BACKGROUND An increasing number of patients with pulmonary arterial hypertension (PAH) have cardiovascular comorbidities. However, the effects of comorbidities on responses to PAH treatment are not well understood. RESEARCH QUESTION Do cardiovascular comorbidities in patients with PAH influence the efficacy and tolerability of inhaled or oral treprostinil? STUDY DESIGN AND METHODS All patients from phase 3 studies TRIUMPH (N = 235) and FREEDOM-EV (N = 690) were included in this post hoc analysis and were classified as having 0, ≥1, or ≥2 cardiovascular comorbidities of interest based on patients' medical histories. The mean difference in 6-minute walk distance (6MWD) and N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to Week 12 was assessed for TRIUMPH and the risk and incidence of clinical worsening was assessed for patients in FREEDOM-EV. Adverse events (AEs) were summarized for each comorbidity grouping for TRIUMPH and FREEDOM-EV. RESULTS In TRIUMPH, there were 79, 156, and 88 patients with 0, ≥1, and ≥2 comorbidities, respectively. Patients on inhaled treprostinil had improvements in 6MWD, with numerically similar improvements for comorbidity subgroups (0: 26 m, P = 0.020; ≥1: 22 m, P = 0.006; ≥2: 21.6 m, P = 0.043). Significant reductions in NT-proBNP were also seen in all subgroups. In FREEDOM-EV, there were 375, 315, and 166 patients with 0, ≥1, and ≥2 comorbidities, respectively. Regardless of comorbidities, patients on oral treprostinil had a significantly reduced risk of clinical worsening compared with placebo (0: 36% reduction, P = 0.034; ≥1: 41% reduction, P = 0.014; ≥2: 45% reduction, P = 0.026). In TRIUMPH and FREEDOM-EV, AE profiles were typical for this class of medication regardless of the number of comorbidities. A sensitivity analysis using a subset of comorbidities confirmed the findings of our primary analysis. INTERPRETATION This post hoc analysis suggests that patients with PAH and cardiovascular comorbidities can benefit from combination therapy with inhaled or oral treprostinil.

中文翻译：

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口服或吸入曲前列尼治疗肺动脉高压和心血管合并症患者。


背景 越来越多的肺动脉高压 （PAH） 患者患有心血管合并症。然而，合并症对 PAH 治疗反应的影响尚不清楚。研究问题 PAH 患者的心血管合并症会影响吸入或口服曲前列环素的疗效和耐受性吗？研究设计和方法 来自 3 期研究 TRIUMPH （N = 235） 和 FREEDOM-EV （N = 690） 的所有患者都被纳入该事后分析，并根据患者的病史被归类为具有 0、≥1 或 ≥2 种感兴趣的心血管合并症。评估 TRIUMPH 从基线到第 12 周 6 分钟步行距离 （6MWD） 和 N 末端脑钠肽前体 （NT-proBNP） 的平均差异，并评估 FREEDOM-EV 患者临床恶化的风险和发生率。总结 TRIUMPH 和 FREEDOM-EV 的每个合并症分组的不良事件 （AEs）。结果 在 TRIUMPH 中，有 79 例、 156 例和 88 例患者分别患有 0 、 ≥1 和 ≥2 合并症。吸入曲前列尼的患者在 6MWD 中有所改善，合并症亚组的改善在数值上相似 （0： 26 m， P = 0.020;≥1： 22 m， P = 0.006;≥2： 21.6 m， P = 0.043）。在所有亚组中也观察到 NT-proBNP 的显着降低。在 FREEDOM-EV 中，有 375 、 315 和 166 例患者分别患有 0 、 ≥1 和 ≥2 合并症。无论合并症如何，与安慰剂相比，口服曲前列尼的患者临床恶化的风险显著降低 （0： 减少 36%， P = 0.034;≥1： 减少 41%， P = 0.014;≥2： 减少 45%， P = 0.026）。在 TRIUMPH 和 FREEDOM-EV 中，无论合并症的数量如何，AE 谱都是这类药物的典型特征。 使用合并症子集的敏感性分析证实了我们主要分析的结果。解释 这项事后分析表明，患有 PAH 和心血管合并症的患者可以从吸入或口服曲前列尼的联合治疗中获益。