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Prognostic benefit of beta-blockers in patients not receiving ACE-Inhibitors
Henry Krum1, Steven Joseph Haas, Eric Eichhorn
1NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University Central and Eastern Clinical School, Alfred Hospital, Melbourne 3004, Australia. henry.krum@med.monash.edu.au
Insights
Beta-blockers (BBs) offer significant survival benefits in systolic chronic heart failure (CHF), even without ACE-Inhibitors (ACE-Is) or ARBs. The prognostic impact of BBs in the absence of these agents is comparable to that of ACE-Is.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Beta-blockers (BBs) are established treatments for systolic chronic heart failure (CHF).
- Major trials have primarily evaluated BBs in patients already receiving ACE-Inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs).
- The prognostic benefit of BBs when used without ACE-Is or ARBs remains unclear.
Purpose of the Study:
- To determine the prognostic benefit of beta-blockers (BBs) in patients with systolic chronic heart failure (CHF) who are not receiving ACE-Inhibitors (ACE-Is) or ARBs.
- To compare the efficacy of BBs with ACE-Is as first-line therapy in systolic CHF.
Main Methods:
- Meta-analysis of placebo-controlled beta-blocker (BB) studies in patients with CHF (n>200).
- Identification of trials through literature searches and contact with study organizations.
- Pooled analysis of all-cause mortality and death or heart failure hospitalization using the Mantel-Haenszel method.
Main Results:
- In the absence of ACE-I or ARB, BBs showed a risk ratio (RR) of 0.73 for all-cause mortality (95% CI 0.53-1.02).
- In the presence of ACE-I or ARB, the RR for BBs was 0.76 (95% CI 0.71-0.83).
- For death or heart failure hospitalization, the RR for BBs was 0.81 (95% CI 0.61-1.08) without ACE-I/ARB and 0.78 (95% CI 0.74-0.83) with ACE-I/ARB.
Conclusions:
- The prognostic benefit of beta-blockers (BBs) in systolic chronic heart failure (CHF) is similar whether or not ACE-Inhibitors (ACE-Is) are used concurrently.
- Either BBs or ACE-Is may serve as initial neurohormonal therapy for systolic CHF.
- Further prospective studies are needed to directly compare BBs and ACE-Is in this patient population.
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.
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