BACKGROUND There is limited evidence to support treatment recommendations in patients with pulmonary arterial hypertension (PAH) and comorbidities. To investigate the impact of riociguat treatment in this patient population, we analyzed pooled data from randomized controlled trials of riociguat. METHODS This post hoc analysis included data from the PATENT-1, PATENT-2, PATENT PLUS, and REPLACE studies. Safety, efficacy (6-minute walk distance [6MWD], World Health Organization functional class [WHO-FC], and N-terminal probrain natriuretic peptide [NT-proBNP]), and COMPERA 2.0 risk status were assessed in patients with 0, 1 to 2, or 3 to 4 cardiometabolic comorbidities (obesity, systemic hypertension, diabetes mellitus, coronary artery disease) in the main phase of the studies. Safety was also assessed in the long-term extensions. RESULTS The analysis included 686 patients (riociguat, n = 440; placebo, n = 132; phosphodiesterase type 5 inhibitors [PDE5i], n = 114), of whom 55%, 39%, and 6% had 0, 1 to 2, and 3 to 4 comorbidities, respectively. In the main phase, rates and severity of adverse events (AEs) were similar in riociguat-treated patients across comorbidity subgroups. After 2 years, discontinuations of riociguat due to AEs were also similar across subgroups. Compared with placebo and PDE5i, riociguat improved 6MWD and NT-proBNP across comorbidity groups and improved WHO-FC and COMPERA 2.0 risk status in patients with 0 or 1 to 2 comorbidities. CONCLUSIONS Riociguat had an acceptable safety profile in PAH patients with cardiometabolic comorbidities. Efficacy and risk assessment results suggest that riociguat can be beneficial for patients with PAH, irrespective of the presence of comorbidities.

中文翻译：

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利奥西呱在肺动脉高压和心脏代谢合并症患者中的安全性和有效性：来自介入临床试验的数据。


背景 支持肺动脉高压 （PAH） 和合并症患者的治疗建议的证据有限。为了调查利奥西呱治疗对该患者群体的影响，我们分析了来自利奥西呱随机对照试验的汇总数据。方法 该事后分析包括来自 PATENT-1 、 PATENT-2 、 PATENT PLUS 和 REPLACE 研究的数据。在研究的主要阶段，评估了 0 、 1 至 2 或 3 至 4 种心脏代谢合并症 （肥胖、全身性高血压、糖尿病、冠状动脉疾病） 的安全性、有效性 （6 分钟步行距离 [6MWD]、世界卫生组织功能分级 [WHO-FC] 和 N 末端脑钠肽前体 [NT-proBNP]）和 COMPERA 2.0 风险状态。在长期扩展中还评估了安全性。结果 分析包括 686 例患者 （riociguat， n = 440;安慰剂， n = 132;磷酸二酯酶 5 型抑制剂 [PDE5i]，n = 114），其中 55% 、 39% 和 6% 分别有 0 、 1 至 2 和 3 至 4 种合并症。在主要阶段，各合并症亚组接受利奥西呱治疗的患者的不良事件 （AEs） 发生率和严重程度相似。2 年后，因 AE 导致的 riociguat 停药情况在亚组之间也相似。与安慰剂和 PDE5i 相比，利奥西呱改善了合并症组的 6MWD 和 NT-proBNP，并改善了 0 或 1 至 2 种合并症患者的 WHO-FC 和 COMPERA 2.0 风险状态。结论 Riociguat 在患有心脏代谢合并症的 PAH 患者中具有可接受的安全性。疗效和风险评估结果表明，无论是否存在合并症，利奥西呱都可能对 PAH 患者有益。