Advertisement

Heart and Vessels

, Volume 29, Issue 2, pp 238–247 | Cite as

Efficacy and safety of bisoprolol fumarate compared with carvedilol in Japanese patients with chronic heart failure: results of the randomized, controlled, double-blind, Multistep Administration of bisoprolol IN Chronic Heart Failure II (MAIN-CHF II) study

  • Masatsugu HoriEmail author
  • Ryozo Nagai
  • Tohru Izumi
  • Masunori Matsuzaki
Original Article

Abstract

Bisoprolol fumarate (bisoprolol) is a β-blocker widely used to treat chronic heart failure (CHF). However, few studies have compared its efficacy and safety with those of the widely used β-blocker carvedilol in Japanese patients with CHF. We designed a confirmatory trial of bisoprolol using carvedilol as a control drug; however, the trial was discontinued after an off-label use of bisoprolol was approved during the study. Bisoprolol and carvedilol were administered for 32 weeks in 31 and 28 patients, respectively. The mean maintenance doses of bisoprolol and carvedilol were 3.3 and 13.6 mg/day, respectively, and the mean durations of treatment were 188.2 and 172.9 days, respectively. Heart-rate changes were similar in both groups. The mean changes from baseline to Week 32 in left ventricular (LV) ejection fraction (EF) (bisoprolol vs carvedilol groups; 11.7 % ± 8.6 % vs 10.1 % ± 10.5 %), LV end-diastolic volume (−37.5 ± 48.7 vs −24.7 ± 29.4 ml), and LV end-systolic volume (−41.9 ± 43.0 vs −29.3 ± 25.9 ml) revealed a decrease in LV volume and an increase in LVEF in both groups. The cumulative event-free rate for a composite of cardiovascular death or admissions to hospital for worsening of CHF was 92.4 % and 94.7 % in the bisoprolol and carvedilol groups, respectively. Overall, 90.3 % and 85.7 % of patients were titrated up to the maintenance doses of bisoprolol and carvedilol, respectively. Bisoprolol, at half the dose used in other countries, is well tolerated and is as effective as carvedilol for treating Japanese patients with mild to moderate CHF.

Keywords

Bisoprolol Carvedilol Chronic heart failure Japan Left ventricular function Randomized controlled trial 

Notes

Acknowledgments

We wish to thank the members of the event evaluation committee and the cardiac function evaluation committee: Dr Hiroyuki Tsutsui, Dr Shin-ichi Momomura, Dr Issei Komuro, Dr Yoshihiko Saito, and Dr Tohru Masuyama. We also thank the staff at each study site for helping with patient enrollment and data collection. We thank Daiichi Sankyo Co., Ltd for providing carvedilol and Mitsubishi Tanabe Pharma Corporation for sponsoring this clinical trial. The trial sites were: Kihara Cardiovascular Clinic; Sapporo Kosei General Hospital; Hitachi General Hospital; Gunma Prefectural Cardiovascular Center; Kan-etsu Chuo Hospital; Cardiovascular Hospital of Central Japan; National Hospital Organization Saitama National Hospital; Shuwa General Hospital; Dokkyo Medical University Koshigaya Hospital; Saitama Medical Center Jichi Medical University; Saitama Medical University International Medical Center; The Jikei University Kashiwa Hospital; Toho University Omori Medical Center; Tokyo Medical University Hospital; Kanto Central Hospital of the Mutual Aid Association of Public School Teachers; Sempo Tokyo Takanawa Hospital; National Hospital Organization Tokyo Medical Center; National Hospital Organization Tokyo Hospital; Nihon University Nerima Hikarigaoka Hospital; Fussa Hospital; Kanagawa Cardiovascular and Respiratory Center; Kitasato University Hospital; Fukui General Clinic; NHO Matsumoto Medical Center Matsumoto Hospital; Ogaki Municipal Hospital; Japanese Red Cross Takayama Hospital; Nagoya Daini Red Cross Hospital; Nagoya City University Hospital; Social Insurance Chukyo Hospital; Fujita Health University Hospital; National Hospital Organization Toyohashi Medical Center; Mie University Hospital; Kusatsu General Hospital; Social Insurance Kyoto Hospital; Mitsubishi Kyoto Hospital; Kitano Hospital, The Tazuke Kofukai Medical Research Institute; Osaka General Medical Center; Osaka Police Hospital; Osaka Red Cross Hospital; Osaka Medical Center for Cancer and Cardiovascular Diseases; Osaka Rosai Hospital; Hokusetsu General Hospital; Takatsuki General Hospital; National Hospital Organization Osaka National Hospital; National Hospital Organization Kobe Medical Center; Hyogo College Of Medicine; Nara Medical University Hospital; Tenri Hospital; Japanese Red Cross Okayama Hospital; KKR Takamatsu Hospital; Kagawa Prefectural Central Hospital; Fukuokaken Saiseikai Futsukaichi Hospital; Fukuoka Red Cross Hospital; Medical Corporation Chiyukai Fukuoka Wajiro Hospital; Shinkoga Hospital; National Hospital Organization Ureshino Medical Center; Oita Oka Hospital; Seijinkai Ikeda Hospital; and Tenyoukai Chuo Clinic.

References

  1. 1.
    CIBIS-II Investigators (1999) The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II); a randomised trial. Lancet 353:9–13Google Scholar
  2. 2.
    Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH (1996) The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 334:1349–1355PubMedCrossRefGoogle Scholar
  3. 3.
    The MERIT-HF Study Group (1999) Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 353:2001–2007CrossRefGoogle Scholar
  4. 4.
    Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, Staiger C, Curtin EL, DeMets DL (2001) Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 344:1651–1658PubMedCrossRefGoogle Scholar
  5. 5.
    Brophy JM, Joseph L, Rouleau JL (2001) Beta-blockers in congestive heart failure. A Bayesian meta-analysis. Ann Intern Med 134:550–560PubMedCrossRefGoogle Scholar
  6. 6.
    The Joint Study Group in 2009 of the Japanese Circulation Society (2010) Guidelines for diagnosis and treatment of cardiovascular diseases; guidelines for treatment of chronic heart failure (JCS 2010) (in Japanese). http://www.j-circ.or.jp/guideline/pdf/JCS2010_matsuzaki_h.pdf
  7. 7.
    Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW (2009) 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 119:e391–e479PubMedGoogle Scholar
  8. 8.
    Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Strömberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K (2008) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 29:2388–2442PubMedCrossRefGoogle Scholar
  9. 9.
    Sasayama S (1990) Severity of heart failure. Curr Med 22:555–560Google Scholar
  10. 10.
    The Joint Study Group in 2003–2004 of the Japanese Circulation Society (2005) Guidelines for the clinical application of echocardiography. Circ J 69 (Suppl IV):1343–1408 (In Japanese)Google Scholar
  11. 11.
    Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 2:358–367PubMedGoogle Scholar
  12. 12.
    McAlister FA, Wiebe N, Ezekowitz JA, Leung AA, Armstrong PW (2009) Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med 150:784–794PubMedCrossRefGoogle Scholar
  13. 13.
    Düngen HD, Apostolovic S, Inkrot S, Tahirovic E, Töpper A, Mehrhof F, Prettin C, Putniković B, Nešković AN, Krotin M, Sakač D, Lainščak M, Edelmann F, Wachter R, Rau T, Eschenhagen T, Doehner W, Anker SD, Waagstein F, Herrmann-Lingen C, Gelbrich G, Dietz R (2011) Titration to target dose of bisoprolol vs carvedilol in elderly patients with heart failure: the CIBIS-ELD trial. Eur J Heart Fail 13:670–680PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Metra M, Torp-Pedersen C, Swedberg K, Cleland JG, Di Lenarda A, Komajda M, Remme WJ, Lutiger B, Scherhag A, Lukas MA, Charlesworth A, Poole-Wilson PA (2005) Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial. Eur Heart J 26:2259–2268PubMedCrossRefGoogle Scholar
  15. 15.
    Lechat P, Hulot JS, Escolano S, Mallet A, Leizorovicz A, Werhlen-Grandjean M, Pochmalicki G, Dargie H (2001) Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial. Circulation 103:1428–1433PubMedCrossRefGoogle Scholar
  16. 16.
    Off-Label Drugs Review Meeting (2011) Non-approved and off-label drugs review meeting. Report on the validity of the application based on publicly known data—addition of chronic heart failure for bisoprolol fumarate (In Japanese). http://www.mhlw.go.jp/seisakunitsuite/bunya/kenkou_iryou/iyakuhin/kaihatsuyousei/index.html
  17. 17.
    Hori M, Sasayama S, Kitabatake A, Toyo-oka T, Handa S, Yokoyama M, Matsuzaki M, Takeshita A, Origasa H, Matsui K, Hosoda S (2004) Low-dose carvedilol improves left ventricular function and reduces cardiovascular hospitalization in Japanese patients with chronic heart failure: the Multicenter Carvedilol Heart Failure Dose Assessment (MUCHA) trial. Am Heart J 147:324–330PubMedCrossRefGoogle Scholar
  18. 18.
    Kramer DG, Trikalinos TA, Kent DM, Antonopoulos GV, Konstam MA, Udelson JE (2010) Quantitative evaluation of drug or device effects on ventricular remodeling as predictors of therapeutic effects on mortality in patients with heart failure and reduced ejection fraction: a meta-analytic approach. J Am Coll Cardiol 56:392–406PubMedCrossRefGoogle Scholar
  19. 19.
    Feola M, Aspromonte N, Canali C, Ceci V, Giovinazzo P, Milani L, Quarta G, Ricci R, Scardovi AB, Uslenghi E, Valle R (2005) Prognostic value of plasma brain natriuretic peptide, urea nitrogen, and creatinine in outpatients >70 years of age with heart failure. Am J Cardiol 96:705–709PubMedCrossRefGoogle Scholar
  20. 20.
    Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AHB, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA (2002) Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 347:161–167PubMedCrossRefGoogle Scholar
  21. 21.
    Berger R, Huelsman M, Strecker K, Bojic A, Moser P, Stanek B, Pacher R (2002) B-type natriuretic peptide predicts sudden death in patients with chronic heart failure. Circulation 105:2392–2397PubMedCrossRefGoogle Scholar
  22. 22.
    Antonopoulos GV, Lau J, Konstam MA, Udelson JE (1999) Are drug-induced changes in left-ventricular ejection fraction or volumes adequate surrogates for long-term natural history outcomes in heart failure? Circulation 100:I296Google Scholar
  23. 23.
    Konstam MA, Udelson JE, Anand IS, Cohn JN (2003) Ventricular remodeling in heart failure: a credible surrogate endpoint. J Cardiac Fail 9:350–353CrossRefGoogle Scholar
  24. 24.
    Konstam MA (2005) Reliability of ventricular remodeling as a surrogate for use in conjunction with clinical outcomes in heart failure. Am J Cardiol 96:867–871PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Masatsugu Hori
    • 1
    Email author
  • Ryozo Nagai
    • 2
  • Tohru Izumi
    • 3
  • Masunori Matsuzaki
    • 4
  1. 1.Osaka Medical Center for Cancer and Cardiovascular DiseasesOsakaJapan
  2. 2.Department of Cardiovascular Medicine, Graduate School of MedicineThe University of TokyoTokyoJapan
  3. 3.Department of Cardio-AngiologyKitasato University School of MedicineSagamiharaJapan
  4. 4.Department of Medicine and Clinical Science, Division of CardiologyYamaguchi University Graduate School of MedicineUbeJapan

Personalised recommendations