POISE 2008.

Methods	RCT, parallel design
Participants	Total number of randomized participants: 8351 Inclusion criteria: undergoing non‐cardiac surgery with, or at risk of atherosclerotic disease; ≥ 45 years of age; expected length of hospital stay of ≥ 24 h; fulfilled any of the following: history coronary artery disease, peripheral vascular disease, stroke, hospitalization for congestive heart failure within previous 3 years, undergoing major vascular surgery, or any 3 of 7 risk criteria (undergoing intrathoracic or intraperitoneal surgery, history of congestive heart failure, TIA, diabetes, serum creatinine > 175 µmol/L, > 70 years of age, undergoing emergent or urgent surgery) Exclusion criteria: HR < 50 bpm; 2nd‐ or 3rd‐degree heart block; asthma; receiving beta‐blocker or physician had planned start of beta‐blocker treatment perioperatively; prior adverse reaction to beta‐blockers; CABG surgery in preceding 5 years and no cardiac ischaemia since; low‐risk surgical proceures; on verapamil; previous enrolment in POISE study Type of surgery: non‐cardiac surgery (vascular, intraperitoneal, orthopaedic and other) Baseline characteristics Intervention group (metoprolol) Age, mean (SD): 68.9 (± 10.5) years Gender, M/F: 2625/1549 History of coronary heart disease, n: 1805 History of hypertension, n: 2635 Control group (placebo) Age, mean (SD): 69.1 (± 10.4) years Gender, M/F: 2668/1509 History of coronary heart disease, n: 1784 History of hypertension, n: 2627 Country: Argentina, Australia, Brazil, Canada, China, Columbia, Cuba, Equador, El Salvador, Finland, Hong Kong, Hungary, India, Malaysia, Mexico, New Zealand, Norway, Peru, Singapore, Spain, Sweden, Thailand, UK Setting: multi‐centre; 190 hospitals in 23 countries
Interventions	Intervention group (metoprolol) Randomized, n = 4174; losses = 8; analysed, n = 4174 (ITT analysis) Details: 1st dose given 2‐4 h before surgery, oral extended‐release metoprolol 100 mg. If HR ≥ 80 bpm, and SBP 100 mmHg, within first 6 h of surgery, then 1st postoperative dose (extended‐release metoprolol 100 mg) was given, or this dose was given 6 h postoperatively, then oral extended‐release metoprolol 200 mg every day for 30 days. If oral medication could not be taken, then metoprolol was given as IV infusion Control group (placebo) Randomized, n = 4177; losses = 12; analysed, n = 4177 (ITT analysis) Details: placebo, given same as the intervention group
Outcomes	Outcomes measured/reported by study authors: cardiovascular death, non‐fatal MI, non‐fatal cardiac arrest, all‐cause mortality, hypotension (not defined), bradycardia (not defined), stroke, congestive heart failure, new‐onset AF, length of hospital stay Outcomes relevant to the review: death due to cardiac causes, non‐fatal MI, all‐cause mortality, hypotension, bradycardia, stroke, congestive heart failure, new‐onset AF, length of hospital stay (see notes below)
Notes	Funding/declarations of interest: Canadian Institutes of Health Research; Commonwealth Government of Australia's National Health and Medical Research Council; Instituto de Salud Carlos III, Spain; British Heart Foundation; AstraZeneca. No funders had any role in trial design, conduct, data collection, analyses, or data interpretation. Two authors declared receipt of research funds or fees or honoraria from AstraZeneca Study dates: October 2002‐July 2007 Note: some participants had surgery under anaesthesia other than GA. This was balanced between groups; 2482 participants (59.5%) in the metoprolol group and 2491 participants (59.6%) in the placebo group had GA we did not include outcome data in analysis for hospital length of stay, because data were reported in median (IQR) values. In the intervention group, median (IQR) length of stay was 8 (4‐14) days, and in the placebo group was 8 (4‐15) days we attempted contact with the primary study author to request data on measures of spread for the parameter length of stay and for the subset of participants receiving general anaesthesia; this was unsuccessful
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerized randomization phone service
Allocation concealment (selection bias)	Low risk	See above
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Randomized, placebo‐controlled, triple‐blind multi‐centre trial
Blinding of outcome assessors (detection bias) All outcomes	Low risk	Outcome adjudicators were masked to treatment allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Few losses and use of ITT analysis
Selective reporting (reporting bias)	Unclear risk	Retrospective clinical trial registration (NCT00182039). Not feasible to use these registration documents to assess risk of reporting bias
Other bias	Low risk	Not detected