Comparison of treatment initiation with bisoprolol vs. enalapril in chronic heart failure patients: rationale and design of CIBIS-III.
BACKGROUND
Angiotensin-converting-enzyme (ACE) inhibitors and beta-blockers are standard therapy for chronic heart failure (CHF). beta-blockers are recommended to be initiated after ACE-inhibitors, but this order is not evidence based. The initiation order may be important since many, especially elderly CHF patients cannot tolerate target doses of both. Data suggest that beta-blockers may be more important to CHF patients than ACE-inhibitors, especially in early stages of CHF.


OBJECTIVE
To compare the effect on combined death or hospitalisation of initial monotherapy with either bisoprolol or enalapril, followed by combination therapy.


METHODS
One-thousand CHF patients without ACE-inhibitor, beta-blocker or angiotensin-receptor-blocker therapy will be randomised 1:1 to monotherapy with either enalapril or bisoprolol for 6 months, followed by combined therapy for 6-18 months. The primary objective is to show non-inferiority for bisoprolol-first vs. enalapril-first regarding combined death or hospitalisation. If that is shown, superiority for bisoprolol-first will be tested.


CONCLUSIONS
If the trial shows non-inferiority for bisoprolol-first vs. enalapril-first, the first CHF therapy may be chosen based on individual judgement in each patient. If bisoprolol-first is superior to enalapril-first, a beta-blocker should be given prior to an ACE-inhibitor in CHF, and the paradigm of testing CHF compounds against a background of ACE-inhibitor therapy will be challenged.
Willenheimer
Ronnie
R
Department of Cardiology, University Hospital, S-205 02 Malmö, Sweden. ronnie.willenheimer@medforsk.mas.lu.se
Erdmann
Erland
E
Follath
Ferenc
F
Krum
Henry
H
Ponikowski
Piotr
P
Silke
Bernard
B
Van Veldhuisen
Dirk J
DJ
Van De Ven
Louis
L
Verkenne
Patricia
P
Lechat
Philippe
P
D000319:Adrenergic beta-Antagonists / Q000592:standards / Q000627:therapeutic use*; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000592:standards / Q000627:therapeutic use*; D017298:Bisoprolol / Q000592:standards / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000592:standards / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects; D016019:Survival Analysis; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D017298:Bisoprolol