Chelation Therapy in Patients With Cardiovascular Disease: A Systematic Review (Ravalli 등, AHA Journals 2022)
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 out
comes 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.
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Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial (Avila 등, Current Opin Cardiol. 2014 Aug 7)
Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial - PMC
Purpose of review
EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment.
Recent findings
The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P = 0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P = 0.0002) and a 43% reduction in total mortality (P = 0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action.
Summary
Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients.
Keywords: atherosclerosis, chelation therapy, diabetes mellitus, myocardial infarction
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Effect of Disodium EDTA Chelation Regimen on Cardiovascular Events in Patients With Previous Myocardial Infarction
The TACT Randomized Trial
(Lamas 등, JAMA 2013 March 27)
Importance Chelation therapy with disodium EDTA has been used for more than 50 years to treat atherosclerosis without proof of efficacy.
Objective To determine if an EDTA-based chelation regimen reduces cardiovascular events.
Design, Setting, and Participants Double-blind, placebo-controlled, 2 × 2 factorial randomized trial enrolling 1708 patients aged 50 years or older who had experienced a myocardial infarction (MI) at least 6 weeks prior and had serum creatinine levels of 2.0 mg/dL or less. Participants were recruited at 134 US and Canadian sites. Enrollment began in September 2003 and follow-up took place until October 2011 (median, 55 months). Two hundred eighty-nine patients (17% of total; n=115 in the EDTA group and n=174 in the placebo group) withdrew consent during the trial.
Interventions Patients were randomized to receive 40 infusions of a 500-mL chelation solution (3 g of disodium EDTA, 7 g of ascorbate, B vitamins, electrolytes, procaine, and heparin) (n=839) vs placebo (n=869) and an oral vitamin-mineral regimen vs an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. Fifteen percent discontinued infusions (n=38 [16%] in the chelation group and n=41 [15%] in the placebo group) because of adverse events.
Main Outcome Measures The prespecified primary end point was a composite of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. This report describes the intention-to-treat comparison of EDTA chelation vs placebo. To account for multiple interim analyses, the significance threshold required at the final analysis was P = .036.
Results Qualifying previous MIs occurred a median of 4.6 years before enrollment. Median age was 65 years, 18% were female, 9% were nonwhite, and 31% were diabetic. The primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.99]; P = .035). There was no effect on total mortality (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0.93 [95% CI, 0.70-1.25]; P = .64), but the study was not powered for this comparison. The effect of EDTA chelation on the components of the primary end point other than death was of similar magnitude as its overall effect (MI: chelation, 6%; placebo, 8%; HR, 0.77 [95% CI, 0.54-1.11]; stroke: chelation, 1.2%; placebo, 1.5%; HR, 0.77 [95% CI, 0.34-1.76]; coronary revascularization: chelation, 15%; placebo, 18%; HR, 0.81 [95% CI, 0.64-1.02]; hospitalization for angina: chelation, 1.6%; placebo, 2.1%; HR, 0.72 [95% CI, 0.35-1.47]). Sensitivity analyses examining the effect of patient dropout and treatment adherence did not alter the results.
Conclusions and Relevance Among stable patients with a history of MI, use of an intravenous chelation regimen with disodium EDTA, compared with placebo, modestly reduced the risk of adverse cardiovascular outcomes, many of which were revascularization procedures. These results provide evidence to guide further research but are not sufficient to support the routine use of chelation therapy for treatment of patients who have had an MI.