Author + information
- Ronnie Willenheimer, MD, PhD⁎ (, )
- Dirk J. van Veldhuisen, MD, PhD,
- Piotr Ponikowski, MD, PhD,
- Philippe Lechat, MD, PhD,
- CIBIS-II Steering Committee and Investigators
- ↵⁎Department of Cardiology, University Hospital, S-205 02 Malmö, Sweden
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 JACCthat, 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.
- American College of Cardiology Foundation
- Sliwa K.,
- Norton G.R.,
- Kone N.,
- et al.
- Leier C.V.