Is There Evidence of Benefit in Edetate Disodium for Patients with Diabetes and Chronic Limb-Threatening Ischemia?

Purpose: Patients with chronic limb-threatening ischemia (CLTI) remain at high risk for lower extremity amputations and death. Even with the advent of lower extremity endovascular revascularization and medications, CLTI remains as deadly as many cancers. Over the past decade, environmental toxicants have been associated with vascular disease, including peripheral artery disease (PAD). We report on nine high-risk patients with diabetes who underwent infusions of edetate disodium (EDTA).

Materials and Methods: This is a retrospective case-series of seven patients who underwent EDTA-based chelation at Mount Sinai Medical Center in Miami Beach and two patients at Instituto Vozzi in Rosario, Argentina. These patients were previously reported as part of a pilot study and individual case reports. Patients with diabetes and CLTI with evidence of two or more infrapopliteal artery stenoses by imaging and serum creatinine less than 2.0 mg/dl were offered 40 infusions over 8 months with an EDTA-based solution. Laboratory safety assessments, clinical history, and lesion photographs were obtained. Contaminant urinary metal excretion was collected in a subset of patients. Optimal medical therapy and wound care were maintained.

Results: Six (of 9) patients with a mean (standard deviation) age of 76 (8) years (56% male) had a history of polyvascular disease. All patients received at least 40 infusions. Seven (78%) patients started treatment with an unhealed ulcer or gangrene with all having wound resolution. In a subset of patients (n = 5), urinary lead excretion increased an average of 3733% and cadmium 500% after the first infusion. No patient underwent surgery for minor or major amputations during the infusion phase, with one patient undergoing lower extremity revascularization. Compared with baseline, post-EDTA urinary lead excretion decreased by 36% (P = 0.0004). No serious side effects related to therapy were reported, and no major cardiovascular endpoints were encountered. All patients have remained free of amputation since completing treatment.

Conclusions: These findings suggest a potential role for EDTA infusions in patients with diabetes and CLTI. The increased excretion of lead and cadmium after EDTA infusion may suggest a mechanism of action. Both metals are known to be associated with atherosclerotic disease. TACT3a, currently enrolling, will reveal a better understanding of the role of EDTA in patients with diabetes and CLTI.