Yang 2006.

Methods	RCT, parallel design
Participants	Total number of randomized participants: 496 Inclusion criteria: scheduled for abdominal aortic surgery, infra‐inguinal or extra‐anatomical revascularization, ASA status ≤ III Exclusion criteria: current or recent beta‐blocker use, current amiodarone use, airflow obstruction requiring treatment, history of congestive heart failure, history of atrioventricular block, previous adverse drug reactions to beta‐blockers, previous participation in the MaVS study Type of surgery: abdominal aortic surgery, infrainguinal or extra‐anatomical revascularization Baseline characteristics Intervention group (metoprolol) Age, mean (SD): 66.4 (± 10) years Gender, M/F: 193/53 ASA status I/II/III/unknown: 1/92/152/1 History of MI, n: 37 Control group (placebo) Age, mean (SD): 65.9 (± 10) years Gender, M/F: 184/66 ASA status I/II/III: 0/91/159 History of MI, n: 30 Country: Canada Setting: multi‐centre; hospital
Interventions	Intervention group (metoprolol) Randomized, n = 246; losses = unclear (see notes below); analysed, n = 246 (use of ITT analysis) Details: metoprolol (dose between 25 mg and 100 mg according to body weight) started 2 h pre‐operatively and continued IV (1 mg/mL) every 6 h or orally twice daily until hospital discharge or a maximum of 5 days postoperatively Control group (placebo) Randomized, n = 250; losses = unclear (see notes below); analysed, n = 250 (use of ITT analysis) Details: placebo given same as the intervention group
Outcomes	Outcomes measured/reported by study authors: MI (non‐fatal), unstable angina, new congestive heart failure, dysrhythmias, all‐cause mortality (30 days and 6 months), death due to cardiac causes, hypotension (SBP < 90 mmHg), bradycardia (HR < 50 bpm), cerebrovascular event, bronchospasm Outcomes relevant to the review: MI (non‐fatal), new congestive heart failure, all‐cause mortality (30 days), death due to cardiac causes, hypotension, bradycardia, cerebrovascular event
Notes	Funding/declarations of interest: funded by the Heart and Stroke Foundation of Canada Study dates: 1999‐2002 Notes: some participants did not undergo GA, but had regional or combined regional with GA. This was balanced between groups; 12.7% of participants in the metoprolol group and 14.8% of those in the placebo group received regional anaesthesia only we did not report mortality data at 6 months because data were reported unclearly study also known as the MaVS study
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was constructed in blocks of four by the study statistician and study medication preparations by the pharmacists"
Allocation concealment (selection bias)	Low risk	See above
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Randomized, placebo‐controlled, double‐blind trial
Blinding of outcome assessors (detection bias) All outcomes	Unclear risk	Not specified
Incomplete outcome data (attrition bias) All outcomes	High risk	We could not be certain of loss of participants (study authors reported discontinuation of treatment in 12% placebo group participants, and 13% metoprolol group participants). Study authors reported use of ITT
Selective reporting (reporting bias)	Unclear risk	Study authors did not report prospective clinical trial registration or publication of a protocol. It was not feasible to effectively assess risk of reporting bias
Other bias	High risk	Although use of beta‐blockers was discouraged, study authors reported that 24 participants in the control group and 14 participants in the intervention group were given additional beta‐blockers. This may influence outcome data for this review