Systematic review with meta-analysis: the haemodynamic effects of carvedilol compared with propranolol for portal hypertension in cirrhosis

Background Propranolol is recommended for prophylaxis of variceal bleeding in cirrhosis. Carvedilol is a nonselective beta-blocker with a mild anti-alfa-1-adrenergic activity. Several studies have compared carvedilol and propranolol, yielding inconsistent results. Aim To perform a systematic review and meta-analysis of the randomised clinical trials comparing carvedilol with propranolol for hepatic vein pressure gradient reduction. Methods Studies were searched on the MEDLINE, EMBASE and Cochrane library databases up to November 2013. The weighted mean difference in percent hepatic vein pressure gradient reduction and the relative risk of failure to achieve a hemodynamic response (reduction >= 20% of baseline or to <= 12mmHg) with each drug were used as measures of treatment efficacy. Results Five studies (175 patients) were included. Indication to treatment was primary prophylaxis of variceal bleeding in 76% of patients. There were overall three acute (60-90min after drug administration) and three long-term (after 7-90days of therapy) comparisons. The summary mean weighted difference in % of reduction in hepatic vein pressure gradient was: acute -7.70 (CI -12.40, -3.00), long-term -6.81 (CI -11.35, -2.26), overall -7.24 (CI -10.50, -3.97), favouring carvedilol. The summary relative risk of failure to achieve a hemodynamic response with carvedilol was 0.66 (CI 0.44, 1.00). Adverse events were nonsignificantly more frequent and serious with carvedilol. However, quality of trials was mostly unsatisfactory. Conclusions Carvedilol reduces portal hypertension significantly more than propranolol. However, available data do not allow a satisfactory comparison of adverse events. These results suggest a potential for a cautious clinical use.