Cochrane Database of Systematic Reviews

2020

DOI: 10.1002/14651858.cd002785.pub2

|View full text |Cite

|

Sign up to set email alerts

|

Chelation therapy for atherosclerotic cardiovascular disease

Maria Vanessa Villarruz-Sulit

¹

,

²

,

Antonio L. Dans

³

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Discussion1

Therapeutic Strategies For Targeting Copper-induced Cell Dea...1

Zn 2+ -Targeted Interventions1

Citation Types

Supporting

0

Mentioning

11

Contrasting

0

Year Published

2020

2020

2024

2024

Publication Types

Select...

Article7

Book1

Relationship

Self Cite0

Independent8

Authors

Journals

Cited by 17 publications

(18 citation statements)

References 28 publications

Supporting

0

Mentioning

11

Contrasting

0

Order By: Relevance

“…One recent meta‐analysis found no evidence of a difference between EDTA chelation and placebo for CVD treatment; however, only one study had a diabetes prevalence of >30%. 15 It is possible that the review failed to fully capture the patient population who stands to benefit most significantly from chelation treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Although several reviews are available on metal chelation and CVD, the totality of evidence on the health benefits of EDTA treatment in patients with CVD is still mixed. 1 , 8 , 10 , 14 , 15 To gain clarity on the state of the evidence and perhaps guide future investigations, our team performed a systematic review of published studies reporting clinical outcomes in adults with atherosclerotic CVD treated with EDTA.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Chelation Therapy in Patients With Cardiovascular Disease: A Systematic Review

¹

,

²

,

³

et al. 2022

View full text Add to dashboard Cite

Background EDTA is an intravenous chelating agent with high affinity to divalent cations (lead, cadmium, and calcium) that may be beneficial in the treatment of cardiovascular disease (CVD). Although a large randomized clinical trial showed benefit, smaller studies were inconsistent. We conducted a systematic review of published studies to examine the effect of repeated EDTA on clinical outcomes in adults with CVD. Methods and Results We searched 3 databases (MEDLINE, Embase, and Cochrane) from database inception to October 2021 to identify all studies involving EDTA treatment in patients with CVD. Predetermined outcomes included mortality, disease severity, plasma biomarkers of disease chronicity, and quality of life. Twenty‐four studies (4 randomized clinical trials, 15 prospective before/after studies, and 5 retrospective case series) assessed the use of repeated EDTA chelation treatment in patients with preexistent CVD. Of these, 17 studies (1 randomized clinical trial) found improvement in their respective outcomes following EDTA treatment. The largest improvements were observed in studies with high prevalence of participants with diabetes and/or severe occlusive arterial disease. A meta‐analysis conducted with 4 studies reporting ankle‐brachial index indicated an improvement of 0.08 (95% CI, 0.06–0.09) from baseline. Conclusions Overall, 17 studies suggested improved outcomes, 5 reported no statistically significant effect of treatment, and 2 reported no qualitative benefit. Repeated EDTA for CVD treatment may provide more benefit to patients with diabetes and severe peripheral arterial disease. Differences across infusion regimens, including dosage, solution components, and number of infusions, limit comparisons across studies. Additional research is necessary to confirm these findings and to evaluate the potential mediating role of metals. Registration URL: https://www.crd.york.ac.uk/ ; Unique identifier: CRD42020166505.

“…One recent meta‐analysis found no evidence of a difference between EDTA chelation and placebo for CVD treatment; however, only one study had a diabetes prevalence of >30%. 15 It is possible that the review failed to fully capture the patient population who stands to benefit most significantly from chelation treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Although several reviews are available on metal chelation and CVD, the totality of evidence on the health benefits of EDTA treatment in patients with CVD is still mixed. 1 , 8 , 10 , 14 , 15 To gain clarity on the state of the evidence and perhaps guide future investigations, our team performed a systematic review of published studies reporting clinical outcomes in adults with atherosclerotic CVD treated with EDTA.…”

mentioning

confidence: 99%

Chelation Therapy in Patients With Cardiovascular Disease: A Systematic Review

¹

,

²

,

³

et al. 2022

View full text Add to dashboard Cite

Background EDTA is an intravenous chelating agent with high affinity to divalent cations (lead, cadmium, and calcium) that may be beneficial in the treatment of cardiovascular disease (CVD). Although a large randomized clinical trial showed benefit, smaller studies were inconsistent. We conducted a systematic review of published studies to examine the effect of repeated EDTA on clinical outcomes in adults with CVD. Methods and Results We searched 3 databases (MEDLINE, Embase, and Cochrane) from database inception to October 2021 to identify all studies involving EDTA treatment in patients with CVD. Predetermined outcomes included mortality, disease severity, plasma biomarkers of disease chronicity, and quality of life. Twenty‐four studies (4 randomized clinical trials, 15 prospective before/after studies, and 5 retrospective case series) assessed the use of repeated EDTA chelation treatment in patients with preexistent CVD. Of these, 17 studies (1 randomized clinical trial) found improvement in their respective outcomes following EDTA treatment. The largest improvements were observed in studies with high prevalence of participants with diabetes and/or severe occlusive arterial disease. A meta‐analysis conducted with 4 studies reporting ankle‐brachial index indicated an improvement of 0.08 (95% CI, 0.06–0.09) from baseline. Conclusions Overall, 17 studies suggested improved outcomes, 5 reported no statistically significant effect of treatment, and 2 reported no qualitative benefit. Repeated EDTA for CVD treatment may provide more benefit to patients with diabetes and severe peripheral arterial disease. Differences across infusion regimens, including dosage, solution components, and number of infusions, limit comparisons across studies. Additional research is necessary to confirm these findings and to evaluate the potential mediating role of metals. Registration URL: https://www.crd.york.ac.uk/ ; Unique identifier: CRD42020166505.

“…Results of a 10-year clinical trial to assess chelation therapy showed that EDTA disodium-based infusion reduced recurrent cardiovascular events in patients with type 1 and type 2 diabetes who had previous myocardial infarction [ 110 ]. However, in a meta-analysis by Villarruz-Sulit et al that included five studies with a total of 1993 randomized patients, chelation had no therapeutic effect on atherosclerotic vascular disease [ 111 ]. In three of the five studies, patients with peripheral vascular disease were recruited; in two studies, patients with coronary artery disease were recruited; and in one study, patients specifically with myocardial infarction were recruited.…”

Section: Therapeutic Strategies For Targeting Copper-induced Cell Dea...mentioning

confidence: 99%

Copper homeostasis and copper-induced cell death in the pathogenesis of cardiovascular disease and therapeutic strategies

¹

,

²

,

³

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

Copper is a vital mineral, and an optimal amount of copper is required to support normal physiologic processes in various systems, including the cardiovascular system. Over the past few decades, copper-induced cell death, named cuproptosis, has become increasingly recognized as an important process mediating the pathogenesis and progression of cardiovascular disease (CVD), including atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. Therefore, an in-depth understanding of the regulatory mechanisms of cuproptosis in CVD may be useful for improving CVD management. Here, we review the relationship between copper homeostasis and cuproptosis-related pathways in CVD, as well as therapeutic strategies addressing copper-induced cell death in CVD.

“…Chelation-based drugs have long been suggested as a potential treatment for the thrombotic complications present in obesity and diabetes [ 133 ]. This treatment has been recommended by clinicians as a method for increasing blood flow in diseased and clotted blood vessels, without the need for surgical intervention [ 133 ]. The basis for this approach is primarily to sequester Ca 2+ , but such agents are also likely to influence the speciation of plasma Zn 2+ .…”

Section: Zn 2+ -Targeted Interventionsmentioning

confidence: 99%

Strategies for Therapeutic Amelioration of Aberrant Plasma Zn2+ Handling in Thrombotic Disease: Targeting Fatty Acid/Serum Albumin-Mediated Effects

¹

,

²

,

³

et al. 2022

View full text Add to dashboard Cite

The initiation, maintenance and regulation of blood coagulation is inexorably linked to the actions of Zn2+ in blood plasma. Zn2+ interacts with a variety of haemostatic proteins in the bloodstream including fibrinogen, histidine-rich glycoprotein (HRG) and high molecular weight kininogen (HMWK) to regulate haemostasis. The availability of Zn2+ to bind such proteins is controlled by human serum albumin (HSA), which binds 70–85% of plasma Zn2+ under basal conditions. HSA also binds and transports non-esterified fatty acids (NEFAs). Upon NEFA binding, there is a change in the structure of HSA which leads to a reduction in its affinity for Zn2+. This enables other plasma proteins to better compete for binding of Zn2+. In diseases where elevated plasma NEFA concentrations are a feature, such as obesity and diabetes, there is a concurrent increase in hypercoagulability. Evidence indicates that NEFA-induced perturbation of Zn2+-binding by HSA may contribute to the thrombotic complications frequently observed in these pathophysiological conditions. This review highlights potential interventions, both pharmaceutical and non-pharmaceutical that may be employed to combat this dysregulation. Lifestyle and dietary changes have been shown to reduce plasma NEFA concentrations. Furthermore, drugs that influence NEFA levels such as statins and fibrates may be useful in this context. In severely obese patients, more invasive therapies such as bariatric surgery may be useful. Finally, other potential treatments such as chelation therapies, use of cholesteryl transfer protein (CETP) inhibitors, lipase inhibitors, fatty acid inhibitors and other treatments are highlighted, which with additional research and appropriate clinical trials, could prove useful in the treatment and management of thrombotic disease through amelioration of plasma Zn2+ dysregulation in high-risk individuals.

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Product

Browser Extension Assistant by scite Citation Statement Search Reference Check Visualizations Dashboards Explore Journals Explore Organizations Explore Funders Embedding Badge Embedding Citation Search Pricing

Resources

Blog Help & FAQ Accessibility Statement API Terms For Universities & Governments For Researchers For Publishers For Corporate, Pharma & Enterprise Author Marketing Become an Affiliate Get an organization trial or quote scite Data & Services

About

News & Press Careers Read our Paper Coverage

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Copyright © 2025 scite LLC. All rights reserved.

Made with 💙 for researchers

Part of the Research Solutions Family.