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.


OBJECTIVE
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 ≤12 mmHg) 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 (60-90 min after drug administration) and three long-term (after 7-90 days 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.
Internal Medicine Unit, A.O. Ospedali Riuniti Villa Sofia Cervello - P.O. Vincenzo Cervello, Palermo, Italy; Endoscopy and Gastroenterology Unit, Fondazione Istituto San Raffaele Giglio, Cefalù, Italy.
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Tinè
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D'Amico
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D006439:Hemodynamics / Q000187:drug effects; D006503:Hepatic Veins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D011433:Propranolol