Survival in patients with pulmonary arterial hypertension treated with first-line bosentan
Survival in patients with pulmonary arterial hypertension treated with first-line bosentan
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DOI：
10.1111/j.1365-2362.2006.01688.x
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发表时间：
2006-09-01
影响因子：
5.5
通讯作者：
McLaughlin, V. V.
中科院分区：
文献类型：
--
作者：
McLaughlin, V. V.
背景：肺动脉高压是一种以内膜纤维化、中膜肥大和丛状病变为主要特征的肺小动脉和小动脉的破坏性疾病。如果不进行治疗，特发性(IPAH，以前称为原发性肺动脉高压，PPH)和与硬皮病(SSC)等各种其他疾病相关的PAH通常都会进展，病死率很高。目前正在寻找能够提高这些患者存活率的针对疾病的治疗方法。在短期研究中，口服双内皮素(ETA/ETB)拮抗剂波生坦已被证明可以改善运动能力、临床恶化时间、血流动力学和生活质量。材料与方法为了确定波生坦对生存的长期影响，来自两个双盲随机试验的患者及其开放标签延长治疗，用一线波生坦治疗，跟踪观察长达3年。生存数据收集于1999年9月(安慰剂对照试验中的第一名患者)至2002年12月之间。对每一位患者的生命状态进行验证。结果：(1)在169例接受一线波生坦治疗的PPH患者中，1年和2年生存率分别为96%和%，与未经治疗的1年和2年生存率分别为69%和57%。2和3年生存率分别为82%、67%和%，而未经治疗的PAH-SSc患者的登记数据分别为-45%、-35%和-28%。(3)在139例VIHO功能III级的PPH患者中，1年和2年生存率分别为97%和91%，而在5个主要转诊中心的346例患者中，1年和2年生存率分别为91%和84%。提高晚期PAH患者的存活率。
Background Pulmonary arterial hypertension (PAH) is a devastating disease of the small pulmonary arteries and arterioles, characterized by intimal fibrosis, medial hypertrophy and plexiform lesions. When untreated both the idiopathic form (IPAH, formerly termed primary pulmonary hypertension, PPH) and PAH related to various other conditions such as scleroderma (SSc) often take a progressive course with high mortality. There is ongoing search for disease-specific treatments that are able to improve survival in these patients. The oral dual endothelin (ETA/ETB) antagonist bosentan has been shown to improve exercise capacity, time to clinical worsening, haemodynamics and quality of life in short-term studies.Materials and methods To determine the long-term effects of bosentan on survival, patients from the two double-blind, randomized trials and their open-label extensions, treated with first-line bosentan, were followed for up to 3 years. Data on survival were collected between September 1999 (first patient included in the placebo-controlled trials) and December 2002. Vital status was verified in each patient. The survival cohorts of these patients were compared with either the predicted survival for each patient based on an equation from the National Institutes of Health (NIH) PPH registry or with historical controls.Results Observed survival up to 36 months was reported as a Kaplan-Meier estimate in three cohorts: (1) In 169 PPH patients treated with first-line bosentan, 1- and 2-year survival was 96% and 89%, respectively, vs. predicted untreated survival at 1 and 2 years of 69% and 57%, respectively-, (2) in 50 patients with PAH associated with SSc (PAH-SSc), 1-, 2- and 3-year survival was 82%, 67% and 64%, respectively, vs. -45%, -35% and -28%, respectively, from registry data of untreated PAH-SSc patients,- and (3) in 139 PPH patients inVIHO functional class III, 1- and 2-year survival was 97% and 91%, respectively, vs. 91 % and 84% in a historical cohort of 346 patients treated with epoprostenol in five major referral centres.Conclusions The present analyses suggest that first-line bosentan therapy, followed by the addition of other disease-specific therapies as required, improves survival in patients with advanced PAH.