Hill Nicholas S, Rahaghi Franck F, Sood Namita, Frey Reiner, Ghofrani Hossein-Ardeschir
Pulmonary, Critical Care, and Sleep Division, Tufts University School of Medicine, Boston, MA, USA.
Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Florida, Weston, FL, USA.
Respir Med. 2017 Aug;129:124-129. doi: 10.1016/j.rmed.2017.05.005. Epub 2017 May 15.
Riociguat is a soluble guanylate cyclase stimulator that has been approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension following pulmonary endarterectomy. Riociguat is administered using an 8-week individual dose-adjustment scheme whereby a patient initially receives riociguat 1.0 mg three times daily (tid), and the dose is then increased every 2 weeks in the absence of hypotension, indicated by systolic blood pressure measurements and symptoms, up to a maximum dose of 2.5 mg tid. The established riociguat dose-adjustment scheme allows the dose of riociguat to be individually optimized in terms of tolerability and efficacy. The majority of patients in the phase III clinical trials and their long-term extension phases achieved the maximum riociguat dose, whereas some patients remained on lower doses. There is evidence that these patients may experience benefits at riociguat doses lower than 2.5 mg tid, with improvement in exercise capacity being observed after only 2-4 weeks of treatment in the phase III studies and in the exploratory 1.5 mg-maximum patient group of PATENT-1. This review aims to provide an overview of the rationale behind the riociguat dose-adjustment scheme and examine its application to both clinical trials and real-life clinical practice.
利奥西呱是一种可溶性鸟苷酸环化酶刺激剂，已被批准用于治疗肺动脉高压、无法手术的慢性血栓栓塞性肺动脉高压或肺动脉内膜剥脱术后持续性/复发性肺动脉高压。利奥西呱采用为期8周的个体化剂量调整方案给药，即患者最初每日三次（tid）服用利奥西呱1.0毫克，然后在无低血压（通过收缩压测量和症状表明）的情况下，每2周增加一次剂量，直至最大剂量为每日三次2.5毫克。既定的利奥西呱剂量调整方案可根据耐受性和疗效对利奥西呱剂量进行个体化优化。在III期临床试验及其长期延长期中，大多数患者达到了利奥西呱最大剂量，而一些患者则维持较低剂量。有证据表明，这些患者在低于每日三次2.5毫克的利奥西呱剂量下可能会获益，在III期研究以及PATENT-1试验中探索性的1.5毫克最大剂量患者组中，治疗仅2 - 4周后即可观察到运动能力有所改善。本综述旨在概述利奥西呱剂量调整方案背后的基本原理，并探讨其在临床试验和实际临床实践中的应用。
