Published online before print September 4, 2005, doi: 10.1161/CIRCULATIONAHA.105.582320
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2005;112:2426-2435.)
© 2005 American Heart Association, Inc.
Heart Failure |
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
From Lund University, Department of Cardiology, University Hospital, Malmö, Sweden (R.W.); Thoraxcenter, Department of Cardiology, University Hospital Groningen, the Netherlands (D.J.v.V.); Department of Pharmacology and Therapeutics, Trinity Centre, St James’ Hospital, Dublin, Ireland (B.S.); Medizinische Klinik III, University of Cologne, Germany (E.E.); Medicine A, University Hospital Zürich, Switzerland (F.F.); Departments of Epidemiology and Preventive Medicine and Medicine, Monash University, Alfred Hospital, Melbourne, Australia (H.K.); Cardiology Department, Clinical Military Hospital, Wroclaw, Poland (P.P.); The Nottingham Clinical Research Limited, Nottingham, UK (A.S.); Merck KGaA, Darmstadt, Germany (L.v.d.V., P.V.); and Service de Pharmacologie, Hopital Pitié-Salpetriere, Paris, France (P.L.).
Correspondence to Dr Ronnie Willenheimer, Department of Cardiology, University Hospital, S-205 02 Malmö, Sweden. E-mail ronnie.willenheimer{at}med.lu.se
Received August 10, 2005; revision received August 29, 2005; accepted August 29, 2005.
Background— In patients with chronic heart failure (CHF), a ß-blocker is generally added to a regimen containing an angiotensin-converting-enzyme (ACE) inhibitor. It is unknown whether ß-blockade as initial therapy may be as useful.
Methods and Results— We randomized 1010 patients with mild to moderate CHF and left ventricular ejection fraction 
35%, who were not receiving ACE inhibitor, ß-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).
Conclusion— 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.
Key Words: heart failure • drugs • adrenergic beta-antagonists • angiotensin-converting enzyme inhibitors
Related Article:
Circulation 2005 112: 2377.
This article has been cited by other articles:
 |
|
 |
|
  L. W. Stevenson Challenges for the Basis of Practice in Heart Failure Circ Heart Fail, May 1, 2008; 1(1): 81 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Duckelmann, F. Mittermayer, D. G. Haider, J. Altenberger, J. Eichinger, and M. Wolzt Asymmetric Dimethylarginine Enhances Cardiovascular Risk Prediction in Patients With Chronic Heart Failure Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 2037 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Rapaport Update in cardiology. Ann Intern Med, October 17, 2006; 145(8): 618 - 625. [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Coca, H. M. Krumholz, A. X. Garg, and C. R. Parikh Underrepresentation of renal disease in randomized controlled trials of cardiovascular disease. JAMA, September 20, 2006; 296(11): 1377 - 1384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Willenheimer How to begin treatment in chronic heart failure? Results of CIBIS III Eur. Heart J. Suppl., June 1, 2006; 8(suppl_C): C43 - C50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lehman Evidently... Evid. Based Med., April 1, 2006; 11(2): 41 - 41. [Full Text] [PDF]
|
|
|
|
|
|
Other articles noted Evid. Based Med., April 1, 2006; 11(2): 63 - 64. [Full Text] [PDF]
|
|
|
|
 |
|
 W.H. W. Tang and G. S. Francis The Year in Heart Failure J. Am. Coll. Cardiol., December 6, 2005; 46(11): 2125 - 2133. [Full Text] [PDF]
|
|
|
|
 |
|
 Which First for Heart Failure: ACE Inhibitor or Beta-Blocker? Journal Watch Cardiology, October 28, 2005; 2005(1028): 2 - 2. [Full Text]
|
|
|
|
 |
|
 J. C. Fang Angiotensin-Converting Enzyme Inhibitors or {beta}-Blockers in Heart Failure: Does It Matter Who Goes First? Circulation, October 18, 2005; 112(16): 2380 - 2382. [Full Text] [PDF]
|
|