Review: Beta Blockers benefit patients with chronic heart failure
Lechat P, Packer M, Chalon S, Cucherat M, Arab
T, Boissel JP. Clinical effects of 
.adrenergic
blockade in chronic heart failure. A meta.analysis of double.blind,
placebo.controlled, randomized trials. Circulation 1998;98:1184.91.
Question
Are beta blockers effective for improving outcomes in
patients with chronic heart failure?
Data sources
Studies were identified by searching Medline and
meeting abstracts; by scanning bibliographies of
relevant studies; and by contacting colleagues, investi.
gators, and pharmaceutical sponsors.
Study selection
Studies were selected if they were randomised, double
blind, placebo controlled studies of beta blockers in
patients with chronic heart failure. Studies were
excluded if patients had had a recent myocardial
infarction, xamoterol was used, or the beta blocker was
given only once.
Data extraction
Data were extracted on specific beta blockers and other
drugs used, the cause of chronic heart failure, New
York Heart Association (NYHA) class, treatment dura.
tion, and main outcomes: all cause mortality, hospitali.
sation for chronic heart failure, the combined end
point of all cause mortality and hospitalisation for
chronic heart failure, functional status, and left
ventricular ejection fraction.
Main results
Altogether 18 trials met the inclusion criteria. Treatment
duration ranged from 1.5 to 44 months (mean 7
months). Most patients had NYHA class II or III
symptoms during treatment with diuretics, angiotensin
converting enzyme inhibitors, and digoxin. Results were
pooled by using a fixed effects model for all outcomes
except functional status, which used a random effects
model. Compared with placebo, beta blockers reduced
death (18 studies, P = 0.003), hospital admissions for
chronic heart failure (18 studies, P < 0.001), death and
admission to hospital for chronic heart failure (9 studies,
P < 0.001), and the number of patients with a deteriora.
tion in NYHA class (16 studies, P = 0.03) and increased
the number of patients with an improvement in NYHA
class (16 studies, P = 0.04) (table) and mean left ventricu.
lar ejection fraction (mean increase 29%, P < 0.001).
Trials using non-selective beta blockers showed a greater
reduction in mortality than did those using selective
beta blockers. For all other outcomes, treatment effects were
similar for selective and non-selective beta blockers.
|
beta Blockers versus placebo for heart failure at a mean follow up of 7 months*
|
 |
| |
Weighted event rates (%) |
|
| |
|
|
| Outcomes |
 blockers |
Placebo |
Relative risk reduction (%) (95% Cl) |
No need to treat (Cl) |
|
| All cause mortality |
9 |
12 |
27 (10 to 41) |
40 (24 to 149) |
|
| Admission to hospital for chronic heart failure |
13 |
17 |
35 (22 to 46) |
24 (16 to 51) |
|
| Combined end point+ |
19 |
25 |
30 (18 to 39) |
16 (11 to 28) |
|
| Functional deterioration |
11 |
15 |
24 (1 to 41) |
25 (13 to 220) |
|
| Functional improvement |
26 |
21 |
22 (0 to 47)# |
20 (11 to 189) |
|
| * Relative risk reduction, relative benefit increase, number needed to treat, and confidence interval calculated from data in article.
+ All cause mortality plus admission to hospital for heart failure.
# Relative benefit increase. |
Conclusion
In patients with chronic heart failure, blockers reduce
death and admission to hospital for chronic heart fail.
ure and improve functional status and left ventricular
ejection fraction.
Funding: Source not stated.
EBM - Commentary
The merits of beta blockers in chronic heart failure have been vigorously
debated for years. A class of drugs once thought forbidden in patients with
chronic heart failure is now widely considered to be beneficial. The
increasing number of positive trials has led to increased use of beta blockers,
particularly carvedilol.
In this valuable review, Lechat et al showed that ejection fraction, morbidity, and mortality outcomes were improved by beta blockers. They also pointed out that meta.analysis, as a research tool, cannot always clarify the
usefulness of certain agents in specific subsets of heterogeneous patient
populations. One trial of bisoprolol1 and one unpublished trial of
metropolol2 support the general conclusion that beta blockers benefit patients with NYHA class II and III chronic heart failure.
In addition to being a non.selective beta blocker, carvedilol has the pharmacologic properties of a beta blocker as well as having putative
antioxidant effects. Non.selective beta blockers (primarily carvedilol) were
associated with a greater survival benefit in this review. Lechat et al pointed
out that ongoing studies are testing the hypothesis that non.selective beta
blockers show a greater benefit than selective agents.
The question remains whether all patients with chronic heart failure can benefit from beta blockers. The answer will probably be "no." The trials to date reflect an unavoidable selection bias and include patients with primarily NYHA class II and III symptoms. The present recommendations for slow
titration of carvedilol treatment under direct supervision should be
considered a necessary haemodynamic precaution. We have, however, more
data on outcomes with carvedilol now than we had on digitalis (until the
Digitalis Investigation Group trial3) during centuries of use. Patients who tolerate carvedilol titration have better outcomes than similar patients who
are treated with placebo.
John F Schmedtje Jr Wake Forest University Baptist Medical Center,
Winston.Salem, North Carolina, USA
- The International Steering Committee Am J Cardiol 1997;80:54J.8J.
- The CIBIS II Investigators and Cornmittees. Lancet 1999;353:9.13.
- The Digitalis Investigation Group. N Engl J Med 1997;336:525.33.
Lechat P, Packer M, Chalon S, Cucherat M, Arab T, Boissel JP
studentBMJ 2000;08:45-88 March ISSN 0966-6494
