Long-Term Safety of a Novel Angiotensin Receptor Blocker, Fimasartan, According to the Absence or Presence of Underlying Liver Disease in Korean Hypertensive Patients: A Prospective, 12-Month, Observational Study

Abstract

Purpose

Fimasartan, the ninth and most recent angiotensin receptor blocker (ARB) approved by the Korea Food and Drug Administration, has shown similar efficacy and safety profiles compared to other ARBs. However, due to being predominantly excreted by the hepatobiliary system, concerns on safety have been raised regarding its use in patients with underlying liver disease.

Patients and Methods

This prospective, 12-month, observational study evaluated patients with essential hypertension (HTN) receiving ≥1 dose of fimasartan. Self-reported and physician-reported events were recorded and classified according to organ class and severity. Outcomes were compared according to the absence and presence of underlying liver disease.

Results

A total of 601 patients were screened, and 566 patients who met predefined inclusion criteria were grouped according to the presence of underlying liver disease. Adverse events (AE) were reported in 28.7% (128/446) of patients without prior liver disease, while 42.5% (51/120) experienced events in the group with chronic liver disease. There was no difference in discontinuations due to liver function between patients with and without baseline liver disease (1.1% [5] vs 2.5% [3], p=0.376), and only a non-significant increase was observed in events associated to the hepatobiliary system in patients with chronic liver disease (9.7% [7] vs 2.7% [9], p=0.061). There were no deaths or serious adverse drug reactions (SADR) during the study period. In multivariate regression analysis, the presence of chronic liver disease (OR 2.01), female sex (OR 1.49) and old age (OR 1.12 for every 5-year increase) were independent predictors for the development of AE. Finally, no significant difference was observed in the reduction of systolic blood pressure after 12 months of treatment (least square mean change −6.57 ± 0.80 mmHg for normal liver function group; −7.65 ± 1.59 mmHg for chronic liver disease group; p=0.546).

Conclusion

Long-term use of fimasartan for treatment of HTN was associated with a low rate of adverse events overall, especially in the absence of underlying liver disease. Even for patients with chronic liver disease, fimasartan treatment was well tolerated. Fimasartan could be a safe option for long-term treatment of essential HTN. ClinicalTrials.gov identifier: NCT02385721.

Keywords:

• fimasartan
• safety
• liver disease
• essential hypertension
• hepatobiliary excretion
• adverse event

Acknowledgments

This study was sponsored by Boryung Pharmaceutical Co. Ltd (Seoul, Korea). The sponsor supported the funding source and participated in the study. The study was designed, conducted, and written by the authors. Independent external monitoring groups (CRSCube, Seoul, Korea; LSK Global PS, Seoul, Korea) were involved in the collection and analysis of data.

Data Sharing Statement

ndividual participant data that underlie the results reported in this article will be available on request, after deidentification, to researchers who provide a methodologically sound proposal. Requests should be sent to the corresponding author.

Disclosure

The authors report no conflicts of interest in this work.