Advertisement

Heart and Vessels

, Volume 34, Issue 2, pp 279–289 | Cite as

Comparison of effects of aldosterone receptor antagonists spironolactone and eplerenone on cardiovascular outcomes and safety in patients with acute decompensated heart failure

  • Masayoshi Yamamoto
  • Yoshihiro SeoEmail author
  • Tomoko Ishizu
  • Isao Nishi
  • Yoshie Hamada-Harimura
  • Tomoko Machino-Ohtsuka
  • Haruhiko Higuchi
  • Seika Sai
  • Tomofumi Nakatsukasa
  • Akinori Sugano
  • Masako Baba
  • Kenichi Obara
  • Kazutaka Aonuma
Original Article
  • 141 Downloads

Abstract

Differences in the clinical impacts of the aldosterone receptor antagonists spironolactone and eplerenone in patients with heart failure (HF) are unclear. Among 838 prospectively enrolled patients hospitalized for HF, 90 treated with eplerenone were compared with 90 treated with spironolactone. The primary endpoint was a composite of cardiovascular death and hospitalization. A serial evaluation of the clinical parameters was performed 1 year after discharge. The mean dose of spironolactone was 27 ± 8 mg and of eplerenone was 34 ± 15 mg. During follow-up (mean 594 ± 317 days), primary endpoints occurred in 27 patients in the eplerenone group (30.0%) and 25 patients in the spironolactone group (27.8%). There were no significant intergroup differences in the primary endpoint (log-rank, p = 0.956). Serial changes in left ventricular ejection fraction, serum brain natriuretic peptide, systolic blood pressure, and estimated glomerular filtration rate did not differ significantly between groups. Although gynecomastia in men was common in the spironolactone group (p = 0.018), the discontinuation rates due to adverse events were similar in the two groups (p = 0.135). Subgroup analyses suggested that eplerenone was associated with a lower hazard rate of the primary endpoint in female patients (interaction, p = 0.076). Among patients with HF, eplerenone and spironolactone have similar impacts on cardiovascular outcomes and safety.

Keywords

Aldosterone receptor antagonist Spironolactone Eplerenone Heart failure 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

  1. 1.
    Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL (2013) 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 128:e240–e327Google Scholar
  2. 2.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37:2129–2200CrossRefGoogle Scholar
  3. 3.
    Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J, Randomized Aldactone Evaluation Study Investigators (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 341:709–717CrossRefGoogle Scholar
  4. 4.
    Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M, Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348:1309–1321CrossRefGoogle Scholar
  5. 5.
    Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B, EMPHASIS-HF Study Group (2011) Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 364:11–21CrossRefGoogle Scholar
  6. 6.
    de Gasparo M, Joss U, Ramjoué HP, Whitebread SE, Haenni H, Schenkel L, Kraehenbuehl C, Biollaz M, Grob J, Schmidlin J (1987) Three new epoxy-spirolactone derivatives: characterization in vivo and in vitro. J Pharmacol Exp Ther 240:650–656Google Scholar
  7. 7.
    Eschalier R, McMurray JJ, Swedberg K, van Veldhuisen DJ, Krum H, Pocock SJ, Shi H, Vincent J, Rossignol P, Zannad F, Pitt B (2013) Safety and efficacy of eplerenone in patients at high risk for hyperkalemia and/or worsening renal function: analyses of the EMPHASIS-HF study subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure). J Am Coll Cardiol 62:1585–1593CrossRefGoogle Scholar
  8. 8.
    McKee PA, Castelli WP, McNamara PM, Kannel WB (1971) The natural history of congestive heart failure: the Framingham study. N Engl J Med 285:1441–1446CrossRefGoogle Scholar
  9. 9.
    Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 28:1–39CrossRefGoogle Scholar
  10. 10.
    Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O’Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM, Investigators TOPCAT (2014) Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 370:1383–1392CrossRefGoogle Scholar
  11. 11.
    Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, Fonarow GC, Jacobs JP, Jaff MR, Lichtman JH, Limacher MC, Mahaffey KW, Mehran R, Nissen SE, Smith EE, Targum SL (2015) 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards. J Am Coll Cardiol 66:403–469CrossRefGoogle Scholar
  12. 12.
    Austin PC (2011) Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat 10:150–161CrossRefGoogle Scholar
  13. 13.
    Albert NM, Yancy CW, Liang L, Zhao X, Hernandez AF, Peterson ED, Cannon CP, Fonarow GC (2009) Use of aldosterone antagonists in heart failure. JAMA 302:1658–1665CrossRefGoogle Scholar
  14. 14.
    Lewis EF, Kim HY, Claggett B, Spertus J, Heitner JF, Assmann SF, Kenwood CT, Solomon SD, Desai AS, Fang JC, McKinlay SA, Pitt BA, Pfeffer MA (2016) Impact of spironolactone on longitudinal changes in health-related quality of life in the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial. Circ Heart Fail 9:e001937Google Scholar
  15. 15.
    Edelmann F, Wachter R, Schmidt AG, Kraigher-Krainer E, Colantonio C, Kamke W, Duvinage A, Stahrenberg R, Durstewitz K, Löffler M, Düngen HD, Tschöpe C, Herrmann-Lingen C, Halle M, Hasenfuss G, Gelbrich G, Pieske B (2013) Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA 309:781–791CrossRefGoogle Scholar
  16. 16.
    Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Heitner JF, Lewis EF, O’Meara E, Rouleau JL, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, McKinlay SM, Pitt B (2015) Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT) trial. Circulation 131:34–42CrossRefGoogle Scholar
  17. 17.
    Lee DS, Gona P, Vasan RS, Larson MG, Benjamin EJ, Wang TJ, Tu JV, Levy D (2009) Relation of disease pathogenesis and risk factors to heart failure with preserved or reduced ejection fraction: insights from the Framingham heart study of the national heart, lung, and blood institute. Circulation 119:3070–3077CrossRefGoogle Scholar
  18. 18.
    Pocock SJ, Ariti CA, McMurray JJ, Maggioni A, Køber L, Squire IB, Swedberg K, Dobson J, Poppe KK, Whalley GA, Doughty RN (2013) Predicting survival in heart failure: a risk score based on 39372 patients from 30 studies. Eur Heart J 34:1404–1413CrossRefGoogle Scholar
  19. 19.
    Welles CC, Ku IA, Kwan DM, Whooley MA, Schiller NB, Turakhia MP (2012) Left atrial function predicts heart failure hospitalization in subjects with preserved ejection fraction and coronary heart disease: longitudinal data from the Heart and Soul Study. J Am Coll Cardiol 59:673–680CrossRefGoogle Scholar
  20. 20.
    Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, Redelmeier DA (2004) Rates of hyperkalemia after publication of the randomized Aldactone evaluation study. N Engl J Med 351:543–551CrossRefGoogle Scholar
  21. 21.
    Bozkurt B, Agoston I, Knowlton AA (2003) Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines. J Am Coll Cardiol 41:211–214CrossRefGoogle Scholar
  22. 22.
    Tamirisa KP, Aaronson KD, Koelling TM (2004) Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure. Am Heart J 148:971–978CrossRefGoogle Scholar
  23. 23.
    White WB, Duprez D, St Hillaire R, Krause S, Roniker B, Kuse-Hamilton J, Weber MA (2003) Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 41:1021–1026CrossRefGoogle Scholar
  24. 24.
    Krum H, Nolly H, Workman D, He W, Roniker B, Krause S, Fakouhi K (2002) Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients. Hypertension 40:117–123CrossRefGoogle Scholar
  25. 25.
    Williams GH, Burgess E, Kolloch RE, Ruilope LM, Niegowska J, Kipnes MS, Roniker B, Patrick JL, Krause SL (2004) Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. Am J Cardiol 93:990–996CrossRefGoogle Scholar
  26. 26.
    Pitt B, Reichek N, Willenbrock R, Zannad F, Phillips RA, Roniker B, Kleiman J, Krause S, Burns D, Williams GH (2003) Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy. The 4E-left ventricular hypertrophy study. Circulation 108:1831–1838CrossRefGoogle Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Masayoshi Yamamoto
    • 1
  • Yoshihiro Seo
    • 1
    Email author
  • Tomoko Ishizu
    • 1
  • Isao Nishi
    • 2
  • Yoshie Hamada-Harimura
    • 3
  • Tomoko Machino-Ohtsuka
    • 1
  • Haruhiko Higuchi
    • 4
  • Seika Sai
    • 3
  • Tomofumi Nakatsukasa
    • 1
  • Akinori Sugano
    • 1
  • Masako Baba
    • 5
  • Kenichi Obara
    • 6
  • Kazutaka Aonuma
    • 1
  1. 1.Department of Cardiology, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  2. 2.Department of Cardiology, Tsuchiura Clinical Education and Training CenterUniversity of Tsukuba HospitalTsukubaJapan
  3. 3.Department of Cardiology, Graduate School of Comprehensive Human SciencesUniversity of TsukubaTsukubaJapan
  4. 4.Department of CardiologyHitachi, Ltd, Hitachi General HospitalHitachinakaJapan
  5. 5.Department of CardiologyIbaraki Prefectural Central HospitalKasamaJapan
  6. 6.Division of CardiologyRyugasaki Saiseikai General HospitalRyugasakiJapan

Personalised recommendations