Chelation Therapy as a Cardiovascular Therapeutic Strategy: the Rationale and the Data in Review

Title Chelation Therapy as a Cardiovascular Therapeutic Strategy: the Rationale and the Data in Review
Journal Cardiovascular Drugs and Therapy
Authors Mathew RO, Schulman-Marcus J, Nichols EL, Newman JD, Bangalore S, Farkouh M, Sidhu MS
Year Published 2017
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Abstract
Chelation therapy, typically used to remove heavy metal toxins, has also been controversially used as a treatment for coronary artery disease. The first Trial to Assess Chelation Therapy (TACT) aimed to provide evidence on chelation therapy’s potential for benefit or harm. Although TACT had some significant results, the trial does not provide enough evidence to recommend routine chelation therapy and has limitations. The second TACT was recently funded reigniting a discussion about the value of chelation therapy, its efficacy, and allocation of research resources. Despite limited evidence, patients continue to pursue chelation therapy as a treatment for coronary artery disease. As the medical community has a responsibility to understand all treatments patients pursue, it is important to comprehensively appraise chelation therapy for cardiovascular disease. Understanding the background of heavy metal toxicity, the putative target of chelation therapy, on the cardiovascular system is important to contextualize the role of chelation therapy in cardiovascular disease prevention. We review the clinical evidence of heavy metal toxicity and cardiovascular disease, and available clinical trial data on use of chelation therapy to minimize the cardiovascular burden of heavy metal toxicity.

Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT)

Title Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT)
Journal American Heart Journal
Authors Omar M. Issa, DO, Rhonda Roberts, MPH, Daniel B. Mark, MD, MPH, Robin Boineau, MD, Christine Goertz, DC, PhD, Yves Rosenberg, MD, MPH, Eldrin F. Lewis, MD, Erminia Guarneri, MD, Jeanne Drisko, MD, Allan Magaziner, DO, Kerry L. Lee, PhD, Gervasio A. Lamas, MD
Year Published 2018
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Abstract
In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials. High-dose oral multivitamin and multimineral supplementation seem to decrease combined cardiac events in a stable, post-MI population not taking statin therapy at baseline. These unexpected findings are being retested in the ongoing TACT2.

Enhanced vasculotoxic metal excretion in post-myocardial infarction patients following a single edetate disodium-based infusion.

Title Enhanced vasculotoxic metal excretion in post-myocardial infarction patients following a single edetate disodium-based infusion.
Journal Environmental Research
Authors Ivan A. Arenasa, Ana Navas-Acienb, Ian Erguia, Gervasio A. Lamasa
Year Published 2017
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Abstract
Toxic metals have been associated with cardiovascular mortality and morbidity. We have hypothesized that enhanced excretion of vasculotoxic metals might explain the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose of this study was to determine whether a single infusion of the edetate disodium based infusion used in TACT led to enhanced excretion of toxic metals known to be associated with cardiovascular events.

Chronic Toxic Metal Exposure and Cardiovascular Disease: Mechanisms of Risk and Emerging Role of Chelation Therapy

Title

Chronic Toxic Metal Exposure and Cardiovascular Disease: Mechanisms of Risk and Emerging Role of Chelation Therapy

Journal Current Atherosclerosis Reports
Authors Ehimen C. Aneni; Esteban Escolar; Gervasio A. Lamas
Year Published 2016
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This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.

Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Chelation Therapy

Title Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Chelation Therapy
Journal Journal of the American College of Cardiology
Authors Lamas GA, Navas-Acien A, Mark DB, Lee KL
Year Published 2016
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Abstract
This review summarizes evidence from 2 lines of research previously thought to be unrelated: the unexpectedly positive results of TACT (Trial to Assess Chelation Therapy), and a body of epidemiological data showing that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease.

Chelation therapy to treat atherosclerosis, particularly in diabetes: is it time to reconsider?

Title Chelation therapy to treat atherosclerosis, particularly in diabetes: is it time to reconsider?
Journal Expert Review of Cardiovascular Therapy
Authors Ergui I, Lamas GA
Year Published 2016
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Expert commentary
Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years, with a 41% relative reduction in risk of a cardiac event (p = 0.0002). These results led to the revision of the ACC/AHA guideline recommendations for chelation therapy, changing its classification from class III to class IIb. TACT2, a replicative trial, will assess the effects of chelation therapy on cardiovascular outcomes in diabetic patients with a prior myocardial infarction. We are seeking participating sites for TACT2.

Enhanced Vasculotoxic Metal Excretion in Post-Myocardial Infarction Patients Receiving Edetate Disodium-Based Infusion

Title Enhanced Vasculotoxic Metal Excretion in Post-Myocardial Infarction Patients Receiving Edetate Disodium-Based Infusion
Journal Journal of the American College of Cardiology
Authors Ivan Arenas; Ana Navas-Acien; Gervasio Lamas
Year Published
2016
Link to article

Conclusions
Edetate disodium markedly increased excretion of lead and cadmium, two toxic metals with established epidemiologic evidence and mechanisms linking them to coronary and vascular events.

Edetate Disodium-Based Treatment for Secondary Prevention in Post-Myocardial Infarction Patients

Title Edetate Disodium-Based Treatment for Secondary Prevention in Post-Myocardial Infarction Patients
Journal Current Cardiology Reports
Authors Lamas GA, Issa, OM
Year Published 2016
Link to article
Link to abstract

Abstract
An abundance of data, known for decades, is available linking metals, such as lead and cadmium, with cardiovascular disease. However, the idea that these toxic metals could be a modifiable risk factor for atherosclerosis did not become apparent clinically until the completion of the Trial to Assess Chelation Therapy in 2012. This pivotal study was the first double-blind, randomized, controlled trial of its kind to demonstrate a clear improvement in cardiovascular outcomes with edetate disodium therapy in a secondary prevention, post-myocardial infarction population. This effect size was most striking in diabetic patients, where the efficacy of edetate disodium was comparable, if not superior, to that of current guideline-based therapies. Given the economic burden of diabetes and cardiovascular disease, the potential impact of this therapy could be enormous if the results of this study are replicated.