Rationale and design of CIBIS III
Cardiology Department, Centre for Heart Disease, Clinical Military Hospital, Weigla 5, 50-891 Wroclaw, Poland
* Corresponding author. Tel: +48 71 7660237; fax: +48 71 7660228. E-mail address: piotrponikowski{at}4wsk.pl
Although European guidelines indicate that treatment for chronic heart failure (CHF) should be started with an angiotensin-converting enzyme (ACE) inhibitor, followed by a beta-blocker, this order is not evidence-based. The order of initiation may be important because patients often cannot tolerate optimum doses of both an ACE-inhibitor and a beta-blocker. The first-prescribed agent is likely to be titrated to a higher dose, and the second agent may not be prescribed at all. There are arguments for starting a beta-blocker first, as the sympathetic nervous system is activated earlier in CHF than the renin–angiotensin–aldosterone system. Beta-blockers have a more pronounced effect on early left ventricular (LV) remodelling than ACE-inhibitors. Moreover, sudden cardiac death (the most prevalent mode of death in early and mild CHF) is markedly reduced by beta-blockers but not by ACE-inhibitors. The third Cardiac Insufficiency Bisoprolol Study was designed to determine whether a beta-blocker could be safely and effectively initiated first in CHF. It was a controlled open-label non-inferiority trial, including 1010 patients aged 
65 years, in stable New York Heart Association class II or III, and with LV ejection fraction 
35%. Patients received 6 months of monotherapy with either bisoprolol (target dose 10 mg od, n=505) or enalapril (target dose 10 mg bid, n=505), followed by their combination for 6–24 months. The combined primary endpoint was all-cause mortality or hospitalization.
Key Words: Beta-blockers • Chronic heart failure