Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine (JMU), JMU Center of Excellence, Community Medicine Cardiovascular Research and Development (JCARD), Jichi, Japan.
Curr Cardiol Rep. 2018 Jan 27;20(1):5. doi: 10.1007/s11886-018-0944-4.
Sacubitril/valsartan (LCZ696) is a first-in-class, novel-acting, angiotensin receptor neprilysin inhibitor (ARNI) that provides inhibition of neprilysin and the angiotensin (AT) receptor. A recent clinical trial PRARDIGM-HF demonstrated that this drug is superior to angiotensin-converting enzyme (ACE) inhibitors for improving the prognosis in the patients with heart failure, and this has resulted in the drug being included in clinical practice guidelines for the management of heart failure with reduced ejection fraction (EF). In addition, sacubitril/valsartan has been developed for the management of hypertension, because it has unique anti-aging properties. However, the clinical evidence of mechanism has not been well validated.
A recent mechanistic study PARAMETER demonstrated that sacubitril/valsartan (LCZ696) is superior to angiotensin receptor blocker (ARB) monotherapy for reducing central aortic systolic pressure (primary endpoint) as well as for central aortic pulse pressure (secondary endpoint) and nocturnal BP preferentially. Considering these results, sacubitril/valsartan may be an attractive therapeutic agent to treat the elderly with age-related hypertension phenotypes, such as drug-uncontrolled (resistant) hypertension characterized as systolic (central) hypertension (structural hypertension) and/or nocturnal hypertension (salt-sensitive hypertension). These are the high-risk hypertension phenotypes which are prone to develop heart failure with preserved EF and chronic kidney disease. Sacubitril/valsartan may be effective to suppress the age-related continuum from hypertension to heart failure, and it could be clinically useful not only for secondary prevention, but also as primary prevention of heart failure in uncontrolled elderly hypertensive patients.
沙库巴曲缬沙坦（LCZ696）是一种首创的、新型作用的血管紧张素受体脑啡肽酶抑制剂（ARNI），可同时抑制脑啡肽酶和血管紧张素（AT）受体。最近的一项临床试验 PRARDIGM-HF 表明，该药在改善心力衰竭患者预后方面优于血管紧张素转换酶（ACE）抑制剂，这使得该药被纳入射血分数降低的心力衰竭（HFREF）管理的临床实践指南。此外，沙库巴曲缬沙坦已被开发用于治疗高血压，因为它具有独特的抗衰老特性。然而，其临床机制证据尚未得到充分验证。
最近的一项机制研究 PARAMETER 表明，与血管紧张素受体阻滞剂（ARB）单药治疗相比，沙库巴曲缬沙坦（LCZ696）更能降低主动脉收缩压（主要终点）以及主动脉脉搏压（次要终点）和夜间血压。考虑到这些结果，沙库巴曲缬沙坦可能是一种有吸引力的治疗药物，可用于治疗年龄相关性高血压表型的老年人，如药物无法控制（耐药）的高血压，其特征为收缩压（中心）升高（结构性高血压）和/或夜间高血压（盐敏感性高血压）。这些是易发生射血分数保留的心力衰竭和慢性肾脏病的高危高血压表型。沙库巴曲缬沙坦可能有效抑制高血压向心力衰竭的年龄相关进展，不仅对二级预防有临床意义，而且对未控制的老年高血压患者的心力衰竭也具有一级预防作用。
