Double-Blind, Placebo-Controlled Clinical Trial With a Rho-Kinase Inhibitor in Pulmonary Arterial Hypertension - A Pilot Efficacy Trial -

作者：Fukumoto Yoshihiro; Yamada Norikazu; Matsubara Hiromi; Mizoguchi Minori; Uchino Kazuaki; Yao Atsushi; Kihara Yasuki; Kawano Mitsuhiro; Watanabe Hiroshi; Takeda Yutaka; Adachi Takeshi; Osanai Shinobu; Tanabe Nobuhiro; Inoue Teruo; Kubo Akihiro; Ota Yuri; Fukuda Koichiro; Nakano Takeshi; Shimokawa Hiroaki^*

来源：Circulation Journal, 2013, 77(10): 2619-2625.

DOI：10.1253/circj.CJ-13-0443

• Pulmonary arterial hypertension
• Rho-kinase inhibitor
• Signal transduction

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. %26lt;br%26gt;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. %26lt;br%26gt;Conclusions: Mid-term treatment with oral AT-877ER showed additional improvement in pulmonary hemodynamics in patients with PAH.

• 出版日期2013-10