Implications of CIBIS III: a commentary

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.