Month: June 2014

TACT Trial: EDTA Chelation Therapy for Atherosclerosis

Effect of Disodium EDTA Chelation Regimen on Cardiovascular Events in Patients With Previous Myocardial Infarction

Lamas-Gervasio-CARDIOLOGYGervasio A. Lamas, MD; Christine Goertz, DC, PhD; Robin Boineau, MD, MA; Daniel B. Mark, MD, MPH; Theodore Rozema, MD; Richard L. Nahin, PhD, MPH; Lauren Lindblad, MS; Eldrin F. Lewis, MD, MPH; Jeanne Drisko, MD; Kerry L. Lee, PhD ;

Importance Chelation therapy with disodium EDTA has been used for more than 50 years to treat atherosclerosis without proof of efficacy.

Objective To determine if an EDTA-based chelation regimen reduces cardiovascular events.

Design, Setting, and Participants Double-blind, placebo-controlled, 2 × 2 factorial randomized trial enrolling 1708 patients aged 50 years or older who had experienced a myocardial infarction (MI) at least 6 weeks prior and had serum creatinine levels of 2.0 mg/dL or less. Participants were recruited at 134 US and Canadian sites. Enrollment began in September 2003 and follow-up took place until October 2011 (median, 55 months). Two hundred eighty-nine patients (17% of total; n=115 in the EDTA group and n=174 in the placebo group) withdrew consent during the trial.

Interventions Patients were randomized to receive 40 infusions of a 500-mL chelation solution (3 g of disodium EDTA, 7 g of ascorbate, B vitamins, electrolytes, procaine, and heparin) (n=839) vs placebo (n=869) and an oral vitamin-mineral regimen vs an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. Fifteen percent discontinued infusions (n=38 [16%] in the chelation group and n=41 [15%] in the placebo group) because of adverse events.

Main Outcome Measures The prespecified primary end point was a composite of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. This report describes the intention-to-treat comparison of EDTA chelation vs placebo. To account for multiple interim analyses, the significance threshold required at the final analysis was P = .036.

Results Qualifying previous MIs occurred a median of 4.6 years before enrollment. Median age was 65 years, 18% were female, 9% were nonwhite, and 31% were diabetic. The primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.99]; P = .035). There was no effect on total mortality (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0.93 [95% CI, 0.70-1.25]; P = .64), but the study was not powered for this comparison. The effect of EDTA chelation on the components of the primary end point other than death was of similar magnitude as its overall effect (MI: chelation, 6%; placebo, 8%; HR, 0.77 [95% CI, 0.54-1.11]; stroke: chelation, 1.2%; placebo, 1.5%; HR, 0.77 [95% CI, 0.34-1.76]; coronary revascularization: chelation, 15%; placebo, 18%; HR, 0.81 [95% CI, 0.64-1.02]; hospitalization for angina: chelation, 1.6%; placebo, 2.1%; HR, 0.72 [95% CI, 0.35-1.47]). Sensitivity analyses examining the effect of patient dropout and treatment adherence did not alter the results.

Conclusions and Relevance Among stable patients with a history of MI, use of an intravenous chelation regimen with disodium EDTA, compared with placebo, modestly reduced the risk of adverse cardiovascular outcomes, many of which were revascularization procedures. These results provide evidence to guide further research but are not sufficient to support the routine use of chelation therapy for treatment of patients who have had an MI.

Trial Registration clinicaltrials.gov Identifier: NCT00044213

Treatment of lead toxicity with chelation was first reported with EDTA in the early 1950s.1Apparent success in reducing metastatic calcium deposits2 led Clarke et al3 in 1956 to treat angina patients with EDTA, and others to use chelation for various forms of atherosclerotic disease.4– 6Chelation therapy evolved to constitute infusions of vitamins and disodium EDTA, a drug that binds divalent and some trivalent cations, including calcium, magnesium, lead, cadmium, zinc, iron, aluminum, and copper, facilitating their urinary excretion.7,8

Over the next decades, based on favorable anecdotal and case report experience, chelation practitioners increased their use of EDTA for coronary and peripheral artery disease. The 2007 National Health Statistics Report compared chelation use since 2002 and noted an increase of 68%, from 66 000 to 111 000 adults using chelation therapy,9 although the indications for therapy were not clearly defined, and the prevalence of use of chelation therapy for cardiovascular disease is unknown.

Three small clinical trials have assessed the effects of chelation on surrogate outcomes, such as walking distance in patients with claudication (2 trials with 185 patients total) and time to exercise-induced ischemia in patients with coronary disease (1 trial with 84 patients). These studies did not find any evidence of treatment efficacy but were underpowered for evaluation of clinical events.10– 12 As a consequence, mainstream medical organizations consider the therapeutic value of chelation for atherosclerotic vascular disease unproven13 and the use of this therapy potentially dangerous. Disodium EDTA, particularly when infused too rapidly, may cause hypocalcemia and death.14 The Trial to Assess Chelation Therapy (TACT) was conducted to respond to the public health problem posed by EDTA chelation therapy: large numbers of patients being exposed to undefined risks for unproven benefits.

http://jama.jamanetwork.com/article.aspx?articleid=1672238

Chelation Therapy for Peripheral Arterial Occlusive Disease

blood-1237550-639x450E. Ernst, MD, PhD, FRCP (Edin)

Abstract:

Chelation therapy is viewed, promoted, and practiced as a form of complementary/alternative medicine (see References 1 and 21 2 ). It uses repeated intravenous administration of EDTA, usually in combination with vitamins, trace elements, and iron supplements as a treatment for a variety of diseases.3 4 5 Oral chelation therapy also has been advocated (see Reference 66 ) but will be excluded from this review. Among others, chelation therapy is claimed to be effective in reversing the arteriosclerotic disease process,7 8 in particular peripheral arterial occlusive disease (PAOD). Proponents claim that it can be an alternative for amputation in severe cases.8 This goes back to an observation made in the 1950s, when it was noted that patients undergoing EDTA therapy for lead poisoning felt a relief of angina pectoris after this therapy.9 While various authors9 10 11 12 13 1415 have subsequently reported promising results in uncontrolled studies, others have been unable to confirm these in similarly designed trials.16 17 The debate of whether or not it is a useful form of therapy for PAOD therefore continues.18 19 2021 22 23 24 25

Meanwhile, numerous clinics have been set up in Europe, the United States, and elsewhere using and promoting chelation therapy for PAOD. In the light of recent trial data, it is therefore timely to systematically review the evidence from randomized, placebo-controlled, double-blind trials and ask whether chelation therapy for PAOD is safe and effective.

http://circ.ahajournals.org/content/96/3/1031.long

 

EDTA chelation therapy in the treatment of vascular disease.

Chappell LT1, Janson M.

Abstract

A retrospective analysis of treatment results from 2870 patients, with various chronic degenerative and age-associated diseases, who were treated with di-sodium magnesium EDTA chelation therapy, suggests that the case against EDTA Chelation Therapy should be re-opened.

Using qualitative but never-the-less standardized criteria for improvement, our analysis shows that EDTA Chelation Therapy resulted in “marked” improvement in 76.89% and “good” improvement in 16.56% of patients with ischemic heart disease; also, “marked” improvement in 91% and “good” improvement in 7.6% of patients with peripheral vascular disease and intermittent claudication. In a group of patients with cerebro-vascular and other degenerative cerebral diseases, 24% had “marked” improvement, and 30% had “good” improvement. Of four patients with scleroderma, three had “marked” improvement and one had “good” improvement. Seventy-five percent of all of the patients had “marked” improvement in “geriatric symptomatology of vascular origin”.

The authors recommend renewed study of EDTA Chelation Therapy. The possibility of a “tomato effect”, i.e., a drug which works, but the majority of physicians believe that it doesn’t work, needs to be ruled out. A favorable climate needs to be created, in which FDA-approved studies of its usefulness in treating peripheral vascular disease can take place.

http://www.ncbi.nlm.nih.gov/pubmed/8820322

Acute prooxidant effects of vitamin C in EDTA chelation therapy and long-term antioxidant benefits of therapy.

Hininger I1, Waters R, Osman M, Garrel C, Fernholz K, Roussel AM, Anderson RA.

Chelation therapy is thought to not only remove contaminating metals but also to decrease free radical production. EDTA chelation therapy, containing high doses of vitamin C as an antioxidant, is often used in the treatment of diseases such as diabetes and cardiovascular diseases but the effectiveness of this treatment may be variable and its efficacy has not been demonstrated conclusively. The objective of this work was to determine if the vitamin C added to standard chelation therapy cocktails was prooxidant. We administered a standard EDTA cocktail solution with or without 5 g of sodium ascorbate. One hour following the standard chelation therapy, there were highly significant prooxidant effects on lipids, proteins, and DNA associated with decreased activities of RBC glutathione peroxidase and superoxide dismutase while in the absence of sodium ascorbate, there were no acute signs of oxidative damage. After 16 sessions of standard chelation therapy, the acute prooxidant effects of vitamin C remained, but, even in the absence of nutrient supplements, there were beneficial long-term antioxidant effects of chelation therapy and plasma peroxide levels decreased. In conclusion, multiple vitamins-1471906-640x480sessions of EDTA chelation therapy protect lipids against oxidative damage. However, standard high amounts of vitamin C added to EDTA chelation solutions also display short term prooxidant effects. The added benefits of lower levels of vitamin C in chelation therapy need to be documented.

http://www.ncbi.nlm.nih.gov/pubmed/15917185

The Edinburgh Artery Study

Blood viscosity and risk of cardiovascular events

Lowe GD1, Lee AJ, Rumley A, Price JF, Fowkes FG.

Abstract

We examined the relationships of whole blood viscosity and its major determinants to incident cardiovascular events (ischaemic heart disease and stroke) in a prospective study of a random population sample of 1592 men and women aged 55-74 years (the Edinburgh Artery Study). 272 fatal and non-fatal cardiovascular events occurred during 5 years of follow-up (cumulative incidence 17.1%). Age and sex adjusted mean levels of blood viscosity (3.70 v 3.55 mPa.s), haematocrit (46.2 v 45.7%), haematocrit-corrected blood viscosity (3.57 v 3.48 mPa.s), plasma viscosity (1.35 v 1.33 mPa.s) and fibrinogen (2.88 v 2.67 g/l) were significantly higher in subjects who experienced events than in subjects who did not. The relationships of these rheological variables to cardiovascular events were at least as strong as those of conventional risk factors (smoking habit, diastolic blood pressure, and low-density lipoprblood-1237550-639x450otein cholesterol). After adjustment for these conventional risk factors, the associations of blood viscosity and haematocrit remained significant for stroke, but not for total events; whereas the associations of plasma viscosity and fibrinogen remained significant for total events and for stroke. These findings suggest that increased blood viscosity may be one plausible biological mechanism through which increases in haematocrit and fibrinogen may promote ischaemic heart disease and stroke. Randomized controlled trials of viscosity reduction in the prevention of cardiovascular events (e.g. by lowering high levels of haematocrit or plasma fibrinogen) are suggested.

http://www.ncbi.nlm.nih.gov/pubmed/9012704

Should EDTA chelation therapy be used instead of long-term clopidogrel plus aspirin to treat patients at risk from drug-eluting stents?

by Chappell LT, 2007red-pills-1526972-639x384

Abstract: The recently discovered increased risk of blood clots, leading to myocardial infarction and sudden death beginning six months after medicated stents are implanted in patients following percutaneous transluminal coronary angioplasty (PTCA), has left cardiologists pondering what course of action to take. The purpose of adding implanted medication to a stent is to prevent thrombin accumulation and restenosis. However, these stents may increase, rather than decrease, the risk. Although long-term treatment with clopidogrel bisulfate (Plavix) plus aspirin for at least 12 months has been suggested as a preventive treatment, there is no evidence from randomized, controlled trials that this treatment is effective for more than six months. Clopidogrel also increases the risk of major bleeding episodes. The author served as the primary investigator for a study that showed cardiovascular patients treated with EDTA chelation therapy had a lower rate of subsequent cardiac events, including myocardial infarction and death, than those treated with cardiac medications, PTCA, or coronary artery bypass graft (CABG). The data also indicated chelation therapy might be effective in preventing thrombosis and cardiac events from stent implantation. There is evidence EDTA chelation therapy might prevent hypercoagulability resulting from the placement of stents, although not specifically medicated stents. Based on the limited data currently available, intravenous EDTA may be safe and effective for treating patients who have implanted medicated stents. Prospective clinical trials are needed, and EDTA should be included in those trials.

http://www.ncbi.nlm.nih.gov/pubmed/17604460

Chelation Therapy: Clinically Relevant or Just Quackery?

ronhoffmanRon Hoffman, MD; Feb 10, 2014

Chelation therapy, a type of intravenous (IV) treatment promoted by some members of the complementary and alternative medicine community, has long been mired in controversy.

Often dismissed as quackery, chelation therapy was the subject of a recently completed NIH study (Trial to Assess Chelation Therapy [TACT]) that showed the practice to be of moderate benefit to heart-attack survivors. Yet the controversy continues unabated, with some calling the study misguided or flawed and few in the conventional medical community willing to embrace chelation therapy as a legitimate option for heart patients.

How Chelation Therapy Works

Chelation therapy consists of a series of IV administrations of disodium or calcium ethylenediaminetetraacetic acid (EDTA) mixed with minerals and vitamins.

Typically, patients recline in a chair in the clinician’s office for one to four hours once to three times weekly for a series of 20 to 80 chelations. “Booster” chelations may be administered on a monthly basis or intermittently for years.

The purported benefits of chelation therapy vary but typically include the following:

  • Improves such circulatory disorders as coronary artery disease (CAD), cerebrovascular disease, or peripheral vascular disease;
  • Detoxifies the body of such heavy metals as lead, cadmium, and mercury; and
  • Combats degenerative diseases and slows the aging process.

The procedure is usually not covered by Medicare or private insurance. The out-of-pocket costs are borne by patients and may total thousands of dollars for a single course of treatment.

History


The term chelation (derived from the Greek chelos or claw) refers to the mineral- or metal-binding properties of certain compounds that can hold a central cation in a pincerlike grip. Developed in Germany in 1935, EDTA was originally used as a means of binding and extracting calcium in the dye industry.

In the 1940s, Martin Rubin, Professor Emeritus of Biochemistry at Georgetown University Medical Center in Washington, D.C., discovered EDTA’s effects on calcium in biological systems. This discovery led to the product’s use as an anticoagulant and is still used in “purple top” blood-collection tubes. Professor Rubin’s research led him to advance the use of EDTA for treatment of hypercalcemia and, eventually, lead poisoning.

In the 1950s and 1960s, several clinicians began to observe that patients treated for lead poisoning with IV EDTA experienced improvements in their cardiovascular conditions. This observation led to the widespread, but mostly empirical, use of EDTA therapy for heart patients within a growing community of alternative medicine practitioners.

Studies were undertaken, but these were mostly observational or uncontrolled and involved only small numbers of patients. Chelation therapy for other than the approved indications of refractory hypercalcemia or severe lead toxicity remained highly touted but poorly substantiated.

Clinicians practicing chelation therapy were sometimes targeted by medical boards for disciplinary action, irrespective of whether specific patient harm had occurred. Some states adopted regulations prohibiting the practice of chelation therapy. To this day, disodium EDTA is not approved by the FDA to treat any diseases. However, disodium EDTA is produced by compounding pharmacies for individual patients, so the treatment can still be obtained.

In 1998, the U.S. Federal Trade Commission (FTC) targeted the American College for Advancement of Medicine (ACAM), an organization that has trained and certified physicians in methods of safe administration of chelation therapy since the 1970s, for allegedly outsized advertising claims made regarding the treatment of atherosclerosis.

The FTC concluded that there was a lack of scientific studies to support these claims and that pro-chelation statements made by ACAM were false. As an alternative to litigation, ACAM stipulated that it would curtail public pronouncements presenting chelation therapy as an effective treatment for heart disease.

The public’s enthusiasm for chelation therapy remained undiminished, however. Between 2002 and 2007, use of chelation therapy to treat heart disease and other conditions grew in the United States by nearly 68% to 111,000 people.1 As of the start of the TACT Study in 2001, it was estimated that patients received 800,000 individual EDTA infusions per year.2

Until the TACT study, mainstream clinicians widely believed that EDTA chelation therapy for conditions other than acute lead intoxication was an unwarranted and dangerous modality. This is true to the extent that excessive doses of EDTA can be nephrotoxic; cases of renal failure resulting in dialysis or death have been recorded. Additionally, transient hypocalcemia provoked by EDTA calcium sequestration can trigger cardiac arrhythmias or sudden death.

But these outcomes have generally occurred only in rare instances where EDTA is administered in too high a dose and/or too rapidly or without regard to a patient’s glomerular flow rate. In 1989, a “Protocol for the Safe and Effective Administration of EDTA” was developed and subsequently updated.3

The detailed protocol provides strict criteria for patient selection and cautions clinicians to perform an initial evaluation of renal function using the Cockcroft-Gault equation and to frequently monitor renal function throughout a series of chelation treatments. Emergency procedures are outlined should adverse reactions occur.

 

Read More:

http://www.empr.com/chelation-therapy-clinically-relevant-or-just-quackery/article/333324/