Carvedilol for reducing portal pressure in primary prophylaxis of variceal bleeding: a dose-response study.

Abstract

Sequential measurements of hepatic venous pressure gradient (HVPG) are used to assess the haemodynamic response to nonselective betablockers (NSBBs) in patients with portal hypertension. To assess the rates of HVPG response to different doses of carvedilol. Consecutive patients with cirrhosis undergoing HVPG-guided carvedilol therapy for primary prophylaxis of variceal bleeding between 08/2010 and 05/2015 were retrospectively included. After baseline HVPG measurement, carvedilol 6.25mg/d was administered and HVPG response (HVPG-decrease ≥20% or to ≤12mm Hg) was assessed after 3-4weeks. In case of nonresponse, carvedilol dose was increased to 12.5mg/d and a third HVPG-measurement was performed after 3-4weeks. We also assessed HVPG-response rates according to the Baveno VI consensus (HVPG decrease ≥10% or to ≤12mm Hg) and changes in systolic arterial pressure (SAP). Seventy-two patients (Child A, 37%; B, 35%; C, 28%) were included. 28 (39%) patients achieved a HVPG-decrease≥20% with carvedilol 6.25mg/d and another 10 (14%) with carvedilol 12.5mg/d. Forty (56%) patients had a HVPG decrease ≥10% with carvedilol 6.25mg/d and 24 (33%) with carvedilol 12.5mg/d. Thus, in total, a HVPG-response of ≥20% and ≥10% and was achieved in 38 (53%) and 55 (76%) and of patients respectively. Notably, 6 patients (n=4 with ascites) did not tolerate an increase to 12.5mg/d due to hypotension/bradycardia. However, none of the other patients had a SAP<90mm Hg at the final HVPG measurement. Carvedilol 12.5mg/d was more effective than 6.25mg/d in decreasing HVPG in primary prophylaxis. A total of 76% of patients achieved a HVPG-response of≥10% to carvedilol 12.5mg/d, however, arterial hypotension might occur, especially in patients with ascites.