Department of Experimental, Diagnostic, and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
University of Giessen and Marburg Lung Center, member of German Center for Lung Research, Giessen, Germany.
J Heart Lung Transplant. 2017 May;36(5):509-519. doi: 10.1016/j.healun.2016.12.012. Epub 2016 Dec 24.
Detailed hemodynamic data from the phase III PATENT-1 study of riociguat in patients with pulmonary arterial hypertension (PAH) were investigated.
Patients with PAH who were treatment naïve or pre-treated with endothelin receptor antagonists or non-intravenous prostanoids were randomly assigned to riociguat up to 2.5 mg 3 times a day or placebo. Hemodynamic parameters were assessed at baseline and week 12.
Riociguat significantly decreased pulmonary vascular resistance in treatment-naïve (n = 221; least squares [LS] mean difference -266 dyne∙sec∙cm [95% confidence interval (CI) -357 to -175; p < 0.0001]) and pre-treated (n = 222; LS mean difference -186 dyne∙sec ∙cm [95% CI -252 to -120; p < 0.0001]) patients and significantly increased cardiac index (LS mean difference +0.7 [95% CI 0.5 to 0.8] and +0.5 [95% CI 0.3 to 0.7], respectively [both p < 0.0001]). Mean pulmonary artery pressure (p = 0.0056 and p = 0.0019 for treatment-naïve and pre-treated patients, respectively), mean arterial pressure (both p < 0.0001), and systemic vascular resistance (both p < 0.0001) were significantly reduced, and there was an increase in mixed venous oxygen saturation (p < 0.0001 and p = 0.0004, respectively). Results were similar in patients pre-treated with endothelin receptor antagonists and patients pre-treated with non-intravenous prostanoids. Improvements in 6-minute walking distance correlated very weakly with improvements in pulmonary vascular resistance (r = -0.21 [95% CI -0.30 to -0.11; p < 0.0001]) and cardiac index (r = 0.16 [95% CI 0.06 to 0.25; p < 0.0016]).
Riociguat significantly improved hemodynamic parameters in pre-treated and treatment-naïve patients with PAH.
对 riociguat 在肺动脉高压（PAH）患者的 III 期 PATENT-1 研究中的详细血液动力学数据进行了研究。
从未接受过治疗或已接受内皮素受体拮抗剂或非静脉内前列腺素治疗的 PAH 患者中随机分配至 riociguat 每日 3 次，每次 2.5mg 或安慰剂。在基线和第 12 周评估血液动力学参数。
在未接受治疗的患者（n=221；最小二乘[LS]平均差异-266 达因·秒·厘米[95%置信区间（CI）-357 至-175；p<0.0001]）和已接受治疗的患者（n=222；LS 平均差异-186 达因·秒·厘米[95%CI-252 至-120；p<0.0001]）中，riociguat 显著降低了肺血管阻力，并显著增加了心指数（LS 平均差异分别为+0.7[95%CI0.5 至 0.8]和+0.5[95%CI0.3 至 0.7]；均<0.0001）。平均肺动脉压（分别为未接受治疗和已接受治疗的患者 p=0.0056 和 p=0.0019）、平均动脉压（均<0.0001）和全身血管阻力（均<0.0001）均显著降低，混合静脉血氧饱和度升高（均<0.0001 和 p=0.0004）。在已接受内皮素受体拮抗剂治疗的患者和已接受非静脉内前列腺素治疗的患者中，结果相似。6 分钟步行距离的改善与肺血管阻力（r=-0.21[95%CI-0.30 至-0.11；p<0.0001]）和心指数（r=0.16[95%CI0.06 至 0.25；p<0.0016]）的改善呈弱相关。
Riociguat 显著改善了 PAH 患者的血液动力学参数，包括未接受治疗和已接受治疗的患者。
