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

Aliment Pharmacol Ther. 2018 Apr;47(8):1162-1169. doi: 10.1111/apt.14576. Epub 2018 Feb 28.

Abstract

Background: Sequential measurements of hepatic venous pressure gradient (HVPG) are used to assess the haemodynamic response to nonselective betablockers (NSBBs) in patients with portal hypertension.

Aims: To assess the rates of HVPG response to different doses of carvedilol.

Methods: 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 6.25 mg/d was administered and HVPG response (HVPG-decrease ≥20% or to ≤12 mm Hg) was assessed after 3-4 weeks. In case of nonresponse, carvedilol dose was increased to 12.5 mg/d and a third HVPG-measurement was performed after 3-4 weeks. We also assessed HVPG-response rates according to the Baveno VI consensus (HVPG decrease ≥10% or to ≤12 mm Hg) and changes in systolic arterial pressure (SAP).

Results: Seventy-two patients (Child A, 37%; B, 35%; C, 28%) were included. 28 (39%) patients achieved a HVPG-decrease ≥ 20% with carvedilol 6.25 mg/d and another 10 (14%) with carvedilol 12.5 mg/d. Forty (56%) patients had a HVPG decrease ≥10% with carvedilol 6.25 mg/d and 24 (33%) with carvedilol 12.5 mg/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 12.5 mg/d due to hypotension/bradycardia. However, none of the other patients had a SAP < 90 mm Hg at the final HVPG measurement.

Conclusion: Carvedilol 12.5 mg/d was more effective than 6.25 mg/d in decreasing HVPG in primary prophylaxis. A total of 76% of patients achieved a HVPG-response of ≥ 10% to carvedilol 12.5 mg/d, however, arterial hypotension might occur, especially in patients with ascites.

MeSH terms

  • Antihypertensive Agents / therapeutic use*
  • Carvedilol / therapeutic use*
  • Dose-Response Relationship, Drug
  • Esophageal and Gastric Varices / drug therapy*
  • Esophageal and Gastric Varices / physiopathology
  • Female
  • Gastrointestinal Hemorrhage / prevention & control*
  • Humans
  • Hypertension, Portal / drug therapy*
  • Hypertension, Portal / physiopathology
  • Male
  • Middle Aged
  • Portal Pressure / drug effects*
  • Primary Prevention
  • Retrospective Studies

Substances

  • Antihypertensive Agents
  • Carvedilol