Department of Biomedicine, Pharmacology, Aarhus University, Aarhus C, Denmark.
Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
Basic Clin Pharmacol Toxicol. 2018 Jan;122(1):9-18. doi: 10.1111/bcpt.12912. Epub 2017 Oct 11.
A novel antihypertensive drug, LCZ696 (Entresto®), has recently been introduced, which combines the action of an antagonist of the renin-angiotensin-aldosterone system (RAAS), effectively decreasing the blood pressure, with an inhibition of neprilysin, which is responsible for metabolizing natriuretic peptides exerting antihypertensive and antifibrotic effects. In this MiniReview, we describe the pharmacokinetics and pharmacodynamics, efficacy and side effects of the combined angiotensin receptor antagonist and neprilysin inhibitor LCZ696. We summarize the effect of LCZ696 treatment of patients suffering from hypertension and heart failure (HF) and further highlight the role of this new drug as a treatment option in the future. In the earlier stages of the treatment of patients with heart failure, LCZ696 was superior in lowering the blood pressure compared to olmesartan, while the effect on blood pressure at long-term treatment was comparable for the two drugs. The numbers of adverse effects were comparable. LCZ696 was superior to enalapril in reducing mortality, hospitalizations and HF symptoms. Adverse effects were reduced with a slower up-titrating regimen of 6 weeks. The current results are promising and suggest that LCZ696 will be a new candidate for first-line treatment of HF. However, it needs to be explored whether LCZ696 is safe in pregnant women, what are the effects of long-term LCZ696 treatment on survival and whether the antifibrotic effects can be of major benefit in, for example HF with preserved ejection fraction.
一种新型的抗高血压药物 LCZ696（Entresto®）最近被引入，它结合了肾素-血管紧张素-醛固酮系统（RAAS）拮抗剂的作用，有效降低血压，同时抑制可代谢具有降压和抗纤维化作用的利钠肽的 Neprilysin。在这篇 MiniReview 中，我们描述了联合血管紧张素受体拮抗剂和 Neprilysin 抑制剂 LCZ696 的药代动力学和药效学、疗效和副作用。我们总结了 LCZ696 治疗高血压和心力衰竭（HF）患者的效果，并进一步强调了这种新药作为未来治疗选择的作用。在心力衰竭患者的早期治疗阶段，LCZ696 降低血压的效果优于奥美沙坦，而长期治疗的血压效果两种药物相当。不良事件的数量相当。LCZ696 在降低死亡率、住院率和 HF 症状方面优于依那普利。不良反应随着 6 周的缓慢滴定方案而减少。目前的结果很有希望，表明 LCZ696 将成为 HF 一线治疗的新候选药物。然而，仍需要探讨 LCZ696 在孕妇中的安全性、长期 LCZ696 治疗对生存的影响以及抗纤维化作用是否能对射血分数保留的心力衰竭等疾病带来主要益处。
