Riociguat

肺高压是一种进行性、致死性疾病,其特征是肺动脉压升高,导致血管重构、右心肥大和心衰.研究表明,肺高压与内源性血管扩张剂NO的产生受损有关.Riociguat是首个新一类可溶性鸟苷酸环化酶(sGC)激动剂,它直接刺激sGC,增强其对低水平NO的敏感度.目前应用本品对肺动脉高压(PAH)患者进行Ⅲ期临床、对慢性血栓栓塞性肺高压(CTEPH)患者进行II期临床研究,表明疗效好,易耐受,不良反应轻微.     

Riociguat for the treatment of pulmonary hypertension: a safety evaluation

ABSTRACT

Introduction: The development of pulmonary hypertension (PH) has multifactorial underlying pathophysiological causes and can be classified into five groups. While three different classes of therapeutic drugs are licensed for the treatment of pulmonary arterial hypertension (PAH, WHO group 1), specific medical therapies are lacking for other forms of PH, such as PH due to left heart disease. In 2013 riociguat, a first-in class soluble guanylate cyclase stimulator, has also become available for the treatment of PAH. Riociguat was further introduced as the first approved pharmacotherapy for the treatment of patients with chronic thromboembolic PH (WHO group 4, CTEPH). Despite these advances in therapeutic options for patients with PH, none of these agents have been approved for the treatment of PH due to left heart disease.

Areas covered: We aim to give an overview of the pathophysiology of PH, pharmacodynamics and pharmacokinetic properties, safety and efficacy of riociguat, including adverse events, contraindications and drug interactions.

Expert opinion: Considering the increasingly broad indications for riociguat in patients with PH, substantial knowledge of data and properties on safety and efficacy of riociguat are becoming more and more important for physicians prescribing riociguat to PH patients.     

Treatment of pulmonary hypertension with riociguat: a review of current evidence and future perspectives

ABSTRACT

Introduction

Pulmonary arterial hypertension (PAH) is still a chronic disorder characterized by high morbidity and mortality. Chronic thromboembolic pulmonary hypertension (CTEPH) is another form of pulmonary hypertension (PH) for which pulmonary endarterectomy (PEA) is the treatment of choice. However, not all patients are operable, while PH is often recurrent or persistent. Thus, for both disorders novel treatment options are urgently needed.     

Riociguat

肺高压是一种进行性、致死性疾病,其特征是肺动脉压升高,导致血管重构、右心肥大和心衰.研究表明,肺高压与内源性血管扩张剂NO的产生受损有关.Riociguat是首个新一类可溶性鸟苷酸环化酶(sGC)激动剂,它直接刺激sGC,增强其对低水平NO的敏感度.目前应用本品对肺动脉高压(PAH)患者进行Ⅲ期临床、对慢性血栓栓塞性肺...     

Safety and efficacy of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis

BACKGROUND The utility of novel oral soluble guanylate cyclase(s GC) stimulators(vericiguat and riociguat), in patients with reduced or preserved ejection fraction heart failure(HFr EF/HFp EF) is currently unclear.AIM To determine the efficacy and safety of s GC stimulators in HF patients.METHODS Multiple databases were searched to identify relevant randomized controlled trials(RCTs). Data on the safety and efficacy of s GC stimulators were compared using relative risk ratio(RR) on a random effect model.RESULTS Six RCTs, comprising 5604 patients(2801 in s GC stimulator group and 2803 placebo group) were included. The primary endpoint(a composite of cardiovascular mortality and first HF-related hospitalization) was significantly reduced in patients receiving s GC stimulators compared to placebo [RR 0.92, 95% confidence interval(CI): 0.85-0.99, P = 0.02]. The incidence of total HF-related hospitalizations were also lower in s GC group(RR 0.91, 95%CI: 0.86-0.96, P = 0.0009), however, s GC stimulators had no impact on all-cause mortality(RR 0.96, 95%CI: 0.86-1.07, P = 0.45) or cardiovascular mortality(RR 0.94, 95%CI: 0.83-1.06,P= 0.29). The overall safety endpoint(a composite of hypotension and syncope) was also similar between the two groups(RR 1.50, 95%CI: 0.93-2.42, P = 0.10). By contrast, a stratified subgroup analysis adjusted by type of s GC stimulator and HF(vericiguat vs riociguat and HFr EF vs HFp EF) showed near identical rates for all safety and efficacy endpoints between the two groups at a mean follow-up of 19 wk. For the primary composite endpoint, the number needed to treat was 35, the number needed to harm was 44.CONCLUSION The use of vericiguat and riociguat in conjunction with standard HF therapy, shows no benefit in terms of decreasing HF-related hospitalizations or mortality.     

基于FDA不良事件报告系统的利奥西呱不良事件信号挖掘与分析

目的：挖掘和分析利奥西呱上市后的不良事件信号，为临床安全合理用药提供参考。方法：将FDA不良事件报告系统中2013年10月1日 ~ 2022年12月31日的原始数据导入SAS 9.4软件，采用报告比值比法以及英国药品和保健产品管理局综合标准法对利奥西呱不良事件信号进行挖掘，分层分析考察不同性别、年龄和体重的人群服用利奥西呱发生不良事件的差异。结果：以利奥西呱为主要可疑药物的不良事件报告共计10 528份，不良事件发生的中位时间为183 d。共挖掘出305个不良事件信号，涉及20个系统和器官分类，发生频次较高的不良事件信号与药品说明书基本一致。说明书未记载的不良事件包括肠道梗阻、食管炎、反应迟缓、听觉障碍等。女性患者出现头痛、心悸和颌骨疼痛的概率显著高于男性，而男性患者发生咯血的概率显著高于女性。18 ~ 64岁的患者发生头痛、心悸、颌骨疼痛和咯血概率显著高于64岁以上患者，而后者出现外周水肿（肿胀）、舒张压降低和贫血的概率显著增加。结论：临床使用利奥西呱时，应关注性别和年龄对不良事件的影响，以及说明书未载入的不良事件，加强药学监护。     

Riociguat

肺高压是一种进行性、致死性疾病，其特征是肺动脉压升高，导致血管重构、右心肥大和心衰。研究表明，肺高压与内源性血管扩张剂NO的产生受损有关。Riociguat是首个新一类可溶性鸟苷酸环化酶（sGC）激动剂，它直接刺激sGC，增强其对低水平NO的敏感度。目前应用本品对肺动脉高压（PAH）患者进行III期临床、对慢性血栓栓塞性肺高压（CTEPH）患者进行II期临床研究，表明疗效好，易耐受，不良反应轻微。