Skip to main content
Top
Published in: Clinical Research in Cardiology 9/2008

01-09-2008 | ORIGINAL PAPER

Bisoprolol vs. carvedilol in elderly patients with heart failure: rationale and design of the CIBIS-ELD trial

Authors: Hans-Dirk Düngen, Svetlana Apostolović, Simone Inkrot, Elvis Tahirović, Florian Krackhardt, Milan Pavlović, Biljana Putniković, Mitja Lainščak, Götz Gelbrich, Frank Edelmann, Rolf Wachter, Thomas Eschenhagen, Finn Waagstein, Ferenc Follath, Mathias Rauchhaus, Wilhelm Haverkamp, Karl-Josef Osterziel, Rainer Dietz, on behalf of the CIBIS-ELD investigators, subproject “Multicenter Trials” in the Competence Network Heart Failure

Published in: Clinical Research in Cardiology | Issue 9/2008

Login to get access

Abstract

Background

Chronic heart failure (CHF) is a widespread disease with severe quality of life impairment and a poor prognosis. Beta-blockers are the mainstay of CHF therapy; yet they are under-prescribed and under-dosed in clinical practice. This is particularly evident in elderly patients, which may be due to a fear of side-effects or intolerance. Beta-blockers have further not been adequately tested in patients with diastolic CHF, which is particularly common in elderly patients. Finally, comparative data on the use of different beta-blockers in patients with CHF is scarce.

Aim

To compare the tolerance of bisoprolol and carvedilol in elderly patients with CHF.

Methods

CIBIS-ELD is an investigator-initiated, multi-centre, 1:1 randomised, double-blind, phase III trial comparing bisoprolol and carvedilol in patients ≥65 years with systolic or diastolic CHF. Recruitment started in April 2005 and is anticipated to be completed by April 2008 with at least 800 patients enrolled.

Perspective

This is the first large scale head to head beta-blockers trial in an elderly population with CHF. Besides determining which of two standard beta-blockers is best tolerated in elderly patients with systolic or diastolic CHF, we expect to gain further insight into the treatment of the particular population of patients with diastolic CHF.
Literature
1.
go back to reference Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, Love TE, Aronow WS, Adams KF, Gheorghiade M (2006) Effects of digoxin on morbidity and mortality in diastolic heart failure. Circulation 114:397–403PubMedCrossRef Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, Love TE, Aronow WS, Adams KF, Gheorghiade M (2006) Effects of digoxin on morbidity and mortality in diastolic heart failure. Circulation 114:397–403PubMedCrossRef
2.
go back to reference Baxter AJ, Spensley A, Hildreth A, Karimova G, O’Connell JE, Gray CS (2002) Beta-blockers in older persons with heart failure: tolerance and impact on quality of life. Heart 88:611–614PubMedCrossRef Baxter AJ, Spensley A, Hildreth A, Karimova G, O’Connell JE, Gray CS (2002) Beta-blockers in older persons with heart failure: tolerance and impact on quality of life. Heart 88:611–614PubMedCrossRef
3.
go back to reference Böhm M, Werner N, Kindermann M (2006) Drug treatment of chronic heart failure. Clin Res Cardiol 95:36–54PubMedCrossRef Böhm M, Werner N, Kindermann M (2006) Drug treatment of chronic heart failure. Clin Res Cardiol 95:36–54PubMedCrossRef
4.
go back to reference Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, Meverden RA, Roger VL (2006) Systolic and diastolic heart failure in the community. JAMA 296:2209–2216PubMedCrossRef Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, Meverden RA, Roger VL (2006) Systolic and diastolic heart failure in the community. JAMA 296:2209–2216PubMedCrossRef
5.
go back to reference CIBIS-II Investigators and Committees (1999) The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomised trial. Lancet 353:9–13CrossRef CIBIS-II Investigators and Committees (1999) The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomised trial. Lancet 353:9–13CrossRef
6.
go back to reference Cleland JG, Charlesworth A, Lubsen J, Swedberg K, Remme WJ, Erhardt L, Di Lenarda A, Komajda M, Metra M, Torp-Pedersen C, Poole-Wilson PA, COMET Investigators (2006) A comparison of the effects of carvedilol and metoprolol on well-being, morbidity, and mortality (the “patient journey”) in patients with heart failure: a report from the carvedilol or metoprolol european trial (COMET). J Am Coll Cardiol 47:1603–1611PubMedCrossRef Cleland JG, Charlesworth A, Lubsen J, Swedberg K, Remme WJ, Erhardt L, Di Lenarda A, Komajda M, Metra M, Torp-Pedersen C, Poole-Wilson PA, COMET Investigators (2006) A comparison of the effects of carvedilol and metoprolol on well-being, morbidity, and mortality (the “patient journey”) in patients with heart failure: a report from the carvedilol or metoprolol european trial (COMET). J Am Coll Cardiol 47:1603–1611PubMedCrossRef
7.
go back to reference Cleland JG, Cohen-Solal A, Aguilar CJ, Dietz R, Eastaugh J, Follath F, Freemantle N, Gavazzi A, van Gilst WH, Hobbs FDR, Korewicki J, Madeira HC, Preda I, Swedberg K, Widimsky J (2002) Management of heart failure in primary care (the IMPROVEMENT of heart failure programme): an international survey. Lancet 360:1631–1639PubMedCrossRef Cleland JG, Cohen-Solal A, Aguilar CJ, Dietz R, Eastaugh J, Follath F, Freemantle N, Gavazzi A, van Gilst WH, Hobbs FDR, Korewicki J, Madeira HC, Preda I, Swedberg K, Widimsky J (2002) Management of heart failure in primary care (the IMPROVEMENT of heart failure programme): an international survey. Lancet 360:1631–1639PubMedCrossRef
8.
go back to reference Dobre D, van Veldhuisen DJ, Mordenti G, Vintila M, Haaijer-Ruskamp FM, Coats AJ, Poole-Wilson PA, Flather MD, SENIORS Investigators (2007) Tolerance and dose-related effects of nebivolol in elderly patients with heart failure: data from the study of the effects of nebivolol intervention on outcomes and rehospitalisation in seniors with heart failure (SENIORS) trial. Am Heart J 154:109–115PubMedCrossRef Dobre D, van Veldhuisen DJ, Mordenti G, Vintila M, Haaijer-Ruskamp FM, Coats AJ, Poole-Wilson PA, Flather MD, SENIORS Investigators (2007) Tolerance and dose-related effects of nebivolol in elderly patients with heart failure: data from the study of the effects of nebivolol intervention on outcomes and rehospitalisation in seniors with heart failure (SENIORS) trial. Am Heart J 154:109–115PubMedCrossRef
9.
go back to reference Dulin BR, Haas SJ, Abraham WT, Krum H (2005) Do elderly systolic heart failure patients benefit from Beta-blockers to the same extent as the non-elderly? Meta-analysis of >12,000 patients in large-scale clinical trials. Am J Cardiol 95:896–898PubMedCrossRef Dulin BR, Haas SJ, Abraham WT, Krum H (2005) Do elderly systolic heart failure patients benefit from Beta-blockers to the same extent as the non-elderly? Meta-analysis of >12,000 patients in large-scale clinical trials. Am J Cardiol 95:896–898PubMedCrossRef
10.
go back to reference Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, Cohen-Solal A, Dumitrascu D, Ferrari R, Lechat P, Soler-Soler J, Tavazzi L, Spinarova L, Toman J, Böhm M, Anker SD, Thompson SG, Poole-Wilson PA, SENIORS Investigators (2005) Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 26:215–225PubMedCrossRef Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, Cohen-Solal A, Dumitrascu D, Ferrari R, Lechat P, Soler-Soler J, Tavazzi L, Spinarova L, Toman J, Böhm M, Anker SD, Thompson SG, Poole-Wilson PA, SENIORS Investigators (2005) Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 26:215–225PubMedCrossRef
11.
go back to reference Hori M, Kitabatake A, Tsutsui H, Okamoto H, Shirato K, Nagai R, Izumi T, Yokoyama H, Yasumura Y, Ishida Y, Matsuzaki M, Oki T, Sekiya M; The J-DHF, Program Committee (2005) Rationale and design of a randomized trial to assess the effects of beta-blocker in diastolic heart failure; Japanese diastolic heart failure study (J-DHF). J Card Fail 11:542–547PubMedCrossRef Hori M, Kitabatake A, Tsutsui H, Okamoto H, Shirato K, Nagai R, Izumi T, Yokoyama H, Yasumura Y, Ishida Y, Matsuzaki M, Oki T, Sekiya M; The J-DHF, Program Committee (2005) Rationale and design of a randomized trial to assess the effects of beta-blocker in diastolic heart failure; Japanese diastolic heart failure study (J-DHF). J Card Fail 11:542–547PubMedCrossRef
12.
go back to reference Kannel WB (1987) Epidemiology and prevention of cardiac failure: Framingham study insights. Eur Heart J 8(Suppl F):23–26PubMed Kannel WB (1987) Epidemiology and prevention of cardiac failure: Framingham study insights. Eur Heart J 8(Suppl F):23–26PubMed
13.
go back to reference Komajda M, Follath F, Swedberg K, Cleland J, Aguilar JC, Cohen-Solal A, Dietz R, Gavazzi A, Van Gilst WH, Hobbs R, Korewicki J, Madeira HC, Moiseyev VS, Preda I, Widimsky J, Freemantle N, Eastaugh J, Mason J, Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology (2003) The Euroheart failure survey programme—a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Heart J 24:464–474PubMedCrossRef Komajda M, Follath F, Swedberg K, Cleland J, Aguilar JC, Cohen-Solal A, Dietz R, Gavazzi A, Van Gilst WH, Hobbs R, Korewicki J, Madeira HC, Moiseyev VS, Preda I, Widimsky J, Freemantle N, Eastaugh J, Mason J, Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology (2003) The Euroheart failure survey programme—a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Heart J 24:464–474PubMedCrossRef
14.
go back to reference Krum H, Hill J, Fruhwald F, Sharpe C, Abraham G, Zhu JR, Poy C, Kragten JA (2006) Tolerance of beta-blockers in elderly patients with chronic heart failure: the COLA II study. Eur J Heart Fail 8:302–307PubMedCrossRef Krum H, Hill J, Fruhwald F, Sharpe C, Abraham G, Zhu JR, Poy C, Kragten JA (2006) Tolerance of beta-blockers in elderly patients with chronic heart failure: the COLA II study. Eur J Heart Fail 8:302–307PubMedCrossRef
15.
go back to reference Lainščak M, Moullet C, Schoen N, Tendera M (2007) Treatment of chronic heart failure with carvedilol in daily practice: the SATELLITE survey experience. Int J Cardiol 122:149–155PubMedCrossRef Lainščak M, Moullet C, Schoen N, Tendera M (2007) Treatment of chronic heart failure with carvedilol in daily practice: the SATELLITE survey experience. Int J Cardiol 122:149–155PubMedCrossRef
16.
go back to reference Maack C, Tyroller S, Schnabel P, Cremers B, Dabew E, Südkamp M, Böhm M (2001) Characterization of beta(1)-selectivity, adrenoceptor-G(s)-protein interaction and inverse agonism of nebivolol in human myocardium. Br J Pharmacol 132:1817–1826PubMedCrossRef Maack C, Tyroller S, Schnabel P, Cremers B, Dabew E, Südkamp M, Böhm M (2001) Characterization of beta(1)-selectivity, adrenoceptor-G(s)-protein interaction and inverse agonism of nebivolol in human myocardium. Br J Pharmacol 132:1817–1826PubMedCrossRef
17.
go back to reference 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 353:2001–2007CrossRef 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 353:2001–2007CrossRef
18.
go back to reference Packer M (2003) Do beta-blockers prolong survival in heart failure only by inhibiting the beta1-receptor? A perspective on the results of the COMET trial. J Card Fail 9:429–443PubMedCrossRef Packer M (2003) Do beta-blockers prolong survival in heart failure only by inhibiting the beta1-receptor? A perspective on the results of the COMET trial. J Card Fail 9:429–443PubMedCrossRef
19.
go back to reference Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Staiger C, Holcslaw TL, Amann-Zalan I, DeMets DL (2002) Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation 106:2194–2199PubMedCrossRef Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Staiger C, Holcslaw TL, Amann-Zalan I, DeMets DL (2002) Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation 106:2194–2199PubMedCrossRef
20.
go back to reference Peters-Klimm F, Müller-Tasch T, Schellberg D, Remmpis A, Barth A, Holzapfel N, Jünger J, Herzog W, Szecsenyi J (2008) Guideline adherence for pharmacotherapy of chronic systolic heart failure in general practice: a close look on evidence-based therapy. Clin Res Cardiol 97:244–252PubMedCrossRef Peters-Klimm F, Müller-Tasch T, Schellberg D, Remmpis A, Barth A, Holzapfel N, Jünger J, Herzog W, Szecsenyi J (2008) Guideline adherence for pharmacotherapy of chronic systolic heart failure in general practice: a close look on evidence-based therapy. Clin Res Cardiol 97:244–252PubMedCrossRef
21.
go back to reference Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S; CHARM Investigators, Committees (2003) Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-overall programme. Lancet 362:759–766PubMedCrossRef Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S; CHARM Investigators, Committees (2003) Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-overall programme. Lancet 362:759–766PubMedCrossRef
22.
go back to reference Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ, Torp-Pedersen C, Scherhag A, Skene A (2003) Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the carvedilol or metoprolol european trial (COMET): randomised controlled trial. Lancet 362:7–13PubMedCrossRef Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ, Torp-Pedersen C, Scherhag A, Skene A (2003) Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the carvedilol or metoprolol european trial (COMET): randomised controlled trial. Lancet 362:7–13PubMedCrossRef
23.
go back to reference Shibata MC, Flather MD, Wang D (2001) Systematic review of the impact of beta-blockers on mortality and hospital admissions in heart failure. Eur J Heart Fail 3:351–357PubMedCrossRef Shibata MC, Flather MD, Wang D (2001) Systematic review of the impact of beta-blockers on mortality and hospital admissions in heart failure. Eur J Heart Fail 3:351–357PubMedCrossRef
24.
go back to reference Shibata MC, Soneff CM, Tsuyuki RT (2005) Utilization of evidence-based therapies for heart failure in the institutionalized elderly. Eur J Heart Fail 7:1122–1125PubMedCrossRef Shibata MC, Soneff CM, Tsuyuki RT (2005) Utilization of evidence-based therapies for heart failure in the institutionalized elderly. Eur J Heart Fail 7:1122–1125PubMedCrossRef
25.
go back to reference Stewart S, MacIntyre K, Hole DJ, Capewell S, McMurray JJV (2001) More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 3:315–322PubMedCrossRef Stewart S, MacIntyre K, Hole DJ, Capewell S, McMurray JJV (2001) More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 3:315–322PubMedCrossRef
26.
go back to reference Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, Tavazzi L, Smiseth OA, Gavazzi A, Haverich A, Hoes A, Jaarsma T, Korewicki J, Lévy S, Linde C, Lopez-Sendon JL, Nieminen MS, Piérard L, Remme WJ (2005) Task force for the diagnosis and treatment of chronic heart failure of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005). Eur Heart J 26:1115–1140PubMedCrossRef Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, Tavazzi L, Smiseth OA, Gavazzi A, Haverich A, Hoes A, Jaarsma T, Korewicki J, Lévy S, Linde C, Lopez-Sendon JL, Nieminen MS, Piérard L, Remme WJ (2005) Task force for the diagnosis and treatment of chronic heart failure of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005). Eur Heart J 26:1115–1140PubMedCrossRef
27.
go back to reference Varney S (2001) A cost-effectiveness analysis of bisoprolol for heart failure. Eur J Heart Fail 3:365–371PubMedCrossRef Varney S (2001) A cost-effectiveness analysis of bisoprolol for heart failure. Eur J Heart Fail 3:365–371PubMedCrossRef
28.
go back to reference Waagstein F, Hjalmarson A, Varnauskas E, Wallentin I (1975) Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy. Br Heart J 37:1022–1036PubMedCrossRef Waagstein F, Hjalmarson A, Varnauskas E, Wallentin I (1975) Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy. Br Heart J 37:1022–1036PubMedCrossRef
29.
go back to reference Willenheimer R, van Veldhuisen DJ, Silke B, Erdmann E, Follath F, Krum H, Ponikowski P, Skene A, van de Ven L, Verkenne P, Lechat P; CIBIS III Investigators (2005) Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the randomized cardiac insufficiency bisoprolol study (CIBIS) III. Circulation 112:2426–2435PubMedCrossRef Willenheimer R, van Veldhuisen DJ, Silke B, Erdmann E, Follath F, Krum H, Ponikowski P, Skene A, van de Ven L, Verkenne P, Lechat P; CIBIS III Investigators (2005) Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the randomized cardiac insufficiency bisoprolol study (CIBIS) III. Circulation 112:2426–2435PubMedCrossRef
Metadata
Title
Bisoprolol vs. carvedilol in elderly patients with heart failure: rationale and design of the CIBIS-ELD trial
Authors
Hans-Dirk Düngen
Svetlana Apostolović
Simone Inkrot
Elvis Tahirović
Florian Krackhardt
Milan Pavlović
Biljana Putniković
Mitja Lainščak
Götz Gelbrich
Frank Edelmann
Rolf Wachter
Thomas Eschenhagen
Finn Waagstein
Ferenc Follath
Mathias Rauchhaus
Wilhelm Haverkamp
Karl-Josef Osterziel
Rainer Dietz
on behalf of the CIBIS-ELD investigators, subproject “Multicenter Trials” in the Competence Network Heart Failure
Publication date
01-09-2008
Publisher
D. Steinkopff-Verlag
Published in
Clinical Research in Cardiology / Issue 9/2008
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-008-0681-6

Other articles of this Issue 9/2008

Clinical Research in Cardiology 9/2008 Go to the issue