Renin–angiotensin–aldosterone inhibitors in the reduction of portal pressure: A systematic review and meta-analysis

Background & Aims

Renin–angiotensin–aldosterone antagonists [ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), aldosterone antagonists (AA)] are potential therapies for portal hypertension. We evaluated the efficacy and safety of RAAS inhibitors in hepatic venous pressure gradient (HVPG) reduction.

Methods

We included full-text controlled trials in patients with cirrhosis and portal hypertension. The primary outcome was mean change in HVPG between treatment and control. Two independent reviewers performed trial selection and quality assessment. An individual patient meta-analysis based on the data of three studies was performed.

Results

From 193 citations, 19 controlled trials (n=678) were included. When compared to placebo, ARB/ACEi resulted in significant HVPG reduction. The best quality trials compared ARB/ACEi to beta-blockers (BB). Pooled individual patient data for three of four of these trials showed that BB decreased the HVPG more than ARB/ACEi. In patients with Child Pugh A cirrhosis, the HVPG reduction with ARB/ACEi (−17%; 95% CI: −28 to −6), was similar to that of BB (−21%; 95% CI: −32 to −9). Significant variation in the comparison groups of AA trials precluded pooling. There was no difference in adverse events in any group but selected studies noted adverse hemodynamic effects in decompensated patients on ARB/ACEi.

Conclusions

ARB/ACEi reduce portal pressure in patients with Child Pugh A cirrhosis without adverse events. The efficacy and safety in this group may be secondary to a targeted effect on the local hepatic RAAS system, as compared to decompensated patients who risk hypotension and renal insufficiency due to activation of the systemic RAAS. Further studies should determine the potential of these drugs as an alternative or adjunct to BB.

Abbreviations: HVPG, hepatic venous pressure gradient, BB, beta-blockers, RAAS, renin–angiotensin–aldosterone system, ARB, angiotensin receptor blockers, ACEi, angiotensin converting enzyme inhibitors, AA, aldosterone antagonists, WMD, weighted mean difference, CI, confidence interval

Keywords: Angiotensin receptor blocker, Aldosterone antagonist, ACE inhibitor, Hepatic venous pressure gradient, Portal hypertension