循環器ジャーナル67巻1号

2019年01月発行

特集 循環器の現場からの検証：そのエビデンスを日本で活用するには？ Ⅳ．心不全

トルバプタンはなぜ使われる？—EVEREST試験やTACTICS/SECRET of AHF試験を顧みて

著者： 田中寿一¹

所属機関： ¹東京慈恵会医科大学循環器内科

ページ範囲：P.104 - P.109

Point
・2010年に日本で心不全治療薬として承認されたトルバプタンは，現在に至るまで日本国内で心不全の急性期および慢性期治療薬として広く使用されている．
・一方，米国や欧州などの海外においてトルバプタンは心不全治療薬としては承認されておらず，著明な低ナトリウム血症に対してのみと非常に限定的なものになっている．
・心不全治療薬としてのトルバプタンの位置付けに関する国内外の見解の相違は，これまでの臨床研究の結果とそこから得られたエビデンスの捉え方によるところが大きい．

参考文献

1) Udelson JE, Orlandi C, Ouyang J, et al:Acute hemodynamic effects of tolvaptan, a vasopressin V2 receptor blocker, in patients with symptomatic heart failure and systolic dysfunction:an international, multicenter, randomized, placebo-controlled trial. J Am Coll Cardiol 52:1540-1545, 2008

2) Udelson JE, McGrew FA, Flores E, et al:Multicenter, randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunction. J Am Coll Cardiol 49:2151-2159, 2007

3) Gheorghiade M, Gattis WA, O'Connor CM, et al:Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure（ACTIV in CHF）Investigators:Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure:a randomized controlled trial. JAMA 291:1963-1971, 2004

4) Konstam MA, Gheorghiade M, Burnett JC, et al:Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan（EVEREST）Investigators:Effects of oral tolvaptan in patients hospitalized for worsening heart failure:the EVEREST Outcome Trial. JAMA 297:1319-1331, 2007

5) Gheorghiade M, Konstam MA, Burnett JC, et al:Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan（EVEREST）Investigators:Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure:the EVEREST Clinical Status Trials. JAMA 297:1332-1343, 2007

6) Felker GM, Mentz RJ, Cole RT, et al:Efficacy and Safety of Tolvaptan in Patients Hospitalized With Acute Heart Failure. J Am Coll Cardiol 69:1399-1406, 2017

7) Konstam MA, Kiernan M, Chandler A, et al:SECRET of CHF Investigators, Coordinators, and Committee Members:Short-Term Effects of Tolvaptan in Patients With Acute Heart Failure and Volume Overload. J Am Coll Cardiol 69:1409-1419, 2017

8) Matsue Y, Suzuki M, Torii S, et al:Clinical Effectiveness of Tolvaptan in Patients with Acute Heart Failure and Renal Dysfunction. J Card Fail 22:423-432, 2016

9) Suzuki S, Yoshihisa A, Yamaki T, et al:AVCMA investigators:Acute heart failure volume control multicenter randomized（AVCMA）trial:comparison of tolvaptan and carperitide. J Clin Pharmacol 53:1277-1285, 2013

10) Shirakabe A, Hata N, Yamamoto M, et al:Immediate administration of tolvaptan prevents the exacerbation of acute kidney injury and improves the mid-term prognosis of patients with severely decompensated acute heart failure. Circ J 78:911-921, 2014

11) Kinugawa K, Sato N, Inomata T, et al:Efficacy and Safety of Tolvaptan in Heart Failure Patients With Volume Overload. Circ J 78:844-852, 2014

12) Packer M, O'Connor C, McMurray JJV, et al:Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure. N Engl J Med 376:1956-1964, 2017

13) Teerlink JR, Voors AA, Ponikowski P, et al:Serelaxin in addition to standard therapy in acute heart failure:rationale and design of the RELAX-AHF-2 study. Eur J Heart Fail 19:800-809, 2017

14) Ferrari R, Bueno H, Chioncel O, et al:Acute heart failure:lessons learned, roads ahead. Eur J Heart Fail 20:842-850, 2018

15) Starling RC, Young JB:Tolvaptan in Acute Heart Failure:Time to Move On. J Am Coll Cardiol 69:1407-1408, 2017

16) Pitt B, Pfeffer MA, Assmann SF, et al:TOPCAT Investigators:Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 370:1383-1392, 2014

17) Pfeffer MA, Braunwald E:Treatment of Heart Failure With Preserved Ejection Fraction:Reflections on Its Treatment With an Aldosterone Antagonist. JAMA Cardiol 1:7-8, 2016

18) Rich MW, Chyun DA, Skolnick AH, et al:American Heart Association Older Populations Committee of the Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council;American College of Cardiology;and American Geriatrics Society:Knowledge Gaps in Cardiovascular Care of the Older Adult Population:A Scientific Statement From the American Heart Association, American College of Cardiology, and American Geriatrics Society. Circulation 133:2103-2122, 2016

19) Fonarow GC, Yancy CW, Hernandez AF, et al:Potential impact of optimal implementation of evidence-based heart failure therapies on mortality. Am Heart J 161:1024-1030. e3, 2011

20) Sherman RE, Anderson SA, Dal Pan GJ, et al:Real-World Evidence-What Is It and What Can It Tell Us? N Engl J Med 375:2293-2297, 2016