TACT 2013.

Study characteristics
Methods	Study design: randomised, double‐blind trial Intention‐to‐treat: yes Country: USA & Canada Setting: outpatient clinics
Participants	Number randomised: N = 1708 (EDTA n = 839; placebo n = 869) Exclusions post‐randomisation: none Losses to follow up: N = 22 (EDTA n = 13; placebo n = 9) Age (mean years (range)): EDTA 65 (58.8 to 71.6); placebo 65.5 (58.7 to 72.2) Gender (M n (%)): EDTA 687 (82%); placebo 83%) Inclusion criteria: history of myocardial infarction 6 weeks or more prior to enrolment; willing to participate Exclusion criteria: women of childbearing potential, serum creatinine level > 2.0 mg/dL, platelet count < 100,000/µL, abnormal liver function studies, blood pressure > 160/100 mmHg, intolerance to chelation or vitamin components, history of chelation treatment within 5 years, planned coronary or carotid revascularisation or history of revascularisation within last 6 months, history of cigarette smoking within 3 months, active heart failure or heart failure hospitalisation within 6 months, or inability to tolerate 500 mL infusions weekly
Interventions	Participants were randomised to one of four groups: active EDTA chelation + oral high‐dose vitamin and mineral supplement; active EDTA chelation + placebo vitamin and mineral supplement; placebo chelation + oral high‐dose vitamin and mineral supplement; or placebo chelation + placebo vitamin and mineral supplement. For the purposes of this review, we combined groups 1 and 2 that were both receiving active EDTA chelation treatment. Treatment: standard multi component disodium EDTA chelation solution x 40 infusions Control: 500 mL of normal saline and 1.2% dextrose x 40 infusions During infusion phase, all participants received a daily low‐dose of vitamin B6 25 mg, zinc 25 mg, copper 2 mg, manganese 15 mg and chromium 50 µg to reduce depletion by chelation treatment. Duration of treatment: first 30 infusions occurred weekly and final 10 infusions could "occur between 2 weeks and up to 8 weeks apart". Follow‐up: total of 5 years, with quarterly telephone contact and annual clinic visits
Outcomes	Primary endpoint was a composite outcome of all cause mortality, reinfarction, stroke, coronary revascularisation, and hospitalisation for angina. Secondary endpoint was the composite of cardiovascular death, reinfarction, or stroke. Quality of life Cost‐effectiveness High‐sensitivity C‐reactive protein eGFR
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was performed using permuted blocks stratified by clinical site.
Allocation concealment (selection bias)	Low risk	Secure web‐based randomisation was performed.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	This was a double‐blind study with the blinded active chelation solution prepared by a central pharmacy. Placebo infusions were shipped with identical packaging and 2 separate placebo syringes.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	A blinded independent clinical events committee at Brigham Women's Hospital adjudicated all nonprocedural components of the primary endpoint.
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were 13 in the chelation group and 9 in the placebo group who were lost to follow‐up. Looking at the results, this may decrease confidence minimally.
Selective reporting (reporting bias)	Low risk	All stated outcomes were reported using between group analysis.
Other bias	Low risk	No other sources of bias were identified.