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Cardiovascular Research Feb 2022Our purpose was to perform a systematic review to assess the prevalence of microvascular angina (MVA) among patients with stable symptoms in the absence of obstructive...
Our purpose was to perform a systematic review to assess the prevalence of microvascular angina (MVA) among patients with stable symptoms in the absence of obstructive coronary artery disease (CAD). We performed a systematic review of the literature to group the prevalence of MVA, based on diagnostic pathways and modalities. We defined MVA using three definitions: (i) suspected MVA using non-invasive ischaemia tests; proportion of patients with non-obstructive CAD among patients with symptoms and a positive non-invasive ischaemia test result, (ii) suspected MVA using specific modalities for MVA; proportion of patients with evidence of impaired microvascular function among patients with symptoms and non-obstructive CAD, and (iii) definitive MVA; proportion of patients with positive ischaemia test results among patients with an objectified impaired microvascular dysfunction. We further examined the ratio of women-to-men for the different groups. Of the 4547 abstracts, 20 studies reported data on MVA prevalence. The median prevalence was 43% for suspected MVA using non-invasive ischaemia test, 28% for suspected MVA using specific modalities for MVA, and 30% for definitive MVA. Overall, more women were included in the studies reporting sex-specific data. The women-to-men ratio for included participants was 1.29. However, the average women-to-men ratio for the MVA cases was 2.50. In patients with stable symptoms of ischaemia in the absence of CAD, the prevalences of suspected and definitive MVA are substantial. The results of this study should warrant cardiologists to support, promote and facilitate the comprehensive evaluation of the coronary microcirculation for all patients with symptoms and non-obstructive CAD.
Topics: Coronary Artery Disease; Coronary Circulation; Female; Humans; Male; Microcirculation; Microvascular Angina; Prevalence
PubMed: 33677526
DOI: 10.1093/cvr/cvab061 -
BMC Medical Imaging Jan 2021Coronary microvascular dysfunction (CMD) is an important underlying cause of angina pectoris. Currently, no diagnostic tool is available to directly visualize the...
BACKGROUND
Coronary microvascular dysfunction (CMD) is an important underlying cause of angina pectoris. Currently, no diagnostic tool is available to directly visualize the coronary microvasculature. Invasive microvascular reactivity testing is the diagnostic standard for CMD, but several non-invasive imaging techniques are being evaluated. However, evidence on reported non-invasive parameters and cut-off values is limited. Thus, we aimed to provide an overview of reported non-invasive parameters and corresponding cut-off values for CMD.
METHODS
Pubmed and EMBASE databases were systematically searched for studies enrolling patients with angina pectoris without obstructed coronary arteries, investigating at least one non-invasive imaging technique to quantify CMD. Methodological quality assessment of included studies was performed using QUADAS-2.
RESULTS
Thirty-seven studies were included. Ten cardiac magnetic resonance studies reported MPRI and nine positron emission tomography (PET) and transthoracic echocardiography (TTE) studies reported CFR. Mean MPRI ranged from 1.47 ± 0.36 to 2.01 ± 0.41 in patients and from 1.50 ± 0.47 to 2.68 ± 0.49 in controls without CMD. Reported mean CFR in PET and TTE ranged from 1.39 ± 0.31 to 2.85 ± 1.35 and 1.69 ± 0.40 to 2.40 ± 0.40 for patients, and 2.68 ± 0.83 to 4.32 ± 1.78 and 2.65 ± 0.65 to 3.31 ± 1.10 for controls, respectively.
CONCLUSIONS
This systematic review summarized current evidence on reported parameters and cut-off values to diagnose CMD for various non-invasive imaging modalities. In current clinical practice, CMD is generally diagnosed with a CFR less than 2.0. However, due to heterogeneity in methodology and reporting of outcome measures, outcomes could not be compared and no definite reference values could be provided.
Topics: Angina Pectoris; Coronary Artery Disease; Coronary Circulation; Echocardiography; Humans; Magnetic Resonance Angiography; Microcirculation; Positron-Emission Tomography; Sex Factors
PubMed: 33407208
DOI: 10.1186/s12880-020-00535-7 -
PloS One 2020Air-pollution and weather exposure beyond certain thresholds have serious effects on public health. Yet, there is lack of information on wider aspects including the role...
BACKGROUND
Air-pollution and weather exposure beyond certain thresholds have serious effects on public health. Yet, there is lack of information on wider aspects including the role of some effect modifiers and the interaction between air-pollution and weather. This article aims at a comprehensive review and narrative summary of literature on the association of air-pollution and weather with mortality and hospital admissions; and to highlight literature gaps that require further research.
METHODS
We conducted a scoping literature review. The search on two databases (PubMed and Web-of-Science) from 2012 to 2020 using three conceptual categories of "environmental factors", "health outcomes", and "Geographical region" revealed a total of 951 records. The narrative synthesis included all original studies with time-series, cohort, or case cross-over design; with ambient air-pollution and/or weather exposure; and mortality and/or hospital admission outcomes.
RESULTS
The final review included 112 articles from which 70 involved mortality, 30 hospital admission, and 12 studies included both outcomes. Air-pollution was shown to act consistently as risk factor for all-causes, cardiovascular, respiratory, cerebrovascular and cancer mortality and hospital admissions. Hot and cold temperature was a risk factor for wide range of cardiovascular, respiratory, and psychiatric illness; yet, in few studies, the increase in temperature reduced the risk of hospital admissions for pulmonary embolism, angina pectoris, chest, and ischemic heart diseases. The role of effect modification in the included studies was investigated in terms of gender, age, and season but not in terms of ethnicity.
CONCLUSION
Air-pollution and weather exposure beyond certain thresholds affect human health negatively. Effect modification of important socio-demographics such as ethnicity and the interaction between air-pollution and weather is often missed in the literature. Our findings highlight the need of further research in the area of health behaviour and mortality in relation to air-pollution and weather, to guide effective environmental health precautionary measures planning.
Topics: Air Pollution; Humans; Mortality; Patient Admission; Weather
PubMed: 33119678
DOI: 10.1371/journal.pone.0241415 -
Open Heart Oct 2020To determine the impact of ivabradine on outcomes important to patients with angina pectoris caused by coronary artery disease. (Meta-Analysis)
Meta-Analysis
Effects of adding ivabradine to usual care in patients with angina pectoris: a systematic review of randomised clinical trials with meta-analysis and Trial Sequential Analysis.
OBJECTIVE
To determine the impact of ivabradine on outcomes important to patients with angina pectoris caused by coronary artery disease.
METHODS
We conducted a systematic review. We included randomised clinical trials comparing ivabradine versus placebo or no intervention for patients with angina pectoris due to coronary artery disease published prior to June 2020. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Cochrane methodology, Trial Sequential Analysis, Grading of Recommendations Assessment, Development, and Evaluation, and our eight-step procedure. Primary outcomes were all-cause mortality, serious adverse events and quality of life.
RESULTS
We included 47 randomised clinical trials enrolling 35 797 participants. All trials and outcomes were at high risk of bias. Ivabradine compared with control did not have effects when assessing all-cause mortality (risk ratio [RR] 1.04; 95% CI 0.96 to 1.13), quality of life (standardised mean differences -0.05; 95% CI -0.11 to 0.01), cardiovascular mortality (RR 1.07; 95% CI 0.97 to 1.18) and myocardial infarction (RR 1.03; 95% CI 0.91 to 1.16). Ivabradine seemed to increase the risk of serious adverse events after removal of outliers (RR 1.07; 95% CI 1.03 to 1.11) as well as the following adverse events classified as serious: bradycardia, prolonged QT interval, photopsia, atrial fibrillation and hypertension. Ivabradine also increased the risk of non-serious adverse events (RR 1.13; 95% CI 1.11 to 1.16). Ivabradine might have a statistically significant effect when assessing angina frequency (mean difference (MD) 2.06; 95% CI 0.82 to 3.30) and stability (MD 1.48; 95% CI 0.07 to 2.89), but the effect sizes seemed minimal and possibly without any relevance to patients, and we identified several methodological limitations, questioning the validity of these results.
CONCLUSION
Our findings do not support that ivabradine offers significant benefits on patient important outcomes, but rather seems to increase the risk of serious adverse events such as atrial fibrillation and non-serious adverse events. Based on current evidence, guidelines need reassessment and the use of ivabradine for angina pectoris should be reconsidered.
PROSPERO REGISTRATION NUMBER
CRD42018112082.
Topics: Aged; Angina Pectoris; Cardiovascular Agents; Female; Humans; Ivabradine; Male; Middle Aged; Patient Safety; Quality of Life; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 33046592
DOI: 10.1136/openhrt-2020-001288 -
Medicine Sep 2020The prevalence of cardiac syndrome X (CSX) is considerable. Some patients show recurrent angina attacks and have a poor prognosis. However, the knowledge of CSX... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of cardiac syndrome X (CSX) is considerable. Some patients show recurrent angina attacks and have a poor prognosis. However, the knowledge of CSX pathophysiological mechanism is still limited, and the treatment fails to achieve a satisfactory suppression of symptoms. Nicorandil has a beneficial effect on improving coronary microvascular dysfunction (CMD). This study aims to evaluate the clinical effects and safety of nicorandil on CSX patients.
METHODS
The Cochrane Library, Pubmed, EMBASE, ClinicalTrials.gov and 4 Chinese databases were searched to identify relevant studies. The Cochrane "Risk of bias" tool was used to assess the methodological quality of eligible studies. Meta-analysis was performed by RevMan 5.3 software. The Eggers test and meta-regression were performed by software Stata 14.0. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Twenty four randomized controlled trials (RCTs) involving 2323 patients were included. Most of the included studies were classified as having an unclear risk of bias because of poor reported methodology. The main outcomes are angina symptoms improvement, resting electrocardiogram (ECG) improvement, treadmill test result, and endothelial function. Meta-analysis showed that nicorandil had some benefit on improving angina symptoms (RR 1.24, 95% CI 1.19 to 1.29, I = 20%, P < .00001), resting ECG (RR = 1.24, 95% IC: 1.15 to 1.33, I = 0%, P < .00001), and prolonged the time to 1 mm ST-segment depression in treadmill test result (WMD = 38.41, 95% IC: 18.46 to 58.36, I = 0%, P = .0002). Besides nicorandil could reduce the level of endothelin-1 (ET-1) (SMD = -2.22, 95% IC: -2.61 to -1.83, I = 77%, P < .00001) and increase the level of nitric oxide (NO) (WMD = 27.45, 95% IC: 125.65 to 29.24, I = 81%, P < .00001). No serious adverse drug event was reported. The Eggers test showed that significant statistical publication bias was detected (Eggers test P = .000). The quality of evidence ranged from very low to low.
CONCLUSIONS
Nicorandil shows the potential of improving angina symptoms, ECG, and endothelial dysfunction in patients with CSX. However, there is insufficient evidence for the clinical benefits of nicorandil due to the very low-quality evidence.
Topics: Electrocardiography; Endothelin-1; Endothelium, Vascular; Exercise Test; Humans; Microvascular Angina; Nicorandil; Nitric Oxide; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 32925783
DOI: 10.1097/MD.0000000000022167 -
The Cochrane Database of Systematic... Sep 2020This is the second update of the review first published in 2017. Hypertension is a prominent preventable cause of premature morbidity and mortality. People with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is the second update of the review first published in 2017. Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure to below standard targets may be beneficial. This strategy could reduce cardiovascular mortality and morbidity but could also increase adverse events. The optimal blood pressure target in people with hypertension and established cardiovascular disease remains unknown.
OBJECTIVES
To determine if lower blood pressure targets (135/85 mmHg or less) are associated with reduction in mortality and morbidity as compared with standard blood pressure targets (140 to 160/90 to 100 mmHg or less) in the treatment of people with hypertension and a history of cardiovascular disease (myocardial infarction, angina, stroke, peripheral vascular occlusive disease).
SEARCH METHODS
For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to November 2019: Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982), along with the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. We applied no language restrictions.
SELECTION CRITERIA
We included RCTs with more than 50 participants per group that provided at least six months' follow-up. Trial reports had to present data for at least one primary outcome (total mortality, serious adverse events, total cardiovascular events, cardiovascular mortality). Eligible interventions involved lower targets for systolic/diastolic blood pressure (135/85 mmHg or less) compared with standard targets for blood pressure (140 to 160/90 to 100 mmHg or less). Participants were adults with documented hypertension and adults receiving treatment for hypertension with a cardiovascular history for myocardial infarction, stroke, chronic peripheral vascular occlusive disease, or angina pectoris.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed search results and extracted data using standard methodological procedures expected by Cochrane. We used GRADE to assess the quality of the evidence.
MAIN RESULTS
We included six RCTs that involved 9484 participants. Mean follow-up was 3.7 years (range 1.0 to 4.7 years). All RCTs provided individual participant data. None of the included studies was blinded to participants or clinicians because of the need to titrate antihypertensives to reach a specific blood pressure goal. However, an independent committee blinded to group allocation assessed clinical events in all trials. Hence, we assessed all trials at high risk of performance bias and low risk of detection bias. Other issues such as early termination of studies and subgroups of participants not predefined were also considered to downgrade the quality evidence. We found there is probably little to no difference in total mortality (risk ratio (RR) 1.06, 95% confidence interval (CI) 0.91 to 1.23; 6 studies, 9484 participants; moderate-quality evidence) or cardiovascular mortality (RR 1.03, 95% CI 0.82 to 1.29; 6 studies, 9484 participants; moderate-quality evidence). Similarly, we found there may be little to no differences in serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 6 studies, 9484 participants; low-quality evidence) or total cardiovascular events (including myocardial infarction, stroke, sudden death, hospitalization, or death from congestive heart failure) (RR 0.89, 95% CI 0.80 to 1.00; 6 studies, 9484 participants; low-quality evidence). The evidence was very uncertain about withdrawals due to adverse effects. However, studies suggest more participants may withdraw due to adverse effects in the lower target group (RR 8.16, 95% CI 2.06 to 32.28; 2 studies, 690 participants; very low-quality evidence). Systolic and diastolic blood pressure readings were lower in the lower target group (systolic: mean difference (MD) -8.90 mmHg, 95% CI -13.24 to -4.56; 6 studies, 8546 participants; diastolic: MD -4.50 mmHg, 95% CI -6.35 to -2.65; 6 studies, 8546 participants). More drugs were needed in the lower target group (MD 0.56, 95% CI 0.16 to 0.96; 5 studies, 7910 participants), but blood pressure targets were achieved more frequently in the standard target group (RR 1.21, 95% CI 1.17 to 1.24; 6 studies, 8588 participants).
AUTHORS' CONCLUSIONS
We found there is probably little to no difference in total mortality and cardiovascular mortality between people with hypertension and cardiovascular disease treated to a lower compared to a standard blood pressure target. There may also be little to no difference in serious adverse events or total cardiovascular events. This suggests that no net health benefit is derived from a lower systolic blood pressure target. We found very limited evidence on withdrawals due to adverse effects, which led to high uncertainty. At present, evidence is insufficient to justify lower blood pressure targets (135/85 mmHg or less) in people with hypertension and established cardiovascular disease. Several trials are still ongoing, which may provide an important input to this topic in the near future.
Topics: Antihypertensive Agents; Bias; Blood Pressure; Cardiovascular Diseases; Diastole; Humans; Hypertension; Patient Dropouts; Randomized Controlled Trials as Topic; Reference Values; Systole
PubMed: 32905623
DOI: 10.1002/14651858.CD010315.pub4 -
Ivabradine for the Therapy of Chronic Stable Angina Pectoris: a Systematic Review and Meta-Analysis.Korean Circulation Journal Sep 2020Coronary artery disease (CAD) is the number one cause of death worldwide. The I channel inhibitor ivabradine serves as second line medication for the CAD leading symptom...
BACKGROUND AND OBJECTIVES
Coronary artery disease (CAD) is the number one cause of death worldwide. The I channel inhibitor ivabradine serves as second line medication for the CAD leading symptom angina pectoris. This systematic review and meta-analysis assess the existing evidence of ivabradine in angina pectoris.
METHODS
We systematically searched MEDLINE, Embase, CENTRAL, and Web of Science (September 2019) for randomized controlled trials (RCTs) that compared ivabradine versus placebo, standard therapy (ST) or other anti-anginal drugs. Two review authors independently assessed trials for inclusion and performed data extraction. We completed a 'risk of bias' assessment for all studies and assessed quality of the trial evidence using the Grading of Recommendations Assessment, Development and Evaluation methodology. We meta-analysed data were applicable and calculated mean differences (MDs) and risk ratios using a random-effects model.
RESULTS
A total of 11 RCTs (n=16,039) were included. Compared to placebo/ST, we found significant effects on the frequency of hospitalisation in a small cohort (n=90; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.04, -0.92; p=0.04), but no effects on cardiovascular mortality (n=19,102; HR, 1.10; 95% CI, 0.94, 1.28; p=0.25) or the frequency of angina pectoris episodes (n=167; weighted MD, -1.06; 95% CI, -2.74, -0.61; p=0.21).
CONCLUSIONS
The present work makes an important contribution to optimal patient care in angina pectoris by complementing the current European Society of Cardiology guideline-recommending class IIa with evidence level B-decisively with 8 further studies.
PubMed: 32725985
DOI: 10.4070/kcj.2020.0031 -
The Cochrane Database of Systematic... May 2020An increasing body of evidence suggests that inflammation plays a key role in stroke, in particular stroke of atherosclerotic origin. Anti-inflammatory medications are a...
BACKGROUND
An increasing body of evidence suggests that inflammation plays a key role in stroke, in particular stroke of atherosclerotic origin. Anti-inflammatory medications are a widely heterogeneous group of drugs that are used to suppress the innate inflammatory pathway and thus prevent persistent or recurrent inflammation. Anti-inflammatory agents have the potential to stabilise atherosclerotic plaques by impeding the inflammatory pathway. By targeting specific cytokines, the inflammatory pathway may be interrupted at various stages.
OBJECTIVES
To assess the benefits and harms of anti-inflammatory medications plus standard care versus standard care with or without placebo for prevention of vascular events (stroke, myocardial infarction (MI), non-fatal cardiac arrest, unstable angina requiring revascularisation, vascular death) and all-cause mortality in people with a prior history of ischaemic stroke or transient ischaemic attack (TIA).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; last searched 29 May 2019); MEDLINE (1948 to 29 May 2019); Embase (1980 to 29 May 2019); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 29 May 2019); and Scopus (1995 to 29 May 2019). In an effort to identify additional published, unpublished, and ongoing trials, we searched several grey literature sources (last searched 30 May 2019). We incorporated all identified studies into the results section. We applied no restrictions with respect to language, date of publication, or study setting.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) and cluster-randomised controlled trials that evaluated anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed for inclusion titles and abstracts of studies identified by the search. Two review authors independently reviewed full-text articles for inclusion in this review. We planned to assess risk of bias and to apply the GRADE method.
MAIN RESULTS
We identified no studies that met the inclusion criteria.
AUTHORS' CONCLUSIONS
There is currently a paucity of evidence on the use of anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA. RCTs are needed to assess whether use of anti-inflammatory medications in this setting is beneficial.
Topics: Angina, Unstable; Anti-Inflammatory Agents; Heart Arrest; Humans; Ischemic Attack, Transient; Myocardial Infarction; Plaque, Atherosclerotic; Secondary Prevention; Stroke
PubMed: 32392374
DOI: 10.1002/14651858.CD012825.pub2 -
Value in Health : the Journal of the... May 2020Spinal cord stimulation (SCS) is a recognized treatment for chronic pain. This systematic review aims to assess economic evaluations of SCS for the management of all...
OBJECTIVES
Spinal cord stimulation (SCS) is a recognized treatment for chronic pain. This systematic review aims to assess economic evaluations of SCS for the management of all chronic pain conditions, summarize key findings, and assess the quality of studies to inform healthcare resource allocation decisions and future research.
METHODS
Economic evaluations were identified by searching general medical and economic databases complemented with screening of reference lists of identified studies. No restrictions on language or treatment comparators were applied. Relevant data were extracted. The quality of included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.
RESULTS
Fourteen studies met the inclusion criteria and were judged to be of acceptable quality. Economic evaluations assessed SCS for the management of refractory angina pectoris, failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), diabetic peripheral neuropathy (DPN), and peripheral arterial disease. Model-based studies typically applied a 2-stage model, i.e. decision tree followed by Markov model. Time horizon varied from 1 year to lifetime. Cost-effectiveness ranged widely from dominant (SCS cost-saving and more effective) to incremental cost-effectiveness ratio of >£100,000 per quality-adjusted life-year. Cost-effectiveness appeared to depend on the time horizon, choice of comparator, and indication. Ten of the studies indicated SCS as cost-saving or cost-effective compared with the alternative strategies.
CONCLUSION
The results consistently suggest that SCS is cost-effective when considering a long-term time horizon, particularly for the management of FBSS and CRPS. Further studies are needed to assess the cost-effectiveness of SCS for ischemic pain and DPN.
Topics: Chronic Pain; Complex Regional Pain Syndromes; Cost-Benefit Analysis; Failed Back Surgery Syndrome; Humans; Peripheral Arterial Disease; Spinal Cord Stimulation
PubMed: 32389232
DOI: 10.1016/j.jval.2020.02.005 -
The Cochrane Database of Systematic... May 2020Chelation therapy is promoted and practiced around the world as a form of alternative medicine in the treatment of atherosclerotic cardiovascular disease. It has been... (Meta-Analysis)
Meta-Analysis
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 METHODS
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.
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.
Topics: Angina Pectoris; Arteriosclerosis; Cause of Death; Chelating Agents; Chelation Therapy; Coronary Artery Disease; Edetic Acid; Humans; Myocardial Infarction; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Stroke
PubMed: 32367513
DOI: 10.1002/14651858.CD002785.pub2