Chelation therapy for atherosclerotic cardiovascular (heart and circulation) disease

Background

Atherosclerosis is caused by fatty deposits that cause a narrowing of people's arteries and restrict blood flow. People with blocked arteries are more likely to have strokes, heart attacks, and narrow blood vessels in their feet. Chelation therapy involves infusions into the bloodstream of substances believed to remove metals from the blood. This treatment is offered to people with atherosclerotic cardiovascular disease as a way of breaking down the blockages in their blood vessels. Chelation therapy is practiced in several places around the world as an alternative form of medicine, but there is currently a lack of knowledge surrounding this treatment. More information is needed to understand if this treatment should be more widely recommended.

Key results

This review included evidence from five studies with a total of 1993 participants (current until August 2019). Three studies enrolled participants with peripheral vascular disease, and two of the studies included participants with coronary artery disease, one of which specifically recruited people who had had a heart attack. All five studies compared chelation therapy with no treatment or placebo. Only two of the studies (both of which included participants with coronary artery disease) reported death from any cause, and these reported no difference in overall deaths between those that received chelation therapy and those who did not. Ony one study (in people with coronary artery disease) reported cardiovascular death, and this study found no difference between in risk between those who had chelation therapy and those who did not. Two studies of people with coronary artery disease reported rates of heart attack and angina, and found no difference in the risk of these between participants who had chelation treatment and those who did not. Similarly, two studies (one in people with coronary artery disease and one in people with peripheral vascular disease) reported the chance of having a stroke, and found no clear difference in the chance of this between people who did or did not received chelation treatment. Two studies in people with peripheral vascular disease used an indirect measure of blood flow known as the ankle-brachial pressure index (ABPI), or ankle brachial index. These studies did not show any differences in this measure between people who received chelation therapy for three or six months and those who did not get the treatment. There was also no clear differences in the distance participants could walk.

We could not combine specific measures of quality of life in a single analysis. Looking at the two studies in people with coronary artery disease that reported this outcome, there was no difference in the quality of life reported by people who received chelation therapy and those who did not get the treatment. Two studies reported information about adverse events, but we could not combine this in a single analysis because they reported them in different ways and the events were different. However, the people who had chelation therapy did not appear to have any increase in either minor or major adverse events, compared with people who did not have the therapy.

Certainty of the evidence

We considered most of the data we found to be of low certainty, mostly because there were very few studies that provided data. Even though we included five studies, not all of them reported on each outcome. There is currently not enough evidence about the effects of chelation therapy on blockages in the blood vessels of people with atherosclerotic cardiovascular (heart and circulation) disease.

Conclusions

Overall, this review did not find any clear differences between people treated with chelation and people given the control, for the outcomes we evaluated. None of the outcomes included more than two studies, therefore it is difficult at this time to determine if these are true findings or just because there is not enough data. Further high-quality trials that focus on clinical outcomes are necessary.

Authors' conclusions: 

There is currently insufficient evidence to determine the effectiveness or ineffectiveness of chelation therapy in improving clinical outcomes of people with atherosclerotic cardiovascular disease. More high-quality, randomised controlled trials are needed that assess the effects of chelation therapy on longevity and quality of life among people with atherosclerotic cardiovascular disease.

Read the full abstract...
Background: 

Chelation therapy is promoted and practiced around the world as a form of alternative medicine in the treatment of atherosclerotic cardiovascular disease. It has been suggested as a safe, relatively inexpensive, non-surgical method of restoring blood flow in atherosclerotic vessels. However, there is currently limited high-quality, adequately-powered research informing evidence-based medicine on the topic, specifically regarding clinical outcomes. Due to this limited evidence, the benefit of chelation therapy remains controversial at present. This is an update of a review first published in 2002.

Objectives: 

To assess the effects of ethylene diamine tetra-acetic acid (EDTA) chelation therapy versus placebo or no treatment on clinical outcomes among people with atherosclerotic cardiovascular disease.

Search strategy: 

For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 6 August 2019. We searched the bibliographies of the studies retrieved by the literature searches for further trials.

Selection criteria: 

We included studies if they were randomised controlled trials of EDTA chelation therapy versus placebo or no treatment in participants with atherosclerotic cardiovascular disease. The main outcome measures we considered include all-cause or cause-specific mortality, non-fatal cardiovascular events, direct or indirect measurement of disease severity, and subjective measures of improvement or adverse events.

Data collection and analysis: 

Two review authors independently extracted data and assessed trial quality using standard Cochrane procedures. A third author considered any unresolved issues, and we discussed any discrepancies until a consensus was reached. We contacted study authors for additional information.

Main results: 

We included five studies with a total of 1993 randomised participants. Three studies enrolled participants with peripheral vascular disease and two studies included participants with coronary artery disease, one of which specifically recruited people who had had a myocardial infarction. The number of participants in each study varied widely (from 10 to 1708 participants), but all studies compared EDTA chelation to a placebo. Risk of bias for the included studies was generally moderate to low, but one study had high risk of bias because the study investigators broke their randomisation code halfway through the study and rolled the placebo participants over to active treatment. Certainty of the evidence, as assessed by GRADE, was generally low to very low, which was mostly due to a paucity of data in each outcome's meta-analysis. This limited our ability to draw any strong conclusions. We also had concerns about one study's risk of bias regarding blinding and outcome assessment that may have biased the results.

Two studies with coronary artery disease participants reported no evidence of a difference in all-cause mortality between chelation therapy and placebo (risk ratio (RR) 0.97, 95% CI 0.73 to 1.28; 1792 participants; low-certainty). One study with coronary artery disease participants reported no evidence of a difference in coronary heart disease deaths between chelation therapy and placebo (RR 1.02, 95% CI 0.70 to 1.48; 1708 participants; very low-certainty). Two studies with coronary artery disease participants reported no evidence of a difference in myocardial infarction (RR 0.81, 95% CI 0.57 to 1.14; 1792 participants; moderate-certainty), angina (RR 0.95, 95% CI 0.55 to 1.67; 1792 participants; very low-certainty), and coronary revascularisation (RR 0.46, 95% CI 0.07 to 3.25; 1792 participants). Two studies (one with coronary artery disease participants and one with peripheral vascular disease participants) reported no evidence of a difference in stroke (RR 0.88, 95% CI 0.40 to 1.92; 1867 participants; low-certainty). Ankle-brachial pressure index (ABPI; also known as ankle brachial index) was measured in three studies, all including participants with peripheral vascular disease; two studies found no evidence of a difference in the treatment groups after three months after treatment (mean difference (MD) 0.02, 95% CI -0.03 to 0.06; 181 participants; low-certainty). A third study reported an improvement in ABPI in the EDTA chelation group, but this study was at high risk of bias. Meta-analysis of maximum and pain-free walking distances three months after treatment included participants with peripheral vascular disease and showed no evidence of a difference between the treatment groups (MD -31.46, 95% CI -87.63 to 24.71; 165 participants; 2 studies; low-certainty). Quality of life outcomes were reported by two studies that included participants with coronary artery disease, but we were unable to pool the data due to different methods of reporting and varied criteria. However, there did not appear to be any major differences between the treatment groups. None of the included studies reported on vascular deaths. Overall, there was no evidence of major or minor adverse events associated with EDTA chelation treatment.

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