Inhaled iloprost for severe pulmonary hypertension
Inhaled iloprost for severe pulmonary hypertension
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DOI：
10.1056/nejmoa020204
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发表时间：
2002-08-01
影响因子：
158.5
通讯作者：
Seeger, W
中科院分区：
文献类型：
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作者：
Olschewski, H;Simonneau, G;Seeger, W
背景非对照研究表明，雾化吸入的伊洛前列素，前列环素的稳定类似物，导致选择性肺血管舒张，改善肺动脉高压患者的血流动力学和运动能力。方法我们比较了每天重复吸入2.5或5.0 μ g伊洛前列素（每天6或9次;平均吸入剂量，每天30 μ g）与吸入安慰剂。共纳入203例患有选定形式的重度肺动脉高压和慢性血栓栓塞性肺动脉高压（纽约心脏协会[NYHA]功能III或IV级）的患者。如果在第12周后，NYHA分级和6分钟步行距离分别改善至少1级和至少10%，并且根据预定标准没有临床恶化和死亡，则满足主要终点。而接受安慰剂治疗的患者中有4.9%的人有此反应（P = 0.007）。伊洛前列素组6分钟步行距离总体增加36.4 m（P = 0.004），原发性肺动脉高压患者亚组增加58.8 m。总体而言，伊洛前列素组4.0%的患者（包括1例死亡）和安慰剂组13.7%的患者（包括4例死亡）没有完成研究（P = 0.024）;退出的最常见原因是临床恶化。与基线值相比，吸入伊洛前列素后12周的血流动力学值显著改善（P <0.001），吸入伊洛前列素前血流动力学值基本不变，安慰剂组血流动力学值显著恶化。伊洛前列素治疗的其他显著有益作用包括NYHA分级（P = 0.03）、呼吸困难（P = 0.015）和生活质量（P = 0.026）的改善。晕厥发生的频率在两组相似，但更频繁地被评为严重的伊洛前列素组，虽然这种不良反应是不相关的临床恶化。结论吸入伊洛前列素是一种有效的治疗重度肺动脉高压患者。
Background Uncontrolled studies suggested that aerosolized iloprost, a stable analogue of prostacyclin, causes selective pulmonary vasodilatation and improves hemodynamics and exercise capacity in patients with pulmonary hypertension.Methods We compared repeated daily inhalations of 2.5 or 5.0 mug of iloprost (six or nine times per day; median inhaled dose, 30 mug per day) with inhalation of placebo. A total of 203 patients with selected forms of severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (New York Heart Association [NYHA] functional class III or IV) were included. The primary end point was met if, after week 12, the NYHA class and distance walked in six minutes were improved by at least one class and at least 10 percent, respectively, in the absence of clinical deterioration according to predefined criteria and death.Results The combined clinical end point was met by 16.8 percent of the patients receiving iloprost, as compared with 4.9 percent of the patients receiving placebo (P = 0.007). There were increases in the distance walked in six minutes of 36.4 m in the iloprost group as a whole (P = 0.004) and of 58.8 m in the subgroup of patients with primary pulmonary hypertension. Overall, 4.0 percent of patients in the iloprost group (including one who died) and 13.7 percent of those in the placebo group (including four who died) did not complete the study (P = 0.024); the most common reason for withdrawal was clinical deterioration. As compared with base-line values, hemodynamic values were significantly improved at 12 weeks when measured after iloprost inhalation (P < 0.001), were largely unchanged when measured before iloprost inhalation, and were significantly worse in the placebo group. Further significant beneficial effects of iloprost treatment included an improvement in the NYHA class (P = 0.03), dyspnea (P = 0.015), and quality of life (P = 0.026). Syncope occurred with similar frequency in the two groups but was more frequently rated as serious in the iloprost group, although this adverse effect was not associated with clinical deterioration.Conclusions Inhaled iloprost is an effective therapy for patients with severe pulmonary hypertension.