Chelation therapy for cardiovascular disease: Difference between revisions

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Yet in spite of the recommendations against chelation therapy by professional organizations, patients continued to seek, and practitioners to administer, chelation infusions.  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]], The National Center for Complementary and Alternative Medicine and the National Heart Lung and Blood Institute released a $30 million Request for Applications to develop a definitive trial.  In 2002, the RFA was awarded to Mount Sinai Medical Center in Miami Beach FL (G Lamas MD, Principal Investigator).  The   Normal  0          false  false  false    EN-US  JA  X-NONE                                                                                                                                                                                                                                                                                                                                                                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.<ref name="pmid23532240">{{cite journal| author=Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL et al.| title=Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. | journal=JAMA | year= 2013 | volume= 309 | issue= 12 | pages= 1241-50 | pmid=23532240 | doi=10.1001/jama.2013.2107 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23532240 }} </ref>
Yet in spite of the recommendations against chelation therapy by professional organizations, patients continued to seek, and practitioners to administer, chelation infusions.  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]], The National Center for Complementary and Alternative Medicine and the National Heart Lung and Blood Institute released a $30 million Request for Applications to develop a definitive trial.  In 2002, the RFA was awarded to Mount Sinai Medical Center in Miami Beach FL (G Lamas MD, Principal Investigator).  The 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 (MI) patients more than 50 years of age and with fairly normal kidney function.  The infusions consisted of disodium EDTA combined with ascorbic acid, vitamin B and other components.  The median age of patients was 65 years, and they were well-treated with evidence-based medicines for post-MI patients.  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 but statistically significant decrease in the primary endpoint (HR: 0.82; 95% CI: 0.69-0.99; p= 0.035). There was an absolute reduction in the 5-year Kaplan-Meier estimate from 38% to 33%, resulting in a 5-year number needed to treat of 20 patients to avoid one    Normal  0          false  false  false    EN-US  JA  X-NONE                                                                                                                                                                                                                                                                                                                                                                adverse cardiovascular outcome.  This is comparable tp the 5-year NNT for statins in post-MI patients.  The point estimate for the risk of each of the components of the primary endpoint was <1, thus consistent with the aggregate result.   Normal  0          false  false false    EN-US  JA  X-NONE                                                                                                                                                                                                                                                                                                                                                                  In an abundance of caution, the investigators called for a cautious interpretation and more research before recommending chelation therapy for post-MI patients.   Normal  0          false  false  false    EN-US  JA  X-NONE                                                                                                                                                                                                                                                                                                                                                                <ref name="pmid23532240">{{cite journal| author=Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL et al.| title=Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. | journal=JAMA | year= 2013 | volume= 309 | issue= 12 | pages= 1241-50 | pmid=23532240 | doi=10.1001/jama.2013.2107 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23532240 }} </ref>




Revision as of 15:52, 21 November 2013

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 is a process by which a charged molecule captures an ion with an opposite charge, inactivates it, and then permits its excretion, usually by a renal route. Thus, chelation therapy, which involves multiple administrations of the chelating agent, helps detoxify the blood. Ethylene diamine tetraacetic acid (EDTA), a commonly used chelating agent, binds to and permits excretion of metals such as lead, cadmium, nickel, cobalt, iron and aluminum. In addition to its use for the treatment of metal poisoning, chelation therapy has been considered an alternative medicine for the treatment of atherosclerotic disease. Many mechanisms have been postulated, including decalcification of atherosclerotic vessels. Other potential mechanisms, more accepted in the modern era, center around metal detoxification. Opinions regarding the use of chelation therapy for cardiovascular diseases (CVD) have long been controversial, as, until recently, there was not enough high-quality evidence for or against its use. Most recently, the 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 more than 50 years of age and with fairly normal kidney function. TACT revealed a modest decrease in major adverse cardiovascular events among enrolled patients randomized to EDTA-based infusions. When the pre-specified subgroup of patients with diabetes was analyzed, the decrease in adverse cardiovascular outcomes was even 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 supporting its use.[2] Several studies investigated the use of chelation therapy as a treatment modality for atherosclerotic diseases, but studies were not prospective nor randomized. For example, according to an extensive case series, there was an association between EDTA chelation therapy and improvement of ischemic heart disease and peripheral vascular disease.[3] Another study demonstrated that EDTA supplemented with vitamin B but not EDTA alone was effective in improving endothelium-dependent 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) in 2002 concluded that the data on chelation therapy and CHD was insufficient.[6] Finally, 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]


Yet in spite of the recommendations against chelation therapy by professional organizations, patients continued to seek, and practitioners to administer, chelation infusions. 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, The National Center for Complementary and Alternative Medicine and the National Heart Lung and Blood Institute released a $30 million Request for Applications to develop a definitive trial. In 2002, the RFA was awarded to Mount Sinai Medical Center in Miami Beach FL (G Lamas MD, Principal Investigator). The 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 (MI) patients more than 50 years of age and with fairly normal kidney function. The infusions consisted of disodium EDTA combined with ascorbic acid, vitamin B and other components. The median age of patients was 65 years, and they were well-treated with evidence-based medicines for post-MI patients. 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 but statistically significant decrease in the primary endpoint (HR: 0.82; 95% CI: 0.69-0.99; p= 0.035). There was an absolute reduction in the 5-year Kaplan-Meier estimate from 38% to 33%, resulting in a 5-year number needed to treat of 20 patients to avoid one Normal 0 false false false EN-US JA X-NONE adverse cardiovascular outcome. This is comparable tp the 5-year NNT for statins in post-MI patients. The point estimate for the risk of each of the components of the primary endpoint was <1, thus consistent with the aggregate result. Normal 0 false false false EN-US JA X-NONE In an abundance of caution, the investigators called for a cautious interpretation and more research before recommending chelation therapy for post-MI patients. Normal 0 false false false EN-US JA X-NONE [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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