J Korean Med Sci.  2022 Aug;37(33):e255. 10.3346/jkms.2022.37.e255.

Incidence and Pattern of Aminotransferase Elevation During Anti-Hypertensive Therapy With Angiotensin-II Receptor Blockers

Affiliations
  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • 2Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, Korea

Abstract

Background
Angiotensin type II receptor blockers (ARBs) are the most widely used antihypertensive drugs. This study aimed to elucidate the likelihood and pattern of ARB-induced liver injury in a hospital-based cohort.
Methods
Data of patients receiving fimasartan (n = 5,543), candesartan (n = 6,406), valsartan (n = 6,040), and losartan (n = 9,126) were retrieved from the clinical data warehouse of two tertiary hospitals. Patients with alanine aminotransferase (ALT) levels > 5 times the upper normal limit were assessed according to the Roussel Uclaf Causality Assessment Method (RUCAM).
Results
A total of 27,115 patients were enrolled, including 14,630 (54.0%) men, with a mean age of 64.6 years (standard deviation, 13.6). During 31,717 person-years of ARB therapy, serum ALT levels > 120 IU/L were found in 558 (2.1%) person-years, and levels > 200 IU/L were found in 155 (0.6%) person-years. The incidence of ALT elevation > 120 IU/L per 10 6 cumulative defined daily doses was 6.6, 3.6, 3.9, and 4.0 in the fimasartan, candesartan, valsartan, and losartan groups, respectively (P = 0.002). An ALT level > 200 IU/L with RUCAM score ≥ 6 was found in 20 patients, suggesting probable drug-induced liver injury for 11 (0.2%) patients receiving fimasartan, five (0.1%) receiving candesartan, four (0.1%) receiving valsartan, and none receiving losartan (P < 0.001).
Conclusion
Approximately 2% of patients receiving ARB therapy had significant ALT elevation (4.24/10 6 cumulative defined daily doses [cDDDs]), which was associated with probable ARB-related liver injury in 0.07% of patients (0.15/10 6 cDDDs). Elevation of ALT was more commonly associated with fimasartan than the other ARBs. Clinicians should be aware of the possibility of ARB-related ALT elevation in patients with unexplained chronic abnormal ALT.

Keyword

Chemical and Drug Induced Liver Injury; Angiotensin II Type 2 Receptor Blockers; Alanine Transaminase; Liver Function Tests; Fimasartan

Figure

  • Fig. 1 Flowchart of patient selection.ARB = angiotensin type II receptor blocker, ALT = alanine aminotransferase, UNL = upper normal limit (40 IU/L), RUCAM = Roussel Uclaf Causality Assessment Method.


Cited by  1 articles

Are Angiotensin II Receptor Blockers Really Safe From Aminotransferase Elevation or Drug-Induced Liver Injury?
Byoung Kuk Jang
J Korean Med Sci. 2022;37(33):e261.    doi: 10.3346/jkms.2022.37.e261.


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