Double-Blind, Placebo-Controlled Clinical Trial With a Rho-Kinase Inhibitor in Pulmonary Arterial Hypertension
| Autor: | Yasuki Kihara, Yoshihiro Fukumoto, Shinobu Osanai, Takeshi Nakano, Norikazu Yamada, Nobuhiro Tanabe, Minori Mizoguchi, Koichiro Fukuda, Teruo Inoue, Akihiro Kubo, Takeshi Adachi, Hiromi Matsubara, Hiroshi Watanabe, Yuri Ota, Mitsuhiro Kawano, Kazuaki Uchino, Yutaka Takeda, Atsushi Yao, Hiroaki Shimokawa |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Heart disease business.industry Cardiac index Fasudil General Medicine medicine.disease Placebo Connective tissue disease Surgery law.invention Randomized controlled trial law Rho kinase inhibitor Internal medicine medicine.artery Pulmonary artery medicine Cardiology Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation Journal. 77:2619-2625 |
| ISSN: | 1347-4820 1346-9843 |
| DOI: | 10.1253/circj.cj-13-0443 |
| Popis: | Background: We have previously demonstrated that long-term inhibition of Rho-kinase ameliorates pulmonary arterial hypertension (PAH) in animal models. In the present study, we examined the clinical effects of mid-term oral treatment with an extended release formulation of AT-877 (fasudil hydrochloride), a specific Rho-kinase inhibitor (AT-877ER) on PAH. Methods and Results: 23 PAH patients were treated with either placebo (10/2 females/males, 51±16 years, idiopathic PAH (IPAH) in 6, PAH associated with connective tissue disease (CTD-PAH) in 3, PAH with congenital heart disease (CHD-PAH) in 2, and portal PAH in 1) or AT-877ER (6/5 females/males, 47±14 years, IPAH in 2, CTD-PAH in 5, and CHD-PAH in 4); 3 patients were excluded. We performed a 6-min walk test and right heart catheterization in the remaining 20 patients, before and 3 months after the treatment (placebo n=11, AT-877ER n=9). Although there were no significant differences between the 2 groups for the 6-min walk distance, pulmonary hemodynamics tended to be improved in the AT-877ER group, especially the prevalence of improved cardiac index from baseline, which was significantly higher in the AT-877ER than in the placebo group. In the AT-877ER group, serum levels of hydroxyfasudil, an active metabolite of AT-877ER tended to correlate with improvements in the cardiac index and mean pulmonary artery pressure. Conclusions: Mid-term treatment with oral AT-877ER showed additional improvement in pulmonary hemodynamics in patients with PAH. (Circ J 2013; 77: 2619–2625) |
| Databáze: | OpenAIRE |
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