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Perez MI, Musini VM, Wright JM. Effect of early treatment with anti-hypertensive drugs on short and long-term mortality in patients with an acute cardiovascular event. Cochrane Database Syst Rev. 2009;(4):CD006743.
Al-Reesi A, MD; Al-Zadjali N, MD; Perry J, Fergusson D, et al. Do β-blockers reduce short-term mortality following acute myocardial infarction? A systematic review and meta-analysis. CJEM. 2008;10(3):215-23
Sinert R, NewmanDH, Paladino L, Brandler E. Immediate Beta-blockade in Patients with Myocardial Infarctions: Is There Evidence of Benefit? An Evidence-Based Review. Annals of Emergency Medicine. 2010; online,doi:10.1016/j.annemergmed.2010.03.036

Efficacy Endpoints

Mortality

Harm Endpoints

Mortality, Congestive Heart Failure

Narrative

This review examined the effects of beta-blocking agents during major heart attacks ('STEMI'). There are 27 trials and at least 3 systematic reviews addressing this issue. A Cochrane review and a CJEM review from 2008 ask this question: do trials randomizing patients to receive immediate beta-blockers or a control (typically placebo) in the initial phases of a heart attack demonstrate improved outcomes? Both reviews find that they do not. One review (Al-Reesi et al.) suggests a potential benefit in one subgroup (patients with little or no risk of heart failure). However this subgroup analysis is of unclear importance given the clinical heterogeneity and varying quality of the included trials.

One trial has driven a longstanding perception of immediate beta-blockers as beneficial. This is ISIS-1, a large, unblinded trial that found a 0.7% reduction in mortality in the beta-blocker group.1 There are 26 trials prior to ISIS-1, however, that suggest no aggregate mortality benefit to beta-blockade. The lack of blinding in ISIS-1 may therefore explain the 0.7% difference, and a more recent, and larger, trial that utilized double-blind techniques (COMMIT, 2004) found no benefit.2

Harm due to beta-blockers is largely in the form of cardiogenic shock. Because this harm appears to occur in the first day of treatment, while the modest benefits of beta-blockers (0.5% less re-infarction and 0.5% less ventricular arrhythmia)2 occur days later, it seems that immediate treatment is, in aggregate, harmful, while delayed treatment may be modestly beneficial.

Caveats

The third review (Sinert et al), while reaching the same conclusion as the others, asks a more nuanced question: do beta-blockers during STEMI result in improved outcomes? Other reviews have examined studies that randomize to two groups: Early beta-blockade followed by continuing beta-blockade after discharge, versus no early AND no continuing beta-blockade. Because beta-blockers are shown to reduce mortality when given after heart attacks, these reviews have conflated immediate treatment with later treatment. Only one trial (identified by the third review) separated these two elements. However, all other trials are biased in favor of immediate beta-blockers by attributing benefits of delayed treatment to immediate treatment. The lack of a benefit even in these biased analyses suggests strongly that the one large study that found no benefit to immediate treatment was indeed correct.

Virtually all of the high quality studies of this topic have utilized intravenous beta-blocker agents, which may increase cardiogenic shock episodes more than orally ingested versions. These shock episodes may offset potential benefits. Some have argued therefore that oral administration would cause less cardiogenic shock and allow the benefits of the drug to be realized. Though plausible this remains hypothetical and untested, while the overall failure of beta-blockers in the one format studied remains apparent and robust.

Note: We have chosen to list beta-blockers as "No benefits" rather than "Caution" based on the apparently offsetting nature of some small benefits (decreased ventricular arrhythmias and decreased repeat heart attacks) with the established harms. We believe that it is likely that beta-blockers, in aggregate offer no benefit, but we cannot state with confidence that harms overwhelm benefits.

Author

David Newman, MD

Published/Updated

August 19, 2010