Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Drug Des Devel Ther. 2020 Apr 3;14:1341-1349. doi: 10.2147/DDDT.S233174. eCollection 2020.
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.
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.
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).
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.
法米沙坦是韩国食品药品监督管理局批准的第九种也是最新的血管紧张素受体阻滞剂（ARB），其疗效和安全性与其他 ARB 相似。然而，由于其主要通过肝胆系统排泄，因此人们对其在患有基础肝病的患者中的安全性表示担忧。
这是一项前瞻性、12 个月、观察性研究，评估了接受≥1 剂法米沙坦治疗的原发性高血压（HTN）患者。根据器官分类和严重程度，记录并分类了患者自我报告和医生报告的事件。根据是否存在基础肝病比较了结局。
共筛选了 601 名患者，符合预先设定的纳入标准的 566 名患者根据是否存在基础肝病进行分组。无既往肝病的患者中，28.7%（128/446）报告了不良事件（AE），而慢性肝病组中，42.5%（51/120）出现了事件。无基线肝病的患者中因肝功能异常而停药的比例与有基线肝病的患者无差异（1.1%[5]与 2.5%[3]，p=0.376），在慢性肝病患者中，与肝胆系统相关的事件仅略有增加（9.7%[7]与 2.7%[9]，p=0.061）。研究期间无死亡或严重药物不良反应（SADR）发生。多变量回归分析显示，慢性肝病的存在（OR 2.01）、女性（OR 1.49）和年龄较大（每增加 5 岁，OR 1.12）是发生 AE 的独立预测因素。最后，治疗 12 个月后收缩压的降低无显著差异（肝功能正常组的最小平方均数变化为-6.57±0.80mmHg；慢性肝病组为-7.65±1.59mmHg；p=0.546）。
长期使用法米沙坦治疗 HTN 总体上不良事件发生率较低，特别是在无基础肝病的情况下。即使是慢性肝病患者，法米沙坦治疗也能很好耐受。法米沙坦可能是治疗原发性 HTN 的安全选择。ClinicalTrials.gov 标识符：NCT02385721。
