Possible clinical implications of the Cardiac Insufficiency Bisoprolol (CIBIS) III trial

The mainstay of heart failure management is angiotensin-converting enzyme inhibitor therapy initially as a vasodilator, followed by beta blockade at a varying time interval, based on clinical judgement. Early beta blockade has theoretical advantages in terms of possible protection against dysrhythmia or disease progression, although there may be short-term concerns regarding a possible deterioration in cardiac function and aggravation of heart failure.
The Cardiac Insufficiency Bisoprolol (CIBIS) III trial examined the optimum paradigm of initiating treatment for chronic heart failure (CHF). A large cohort of 1,010 systolic CHF patients, at least 65 years of age, with stable, mild-to-moderate symptomatic disease, were followed-up for a mean of 1.25 years. Patients were randomly allocated to initial monotherapy with bisoprolol for six months, followed by the addition of enalapril, or the opposite sequence. Efficacy and safety of the bisoprolol-first strategy versus the enalapril-first strategy was similar in terms of the combined primary end point of mortality or all-cause hospitalisation (hazard ratio 0.94, 95% confidence interval 0.77–1.16, non-inferiority p=0.02). The two approaches also showed similar safety. The bisoprolol-first strategy showed a 28% mortality reduction after the monotherapy phase (p=0.24) and a 31% borderline-significant mortality reduction during the first year (p=0.06), but was associated with a 25% increase in worsening of CHF events (p=0.23). This paper highlights important features of the study design and patient population. Both the clinical perspective and possible clinical implications of CIBIS III are discussed.