Benza Raymond L, Rayburn Barry K, Tallaj Jose A, Pamboukian Salpy V, Bourge Robert C
Department of Medicine, Division of Cardiovascular Diseases, University of Alabama at Birmingham, 321 THT, 1900 University Blvd, Birmingham, AL 35294, USA.
Chest. 2008 Jul;134(1):139-45. doi: 10.1378/chest.07-2111. Epub 2008 Apr 10.
Treprostinil, a long-acting prostacyclin analog, diminished the symptoms of pulmonary arterial hypertension (PAH) in controlled 12-week clinical efficacy studies. This retrospective, single-center, open-label study was designed to assess the efficacy of long-term, subcutaneously administered, treprostinil-based therapy alone or in combination with bosentan for the treatment of moderate-to-severe PAH.
Thirty-eight patients with pulmonary hypertension treated with subcutaneous treprostinil were followed up for a mean (+/-SD) duration of 984+/-468 days (range, 165 to 1,847 days). Oral bosentan was added to the treprostinil regimen if patients remained in New York Heart Association (NYHA) functional class III or II with intolerable prostacyclin side effects that limited therapy. Hemodynamic studies, Borg dyspnea score evaluations, 6-min walk (6MW) tests, and NYHA functional class determinations were performed at approximately 6-month intervals.
Mean pulmonary artery pressure decreased from 59.7 to 50.5 mm Hg (p<0.001). Significant and sustained improvement in 6MW distance (p=0.022) and Borg dyspnea score (p=0.023) were observed. At the final observation, the mean dose of treprostinil was 37.8 ng/kg/min (range, 7.5 to 115 ng/kg/min). At baseline, 5% of patients were in NYHA functional class 2 or lower vs 58% at the last follow-up. Bosentan was added to the regimens of 19 patients. In those patients, significant additional improvement occurred in the pulmonary arterial pressure (p<0.001), 6MW distance (p=0.001), and Borg dyspnea scale (p=0.020) compared to baseline.
Long-term treatment with subcutaneous treprostinil-based therapy improved functional parameters and hemodynamics in patients with moderate-to-severe PAH. In patients requiring combination therapy, the addition of oral bosentan to treprostinil-based therapy was safe, well-tolerated, and associated with further clinical improvements.
在为期12周的对照临床疗效研究中，长效前列环素类似物曲前列尼尔减轻了肺动脉高压（PAH）的症状。这项回顾性、单中心、开放标签研究旨在评估长期皮下注射曲前列尼尔单药治疗或联合波生坦治疗中重度PAH的疗效。
38例接受皮下曲前列尼尔治疗的肺动脉高压患者，平均随访时间为984±468天（范围165至1847天）。如果患者仍处于纽约心脏协会（NYHA）功能分级III或II级，且因难以耐受的前列环素副作用而限制治疗，则在曲前列尼尔治疗方案中添加口服波生坦。大约每6个月进行一次血流动力学研究、Borg呼吸困难评分评估、6分钟步行（6MW）测试和NYHA功能分级测定。
平均肺动脉压从59.7 mmHg降至50.5 mmHg（p<0.001）。观察到6MW距离（p=0.022）和Borg呼吸困难评分（p=0.023）有显著且持续的改善。在最后一次观察时，曲前列尼尔的平均剂量为37.8 ng/kg/min（范围7.5至115 ng/kg/min）。基线时，5%的患者处于NYHA功能分级2级或更低，而在最后一次随访时这一比例为58%。19例患者的治疗方案中添加了波生坦。与基线相比，这些患者的肺动脉压（p<0.001）、6MW距离（p=0.001）和Borg呼吸困难量表（p=0.020）有显著的进一步改善。
长期皮下注射曲前列尼尔治疗可改善中重度PAH患者的功能参数和血流动力学。在需要联合治疗的患者中，在基于曲前列尼尔的治疗方案中添加口服波生坦是安全的，耐受性良好，且与进一步的临床改善相关。
