From the Service de Pharmacologie, Hôpital
Pitié-Salpêtrière, Paris, France; the Division of
Circulatory Physiology, Columbia University, College of Physicians and
Surgeons, New York, NY; and the Unité de Pharmacologie Clinique,
Hôpitaux de Lyon, Lyon, France.
Background—ß-Blockers have
improved symptoms and reduced the risk of
cardiovascular events in studies of patients with heart
failure, but it is unclear which end points are most sensitive to the
therapeutic effects of these drugs.
Methods and Results—We combined the results of all 18 published
double-blind, placebo-controlled, parallel-group trials of ß-blockers
in heart failure. From this combined database of 3023 patients, we
evaluated the strength of evidence supporting an effect of treatment on
left ventricular ejection fraction, NYHA functional class,
hospitalizations for heart failure, and death. ß-Blockers exerted
their most persuasive effects on ejection fraction and on the combined
risk of death and hospitalization for heart failure. ß-Blockade
increased the ejection fraction by 29%
(P<10-9) and reduced the combined risk of
death or hospitalization for heart failure by 37%
(P<0.001). Both effects remained significant even if
>90% of the trials were eliminated from the analysis or if a
large number of trials with a neutral result were added to the
analysis. In contrast, the effect of ß-blockade on NYHA
functional class was of borderline significance (P=0.04)
and disappeared with the addition or removal of only 1 moderate-size
study. Although ß-blockade reduced all-cause mortality by 32%
(P=0.003), this effect was only moderately robust and
varied according to the type of ß-blocker tested, ie, the reduction
of mortality risk was greater for nonselective ß-blockers than for
ß1-selective agents (49% versus 18%,
P=0.049). However, selective and nonselective
ß-blockers did not differ in their effects on other measures of
clinical efficacy.
Conclusions—These analyses indicate that there is
persuasive evidence supporting a favorable effect of ß-blockade on
ejection fraction and the combined risk of death and hospitalization
for heart failure. In contrast, the effect of these drugs on other end
points requires additional study.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Clinical Effects of ß-Adrenergic Blockade in Chronic Heart Failure
A Meta-Analysis of Double-Blind, Placebo-Controlled, Randomized Trials
Key Words: heart failure • meta-analysis • receptors, adrenergic, ß • trials
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