口服西地那非作为吸入伊洛前列素治疗重度肺动脉高压的长期辅助疗法。

Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension.

作者信息

Ghofrani Hossein A, Rose Frank, Schermuly Ralph T, Olschewski Horst, Wiedemann Ralph, Kreckel André, Weissmann Norbert, Ghofrani Stefanie, Enke Beate, Seeger Werner, Grimminger Friedrich

机构信息

Department of Internal Medicine, Pulmonary and Critical Care Medicine, University Hospital, Justus-Liebig-University Giessen, Klinikstrasse 36, 35392 Giessen, Germany.

出版信息

J Am Coll Cardiol. 2003 Jul 2;42(1):158-64. doi: 10.1016/s0735-1097(03)00555-2.

DOI:10.1016/s0735-1097(03)00555-2

PMID:12849677

Abstract

OBJECTIVES

We sought to investigate the impact of adjunct sildenafil on exercise capacity and hemodynamic parameters in patients with pulmonary arterial hypertension (PAH) who fulfilled predefined criteria of deterioration despite ongoing treatment with inhaled iloprost.

BACKGROUND

Inhaled iloprost is an effective therapy in PAH. The phosphodiesterase-5 inhibitor sildenafil exerts pulmonary vasodilation and may amplify prostanoid efficacy.

METHODS

Of 73 PAH patients receiving long-term inhaled iloprost treatment, 14 fulfilled criteria of deterioration unresponsive to conventional treatment. These patients received adjunct oral sildenafil over a period of nine to 12 months, leaving the inhalative iloprost regimen unchanged.

RESULTS

Before iloprost therapy, the baseline 6-min walking distance was 217 +/- 31 m (mean +/- SEM), with an improvement to 305 +/- 28 m within the first three months of iloprost treatment and a subsequent decline to 256 +/- 30 m after 18 +/- 4 months. Adjunct therapy with sildenafil reversed the deterioration and increased the 6-min walk distance to 346 +/- 26 m (p = 0.002, Wilcoxon test) at three months of combined therapy, with a sustained efficacy up to 12 months (349 +/- 32 m, p = 0.002). The distribution of New York Heart Association functional classes (IV/III/II) improved from September 9, 2000, before sildenafil, to January 8, 2003, after nine to 12 months with sildenafil. All hemodynamic variables changed favorably: pulmonary vascular resistance decreased from 2,494 +/- 256 before sildenafil to 1,950 +/- 128 dynes.s.cm(-5).m(2) after three months of adjunct sildenafil (p = 0.036). Two patients died of severe pneumonia during the period of combined therapy. No further serious adverse events occurred. CONCLUSIONS; In patients with severe PAH deteriorating despite ongoing prostanoid treatment, long-term adjunct oral sildenafil improves exercise capacity and pulmonary hemodynamics. A combination of prostanoids and sildenafil is an appealing concept for future treatment of pulmonary hypertension.

摘要

目的

我们试图研究辅助使用西地那非对尽管正在接受吸入伊洛前列素治疗但仍符合预先定义的病情恶化标准的肺动脉高压（PAH）患者运动能力和血流动力学参数的影响。

背景

吸入伊洛前列素是PAH的一种有效治疗方法。磷酸二酯酶-5抑制剂西地那非可使肺血管扩张，并可能增强前列腺素的疗效。

方法

在73例接受长期吸入伊洛前列素治疗的PAH患者中，14例符合对常规治疗无反应的病情恶化标准。这些患者接受了为期9至12个月的辅助口服西地那非治疗，吸入伊洛前列素治疗方案不变。

结果

在伊洛前列素治疗前，基线6分钟步行距离为217±31米（平均值±标准误），在伊洛前列素治疗的前三个月内改善至305±28米，在18±4个月后随后降至256±30米。联合使用西地那非治疗可逆转病情恶化，并在联合治疗三个月时将6分钟步行距离增加至346±26米（p = 0.002，Wilcoxon检验），持续疗效长达12个月（349±32米，p = 0.002）。纽约心脏协会功能分级（IV/III/II）的分布从2000年9月9日西地那非治疗前改善至2003年1月8日西地那非治疗9至12个月后。所有血流动力学变量均发生有利变化：肺血管阻力从西地那非治疗前的2494±256降至联合使用西地那非三个月后的1950±128达因·秒·厘米⁻⁵·米²（p = 0.036）。在联合治疗期间，两名患者死于重症肺炎。未发生进一步的严重不良事件。结论：在尽管正在接受前列腺素治疗但仍病情恶化的重度PAH患者中，长期辅助口服西地那非可改善运动能力和肺血流动力学。前列腺素与西地那非联合使用是未来肺动脉高压治疗的一个有吸引力的概念。