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European Heart Journal Advance Access published online on July 13, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi409
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European Heart Journal © The European Society of Cardiology 2005; all rights reserved
Received November 25, 2004
Revised June 6, 2005
Accepted June 16, 2005

Clinical research

Prognostic benefit of beta-blockers in patients not receiving ACE-Inhibitors

Henry Krum 1*, Steven Joseph Haas 1, Eric Eichhorn 2, Jalal Ghali 3, Edward Gilbert 4, Philippe Lechat 5, Milton Packer 6, Ellen Roecker 7, Patricia Verkenne 8, Hans Wedel 9, and John Wikstrand 10

1 NHMRC Centre of Clinical Research Excellence in Therapeutics. Departments of Epidemiology and Preventive Medicine and Medicine, Monash University Central and Eastern Clinical School, Alfred Hospital, Melbourne 3004, Australia
2 Cardiology Division, Department of Internal Medicine, University of Texas Southwestern and Dallas VA Medical Centers, Dallas, TX, USA
3 Cardiac Centers of Louisiana, Shreveport, LA, USA
4 Division of Cardiology, School of Medicine, University of Utah, Salt Lake City, UT, USA
5 Pharmacology Department, Pitie-Salpetriere Hospital, Paris, France
6 Division of Circulatory Physiology, Columbia University College of Physicians and Surgeons, New York, NY, USA
7 University of Wisconsin, Madison, WI, USA
8 Global Head Established Products--Clinical Research, Merck KGaA, Darmstradt, Germany
9 Nordic School of Public Health, Göteborg, Sweden
10 Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden; AstraZeneca, Mölndal, Sweden

* To whom correspondence should be addressed.
Henry Krum, E-mail: henry.krum{at}med.monash.edu.au


  Abstract

Aims Beta-blockers (BBs) confer significant prognostic benefit in patients (pts) with systolic chronic heart failure (CHF). However, major trials have thus far studied BBs mainly in addition to ACE-Inhibitors or angiotensin receptor blockers (ARBs) as background therapy. The magnitude of the prognostic benefit of BBs in the absence of ACE-I or ARB has not as yet been determined.

Methods and results We performed a meta-analysis of all placebo-controlled BB studies in patients with CHF (n > 200). Trials were identified via Medline literature searches, meeting abstracts, and contact with study organizations. Results for all-cause mortality and death or heart failure hospitalization were pooled using the Mantel-Haenszel (fixed effects) method. The impact of BB therapy on all-cause mortality in CHF, in the absence (4.8%) and presence (95.2%) of ACE-I (or ARB), was determined from six trials of 13 370 patients. The risk ratio (RR) for BBs vs. placebo was 0.73 [95% confidence interval (CI) 0.53-1.02] in the absence of ACE-I or ARB at baseline, compared with a RR of 0.76 (95% CI 0.71-0.83) in the presence of these agents. When ACE-Inhibitors were analysed in the same way (pre-BB), a RR of 0.89 (0.80-0.99) vs. placebo was observed in studies of > 90 days. The impact of BB therapy on death or HF hospitalization in systolic CHF, in the absence and presence of ACE-I, was determined from three trials of 8988 patients. The RR for BBs vs. placebo was 0.81 (95% CI 0.61-1.08) in the absence of ACE-I or ARB at baseline, compared with a RR of 0.78 (95% CI 0.74-0.83) in the presence of these agents. When ACE-Is were analysed in the same way (pre-BB), a RR of 0.85 (95% CI 0.78-0.93) vs. placebo was observed in studies of > 90 days.

Conclusion The magnitude of the prognostic benefit conferred by BBs in the absence of ACE-I appears to be similar to those of ACE-Is in systolic CHF. These data therefore suggest that either ACE-Is or BBs could be used as first-line neurohormonal therapy in patients with systolic CHF. Prospective studies directly comparing these agents are required to definitively address this issue.

Keywords: Chronic heart failure; Beta-blocker; ACE-Inhibitor; Mortality; Hospitalization.
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