Study designs of evaluations included in the review
The inclusion criteria stated randomised controlled studies; other studies were acceptable if they involved more than 100 people. Only RCTs were identified.
Specific interventions included in the review
The inclusion criteria stated that chelation therapy had to involve repeated intravenous administration of EDTA solutions containing at least 1 g EDTA per infusion, and at least 10 infusions in total. For randomised controlled trials (RCTs), the comparators were placebos or other interventions that were not chelation therapy; for case-control studies, the comparators were matched untreated controls. Studies involving chelation therapy with agents other than EDTA were excluded.
In the IC studies, the treatment consisted of an infusion of EDTA with heparin in Ringers solution, sodium chloride or magnesium chloride. The control groups also received the additional treatments. Where specified, the treatments comprised 10 to 20 infusions over 31 days to 10 weeks. Full details of the regimens were provided in the report. In the CHD studies, the treatment consisted of EDTA in solution with other agents (further details provided) for 20 to 33 treatments. The control groups were given the same treatment, but without EDTA or isotonic saline solution. All participants also received oral multivitamins.
Participants included in the review
Participants with atherosclerosis causing peripheral arterial disease with IC, or CHD were included. Participants with atherosclerotic cerebral disease were excluded. In the included IC studies, the mean ages were between 47 and 67 years, and both men and women were included. The patients had IC and pain-free walking distances of 50 to 200 m (where given). In the included CHD studies, the participants were men and women aged 21 years or older, to 64 years. The patients had angina of effort, proven ischaemic heart disease and stable angina or angiographically confirmed CHD. Candidates for revascularisation, or those who had been treated previously with chelation therapy, were excluded.
Outcomes assessed in the review
The inclusion criteria stated a measure of effectiveness, determined using an exercise test. Studies were excluded if no objective measure of outcome was reported.
The primary outcome in the included IC studies was walking distance, as tested by Master's two-step test, a bicycle exercise test, and pain-free and maximal walking distances on a treadmill. Measurements of the differences between baseline and various time points were used, as well as comparisons of distances between treatment and placebo groups. The follow-up time was up to 6 months. Summary walking distances were calculated, together with 95% confidence intervals (CIs), for the treatment and control groups in the individual trials. The secondary outcome measures in the studies included blood-pressure measurements, subjective evaluation of patients, other physiological measures, quality of life and patient assessment of treatment.
The primary outcomes in the included CHD studies were comparisons of exercise stress testing and 'ischaemic score', in some cases, compared with baseline measures (more details in report) or measures of 'work' (increase in time of work duration). The follow-up times were 3 to 12 months. Summary 'time to ischemia' or 'work' and 95% CIs were calculated for the treatment and control groups in each study. The secondary outcomes included well-being, side-effects, laboratory measures and clinical events.
How were decisions on the relevance of primary studies made?
The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.