Summary of findings for the main comparison. Carvedilol compared to traditional, non‐selective beta‐blockers for adults with cirrhosis, portal hypertension and gastroesophageal varices.
| Carvedilol compared to traditional, non‐selective beta‐blockers for adults with cirrhosis and gastroesophageal varices | ||||||
| Patient or population: adults with cirrhosis and gastroesophageal varices Setting: outpatient Intervention: carvedilol Comparison: traditional, non‐selective beta‐blockers: propranolol (9 trials); nadolol (1 trial) | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with non‐selective beta‐blockers | Risk with carvedilol | |||||
| Mortality | Trial population | RR 0.86 (0.48 to 1.53) | 507 (7 RCTs) | ⊕⊕⊝⊝ Low1,2 | Downgraded due to bias risk (one level) and imprecision (one level) | |
| 75 per 1000 | 65 per 1000 (36 to 115) | |||||
| Upper gastrointestinal bleeding | Trial population | RR 0.77 (0.43 to 1.37) | 810 (10 RCTs) | ⊕⊝⊝⊝ Very low1,2,3 | Downgraded due to bias risk (one level), inconsistency (one level), and imprecision (one level) | |
| 180 per 1000 | 139 per 1000 (77 to 247) | |||||
| Serious adverse events | Trial population | RR 0.97 (0.67 to 1.42) | 810 (10 RCTs) | ⊕⊕⊝⊝ Low1,2 | Downgraded due to bias risk (one level) and imprecision (one level) | |
| 198 per 1000 | 191 per 1000 (123 to 289) | |||||
| Non‐serious adverse events | Trial population | RR 0.55 (0.23 to 1.29) | 596 (6 RCTs) | ⊕⊝⊝⊝ Very low1,2,3 | Downgraded due to bias risk (one level), inconsistency (one level), and imprecision (one level) | |
| 298 per 1000 | 164 per 1000 (69 to 384) | |||||
| Hepatic venous pressure gradient at end of treatment (mmHg) | The mean hepatic venous pressure gradient at end of treatment (mmHg) ranged from 10.01 to 15.20 mmHg | MD 1.75 lower (2.6 lower to 0.89 lower) | ‐ | 368 (6 RCTs) | ⊕⊕⊝⊝ Low1,2,4 | Downgraded due to bias risk (one level) and imprecision (one level) |
| Reduction in hepatic venous pressure gradient (%) | The mean reduction in hepatic venous pressure gradient (%) ranged from 19.2 to 28.3 mmHg | MD 8.02 lower (11.49 lower to 4.55 lower) | ‐ | 368 (6 RCTs) | ⊕⊕⊝⊝ Low1,2,4 | Downgraded due to bias risk (one level) and imprecision (one level) |
| Haemodynamic treatment failure | Trial population | RR 0.76 (0.57 to 1.02) | 368 (6 RCTs) | ⊕⊝⊝⊝ Very low1,2,3 | Downgraded due to bias risk (one level), inconsistency (one level), and imprecision (one level) | |
| 591 per 1000 | 449 per 1000 (337 to 603) | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
1None of the included trials were at 'low risk of bias' in the overall assessment based on the Cochrane Hepato‐Biliary domains (hbg.cochrane.org/information‐authors). 2The number of events, participants and trials were small and the confidence intervals very wide. 3Heterogeneity between studies was significant. 4The hepatic venous pressure gradient is a validated surrogate outcome reflecting the risk of bleeding and mortality.