Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

EDTA chelation therapy was not effective for intermittent claudication

ACP J Club. 1992 July-Aug;117:8. doi:10.7326/ACPJC-1992-117-1-008


Source Citation

Guldager B, Jelnes R, Jørgensen SJ, et al. EDTA treatment of intermittent claudication—a double-blind, placebo-controlled study. J Intern Med. 1992 Mar;231:261-7.


Abstract

Objective

To assess the effectiveness and safety of chelation therapy with ethylenediamine-tetraacetic acid (EDTA) for patients with stable intermittent claudication.

Design

Randomized, double-blind, placebo-controlled trial with 6-month follow-up after therapy.

Setting

7 departments of vascular surgery in Denmark.

Patients

56 women and 103 men > 40 years of age, with stable intermittent claudication for a duration ≥ 12 months; a pain-free walking distance of 50 to 200 m on a treadmill at 3.6 km/h, with an inclination of 10°; and ankle/brachial blood pressure index < 0.8 in the worse leg. 69% of patients were smokers. Patients with recent changes in medication, serious illness, or contraindications to EDTA were excluded. 3-month and 6-month follow-up was 94% and 77% complete, respectively.

Intervention

Patients were randomized to 20 intravenous infusions of NA2EDTA, 3 g, and NaCl, 8.4 g, diluted in 1 L L H2O (n = 80), or to placebo solution (n = 79). The duration of each treatment was 3 to 4 hours. Treatment took 5 to 9 weeks. Vitamins, trace elements, and mineral supplements were given as 1 tablet daily during the treatment period. Patients were given advice on diet, smoking cessation, and exercise. 153 patients completed the treatment period.

Main outcome measures

Pain-free and maximal walking distances; ankle/brachial blood pressure index; patients' subjective ratings of effectiveness.

Main results

Walking distances improved similarly over 6 months for both groups of patients: Mean (SD) pain-free walking distance increased from 74 (25) m to 97 (47) m for the EDTA group compared with 82 (36) m to 119 (93) m for the placebo group. For all comparisons of pain-free and maximum walking distances between patient groups during the treatment period and follow-up, the ratio of percent change was between 0.91 and 1.04, and neither group was consistently superior to the other. The groups did not differ in ankle/brachial index. Patients in both groups evaluated their treatment similarly, with approximately 50% noting some improvement. The groups did not differ during treatment in hypocalcemic symptoms, gastrointestinal symptoms, renal complications, or phlebitis.

Conclusion

EDTA chelation therapy was not more effective than placebo in treating intermittent claudication.

Sources of funding: Danish Heart Foundation; Medical Research Foundation for Region 3, Denmark; Fru Olga Bryde Nielsen Foundation; Kaptajnløjtnant Harald Jensen og Hustru's Foundation; Else og Mogens Wedell-Wedellsborg Foundation; Danish Medical Research Council.

Address for article reprint: Dr. S.J. Jørgensen, Kirurgisk afd. A, Central Hospital Hillerød, DK-3400 Hillerød, Denmark.


Commentary

This article is important because it may be the first scientific study of chelation therapy for atherosclerosis. The therapy was administered in a manner consistent with the recommendations of those who support chelation therapy, and the effectiveness of the therapy was objectively measured in a credible way. Those who believe in EDTA therapy will be confounded by the study, which proves the need for properly controlled trials to assess efficacy of this therapy. The 45% improvement in treadmill walking time on placebo is consistent with observations in studies comparing placebo with other treatments such as pentoxifylline.

A study design that I would recommend to investigators is the sequential crossover study because it minimizes the extent to which patients would be denied any benefit of treatment (1). In such a trial, if the therapy is effective, all patients would be on or have had the therapy at the end of 1 crossover.

The results of the study by Guldager and colleagues do not preclude a small benefit in intermittent claudication, nor do they preclude a benefit in stasis ulcers, dry gangrene, or other manifestations of atherosclerosis. There is, however, no evidence of such benefits. Thus, the practice and policy implications of this article are that previous recommendations by such bodies as the American Heart Association should stand: Treatment of atherosclerosis by infusion of chelating agents such as EDTA is of unproven benefit, with known toxicity (2, 3). They should be used only in the setting of properly controlled clinical trials.

J. David Spence, MD
Victoria HospitalLondon, Ontario, Canada


References

1. Whitehead J. The Design and Analysis for Sequential Clinical Trials. Chichester, England: Ellis Horwood Ltd.; 1983.

2. EDTA chelation therapy for arteriosclerotic heart disease. Medical Letter. 1981;23:51.

3. Ad Hoc Committee on Chelation Therapy, American Heart Association. Edetate disodium (EDTA) chelation therapy for atherosclerosis. Report of Ad Hoc Committee on Chelation Therapy, American Heart Association. Dallas, Texas. April 1982.