Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
J Am Coll Cardiol. 2012 Aug 21;60(8):768-74. doi: 10.1016/j.jacc.2012.05.004. Epub 2012 Jul 18.
The aim of this study was to evaluate the long-term safety and durability of efficacy of tadalafil for pulmonary arterial hypertension.
Tadalafil is an oral phosphodiesterase-5 inhibitor approved for PAH treatment. In the multicenter, placebo-controlled, randomized, 16-week PHIRST (Pulmonary Arterial Hypertension and Response to Tadalafil) study, tadalafil 40 mg improved exercise capacity and delayed clinical worsening.
Eligible patients from PHIRST received once-daily tadalafil 20 mg (T20 mg) or 40 mg (T40 mg) (n = 357) in the double-blind, 52-week, uncontrolled extension study (PHIRST-2); 293 patients completed PHIRST-2. Durability of efficacy was explored using the 6-min walk distance (6MWD) test. Clinical worsening and changes in World Health Organization functional class were evaluated.
The safety profile of tadalafil in PHIRST-2 was similar to that in PHIRST, with typical phosphodiesterase-5 inhibitor adverse events. The 6MWDs achieved in PHIRST for the subset of patients receiving T20 mg and T40 mg in both PHIRST and PHIRST-2 (406 ± 67 m [n = 52] and 413 ± 81 m [n = 59] at PHIRST-2 enrollment, respectively) were maintained at PHIRST-2 completion (415 ± 80 m [n = 51] and 410 ± 78 m [n = 59], respectively). Numerically fewer patients who were on T40 mg in PHIRST and PHIRST-2 experienced World Health Organization functional class deterioration (6% [n = 5]) compared with those randomized to T20 mg (9% [n = 7]) across both studies. Post hoc analyses showed that background bosentan use and higher 6MWD at PHIRST baseline were associated with fewer clinical worsening events.
Long-term treatment with tadalafil was well tolerated in patients with pulmonary arterial hypertension. In patients receiving either T20 mg or T40 mg, the improvements in 6MWD demonstrated in the 16-week PHIRST study appeared sustained for up to 52 additional weeks of treatment in PHIRST-2. (Pulmonary Arterial Hypertension and Response to Tadalafil Study; NCT00549302).
本研究旨在评估他达拉非治疗肺动脉高压的长期安全性和疗效持久性。
他达拉非是一种口服磷酸二酯酶-5 抑制剂，已被批准用于肺动脉高压的治疗。在多中心、安慰剂对照、随机、16 周的 PHIRST（肺动脉高压和对他达拉非的反应）研究中，他达拉非 40mg 改善了运动能力并延缓了临床恶化。
PHIRST 中符合条件的患者在双盲、52 周、非对照扩展研究（PHIRST-2）中接受每日一次他达拉非 20mg（T20mg）或 40mg（T40mg）（n=357）；293 名患者完成了 PHIRST-2。使用 6 分钟步行距离（6MWD）测试探索疗效的持久性。评估临床恶化和世界卫生组织功能分类的变化。
PHIRST-2 中他达拉非的安全性与 PHIRST 中的安全性相似，具有典型的磷酸二酯酶-5 抑制剂不良反应。在 PHIRST 中接受 T20mg 和 T40mg 的亚组患者在 PHIRST 和 PHIRST-2 中的 6MWD 分别为 406±67m（n=52）和 413±81m（n=59），在 PHIRST-2 完成时保持不变（分别为 415±80m[n=51]和 410±78m[n=59]）。在两项研究中，与随机接受 T20mg 的患者相比（9%[n=7]），接受 T40mg 的患者中（6%[n=5]）有较少的患者出现世界卫生组织功能分类恶化。事后分析表明，背景波生坦的使用和 PHIRST 基线时的 6MWD 较高与较少的临床恶化事件相关。
肺动脉高压患者长期接受他达拉非治疗耐受性良好。在接受 T20mg 或 T40mg 的患者中，PHIRST 研究中 16 周显示的 6MWD 改善在 PHIRST-2 的 52 周额外治疗中似乎持续存在。（肺动脉高压和对他达拉非的反应研究；NCT00549302）。
