CORRESPONDENCE: LETTERS TO THE EDITOR
Beta-Blocker Treatment Before Angiotensin-Converting Enzyme Inhibitor Therapy in Newly Diagnosed Heart Failure
Ronnie Willenheimer, MD, PhD*,
Dirk J. van Veldhuisen, MD, PhD,
Piotr Ponikowski, MD, PhD,
Philippe Lechat, MD, PhD on behalf of the CIBIS-II Steering Committee and Investigators
* Department of Cardiology, University Hospital, S-205 02 Malmö, Sweden (Email: ronnie.willenheimer{at}med.lu.se).
We read with great interest the study by Sliwa et al. (1) recently published in the Journal. In their report they observed that, compared to the commonly recommended order of starting therapy for newly diagnosed heart failure with an angiotensin-converting enzyme inhibitor (ACEI) followed by a beta-blocker, the opposite order of starting with the beta-blocker carvedilol followed by the ACEI perindopril had a superior effect on New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), plasma N-terminal pro-brain natriuretic peptide concentration, and LV volumes. We believe that this is a very important study and the investigators are to be congratulated for their achievement. In his accompanying editorial (2), Dr. Leier points out that a large multicenter morbidity/mortality trial would have to be performed to verify the results obtained by Sliwa et al.
In response to this we would like to inform readers of JACC that, based on a hypothesis similar to the one by Sliwa et al., we started planning such a morbidity/mortality trial more than four years ago. The rationale and design of this trial, the Cardiac Insufficiency Bisoprolol Study (CIBIS)-III, has been published (3), and the study is now concluded. In 18 European countries, as well as in Tunisia and Australia, 1,013 patients with NYHA functional class II to III heart failure have been included.
The CIBIS-III trial is designed to provide evidence for the best order of initiating therapy. The end point rate is as expected, ensuring an adequate statistical power to show noninferiority or superiority for bisoprolol-first, should that be the case. If superiority for either treatment regimen is shown we will know if we generally should start heart failure therapy with an ACEI or a beta-blocker. If the trial shows noninferiority for bisoprolol-first versus enalapril-first, there is evidence supporting a free choice with regard to the first therapy, based on individual judgment in each patient. A result showing that bisoprolol-first is superior to enalapril-first will challenge the paradigm of testing compounds for the treatment of heart failure against a background of ACEI therapy.
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- 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;44:1825-1830.[Abstract/Free Full Text]
- Leier CV. Dismantling mandates in the treatment of heart failure J Am Coll Cardiol 2004;44:1831-1833.[Free Full Text]
- Willenheimer R, Erdmann E, Follath F, et al. CIBIS-III investigators Comparison of treatment initiation with bisoprolol versus enalapril in chronic heart failure patientsrationale and design of CIBIS-III. Eur J Heart Fail 2004;6:493-500.[CrossRef][ISI][Medline]
Related Article
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- Karen Sliwa and Mohammed Rafique Essop
J. Am. Coll. Cardiol. 2005 46: 183.
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