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Journal of Renin-Angiotensin-Aldosterone System
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Implications of CIBIS III: A Commentary

Ronnie Willenheimer

Lund University, Department of Cardiology, University Hospital, Malmö, Sweden, ronnie.willenheimer{at}med.lu.se

Combined therapy with optimum doses of a beta-blocker and an angiotensin-converting enzyme inhibitor (ACE-I) is the mainstay for the treatment of chronic heart failure (CHF). However, patients cannot be started on full doses of both drugs and treatment has to be initiated one way or the other. The Cardiac Insufficiency Bisoprolol Study (CIBIS) III was the first trial investigating the optimum sequence of initiating treatment of CHF, in terms of mortality and morbidity. CIBIS III compared randomised, open-label initial monotherapy with bisoprolol or enalapril for six months, followed by their combination for six to 24 months, in 1,010 patients at least 65 years of age, with stable, mildly or moderately symptomatic, systolic CHF. The two strategies were similarly efficacious in terms of the combined primary endpoint of mortality or all-cause hospitalisation, and showed similar safety. The bisoprolol-first approach showed a 28% lower mortality at the end of the monotherapy phase (p=0.24) and a 31% lower mortality at the end of the first year (p=0.06), but a 25% increase in worsening of CHF events (p=0.23). The main conclusion is that, CHF therapy may be started with bisoprolol or enalapril in patients like those in CIBIS III. However, it may be argued that the primary therapeutic goal in the early phase of CHF should be improved survival, whereas the long-term aim, achievable during combined therapy with optimum doses of several drugs, should be improved quality of life, physical function, morbidity and survival. In such case, the CIBIS III findings would tend to support starting CHF therapy with bisoprolol rather than enalapril in stable patients with mild or moderate symptoms.

Key Words: Beta-blocker • Angiotensin-converting enzyme inhibitor • Chronic heart failure • Therapy • Order of treatment initiation

References

  • Swedberg K., Cleland J., Dargie H. et al. 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 20 H 05). Eur Heart J 2005;26:1115-40.[Free Full Text]
  • Garg R., Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA 1995;273:1450-6.[Abstract/Free Full Text]
  • Cibis II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS II): a randomized trial. Lancet 1999;353:9-13.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • MERIT-HF Study group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). Lancet 1999;353:2001-07.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Packer M., Coats AJ, Fowler MB et al. Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651-8.[Abstract/Free Full Text]
  • Willenheimer R., Erdmann E., Follath F. et al., on behalf of the CIBIS-III investigators. Comparison of treatment initiation with bisoprolol versus enalapril in chronic heart failure patients: Rationale and Design of CIBIS-III. Eur J Heart Fail 2004;6:493-500.[Abstract/Free Full Text]
  • Willenheimer R., van Veldhuisen DJ, Silke B. et al. 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 2005;112:2426-35.[Abstract/Free Full Text]
  • Packer M. Pathophysiology of heart failure. Lancet 1992;340:88-95.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Campbell DJ, Aggarwal A., Esler M., Kaye D. Beta-blockers, angiotensin II, and ACE inhibitors in patients with heart failure. Lancet 2001;358:1609-10.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Teisman AC, van Veldhuisen DJ, Boomsma F. et al. Chronic beta-blocker treatment in patients with advanced heart failure. Effects on neurohormones. Int J Cardiol 2000;73:7-14.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Uretsky BF, Sheahan RG Primary Prevention of Sudden Cardiac Death in Heart Failure: Will the Solution Be Shocking? J Am Coll Cardiol 1997;30:1589-97.[Abstract]
  • Huirkuri HV, Castellanos A., Myerburg RJ Sudden death due to cardiac arrhythmias. N Engl J Med 2001;345:1473-82.[Free Full Text]
  • Lane RE, Cowie MR, Chow AW Prediction and prevention of sudden cardiac death in heart failure. Heart 2005;91:674-80.[Free Full Text]
  • Krum H. ß-adrenoceptor blockers in chronic heart failure - a review. Br J Clin Pharmacol 1997;44:111-18.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Heidenreich PA, Lee TT, Massie BM Effect of beta-blockade on mortality in patients with heart failure: a meta analysis of randomized clinical trials. J Am Coll Cardiol 1997;30:27-34.[Abstract]
  • Lechat P., Packer M., Chalon S., Cucherat M., Arab T., Boissel JP Clinical effects of beta-adrenergic blockade in chronic heart failure. A meta-analysis of double blind, placebo controlled, randomized trials. Circulation 1998;98:1184-91.[Abstract/Free Full Text]
  • Cleland JG, Massie BM, Packer M. Sudden death in heart failure: vascular or electrical? Eur J Heart Fail 1999;1:41-5.[Free Full Text]
  • Davies M., Hobbs F., Davis R. et al. Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study. Lancet 2001;358:439-44.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Cleland JG, Cohen-Solal A., Aguilar JC et al. IMPROVEMENT of Heart Failure Programme Committees and Investigators. Improvement programme in evaluation and management; Study Group on Diagnosis of the Working Group on Heart Failure of The European Society of Cardiology Management of heart failure in primary care (the IMPROVEMENT of Heart Failure Programme): an international survey. Lancet 2002;360:1631-9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Komajda M., Lapuerta P., Hermans N. et al. Adherence to guidelines is a predictor of outcome in chronic heart failure: the MAHLER survey. Eur Heart J 2005;26:1653-9.[Abstract/Free Full Text]
  • Hunt SA, Baker DW, Chin MH et al. American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure); International Society for Heart and Lung Transplantation; Heart Failure Society of America. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration with the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America. Circulation 2001;104:2996-3007.[Free Full Text]
  • Remme WJ, Riegger G., Hildebrandt P. et al. The benefits of early combination treatment of carvedilol and an ACE-inhibitor in mild heart failure and left ventricular systolic dysfunction. The carvedilol and ACE-inhibitor remodelling mild heart failure evaluation trial (CARMEN). Cardiovasc Drugs Ther 2004;18:57-66.
  • Sliwa K., Norton GR, Kone N. et al. Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure. J Am Coll Cardiol 2004;44:1825-30.[Abstract/Free Full Text]

Journal of Renin-Angiotensin-Aldosterone System, Vol. 6, No. 3, 115-120 (2005)
DOI: 10.3317/jraas.2005.017


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This Article
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PubMed
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