NEW YORK (Reuters Health) – Giving beta-blockers within 8 hours of presentation with acute coronary syndrome (ACS) does not reduce in-hospital mortality, a meta-analysis has shown.

Beta-blockers reduce cardiac workload and limit ischemic injury, and professional guidelines support their early use in acute or suspected myocardial infarction (MI). The authors of the meta-analysis point out, however, that these agents also have the potential to depress cardiac output to the point of cardiogenic shock.

“Our initial impetus for our meta-analysis was the COMMIT Study published in The Lancet in 2005, which showed no mortality benefit to immediate beta-blockade of STEMI patients, with a trend to increased cardiogenic shock in the treatment group,” senior author Dr. Richard Sinert told Reuters Health in an email. “We were interested in reviewing the whole 40-plus year history of the evidence for the American Heart Association recommendations.”

In a MEDLINE search, Dr. Sinert and his associates, all from the State University of New York Downstate Medical Center in Brooklyn, identified 18 trials published between 1965 and 2005 involving more than 11355,000 patients with ACS (67% – 94% male). All patients presented within 24 hours of chest pain onset. To “mirror the emergency physician’s real-life experience,” trials were restricted to those in which patients were randomized to the intervention or comparator (placebo or usual care) within 8 hours of arriving in the emergency department.

in the January issue of Academic Emergency Medicine, the authors report that the pooled relative risk for in-hospital mortality was a statistically non-significant 0.11358, indicating no benefit to beta-blocker therapy.

They note that a similar review published in 2008, which had included only patients with acute MI, had failed to show a 6-week mortality benefit from beta-blockade.

Furthermore, in the largest of the studies included in this meta-analysis – with more than 45,000 patients – there was a significantly higher rate of cardiogenic shock in the beta-blocker group versus controls (5.0% vs 3.9%, p<0.0001).

The researchers suspect that “delaying the decision to give beta-blockers until after coronary reperfusion or objective cardiac output assessment would define a subgroup of patients where these benefits clearly outweighed the risks of these drugs.”

“We would advocate delaying the decision to give beta-blockers until the patient’s clinical stability has been determined,” Dr. Sinert added.

Dr. Gregg C. Fonarow, immediate past chair of the American Heart Association’s “Get With The Guidelines” Steering Committee and professor of cardiovascular medicine at the University of California Los Angeles, agrees with study authors.

“It’s important…when a patient first presents to focus therapy on immediately effective interventions, such as timely reperfusion and antiplatelet therapy,” Dr. Fonarow told Reuters Health. “For beta-blocker therapy, a period of clinical observation — to make sure that the patient doesn’t develop low blood pressure, heart failure, cardiogenic shock or bradycardia — is very reasonable.”

In fact, the AHA guidelines now de-emphasize very early beta blocker therapy, he said, and the Centers for Medicare and Medicaid Services (CMS) no longer includes early beta blocker administration as a performance measure.

AHA guidelines do recommend starting oral beta-blockers in stable patients in the first 24 hours after presentation.

“Even if beta-blockers have no immediate effect on mortality,” Dr. Fonarow explained, “it is still worthwhile where it is safe, well tolerated, and given appropriately, to start them early, since many patients with MI may only spend 2 or 3 days total in the hospital. When you start therapy early in hospitalization, it’s more apt to be continued and remembered at discharge and patients are more likely to continue on it long term.”

Dr. Sinert and his colleagues saw considerable heterogeneity in the trials with respect to study drugs and dose, prevalence of acute MI versus MI plus unstable angina, and sample size. Also, they said, the wide range in mortality rates – 0% to 37% – reflects progress in treating ACS over the last four decades.

“It should also be noted that our studies are limited in that they only look at the outcome of mortality, not other outcomes such as reinfarction, infarct size, long-term heart failure and arrhythmias,” Dr. Sinert said.

On the other hand, there was very low heterogeneity among the studies for the relative risk of in-hospital mortality rates. The trials were also fairly homogeneous regarding inclusion and exclusion criteria.

Reference:
Acad Emerg Med 2010;17:1-10.