Prognostic value of bisoprolol-induced hemodynamic effects in heart failure during the Cardiac Insufficiency BIsoprolol Study (CIBIS)

Abstract

Background: To further evaluate the mechanism of beta-blocker-induced benefits in heart failure, the relationships between bisoprolol-induced hemodynamic effects and survival were studied during the Cardiac Insufficiency BIsoprolol Study (CIBIS).

Methods and results: In 557 patients studied, bisoprolol significantly reduced heart rate (-16.3+/-15.3 versus -1.6+/-13.4 bpm, respectively; P<.001) compared with placebo at 2 months after inclusion in the study. Heart rate change over time had the highest predictive value for survival (P<.01). Left ventricular fractional shortening (LVFS) significantly increased in the bisoprolol group compared with the placebo group 5 months after inclusion (+0.04+/-0.06 versus -0.001+/-0.05, respectively; P<.001; n=160). LVFS change over time was also significantly correlated with further survival (P<.02 by Cox analysis). Using a nonparametric approach, we demonstrated a significant interaction between study treatment group and LVFS over time. Patients who demonstrated improvement of LVFS over time (82% and 51% of patients in the bisoprolol and the placebo groups, respectively; P<.02) were at lower risk, but the hazard did not further decrease with a further increase of fractional shortening, and there was no significant difference between study treatment groups. Finally, it could be demonstrated that each of the three factors (heart rate change over time, LVFS change over time, and bisoprolol treatment) made a specific contribution to mortality rate.

Conclusions: Preservation of left ventricular function appears to play a key role in the bisoprolol-induced beneficial effects on prognosis in heart failure. Short-term beta-blocker-induced cardiac effects could provide a means to identify those patients who will experience improved survival over the long term.