title: Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III.
abstract: BACKGROUND
  In patients with chronic heart failure (CHF), a beta-blocker is generally added to a regimen containing an angiotensin-converting-enzyme (ACE) inhibitor. It is unknown whether beta-blockade as initial therapy may be as useful.
  
  
  RESULTS
  We randomized 1010 patients with mild to moderate CHF and left ventricular ejection fraction < or =35%, who were not receiving ACE inhibitor, beta-blocker, or angiotensin receptor blocker therapy, to open-label monotherapy with either bisoprolol (target dose 10 mg QD; n=505) or enalapril (target dose 10 mg BID; n=505) for 6 months, followed by their combination for 6 to 24 months. The 2 strategies were blindly compared with regard to the combined primary end point of all-cause mortality or hospitalization and with regard to each of these end point components individually. Bisoprolol-first treatment was noninferior to enalapril-first treatment if the upper limit of the 95% confidence interval (CI) for the absolute between-group difference was <5%, corresponding to a hazard ratio (HR) of 1.17. In the intention-to-treat sample, the primary end point occurred in 178 patients allocated to bisoprolol-first treatment versus 186 allocated to enalapril-first treatment (absolute difference -1.6%, 95% CI -7.6 to 4.4%, HR 0.94; 95% CI 0.77 to 1.16). In the per-protocol sample, 163 patients allocated to bisoprolol-first treatment had a primary end point, versus 165 allocated to enalapril-first treatment (absolute difference -0.7%, 95% CI -6.6 to 5.1%, HR 0.97; 95% CI 0.78 to 1.21). With bisoprolol-first treatment, 65 patients died, versus 73 with enalapril-first treatment (HR 0.88; 95% CI 0.63 to 1.22), and 151 versus 157 patients were hospitalized (HR 0.95; 95% CI 0.76 to 1.19).
  
  
  CONCLUSIONS
  Although noninferiority of bisoprolol-first versus enalapril-first treatment was not proven in the per-protocol analysis, our results indicate that it may be as safe and efficacious to initiate treatment for CHF with bisoprolol as with enalapril.
authors.affiliation: Department of Cardiology, University Hospital, Lund University, Malmö, Sweden. ronnie.willenheimer@med.lu.se
authors.forename: Ronnie
authors.initials: R
authors.lastname: Willenheimer
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Bernard
authors.initials: B
authors.lastname: Silke
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: Allan
authors.initials: A
authors.lastname: Skene
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 / Q000627:therapeutic use*; D017668:Age of Onset; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D017298:Bisoprolol / Q000627:therapeutic use*; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D017298:Bisoprolol