Department of Medicine, University of California at San Diego, La Jolla, CA.
Department of Medicine, University of Colorado Denver, Denver, CO.
Chest. 2011 Nov;140(5):1274-1283. doi: 10.1378/chest.10-0969. Epub 2011 May 5.
The long-term safety and tolerability of sildenafil treatment of pulmonary arterial hypertension (PAH) were assessed.
Two hundred fifty-nine of 277 randomized and treated patients completed a 12-week, double-blind, placebo-controlled trial (SUPER-1 [Sildenafil Use in Pulmonary Arterial Hypertension]) of oral sildenafil in treatment-naive patients with PAH (96% functional class II/III) and entered an open-label uncontrolled extension study (SUPER-2) that continued until the last patient completed 3 years of sildenafil treatment. Patients titrated to sildenafil 80 mg tid; one dose reduction for tolerability was allowed during the titration phase.
The median duration of sildenafil treatment across SUPER-1 and SUPER-2 was 1,242 days (range, 1-1,523 days); 170 patients (61%) completed both studies, and 89 patients discontinued from SUPER-2. After 3 years, 87% of 183 patients on treatment were receiving sildenafil 80 mg tid. Of patients remaining under follow-up, 3%, 10%, and 18% were receiving a second approved PAH therapy at 1, 2, and 3 years, respectively. At 3 years post-SUPER-1 baseline, 127 patients had an increased 6-min walk distance (6MWD); 81 improved and 86 maintained functional class. Most adverse events were of mild or moderate severity. At 3 years, 53 patients had died (censored, n = 37). Three-year estimated survival rate was 79%; if all censored patients were assumed to have died, 3-year survival rate was 68%. No deaths were considered to be treatment related.
Long-term treatment of PAH initiated as sildenafil monotherapy was generally well tolerated. After 3 years, the majority of patients (60%) who entered the SUPER-1 trial improved or maintained their functional status, and 46% maintained or improved 6MWD.
评估了西地那非治疗肺动脉高压（PAH）的长期安全性和耐受性。
277 名随机和治疗的患者中有 259 名完成了一项为期 12 周的、双盲、安慰剂对照的口服西地那非治疗初治 PAH 患者（96%为功能分级 II/III）的试验（SUPER-1[Sildenafil Use in Pulmonary Arterial Hypertension]），并进入了一项开放标签的无对照扩展研究（SUPER-2），该研究一直持续到最后一名患者完成 3 年的西地那非治疗。患者滴定至西地那非 80mg，tid；在滴定阶段允许一次剂量减少以耐受。
SUPER-1 和 SUPER-2 中西地那非的中位治疗时间为 1242 天（范围为 1-1523 天）；170 名患者（61%）完成了两项研究，89 名患者从 SUPER-2 中退出。3 年后，183 名接受治疗的患者中有 87%接受西地那非 80mg，tid。在继续接受随访的患者中，分别有 3%、10%和 18%在 1、2 和 3 年后接受了第二种批准的 PAH 治疗。在 SUPER-1 基线后 3 年，127 名患者的 6 分钟步行距离（6MWD）增加；81 名患者改善，86 名患者保持功能分级。大多数不良事件为轻度或中度。3 年后，53 名患者死亡（删失，n=37）。3 年估计生存率为 79%；如果所有删失患者均假定死亡，则 3 年生存率为 68%。没有死亡被认为与治疗有关。
作为单药治疗起始的 PAH 的长期治疗通常具有良好的耐受性。3 年后，大多数进入 SUPER-1 试验的患者（60%）改善或保持了他们的功能状态，46%保持或改善了 6MWD。
