(Circulation. 1999;99:164-167.)
© 1999 American Heart Association, Inc.
Correspondence |
Chelation Therapy for Vascular Disease
Bluffton, Ohio
Asheville, NC
To the Editor:
The review of chelation therapy for vascular disease by Ernst1 was flawed because of important omissions and inaccuracies. By omitting a discussion of the critiques of the studies he presented, which have been published in several journals,2 3 the author cannot convincingly conclude that those studies were "of outstanding methodological rigor." By ignoring a vast body of literature4 5 that documents multiple mechanisms of action for EDTA on the vascular system, he has no basis to say that proponents of chelation therapy are "in overt discordance with our present knowledge." By reporting on a few isolated incidences of adverse effects, he erroneously implies that chelation therapy is dangerous.
Both of the studies presented used inappropriate statistical analyses that distorted the fact that the EDTA groups did in fact improve more than the placebo groups, but neither study had enough subjects to draw significant conclusions.
The two Danish reports of the same study did not follow the published protocol5 as they claimed, which is taught to physicians by the medical societies for which we have served as presidents, the American College for Advancement in Medicine and the Great Lakes College of Clinical Medicine. Furthermore, the study was criticized by the Danish Council for Scientific Dishonesty because it was not properly randomized, the code was broken prematurely, and the study had an extremely high dropout rate.
The van Rij study had a much better design but was far too small to have power enough to support its conclusions. Only 15 patients were in the treatment group. Both the treatment and the control groups increased walking distance by 60%. After publication, it was discovered3 that the control group had a single outlier that accounted for almost all of the improvement in the placebo group. Without the outlier, the EDTA group clearly improved more than the control group.
The recent edition of Messerli's textbook, Cardiovascular Drug Therapy,6 devotes an entire chapter to the use of EDTA, demonstrating removal of calcium from coronary arteries. Chelation therapy has also been shown to reduce oxidized LDL, increase the effectiveness of hydroxyl radical scavengers, reduce reperfusion injury, reduce platelet adhesiveness, and result in other beneficial effects.4 5
As long as the protocol is adhered to, EDTA has been shown to be safe,5 especially compared with more conventional cardiovascular treatments.
Not only did Ernst omit important information, he also listed an inaccurate reference for the meta-analysis4 by Chappell and Stahl. The meta-analysis contains reports from thousands of patients with vascular disease who have been successfully treated with EDTA chelation therapy, some of whom were told by cardiologists that there was nothing else that could be done to help them. This alone is sufficient reason to allow patients the option of receiving the therapy, and it should be a compelling reason for adequate clinical trials to be accomplished.
Proponents of chelation therapy and the leadership of our organizations have worked very hard and have spent much of their resources to try to get unbiased, randomized, controlled clinical trials preformed by appropriate researchers.
Fortunately, there are medical schools and governmental agencies in several countries that do not believe that chelation therapy has been fairly or accurately studied. New clinical trials have been planned, and hopefully they will have commenced by the time this letter is published.
References
1.
Ernst E. Chelation therapy for
peripheral arterial occlusive disease.
Circulation. 1997;96:1031–1033.
2. Chappell LT, Miranda R, Hancke C, Frackelton JP, Carter J. EDTA chelation treatment for peripheral vascular disease. J Intern Med. 1995;237:429–434.[Medline] [Order article via Infotrieve]
3. Godfrey ME, Chappell LT. Chelation therapy for intermittent claudication: a reappraisal. NZ Med J. 1996;109:83. Letter.[Medline] [Order article via Infotrieve]
4. Chappell LT, Stahl JP. The correlation between EDTA chelation therapy and improvement in cardiovascular function: a meta-analysis. J Adv Med. 1993;6:139–160.
5. Cranton EM, ed. A textbook on EDTA chelation therapy. J Adv Med. 1989;2:1–416.
6. Rubin M. Other drugs for the treatment of cardiovascular disease. In: Messerli FH, ed. Cardiovascular Drug Therapy. Philadelphia, Pa: WB Saunders Co; 1996.
Response
Department of Complementary Medicine School of Postgraduate Medicine & Health Sciences, Exeter, UK
Chappell and Wilson have misunderstood my article1 and the methodology of systematic reviews (SRs). SRs represent the attempt to objectively evaluate the evidence on a given subject. They follow a stepwise procedure of (1) identifying all trials fulfilling predefined inclusion/exclusion criteria, (2) critically evaluating all reports, and (3) drawing conclusions from the overall results (eg, Reference 2). Thus, my SR followed a protocol described in its Methods section. I also invited national organizations of chelation therapy to contribute material. "Studies were admitted ... if they related to randomized, placebo-controlled, double-blind clinical trials."1 The evidence cited by Chappell and Wilson does not stem from controlled clinical trials and was thus excluded. The trials included in my SR are "of outstanding quality" in that they are randomized, placebo-controlled, and double-blind, thus minimizing various sources of bias. Collectively, their results are dimensions more reliable than the evidence quoted by Chappell and Wilson. Regardless of what Chappell (president-elect of the American College for Advancement in Medicine, an organization that promotes chelation therapy and sponsors the Journal of Advanced Medicine, which published his "meta-analysis"3) and Wilson state, chelation therapy is not based on good science.4
A perhaps more important point relates to a repetitive pattern in the scientific investigation of "bogus" therapies. Proponents first manage to mobilize supporters to campaign in their favor. This brings financial gain. When skeptics ask about the evidence, the burden of proof is swiftly put on their shoulders, and the lack of evidence is made to look like a "conspiracy" of orthodoxy against the alternative. If scientists then decide to rigorously test the method, its proponents would celebrate this as a breakthrough for their method. Again, this amounts to financial gain. Subsequently, a study may prove that the method is ineffective. Proponents now claim that the research was flawed, did not adhere to their protocol, or was wrongly analyzed. The press coverage yet again brings financial gain. This pattern repeats itself with depressing regularity, eg, when laetrile or Di Bella's cancer cure were promoted.5 I wonder whether chelation therapists are trying to play a similar game.
References
1. Ernst E. Chelation therapy for peripheral arterial occlusive disease: a systematic review. Circulation. 1997;96:1031–1033.
2. Crombie IK, McQuay HJ. The systematic review, a good guide rather than a guarantee. Pain. 1998;76:1–2.[Medline] [Order article via Infotrieve]
3. Chappell HT, Stahl JP. The correlation between EDTA chelation therapy and improvement in cardiovascular function. J Adv Med. 1989;2:139–160.
4. Grier MT, Meyers DG. So much writing, so little science: a review of 37 years of literature on EDTA chelation therapy. Ann Pharmacother. 1993;27:1504–1509.[Abstract]
5.
Abbasi K. Di Bella's cure declared ineffective.
BMJ. 1998;317:366.
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