Abstract

Background The use of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) carries a risk of renal function deterioration in cirrhotic patients with ascites. However, whether the long-term use of ACEis/ARBs is safe in cirrhotic patients without ascites remains unknown. Methods In this nationwide cohort study, we identified 311,361 newly diagnosed cirrhotic patients between January 1997 and December 2013. To avoid indication and immortal time biases, patients receiving regular ACEi/ARB therapy, defined as the ACEi/ARB cohort, were matched to patients receiving regular calcium channel blockers (CCBs), defined as the CCB cohort, at a ratio of 1 : 1 by age, sex, and propensity scores for comorbidities and medications (2,188 patients in each cohort). Cumulative incidence rates and multivariate analyses of end-stage renal disease (ESRD) risk were adjusted for competing mortality. Results The 10-year cumulative incidence rates of ESRD were 2.32% (95% confidence interval [CI]: 1.45–3.20) in the ACEi/ARB cohort and 1.70% (95% CI: 1.03–2.36) in the CCB cohort (P = 0.610). In multivariate analyses, ACEi/ARB use was not associated with a higher risk of ESRD in cirrhotic patients (hazard ratio [HR] = 1.15; 95% CI: 0.69–1.94, P = 0.591). In the sensitivity test, the 10-year cumulative incidence rates of ESRD in cirrhotic patients with ascites were 6.50% (95% CI: 0.54–12.46) and 1.24% (95% CI: 0.00–2.71) in ACEi/ARB and CCB cohorts, respectively (P = 0.090). Conclusions Long-term ACEi/ARB use was not associated with a higher risk of ESRD in cirrhotic patients. However, the risk of ESRD tended to increase in cirrhotic patients with ascites.

Highlights

  • Portal hypertension is the main complication and prognostic marker of liver cirrhosis, and it results in gastroesophageal varices, hepatic encephalopathy, and ascites [1]

  • After propensity score matching of patients in the two cohorts who showed no differences in demographic factors, viral hepatitis B, viral hepatitis C, hypertension, diabetes mellitus, congestive heart failure, hyperlipidemia, and concomitant use of BBs, statin, metformin, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 inhibitors (COX-2), 4,376 patients (2,188 patients in each cohort) were eligible for comparison (Figure 1)

  • We identified a subgroup of cirrhotic patients with ascites (n = 1,248; 540 in the angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) cohort and 708 in the calcium channel blockers (CCBs) cohort) who met the inclusion criteria

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Summary

Introduction

Portal hypertension is the main complication and prognostic marker of liver cirrhosis, and it results in gastroesophageal varices, hepatic encephalopathy, and ascites [1]. Studies have found that irbesartan or losartan was not more effective in lowering portal pressure than BBs but, deteriorated renal function in patients with liver cirrhosis [5, 6]. The American Association for the Study of Liver Diseases (AASLD) cautions that use of angiotensin-converting enzyme inhibitors (ACEis) and ARBs in cirrhotic patients with ascites may be harmful [8]. The use of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) carries a risk of renal function deterioration in cirrhotic patients with ascites. The 10-year cumulative incidence rates of ESRD in cirrhotic patients with ascites were 6.50% (95% CI: 0.54–12.46) and 1.24% (95% CI: 0.00–2.71) in ACEi/ARB and CCB cohorts, respectively (P = 0:090). The risk of ESRD tended to increase in cirrhotic patients with ascites

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