Effect on mode and cause of death of initiation of treatment for chronic heart failure with bisoprolol followed by additionnal enalapril compared to the opposite sequence: results of the randomized CIBIS-III trial. 

In chronic heart failure initiating bisoprolol first results in reductions in sudden death compared to initiating enalapril first, finds the CIBIS III study in clinical trial update I, comparing two therapeutic strategies of sequential administration of a beta blocker or ACE inhibitor. Here the presenter Ronnie Willenheimer (Malmo, Sweden) and discussant Luigi Tavazzi (Pavia, Italy) provide an overview of the results.


Study objective
 
To compare initiation of treatment in patients with chronic heart failure (CHF) with the β1-selective β-blocker bisoprolol (to which enalapril is subsequently added) to a regimen beginning with enalapril (to which bisoprolol is subsequently added) in terms of the effect on sudden death.

Slide Presentation by the presenter Prof. Ronnie Willenheimer

Slide presentation .... [Available]

In chronic heart failure initiating bisoprolol first results in reductions in sudden death compared to initiating enalapril first, finds the CIBIS III study in clinical trial update I, comparing two therapeutic strategies of sequential administration of a beta blocker or ACE inhibitor. Here the presenter Ronnie Willenheimer (Malmo, Sweden) and discussant Luigi Tavazzi (Pavia, Italy) provide an overview of the results.


Study objective
 
To compare initiation of treatment in patients with chronic heart failure (CHF) with the β1-selective β-blocker bisoprolol (to which enalapril is subsequently added) to a regimen beginning with enalapril (to which bisoprolol is subsequently added) in terms of the effect on sudden death.

Slide Presentation by the presenter Prof. Ronnie Willenheimer

Slide presentation .... [Available]

The design of CIBIS III trial looks as a compromise between two objectives: 1) to compare two therapeutic strategies of sequential administration of a beta –blocker first (BB) or an ACE-I first (ACE-I) followed by their association in chronic HF patients, 2) to compare the early effects of both as monotherapy. Actually any therapeutical strategy based on 9 steps of drug uptitration along 8 months will never be incorporated in the clinical practice. As for the second objective, monotherapy phases were too short to evaluate the effects on any drug with hard end-points.

Actually, the apparently favourable effect of BB on sudden death (SD) as compared to ACE-I is mostly based on the differences in SD rate during the monotherapy phases (SD:8vs 16). However this is balanced by a symmetrical inverse trend in non sudden CV deaths (12 vs 6) in the same period. This, coupled with higher rate of SD in the BB group during the last part of follow-up and a between-group unbalance in non-CV deaths at the trial end (8 vs 18) simply portends a trial underpower. Moreover, according to the published protocol, SD was not an end-point and the one-year analysis was not foreseen .

Finally, no one of the 1010 patients with symptomatic HF and mean LVEF of 29% (62% with CAD) enrolled in CIBIS III and followed-up for 1-2.4 years received an implantable defibrillator.

I feel that beta-blocker therapy can be initiated first in selected HF patients but the CIBIS III trial results do not allow to recommend this strategy in the clinical practice.