title: Comparison of treatment initiation with bisoprolol vs. enalapril in chronic heart failure patients: rationale and design of CIBIS-III.
abstract: 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.
authors.affiliation: Department of Cardiology, University Hospital, S-205 02 Malmö, Sweden. ronnie.willenheimer@medforsk.mas.lu.se
authors.forename: Ronnie
authors.initials: R
authors.lastname: Willenheimer
authors.forename: Erland
authors.initials: E
authors.lastname: Erdmann
authors.forename: Ferenc
authors.initials: F
authors.lastname: Follath
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Bernard
authors.initials: B
authors.lastname: Silke
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Van Veldhuisen
authors.forename: Louis
authors.initials: L
authors.lastname: Van De Ven
authors.forename: Patricia
authors.initials: P
authors.lastname: Verkenne
authors.forename: Philippe
authors.initials: P
authors.lastname: Lechat
mesh_terms: 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
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D017298:Bisoprolol