循環器ジャーナル65巻1号

2017年01月発行

特集 Clinical Scenarioによる急性心不全治療 Ⅷ．トピックス

新しい心不全治療薬の可能性

著者： 絹川真太郎¹

所属機関： ¹北海道大学大学院医学研究科循環病態内科学

ページ範囲：P.170 - P.174

Point
・急性心不全治療において，退院後の死亡率に良い影響を及ぼす急性期治療薬剤は知られていない．
・現在，serelaxin（relaxinファミリーぺプチド）やularitide（ナトリウム利尿ペプチド）の第Ⅲ相試験が行われている．
・複数の血管拡張作用を有し，その他付加的な作用がある薬剤の開発が進行中である．

参考文献

1) Teichman SL, Unemori E, Teerlink JR, et al:Relaxin:review of biology and potential role in treating heart failure. Curr Heart Fail Rep 7:75-82, 2010

2) Teerlink JR, Metra M, Felker GM, et al:Relaxin for the treatment of patients with acute heart failure（Pre-RELAX-AHF):a multicentre randomized placebo-controlled parallel-group dose-finding phase IIb study. Lancet 373:1429-1439, 2009

3) Teerlink JR, Cotter G, Davison BA, et al:Serelaxin, recombinant human relaxin-2 for treatment of acute heart failure（RELAX-AHF):a randomised, placebo-controlled trial. Lancet 381:29-39, 2013

4) Munagala VK, Burnett JC Jr, Redfield MM:The natriuretic peptides in cardiovascular medicine. Curr Probl Cardiol 29:707-769, 2004

5) Jensen KT, Carstens J, Pedersen EB:Effect of BNP on renal hemodynamics, tublar function and vasoactive hormones in humans. Am J Physiol 274:F63-F72, 1998

6) Mitrovic V, Lüss H, Nitsche K, et al:Effects of the renal natriuretic peptide urodilatin（ularitide）in patients with decompensated chronic heart failure:A double-blind, placebo-controlled, ascending-dose trial. Am Heart J 150:1239, 2005

7) Mitrovic V, Seferovic PM, Simeunovic D, et al:Haemodynamic and clinical effects of ularitide in decomensated heart failure. Eur Heart J 27:2823-2832, 2006

8) Patel PA, Tilley DG, Rockman HA:Beta-arrestin-mediated signaling in the heart. Circ J 72:1725-1729, 2008

9) Violin JD, DeWire SM, Yamashita D, et al:Selectively engaging β-arretins at the angiotensin II type 1 receptor reduces blood pressure and increases cardiac performance. J Pharmacol Exp Ther 335:572-579, 2010

10) Boerrigter G, Lark MW, Whalen EJ, et al:Cardiorenal actions of TRV120027, a novel β-arrestin-biased ligand at the angiotensin Ⅱ type 1 receptor, in healthy and heart failure canines:a novel therapeutic strategy for acute heart failure. Circ Heart Fail 4:770-778, 2011

11) Soergel DG, Subach RA, Cowan CL, et al:First clinical experience with TRV027:Pharmacokinetics and pharmacodynamics in healthy volunteers. J Clin Pharmacol 53:892-899, 2013

12) Irvine JC, Ritchie RH, Favaloro JL, et al:Nitroxyl（HNO):the Cinderella of the nitric oxide story. Trends Pharmacol Sci 29:601-608, 2008

13) Tocchetti CG, Stanley BA, Murray CI, et al:Playing with cardiac “redox switches”:the “HNO way” to modulate cardiac function. Antioxide Redox Signal 14:1687-1698, 2011

14) Cowart D, Venuti R, Guptill J, et al:A phase 1 study of the safety and pharmacokinetics of the intravenous nitroxyl prodrug, CXL-1427. J Am Coll Cardiol 65(10_S):doi 10.1016/S0735-1097(15)60876-2, 2015

15) Evgenov OV, Pacher P, Schmidt PM, et al:NO-independent stimulators and activators of soluble guanylate cyclase:discovery and therapeutic potential. Nat Rev Drug Discov 5:755-768, 2006

16) Erdmann E, Semigran MJ, Nieminen MS, et al:Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure. Eur Heart J 34:57-67, 2013