Capital‐RCT 2018.

Study characteristics
Methods	Multi‐centre randomised controlled trial at 67 centres in Japan between August 2010 and May 2014
Participants	Patients > 18 years old who underwent primary PCI within 24 hours after onset of STEMI successfully and had preserved left ventricular ejection fraction (LVEF > 40%) as assessed by echocardiography were included in the trial within 7 days Male:female = 639:155 Mean age = 64 years old Exclusion criteria: reduced LVEF (LVEF < 40%), prior cardioverter‐defibrillator implantation, contraindications to beta‐blocker therapy such as unstable haemodynamic status, bradyarrhythmias, symptomatic HF, severe bronchial asthma and/or chronic obstructive lung disease
Interventions	Experimental group: carvedilol (oral, maximal dose of 20 mg) Control group: no intervention other than the co‐intervention Co‐intervention: administration of other standard medications for STEMI patients such as aspirin, thienopyridines, statins, and inhibitors of the renin‐angiotensin system were left to the physician's decision Excluded medication: not reported
Outcomes	Primary: composite of all‐cause death, myocardial infarction, hospitalisation for acute coronary syndrome (ACS), and hospitalisation for HF Secondary outcomes: individual components of the primary endpoint as well as cardiac death, non‐cardiac death, stroke, vasospastic angina, major bleeding, definite stent thrombosis (ST), target‐lesion revascularisation (TLR), and any coronary revascularisation. 3 composite endpoints including cardiac death/MI/ACS/HF, cardiovascular death/MI/stroke, and death/MI/stroke/ACS/HF/any coronary revascularisation Time points reported: at 3 months, 1 year, and 3.9 years of follow‐up
Notes	Study author was contacted at taketaka@kuhp.kyoto‐u.ac.jp on 28 February 2021 to clarify the definition of myocardial infarction used in the study. According to the study author, the definition of myocardial infarction included both fatal and non‐fatal cases; however, in reality, there were no fatal myocardial infarctions. Hence, reported myocardial infarction included only non‐fatal myocardial infarction cases Participants were randomised within 1 to 7 days after their successfully performed primary PCI; hence, beta‐blockers were administered to stabilised patients in the non‐acute phase following acute myocardial infarction MACE was not reported in accordance with our definition; however, after study authors clarified the outcome 'myocardial infarction' as reported in the study representing only non‐fatal myocardial infarction, we calculated and reported MACE as a composite of non‐fatal reinfarction + cardiac death Study was supported by an educational grant from the Research Institute for Production Development (Kyoto, Japan) ClinicalTrials.gov Identifier: NCT01155635
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was performed centrally through the electronic data capture system with a stochastic minimisation algorithm to balance treatment assignment
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	Low risk	An independent clinical event committee adjudicated both primary and secondary endpoints in a fashion blinded to the assigned treatment group
Incomplete outcome data (attrition bias) All outcomes	Low risk	29 participants in total were lost to follow‐up without further description. However, this was less than 5% of the total number of participants included in the analysis
Selective reporting (reporting bias)	Low risk	Registered at clinicaltrials.gov before randomisation (NCT01155635). All outcomes in the protocol are mentioned in the paper
Other bias	Unclear risk	Trial was prematurely terminated due to slow enrolment, which could lead to bias