European Heart Journal Advance Access originally published online on July 13, 2005
European Heart Journal 2005 26(20):2154-2158; doi:10.1093/eurheartj/ehi409
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Prognostic benefit of beta-blockers in patients not receiving ACE-Inhibitors
1NHMRC 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
2Cardiology Division, Department of Internal Medicine, University of Texas Southwestern and Dallas VA Medical Centers, Dallas, TX, USA
3Cardiac Centers of Louisiana, Shreveport, LA, USA
4Division of Cardiology, School of Medicine, University of Utah, Salt Lake City, UT, USA
5Pharmacology Department, Pitie-Salpetriere Hospital, Paris, France
6Division of Circulatory Physiology, Columbia University College of Physicians and Surgeons, New York, NY, USA
7University of Wisconsin, Madison, WI, USA
8Global Head Established Products—Clinical Research, Merck KGaA, Darmstradt, Germany
9Nordic School of Public Health, Göteborg, Sweden
10Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden
11AstraZeneca, Mölndal, Sweden
Received 25 November 2004; revised 6 June 2005; accepted 16 June 2005; online publish-ahead-of-print 13 July 2005.
* Corresponding author. Tel: +61 3 9903 0042; fax: +61 3 9903 0556. E-mail address: henry.krum{at}med.monash.edu.au
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.
Key Words: Chronic heart failure • Beta-blocker • ACE-Inhibitor • Mortality • Hospitalization
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