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Three Part Question

In [adults with acute coronary syndrome] is [early administration of a beta blocker more effective than withholding a beta blocker] at [reducing in-hospital mortality]?

Clinical Scenario

A 65 year old man arrives at the Emergency Department with a history of crushing chest pain and shortness of breath. His EKG demonstrates ST elevations the inferior leads, his JVP is elevated and you hear inspiratory rales on lung exam. You have read about the benefits of beta-blockers in the acute phase of MI, but are concerned about the risk of cardiogenic shock in this patient with signs of congestive heart failure.

Search Strategy

Medline 1950-6/2009 using the OVID interface


[exp acs or acute coronary syndrome or acute myocard$ infarct$ ti.ab.sh.] AND [exp beta block$ or beta antagonist or propranolol or metoprolol or atenolol or carvedilol or esmolol or bisoprolol ti.ab.sh.] AND (exp clinical trial or randomized control ti.ab.sh.]
LIMIT to English language and humans.

Search Outcome

512 papers were found. A systematic review submitted in 2007 was found. Since 2007 1 additional paper was found. The pertinent findings from each paper are tabulated on the next page.

*OR: Odds ratio, AOR: Adjusted Odds Ratio, CI: Confidence Interval

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Al-Reesi A, Al-Zadjali N et al. 2007 Canada	Meta-analysis of 18 randomized control trials (13 deemed high-quality) dating 1966-2005. 74,643 total patients enrolled, comparing the effect of early intravenous then oral beta-blockers to placebo given within 72 hrs of acute MI on 6-week mortality.	Systematic Review and Meta-analysis	6-week mortality	-No significant reduction in 6-week mortality for all patients receiving beta-blockers vs. placebo. -Significant short-term mortality reduction found (OR 0.93, CI 0.88-0.99) when patients w/ Killip Class III heart failure and above were excluded from the analysis. Benefits were mainly decreased rates of V-fib and re-infarction. -Use of β-blockers was associated with increased rates of cardiogenic shock, mainly in patients presenting with hypotension, tachycardia or Killip Class III heart failure. Increased mortality associated w/ cardiogenic shock offset mortality benefits in these subgroups.	-Patients with strong contraindications to beta blockade (e.g. AV block, HR <40, cardiogenic shock) were excluded in all studies. -All studies followed IV with oral beta blockers on the ward. -Beta-blockers used varied between studies.
Miller C, Roe M, et al. 2007 United States	Retrospective study of 72,054 patients with NSTEMI who were treated with beta-blockers <24 hours after presentation.	Retrospective study	All-cause mortality	Reduced in pts receiving beta-blockers (AOR 0.66, CI 0.6-0.72)	Retrospective study. Patients not randomized.
			Post-admission infarction	Reduced in pts receiving beta-blockers (AOR 0.80, CI 0.72-0.89)
			Heart failure	No significant difference between groups (AOR 1.0, CI 0.92-1.08)
			Cardiogenic shock	Reduced in pts receiving beta-blockers (AOR 0.76, CI 0.67-0.87)

Comment(s)

A good meta-analysis of randomized controlled trials exists with sufficient statistical power to answer the question posed. There is consistent evidence that early administration of beta-blockers in acute coronary syndromes reduces short-term mortality in most patients. However, increased mortality due to cardiogenic shock offsets these benefits when beta-blockers are used in patients presenting with hypotension, tachycardia or Killip Class III-IV heart failure. The COMMIT trial found that cardiogenic shock occurred predominantly in hospital days 0-1 and reasoned that patients with contra-indications to beta-blockade on presentation could be started on oral beta blockers if stabilized by hospital day 2. Mortality rates were similar in study vs. placebo groups for patients with Killip Class II heart failure.

Clinical Bottom Line

Early use of beta blockers (within 48 hours of presentation) significantly reduces short-term mortality in many patients with ACS. Beta-blockers should not be given early to patients at increased risk for cardiogenic shock – those who present with SBP <120, HR >110 or Killip Class II-IV CHF.

References

1. 1. Al-Reesi A, Al-Zadjali N et al. Do β-blockers reduce short-term mortality following acute myocardial infarction? A systematic review and meta-analysis. Canadian Journal of Emergency Medicine 2007;10(3):215-23
2. Miller C, Roe M, et al. Impact of acute beta-blocker therapy for patients with non-ST-segment elevation myocardial infarction. American Journal of Medicine 2007;120(8):685-92