Keogh Anne M, Jabbour Andrew, Weintraub Robert, Brown Karen, Hayward Chris S, Macdonald Peter S
Heart Lung Transplant Unit, St Vincent's Hospital, Sydney, Australia.
J Heart Lung Transplant. 2007 Nov;26(11):1079-83. doi: 10.1016/j.healun.2007.07.040. Epub 2007 Oct 24.
Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5), and has been shown to improve 6-minute walk distance (SMWD) and World Health Organization (WHO) functional class in patients with idiopathic pulmonary arterial hypertension (iPAH) and PAH associated with connective tissue disease or with repaired congenital systemic-to-pulmonary shunts. Despite the efficacy of sildenafil in patients on conventional therapy with diuretics and anti-coagulants, little is known of the safety and efficacy of transitioning patients already established on parenteral prostanoid therapy to sildenafil.
We studied 14 patients on long-term subcutaneous treprostinil for PAH (from a cohort of 51 patients [27%]), who wished to discontinue treatment because of injection-site pain. The etiology of their PAH included iPAH (7 of 14), PAH secondary to scleroderma (2 of 14), thromboembolic disease (3 of 14) and PAH post-surgical correction of ventricular septal defect (2 of 14). Treprostinil was gradually weaned and all patients were started open-label with 50 mg sildenafil four times per day for 3 months. New York Heart Association (NYHA) functional class, SMWD, echocardiogram and quality-of-life (QOL) measures were determined at baseline and after 3 months of therapy with sildenafil.
Of 14 patients, 4 discontinued the transition because of deterioration during treprostinil withdrawal, despite the introduction of sildenafil. Replacement of chronic subcutaneous treprostinil with sildenafil was possible in 10 of 14 patients (71%), who demonstrated stable NYHA class (mean +/- SD: 3.1 +/- 0.3 at baseline to 2.6 +/- 0.8 at 3 months, p = 0.138), stable SMWD (434 +/- 83 m at baseline, 451 +/- 72 at 3 months, p = 0.23) and significantly improved QOL measures at 3 months.
The transition from subcutaneous treprostinil to sildenafil was safely achieved in most (71%), but not all, patients with pulmonary arterial hypertension of varied etiology. These patients had an improvement in both NYHA functional class and QOL, and maintained stable walk distances over a 3-month period on sildenafil therapy.
西地那非是一种选择性5型磷酸二酯酶（PDE5）抑制剂，已被证明可改善特发性肺动脉高压（iPAH）以及与结缔组织病或先天性体-肺分流修复相关的肺动脉高压（PAH）患者的6分钟步行距离（SMWD）和世界卫生组织（WHO）功能分级。尽管西地那非对接受利尿剂和抗凝剂常规治疗的患者有效，但对于已经接受肠外前列腺素治疗的患者转换为西地那非治疗的安全性和有效性知之甚少。
我们研究了14例因PAH接受长期皮下注射曲前列尼尔治疗的患者（来自51例患者队列[27%]），这些患者因注射部位疼痛希望停止治疗。他们PAH的病因包括iPAH（14例中的7例）、硬皮病继发的PAH（14例中的2例）、血栓栓塞性疾病（14例中的3例）以及室间隔缺损手术后的PAH（14例中的2例）。曲前列尼尔逐渐减量，所有患者开始每日4次开放标签服用50mg西地那非，持续3个月。在基线以及西地那非治疗3个月后，测定纽约心脏协会（NYHA）功能分级、SMWD、超声心动图和生活质量（QOL）指标。
14例患者中，4例尽管开始使用了西地那非，但在曲前列尼尔撤药期间因病情恶化而停止转换治疗。14例患者中有10例（71%）成功将慢性皮下注射曲前列尼尔替换为西地那非，这些患者NYHA分级稳定（平均±标准差：基线时为3.1±0.3，3个月时为2.6±0.8，p = 0.138），SMWD稳定（基线时为434±83m，3个月时为451±72m，p = 0.23），且3个月时QOL指标显著改善。
大多数（71%）但并非所有不同病因的肺动脉高压患者都能安全地从皮下注射曲前列尼尔转换为西地那非治疗。这些患者的NYHA功能分级和QOL均有改善，且在西地那非治疗的3个月期间步行距离保持稳定。
