期刊
PULMONARY CIRCULATION
卷 3, 期 3, 页码 632-638出版社
SAGE PUBLICATIONS INC
DOI: 10.1086/674311
关键词
pulmonary hypertension; treatment; mTOR inhibitor; exercise; hemodynamic
资金
- Novartis Pharma, Basel, Switzerland
Despite the availability of vasodilating compounds, pulmonary hypertension (PH) of various origins remains a disease with a poor prognosis. In recent years, pulmonary arterial hypertension (PAH) has been recognized as a predominantly proliferative process. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), inhibits cellular protein synthesis and growth not only in lymphocytes but also in cells of the vascular wall. Ten patients suffering from PAH (n = 8) or chronic thromboembolic PH (n = 2) with progressive disease despite therapy with at least 2 vasodilating drugs were included in a prospective open-label pilot study. All patients were treated with everolimus in addition to their prior medication. Safety and tolerability were observed throughout the study. Pulmonary vascular resistance (PVR) and 6-minute walk distance (6MWD) were considered coprimary end points. In 2 patients, study medication was stopped prematurely because of an adverse event. One patient had acute bronchitis, and the other had right heart decompensation. The remaining 8 patients exhibited a significant 31% decrease in PVR (median [interquartile range], 1,012 [688-1,344] vs. 663 [546-860] dyn s cm(-5); P = 0.018) and an increase in 6MWD (median [interquartile range], 236 [139-350] vs. 298 [207-450] m; P = 0.069) after 6 months of treatment with everolimus. In conclusion, in this pilot study antiproliferative therapy with everolimus was well tolerated in patients with PH. The observed improvements in PVR and 6MWD may stimulate further consideration of mTOR inhibition with everolimus for the treatment of PH.
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