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


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.


CONCLUSIONS
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.
Krum
Henry
H
NHMRC 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
Haas
Steven Joseph
SJ
Eichhorn
Eric
E
Ghali
Jalal
J
Gilbert
Edward
E
Lechat
Philippe
P
Packer
Milton
M
Roecker
Ellen
E
Verkenne
Patricia
P
Wedel
Hans
H
Wikstrand
John
J
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002423:Cause of Death; D002908:Chronic Disease; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors