Mathai S C, Girgis R E, Fisher M R, Champion H C, Housten-Harris T, Zaiman A, Hassoun P M
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, 1830 East Monument Street, 5th Floor, Baltimore, MD 21205, USA.
Eur Respir J. 2007 Mar;29(3):469-75. doi: 10.1183/09031936.00081706. Epub 2006 Nov 1.
Combination therapy has been recommended for the treatment of pulmonary arterial hypertension (PAH). However, there is scant information on combination therapy after failure of monotherapy, particularly in patients with scleroderma-associated PAH (PAH-SSD). From a group of 82 consecutive patients with PAH who received initial bosentan monotherapy, a total of 13 idiopathic PAH (IPAH) and 12 PAH-SSD patients requiring additional therapy with sildenafil were studied. Sildenafil was added for clinical deterioration based upon symptoms, New York Heart Association (NYHA) classification or 6-min walk distance (6MWD). Clinical data and haemodynamics were collected at baseline. Assessments were made at 1-3-month intervals. At baseline, there were no differences in demographics, NYHA classification, haemodynamics or 6MWD between the two groups. After initiation of bosentan, both groups experienced clinical improvement but ultimately deteriorated (median time to monotherapy failure 792 versus 458 days for IPAH and PAH-SSD patients, respectively). After addition of sildenafil, more IPAH patients tended to improve in NYHA class (five out of 13 versus two out of 12) and walked further (mean difference in 6MWD 47+/-77 m versus -7+/-40 m) compared with PAH-SSD patients. In conclusion, addition of sildenafil after bosentan monotherapy failure improved New York Heart Association class and 6-min walk distance in idiopathic pulmonary arterial hypertension patients but failed to improve either parameter in scleroderma-associated pulmonary arterial hypertension patients. Additional studies are needed to assess the tolerability and efficacy of this combination in patients with scleroderma-associated pulmonary arterial hypertension.
联合治疗已被推荐用于治疗肺动脉高压（PAH）。然而，关于单一疗法失败后的联合治疗的信息很少，尤其是在硬皮病相关PAH（PAH-SSD）患者中。在一组连续接受初始波生坦单一疗法的82例PAH患者中，共研究了13例特发性PAH（IPAH）患者和12例需要西地那非辅助治疗的PAH-SSD患者。根据症状、纽约心脏协会（NYHA）分级或6分钟步行距离（6MWD），因临床病情恶化而加用西地那非。在基线时收集临床数据和血流动力学数据。每隔1 - 3个月进行一次评估。在基线时，两组在人口统计学、NYHA分级、血流动力学或6MWD方面没有差异。开始使用波生坦后，两组患者的临床症状均有改善，但最终病情恶化（IPAH和PAH-SSD患者单一疗法失败的中位时间分别为792天和458天）。与PAH-SSD患者相比，加用西地那非后，更多的IPAH患者NYHA分级有改善（13例中有5例，而12例中有2例），步行距离更远（6MWD的平均差异为47±77米，而PAH-SSD患者为 - 7±40米）。总之，波生坦单一疗法失败后加用西地那非可改善特发性肺动脉高压患者的纽约心脏协会分级和6分钟步行距离，但在硬皮病相关肺动脉高压患者中未能改善这两个参数。需要进一步的研究来评估这种联合治疗在硬皮病相关肺动脉高压患者中的耐受性和疗效。
