Chelation therapy for cardiovascular disease

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]

Synonyms and keywords: Chelation therapy, EDTA, post-myocardial infarction, diabetes

Overview

Chelation therapy helps detoxify the blood from metals such as lead, cadmium, iron and calcium. In addition to its use for the treatment of heavy metal poisoning, chelation therapy has been considered an alternative medicine for the treatment of atherosclerotic disease. It has been postulated that chelation therapy might contribute to the improvement of vascular disease through metal detoxification. Opinions regarding the use of chelation therapy for cardiovascular diseases (CVD) have long been controversial as there was not enough evidence on the benefits of their use. Most recently, Trial to Assess Chelation Therapy (TACT), a randomized, double blind, placebo controlled, 2x2 factorial trial, investigated the effect of EDTA based infusions among stable post-myocardial infarction patients who are more than 50 years of age. TACT revealed a modest decrease in the adverse cardiovascular outcomes risks among enrolled patients. When only diabetic patients were taken into consideration, the decrease in the adverse cardiovascular outcomes was more robust.

Chelation Therapy and CVD

The use of chelation therapy as a treatment for atherosclerotic disease dates back to the 1950’s when Clarke et al investigated the use of EDTA for the treatment of angina pectoris.[1] Opinions regarding the use of chelation therapy for CVD have long been controversial as there was not enough evidence on the benefits of their use.[2] Several studies investigated the use of chelation therapy as a treatment modality for atherosclerotic diseases. According to a study, there was an association between EDTA chelation therapy and improvement of ischemic heart disease and peripheral vascular disease.[3] Another study demonstrated that vitamin B supplemented EDTA and not EDTA alone was effective in improving vasodilation reflected by improved forearm blood flow.[4] A systematic review of four randomized clinical trial on chelation therapy and peripheral artery occlusive disease revealed no benefit associated with chelation therapy.[5] In addition, a systematic review on the role of chelation therapy in coronary heart disease (CHD) revealed that the data on chelation therapy and CHD is insufficient and hence chelation therapy cannot be recommended yet in this context.[6] In fact, according to the 2012 summary of clinical practice guidelines from the American College of Physicians/American College of Cardiology Foundation/American Heart Association/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic Surgeons, it was recommended that chelation therapy should not be used for symptomatic treatment or cardiovascular risk reduction among patients with stable ischemic heart disease.[7]


In the light of the controversies regarding the benefits of chelation therapy and the absence of any previous large clinical trial investigating its use in coronary artery disease, Trial to Assess Chelation Therapy (TACT), a randomized, double blind, placebo controlled 2x2 factorial trial, investigated the effect of EDTA based infusions among 1708 stable post-myocardial infarction patients who are more than 50 years of age. The infusions consisted of disodium EDTA combined with ascorbic acid, vitamin B and other components. The primary outcome of this trial was a composite of all-cause mortality, coronary revascularization, recurrence of myocardial infarction, stroke or angina requiring hospitalization. A follow up period of 55 months revealed a modest decrease in the adverse cardiovascular outcomes risks. In fact, 30% of post-MI patients who did not receive chelation therapy were reported to have the primary outcome compared to 26% of those who received the chelation therapy ( HR: 0.82; 95% CI: 0.69-0.99; p= 0.035). The association between chelation therapy and decrease in the risk of each of the components of the primary outcome was significant except for total mortality. Despite the moderate improvement in the cardiovascular outcomes, the findings of this study are not enough to promote chelation therapy as a treatment for stable post-myocardial infarct patients.[8]


The effect of chelation therapy on cardiovascular outcomes was further investigated among diabetic patients enrolled in TACT. Among TACT enrolled patients, 633 patients had diabetes defined as self-reported diabetes, taking treatment for diabetes or having a fasting blood glucose superior to 126 mg/dL at enrollment. The use of chelation therapy infusions among post-myocardial infarction diabetic patients was associated with a decrease in the primary end point. In fact, the primary end point occurred in 25% of diabetic patients who were administered the chelation therapy compared to 38% in those who were not (HR, 0.59; 95% CI, 0.44–0.79; P<0.001). The effect of chelation therapy on the primary end point remained significant following adjustment for multiple subgroups (99.4% CI, 0.39–0.88; adjusted P=0.002). In addition, chelation therapy was significantly associated with decreased all-cause mortality, reinfarction and stroke; however, these associations were no longer significant following adjustment for multiple subgroups. The findings of these studies are hypothesis generating and not yet definitive. Hence, despite the significant decrease in cardiovascular adverse events observed among post-myocardial infarction diabetic patients, the results of this study are not sufficient yet to recommend the use of chelation therapy among this subgroup of patients.[9]

Mechanism of Action

Ethylenediamine tetraacetic acid (EDTA), a type of chelation therapy, binds to metals and forms soluble complexes facilitating their subsequent excretion in the urine.[10] Hence, chelation therapy helps in the elimination of metals including lead, iron, copper and calcium from the blood. The chelation therapy consists of EDTA along with additives such as vitamin B, ascorbic acid and magnesium which are thought to have a protective effect on the endothelial cells.[11] Cardiovascular benefits of chelation therapy are thought to result from its antioxidant effect as it decreases the metal-dependent formation of reactive oxygen species and lipid peroxidation]].[11] In addition, the removal of calcium from arterial wall by chelation therapy can possibly lead to a regression of the atherosclerotic plaques.[12][13] In addition, metal detoxification in the context of diabetes possibly decreases inflammation and oxidative stress that characterize atherosclerosis by decreasing metal-dependent formation of glycation end products.[14]

Side Effects

Landmark Trials

TACT

References

  1. ↑ CLARKE CN, CLARKE NE, MOSHER RE (1956). "Treatment of angina pectoris with disodium ethylene diamine tetraacetic acid". Am J Med Sci. 232 (6): 654–66. PMID 13372537.
  2. ↑ Villarruz MV, Dans A, Tan F (2002). "Chelation therapy for atherosclerotic cardiovascular disease". Cochrane Database Syst Rev (4): CD002785. doi:10.1002/14651858.CD002785. PMID 12519577.
  3. ↑ Olszewer E, Carter JP (1988). "EDTA chelation therapy in chronic degenerative disease". Med Hypotheses. 27 (1): 41–9. PMID 3144646.
  4. ↑ Green DJ, O'Driscoll JG, Maiorana A, Scrimgeour NB, Weerasooriya R, Taylor RR (1999). "Effects of chelation with EDTA and vitamin B therapy on nitric oxide-related endothelial vasodilator function". Clin Exp Pharmacol Physiol. 26 (11): 853–6. PMID 10561804.
  5. ↑ Ernst E (1997). "Chelation therapy for peripheral arterial occlusive disease: a systematic review". Circulation. 96 (3): 1031–3. PMID 9264515.
  6. ↑ 6.0 6.1 Ernst E (2000). "Chelation therapy for coronary heart disease: An overview of all clinical investigations". Am Heart J. 140 (1): 139–41. doi:10.1067/mhj.2000.107548. PMID 10874275.
  7. ↑ Qaseem A, Fihn SD, Dallas P, Williams S, Owens DK, Shekelle P; et al. (2012). "Management of stable ischemic heart disease: summary of a clinical practice guideline from the American College of Physicians/American College of Cardiology Foundation/American Heart Association/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic Surgeons". Ann Intern Med. 157 (10): 735–43. doi:10.7326/0003-4819-157-10-201211200-00011. PMID 23165665.
  8. ↑ 8.0 8.1 Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL; et al. (2013). "Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial". JAMA. 309 (12): 1241–50. doi:10.1001/jama.2013.2107. PMID 23532240.
  9. ↑ Escolar E, Lamas G, Mark D et al(2013) "The Effect of an EDTA-based Chelation Regimen on Patients With Diabetes Mellitus and Prior Myocardial Infarction in the Trial to Assess Chelation Therapy (TACT)". Circulation. 2013
  10. ↑ WILDER LW, DE JODE LR, MILSTEIN SW, HOWARD JM (1962). "Mobilization of atherosclerotic plaque calcium with EDTA utilizing the isolation-perfusion principle". Surgery. 52: 793–5. PMID 14000694.
  11. ↑ 11.0 11.1 Lamas GA, Ackermann A (2000). "Clinical evaluation of chelation therapy: is there any wheat amidst the chaff?". Am Heart J. 140 (1): 4–5. doi:10.1067/mhj.2000.107549. PMID 10874253.
  12. ↑ CLARKE NE (1960). "Atherosclerosis, occlusive vascular disease and EDTA". Am J Cardiol. 6: 233–6. PMID 13810514.
  13. ↑ KITCHELL JR, PALMON F, AYTAN N, MELTZER LE (1963). "The treatment of coronary artery disease with disodium EDTA. A reappraisal". Am J Cardiol. 11: 501–6. PMID 14033183.
  14. ↑ Escolar E, Lamas G, Mark D et al(2013) "The Effect of an EDTA-based Chelation Regimen on Patients With Diabetes Mellitus and Prior Myocardial Infarction in the Trial to Assess Chelation Therapy (TACT)". Circulation. 2013


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