Association of renin-angiotensin system inhibition with liver-related events and mortality in compensated cirrhosis

Background and aims: While renin-angiotensin system inhibition lowers the hepatic venous gradient, the effect on more clinically meaningful end points is less studied. The authors aimed to quantify the relationship between renin-angiotensin system inhibition and liver-related events (LREs) among adults with compensated cirrhosis.
Methods: In this national cohort study using the Optum database, they quantified the association between angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) use and LREs (hepatocellular carcinoma, liver transplantation, ascites, hepatic encephalopathy, or variceal bleeding) among patients with cirrhosis between 2009 and 2019. Selective beta-blocker (SBB) users served as the comparator group. Demographic and clinical features were used to calculate inverse-probability treatment weighting-weighted cumulative incidences, absolute risk differences, and Cox proportional hazard ratios.
Results: Among 4214 adults with cirrhosis, 3155 were ACE inhibitor/ARB users and 1059 were SBB users. In inverse probability treatment weighting-weighted analyses, ACE inhibitor/ARB (vs. SBB) users had lower 5-year cumulative incidence (30.6% [95% confidence interval {CI}: 27.8–33.2%] vs. 41.3% [95% CI: 34.0–47.7%]; absolute risk difference, -10.7% [95% CI: -18.1% to -3.6%]) and lower risk of LREs (adjusted hazard ratio [aHR] = 0.69; 95% CI: 0.60–0.80). There was a dose-response relationship: compared with SBB use, ACE inhibitor/ARB prescriptions ≥ 1 defined daily dose (aHR = 0.65; 95% CI: 0.56–0.76) were associated with a greater risk reduction compared with < 1 defined daily dose (aHR = 0.87; 95% CI: 0.71–1.07). Results were robust across sensitivity analyses such as comparing ACE inhibitor/ARB users with non-users and as-treated analysis.

Conclusions: In this national cohort study, angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker use was associated with significantly lower risk of liver-related events in patients with compensated cirrhosis. These results provide support for a randomized clinical trial to confirm clinical benefit.

B.P. Lee, M.D., Assistant Professor of Clinical Medicine, Division of Gastroenterology and Liver Diseases, University of Southern California, Los Angeles, CA, USA, E-Mail: brian.lee@med.usc.edu

DOI: 10.1016/j.cgh.2023.07.009

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