Hobolth 2012.

Methods	Double‐blind, parallel‐arm, multi‐centre, randomised clinical trial evaluating pre‐prevention, primary, and secondary prevention
Participants	46 participants with portal hypertension (hepatic venous pressure gradient ≥ 12 mmHg). We excluded 12 participants without varices and included 34 participants with oesophageal varices. We combined all participants in our analyses (as primary or secondary prevention) because we did not have information on previous bleeding episodes (see notes). Proportion of men: carvedilol 56.3%; propranolol 72.2% Proportion for primary prevention: carvedilol 76.2%; propranolol 70.6% Mean age: carvedilol 58.1 years; propranolol 54.4 years Proportion with: alcohol‐related cirrhosis: carvedilol 80%; propranolol 75% hepatitis B/C‐related cirrhosis: carvedilol 16%; propranolol 18% large varices: information not available (see notes). ascites: carvedilol 25%; propranolol 18%
Interventions	Type of beta‐blockers: carvedilol vs propranolol Dose of carvedilol: initially 6.25 mg, the dose was titrated to achieve a 25% reduction in heart rate; mean 14 mg ± standard deviation 7 mg Dose of propranolol: initially 80 mg, the dose was titrated to achieve a 25% reduction in heart rate; mean 122 mg ± standard deviation 64 mg Treatment duration: 3 months
Outcomes	Outcomes included in meta‐analysis: mortality, variceal bleeding, adverse events, reduction in hepatic venous pressure gradient, treatment response (gradient reduction by ≥ 20% from baseline or to < 12 mmHg), after a mean duration of 92.7 days
Country of origin	Denmark
Publication status	Full‐paper
Inclusion period	September 2003‐August 2009
Notes	Two of the review authors (LH and FB) were trial investigators. The trial included 47 participants. We did not have access to information about variceal status, bleeding or haemodynamic response for 1 participant, who we then excluded from the analyses. None of the 12 participants without varices died, experienced bleeding or serious adverse events. We did not have information about the size of the varices for any of the participants or the history of previous bleeding for 8 participants. We therefore decided to combine primary/secondary prevention in the analyses. Outcome data were not available by type of prevention.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Table of random numbers (block randomisation)
Allocation concealment (selection bias)	Low risk	Serially numbered, opaque, sealed envelopes
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding of participants and personnel
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinded outcome assessment
Incomplete outcome data (attrition bias) All outcomes	High risk	We did not have access to information about 1 participant. The published trial reports per protocol analyses. We were only able to undertake per protocol analyses for continuous outcomes
Selective reporting (reporting bias)	Low risk	Clinically relevant outcomes are described. We had access to the trial protocol.
For‐profit funding	High risk	Funding from Roche; propranolol supplied by Nycomed, Denmark and carvedilol by Roche, Switzerland.
Other bias	Low risk	No other biases identified
Overall bias assessment (mortality)	High risk	High risk of bias
Overall bias assessment (non‐mortality outcomes)	High risk	High risk of bias