Sezai 2012.

Methods	RCT, parallel design
Participants	Total number of randomized participants: 101 Inclusion criteria: scheduled for CABG surgery under cardiopulmonary bypass Exclusion criteria: people with cardiogenic shock; sinus bradycardia, 2nd‐ or 3rd‐degree atrioventricular block, clinical hypothyroidism or hyperthyroidism, history of arrhythmias; undergoing off‐pump surgery Type of surgery: elective CABG Baseline characteristics Intervention group (landiolol) Age, mean (SD): 68.5 (± 9.6) years Gender, M/F: 26/8 History of MI, n: 12 History of hypertension, n: 26 Ejection fraction, mean (SD), %: 60.4 (± 10.1) History of COPD, n: 2 Preoperative use of beta‐blockers, n: 9 Intervention group (landiolol + bisoprolol) Age, mean (SD): 68.1 (± 8.2) years Gender, M/F: 26/7 History of MI, n: 16 History of hypertension, n: 26 Ejection fraction, mean (SD), %: 53.9 (± 14.5) History of COPD, n: 1 Preoperative use of beta‐blockers, n: 7 Control group (placebo) Age, mean (SD): 68.2 (± 7.5) years Gender, M/F: 30/4 History of MI, n: 13 History of hypertension, n: 28 Ejection fraction, mean (SD), %: 60.0 (± 13.6) History of COPD, n: 2 Preoperative use of beta‐blockers, n: 9 Country: Japan Setting: single centre; hospital
Interventions	Intervention group (landiolol) Randomized, n = 34; losses = 0; analysed, n = 34 (use of ITT analysis was not reported) Details: started during surgery, 5 µg/kg/min, IV, for 3 days Intervention group (landiolol + bisoprolol) Randomized, n = 33; losses = 0; analysed, n = 33 (use of ITT analysis was not reported) Details: landiolol given as above, with bisoprolol 2.5 mg/day given orally or directly to the stomach via a tube, starting on the day after surgery Control group (placebo) Randomized, n = 34; losses = 0; analysed, n = 34 (use of ITT analysis was not reported) Details: normal saline given same as the landiolol group
Outcomes	Outcomes measured/reported by study authors: AF (in 1st postoperative week); haemodynamic parameters, multiple lab parameters indicating myocardial ischaemia or inflammation, mortality, acute MI, congestive heart failure, length of hospital stay; hypotension and bradycardia leading to discontinuation of treatment (cut‐off points not defined) Outcomes relevant to the review: AF, mortality, MI, congestive heart failure; length of hospital stay; hypotension and bradycardia leading to discontinuation of treatment (cut‐off points not defined)
Notes	Funding/declarations of interest: supported by grants from the Japanese Ministry of Education, Culture, Sports, Science, and Technology; from Takeda Science Foundation; and from Nihon University School of Medicine. Study authors declare no conflicts Study dates: not reported Notes: we combined data in analysis from both intervention groups the trial was stopped early after an interim analysis for ethical reasons (occurrence of atrial fibrillation was statistically significantly less in the beta‐blocker group than in the control group, but the incidences of adverse events were not different)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomised into three groups by the lottery method'" Comment: insufficient details
Allocation concealment (selection bias)	Unclear risk	See above
Blinding of participants and personnel (performance bias) All outcomes	High risk	Medical staff were blinded for landiolol and placebo treatments but not for group that was given bisoprolol
Blinding of outcome assessors (detection bias) All outcomes	Low risk	Personnel involved in outcome measurements were blinded to study groups
Incomplete outcome data (attrition bias) All outcomes	Low risk	4 participants were excluded after randomization (off‐pump CABG, other surgery done concomitantly), however this was part of the exclusion criteria and we have not included these participants as randomized
Selective reporting (reporting bias)	Unclear risk	Study reports clinical trial registration (UMIN000002489). However, it is unclear whether the study is prospectively registered and it is not feasible to assess risk of reporting bias from these documents
Other bias	Low risk	Not detected