Review: Long term use of ß blockers reduces mortality after myocardial infarction
Freemantle N, Cleland J, Young P, Mason J, Harrison J. ß² Blockade after myocardial infarction: systematic review and meta regression analysis. BMJ 1999 Jun 26,318:1730-7.
Question
In patients with myocardial infarction, do ß² blockers reduce all
cause mortality and recurrent myocardial infarction without adverse
effects?
Data sources
Studies were identified by searching databases from their
inception to 1997 (Medline, EMBASE/Excerpta Medica, Biosis,
Sigle, HealthStar, IHTA, Conference Papers Index, Derwent
Drug File, Dissertation Abstracts, International Pharmaceutical
Abstracts, Pascal, and Science Citation Index). Bibliographies of
relevant studies and reviews were also checked.
Study selection
Randomised controlled trials were selected if treatment
lasted >=1 day, patients had had an MI, and ² blockers were compared
with placebo or other treatments.
Data extraction
Data were extracted on patient numbers and characteristics; type,
route, and dose of treatments; duration of treatment and follow up;
loss to follow up; blinding; concealment of randomisation; study
inclusion and exclusion criteria; and outcomes (deaths, recurrent
myocardial infarction, and withdrawals).
Main results
82 trials met the inclusion criteria (54 234 patients). Short
term (treatment duration <6 weeks from onset of pain) studies (n=51)
had an overall mortality of 10.5%. In these studies, ² blockers did
not reduce mortality (odds ratio (OR) for random-effects model 0.96,
95% CI 0.85 to 1.08); subgroup analyses did not differ in mortality
for individual drugs.
Long term (treatment duration 6 to 48 months) studies (n=31) had a
mortality of 9.71%. Mortality was reduced for all ² blockers
combined (OR 0.77, CI 0.69 to 0.85) and also for metoprolol (OR 0.80,
CI 0.66 to 0.96, 7 studies), propranolol (OR 0.71, CI 0.59 to 0.77, 7
studies), and timolol (OR 0.59, CI 0.46 to 0.77, 2 studies). Drugs with
cardioselectivity showed no reduction in mortality (OR 1.10, CI 0.89 to
1.39). Drugs with intrinsic sympathomimetic activity showed a trend
towards increased mortality (OR 1.19, CI 0.96 to 1.47). Data on
reinfarction showed similar trends for a reduction with long term ²
blocker use. No additional benefit was shown if the initial treatment
started with an intravenous dose (OR 0.87, CI 0.61 to 1.22). Subgroup
analyses did not differ in reductions in mortality over time.
Withdrawal rates ranged from 10% to 30% and were similar in the
treatment and control groups.
Conclusion
Long-term treatment (6 to 48 months) with ² blockers reduces
mortality in patients who have had a myocardial
infarction.
Funding: SmithKline Beecham
EBM-Commentary
² Adrenergic receptor blockade in the acute and the
convalescent phases of myocardial infarction is the standard of
care1 established in a remarkable series of clinical
trials. Despite the evidence, ² blockers after myocardial infarction
continue to be underused.2 Freemantle et al, who have
collated data from many ² blocker trials, have shown that, although
short term use of ² blockers does not decrease mortality, long
term trials of ² blockade show consistent benefit. Early intravenous
treatment with ² blockers in acute myocardial infarction is
recommended by the joint American College of Cardiology and American
Heart Association guidelines for the management of patients with acute
myocardial infarction.1 The present review calls into
question the benefit of early intravenous use of ² blockers in acute
myocardial infarction. The widespread use of thrombolysis and primary
percutaneous coronary angioplasty (where available) improves prognosis
so markedly that any additional short-term benefit of ² blockers may
be hard to prove. Clinicians faced with this question can wonder what
role ² blockers have in treating acute myocardial infarction.
However, the clinical setting often includes an important subset of
patients in whom thrombolysis either fails or results in suboptimal
outcomes.3 Here, ² blockers are likely to improve
mortality, attenuate ischaemic pain, and prevent tachyarrhythmias.
After a myocardial infarction patients often develop further clinical
and subclinical myocardial damage, which can increase the chance of
arrhythmias by altering the heart muscle with more scar tissue.
Therefore, ² blockers should probably be used indefinitely.
Kalyanam Shivkumar University of California at Los Angeles Medical Center, Los Angeles, California, USA
- Ryan TJ, Anderson JL, Antman
EM, Braniff BA, Brooks NH, Califf RM, et al. ACC/AHA
guidelines for the management of patients with acute myocardial
infarction: executive summary. A report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines
(Committee on Management of Acute Myocardial Infarction).
Circulation 1996;94:2341-50.
- Viskin S, Barron HV. Beta blockers
prevent cardiac death following a myocardial infarction: so why are so
many infarct survivors discharged without beta blockers? Am J
Cardiol 1996;78:821-2.
- Davies CH, Ormerod OJ. Failed coronary
thrombolysis. Lancet 1998;351:1191-6.
Freemantle N, Cleland J, Young P, Mason J, Harrison J
Pharmaceuticals UK. Correspondence to: Dr N Freemantle, Medicines Evaluation Group, Centre for Health Economics, University of York, York YO10 5DD, UK (Fax: +44-(0)1904-434568)
studentBMJ 2000;08:175-216 June ISSN 0966-6494
