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[肺动脉高压和慢性血栓栓塞性肺动脉高压现代特异性治疗的成就:聚焦可溶性鸟苷酸环化酶刺激剂利奥西呱]

[The achievements of the modern specific therapy of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: focus on the stimulator of soluble guanylate cyclase riociguat].

作者信息

Gratsianskaya S E, Valieva Z S, Martynyuk T V

机构信息

Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology.

Pirogov Russian National Research Medical University.

出版信息

Ter Arkh. 2020 Oct 14;92(9):77-84. doi: 10.26442/00403660.2020.09.000717.

Abstract

Currently, treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) is focused on three signaling pathways: the NO pathway, the endothelin pathway, and the prostacyclin pathway. Riociguat is the only representative of stimulators of the soluble guanylate cyclase (sGC) class that is approved for the treatment of PAH and inoperable and persistent/recurrent CTEPH. The review presents data from clinical trials showing a positive effect of riociguat on the functional and hemodynamic profile of patients with PAH and CTEPH. In recent years there has been much discussion about the possibility of optimizing therapy by switching to drugs that affect a single pathogenesis target. Thus, sGC stimulants have obvious advantages over phosphodiesterase type 5 (PDE-5) inhibitors, including the ability of riociguat to exert pharmacological effects (due to a NO-independent mechanism of action) even in conditions of reduced NO production. Switching from PDE-5 to riociguat may be safe and appropriate, according to clinical trials presented in the review. In accordance with the guidelines for the diagnosis and treatment of pulmonary hypertension of the Eurasian Association of cardiologists from 2019, this strategy is approved when PDE5 therapy is ineffective in patients with PAH FC III (WHO).

摘要

目前,肺动脉高压(PAH)和慢性血栓栓塞性肺动脉高压(CTEPH)的治疗主要集中在三条信号通路:一氧化氮(NO)通路、内皮素通路和前列环素通路。利奥西呱是可溶性鸟苷酸环化酶(sGC)刺激剂类中唯一被批准用于治疗PAH以及无法手术和持续性/复发性CTEPH的药物。该综述展示了临床试验数据,表明利奥西呱对PAH和CTEPH患者的功能和血流动力学状况具有积极影响。近年来,关于通过改用影响单一发病机制靶点的药物来优化治疗的可能性有诸多讨论。因此,sGC刺激剂比5型磷酸二酯酶(PDE-5)抑制剂具有明显优势,包括利奥西呱即使在NO生成减少的情况下也能发挥药理作用(由于非依赖NO的作用机制)。根据该综述中呈现的临床试验,从PDE-5转换为利奥西呱可能是安全且合适的。根据2019年欧亚心脏病学家协会肺动脉高压诊断和治疗指南,当PDE5治疗对PAH FC III(WHO)患者无效时,这种策略是被认可的。

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