Department of Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, 9500 Euclid Avenue, A90, Cleveland, OH, 44195, USA.
United Therapeutics, Durham, NC, USA.
Lung. 2020 Dec;198(6):933-938. doi: 10.1007/s00408-020-00402-w. Epub 2020 Nov 19.
Guidelines recommend specific treatment goals for pulmonary arterial hypertension (PAH) patients: functional class I or II, 6-min walk distance (6MWD) ≥ 380 to 440 m, normal natriuretic peptide levels, and normal right-sided invasive hemodynamics. Only observational registry data support this recommendation. Our aim was to test these goals in a large group 1 PAH cohort against long-term survival.
We analyzed the PHIRST and TRIUMPH populations (n = 563, age 53.5 ± 14.7 years, female sex 79%). The predictor variables were the treatment goals measured at the end of the placebo-controlled phase (16 and 12 weeks, respectively). The primary outcome was all-cause mortality at the end of follow-up during the open-label extension phase.
There were 73 deaths during median follow of 1072 days (range 27 to 2177). Patients who achieved a functional class I or II had better survival. Both a 6MWD ≥ 380 m and ≥ 440 m were associated with lower mortality, but survival was better in patients able to walk ≥ 440 m. The best long-term survival was achieved with functional class I or II and 6MWD ≥ 440 m. In a subset of the population, cardiac index > 2.5 L/min/m was weakly associated with better survival.
WHO functional class I or II, 6MWD ≥ 440 m and CI > 2.5 L/min/m measured 12-16 weeks after the introduction of PAH-targeted therapy are associated with better long-term survival in PAH. Best survival is observed by reaching both the functional class and the 6MWD goals.
指南建议肺动脉高压 (PAH) 患者达到特定的治疗目标：心功能 I 或 II 级、6 分钟步行距离（6MWD）≥380 至 440m、正常利钠肽水平和正常右侧有创血流动力学。目前仅观察性登记数据支持这一建议。我们的目的是在一个较大的 1 类 PAH 队列中检验这些目标与长期生存之间的关系。
我们分析了 PHIRST 和 TRIUMPH 队列（n=563，年龄 53.5±14.7 岁，女性占 79%）。预测变量为安慰剂对照阶段结束时（分别为第 16 周和第 12 周）测量的治疗目标。主要结局是在开放标签扩展阶段的随访期末全因死亡率。
中位随访 1072 天（范围 27 至 2177 天）期间有 73 例死亡。达到心功能 I 或 II 级的患者生存情况更好。6MWD≥380m 和≥440m 均与较低的死亡率相关，但能行走≥440m 的患者生存情况更好。心功能 I 或 II 级和 6MWD≥440m 时患者长期生存情况最佳。在人群的亚组中，心脏指数（CI）>2.5 L/min/m 与生存情况改善有弱相关性。
PAH 靶向治疗开始后 12-16 周测量的 WHO 心功能 I 或 II 级、6MWD≥440m 和 CI>2.5 L/min/m 与 PAH 患者的长期生存相关。同时达到心功能和 6MWD 目标可获得最佳生存。
