less likely to experience death from any cause, heart attack, stroke, coronary revascularization, or unstable angina. There was no difference in the composite primary outcome of hospitalization. .

Dr. Gervasio A. Lamas

“Despite effectively lowering lead concentrations, edetate disodium-based chelation was ineffective in reducing cardiovascular events in patients in the United States and Canada with diabetes and a history of heart attack. “There was no,” said Dr. Gervasio A. Lamas, dean of the Columbia University School of Medicine and director of the hospital. University Department of Cardiology at Mount Sinai Medical Center in Miami and lead author of the study. “At this time, edetate disodium-based chelation is not effective as a treatment for patients following a heart attack in modern humans with low lead levels.”

Chronic exposure to lead and cadmium can damage cells and blood vessels by inhibiting the action of essential elements such as calcium and zinc in important biochemical processes. Chelation involves intravenous infusion of edetate disodium, a chelating agent that binds to metals such as lead and cadmium and is excreted in the urine. A slightly different compound, calcium disodium edetate, has been approved by the U.S. Food and Drug Administration to treat lead poisoning, but studies investigating its use for other conditions have yielded mixed results.

The original TACT trial, conducted from 2003 to 2012, showed modest efficacy of edetate disodium-based infusions in reducing cardiovascular events after heart attack, particularly in patients with diabetes, over a median follow-up of 55 months. It was suggested.

TACT2, which began enrollment in 2016, enrolled 1,000 patients at 88 sites in the United States and Canada, primarily those with type 2 diabetes (more than 90% of enrolled patients) and a previous heart attack. Patients were randomly assigned to receive either active treatment consisting of edetate disodium infusions 40 times per week or a matching placebo. Overall, 68% of participants received all 40 of their allotted injections, and 78% received at least 20 injections.

After a median follow-up of 48 months, no significant difference was observed in the rate of achievement of the primary composite endpoint, which occurred in approximately 35% of patients in both groups. However, over the same period, blood lead levels in participants decreased by an average of 61% in participants who received the chelating agent compared to those who received a placebo. Chelation therapy also showed a favorable safety profile, with no increased risk of serious adverse events in the chelation group and no unexpected serious adverse events reported.

The researchers said two factors may help explain why TACT and TACT2, which were supervised by the same research team and used the same drug and study protocol, ultimately had different results. . One is that TACT2 participants may have had more advanced diabetes and associated more severe health consequences than participants in the first TACT trial, which could have a meaningful impact on clinical outcomes. This may reduce the test’s ability to give Second, participants’ baseline lead levels were more than 30% lower in his TACT2 than in her TACT. This likely reflects the fact that public health interventions, such as eliminating leaded gasoline, have been successful in reducing lead exposure in most developed countries over the past few decades.

The new study suggests that either or both of these factors may have blunted chelation’s ability to reduce cardiovascular events, but the study results in terms of overall lead reduction are Professor Lamas said it could still be relevant for informing community health interventions. Exposure to lead is more common.

“Our treatment was effective and safe in reducing lead, even in patients who started with low lead levels,” Lamas said. “Lead remains a serious cardiovascular and neurological problem in most countries outside of North America and Western Europe. Although this study may be more relevant to these regions of the world, this is a hypothesis that requires further study. But for now, edetate disodium-based chelation is not useful in treating patients with diabetes or a history of heart attack in the United States and Canada,” said Lamas. Ta.

This study was funded by the National Institutes of Health.

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