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Clinical Question:
Does the early use of metoprolol improve outcomes in patients with acute
myocardial infarction?
Bottom Line:
The early use of metoprolol in patients with acute myocardial infarction who
are also receiving thrombolytics and aspirin provides no short-term benefit
compared with placebo. Since the early use, however, increases the risk of
cardiogenic shock, it may be wise to delay starting metoprolol until the
patient is hemodynamically stable. (LOE = 1b)
Reference:
Chen ZM, Pan HC, Chen YP, et al for the COMMIT (ClOpidogrel and Metoprolol
in Myocardial Infarction Trial) Collaborative Group. Early intravenous then
oral metoprolol in 45,852 patients with acute myocardial infarction:
randomised placebo-controlled trial. Lancet 2005; 366:1622-32.
Study Design:
Randomized controlled trial (double-blinded)
Synopsis:
Despite previous randomised trials of early beta-blocker therapy in the
emergency treatment of myocardial infarction (MI), uncertainty has persisted
about the value of adding it to current standard interventions (eg, aspirin
and fibrinolytic therapy), and the balance of potential benefits and hazards
is still unclear in high-risk patients. 45,852 patients admitted to 1250
hospitals within 24 h of suspected acute MI onset were randomly allocated
metoprolol (up to 15 mg intravenous then 200 mg oral daily; n=22,929) or
matching placebo (n=22,923). 93% had ST-segment elevation or bundle branch
block, and 7% had ST-segment depression. Treatment was to continue until
discharge or up to 4 weeks in hospital (mean 15 days in survivors) and 89%
completed it. The two prespecified co-primary outcomes were: (1) composite
of death, reinfarction, or cardiac arrest; and (2) death from any cause
during the scheduled treatment period. Comparisons were by intention to
treat, and used the log-rank method. This study is registered with
ClinicalTrials.gov, number NCT 00222573. Neither of the co-primary outcomes
was significantly reduced by allocation to metoprolol. For death,
reinfarction, or cardiac arrest, 2166 (9.4%) patients allocated metoprolol
had at least one such event compared with 2261 (9.9%) allocated placebo
(odds ratio [OR] 0.96, 95% CI 0.90-1.01; p=0.1). For death alone, there were
1774 (7.7%) deaths in the metoprolol group versus 1797 (7.8%) in the placebo
group (OR 0.99, 0.92-1.05; p=0.69). Allocation to metoprolol was associated
with five fewer people having reinfarction (464 [2.0%] metoprolol vs 568
[2.5%] placebo; OR 0.82, 0.72-0.92; p=0.001) and five fewer having
ventricular fibrillation (581 [2.5%] vs 698 [3.0%]; OR 0.83, 0.75-0.93;
p=0.001) per 1000 treated. Overall, these reductions were counterbalanced by
11 more per 1000 developing cardiogenic shock (1141 [5.0%] vs 885 [3.9%]; OR
1.30, 1.19-1.41; p<0.00001). This excess of cardiogenic shock was mainly
during days 0-1 after admission, whereas the reductions in reinfarction and
ventricular fibrillation emerged more gradually. Consequently, the overall
effect on death, reinfarction, arrest, or shock was significantly adverse
during days 0-1 and significantly beneficial thereafter. There was
substantial net hazard in haemodynamically unstable patients, and moderate
net benefit in those who were relatively stable (particularly after days
0-1). |