Chin Kelly Marie, Ruggiero Rosechelle, Bartolome Sonja, Velez-Martinez Mariella, Darsaklis Konstantina, Kingman Martha, Harden Scarlet, Torres Fernando
Pulmonary and Critical Care Division, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Cardiology Division, University of Maryland Medical Center, Baltimore, Maryland, USA.
Pulm Circ. 2015 Sep;5(3):513-20. doi: 10.1086/682224.
Sustained-release oral treprostinil, an oral prostacyclin, led to significant improvement in 6-minute walk distance (6MWD) versus placebo in treatment-naive patients with pulmonary arterial hypertension (PAH) but failed to lead to significant improvement in two 16-week trials in patients receiving background PAH therapies (FREEDOM studies). Long-term studies are lacking. Our objective was to evaluate 6MWD, functional class, hemodynamics, and other long-term outcomes during oral treprostinil administration in PAH. Patients receiving oral treprostinil through the FREEDOM studies at our institution were included and were followed for up to 7 years. The primary end point was change in pulmonary vascular resistance (PVR) at first follow-up catheterization. Other end points included 6MWD, functional class, and other hemodynamic results. Thirty-seven patients received oral treprostinil for a median of 948 days, with 81%, 61%, and 47% continuing therapy at 1, 2, and 3 years, respectively. Mean treprostinil dose at 3, 12, and 24 months was 4.3 ± 2.3, 8.6 ± 3.2, and 11.7 ± 5.8 mg/24 h, respectively. Compared with pretreatment values, there was no significant change in 6MWD at 3 or 12 months, no improvement in functional class at 12 months, and no significant change in hemodynamics at the first follow-up catheterization (N = 34). Oral treprostinil dose was inversely associated with change in PVR (r = -0.42, P < 0.05), and change in PVR was numerically better among patients in the highest dosing quartile. No significant improvement in 6MWD, functional class, or hemodynamics versus pretreatment values was seen with long-term oral treprostinil therapy, potentially because of inability to achieve a clinically effective dose.
口服曲前列尼尔缓释片是一种口服前列环素，在初治肺动脉高压（PAH）患者中，与安慰剂相比，可显著改善6分钟步行距离（6MWD），但在两项针对接受PAH背景治疗患者的16周试验（FREEDOM研究）中未能带来显著改善。目前缺乏长期研究。我们的目的是评估PAH患者口服曲前列尼尔期间的6MWD、功能分级、血流动力学及其他长期结局。纳入了在我们机构通过FREEDOM研究接受口服曲前列尼尔治疗的患者，并对其进行长达7年的随访。主要终点是首次随访导管插入时肺血管阻力（PVR）的变化。其他终点包括6MWD、功能分级及其他血流动力学结果。37例患者接受口服曲前列尼尔治疗，中位时间为948天，1年、2年和3年继续治疗的患者分别为81%、61%和47%。3个月、12个月和24个月时曲前列尼尔的平均剂量分别为4.3±2.3、8.6±3.2和11.7±5.8mg/24小时。与治疗前值相比，3个月或12个月时6MWD无显著变化，12个月时功能分级无改善，首次随访导管插入时血流动力学无显著变化（N = 34）。口服曲前列尼尔剂量与PVR变化呈负相关（r = -0.42，P < 0.05），最高剂量四分位数组患者的PVR变化在数值上更好。长期口服曲前列尼尔治疗与治疗前值相比，6MWD、功能分级或血流动力学无显著改善，可能是因为无法达到临床有效剂量。
