Signs of Cardioprotection Seen in Acute STEMI Patients Receiving IV Beta-blocker Post-PCI


Patients with STEMI who receive IV infusion of the beta-blocker esmolol within 60 minutes after successful PCI tend to release smaller amounts of cardiac biomarkers than those given placebo, researchers of a single-center, randomized trial reported this week.

Take Home: Signs of Cardioprotection Seen in Acute STEMI Patients Receiving IV Beta-blocker Post-PCI

BEAT-AMI, published in the February 8, 2016 issue of JACC: Cardiovascular Interventions, is not the first trial to show positive results for beta-blocker use in the STEMI setting. Back in 2013, METOCARD-CNIC found that metoprolol given ahead of primary PCI reduced myocardial injury and improved LVEF.

While oral beta-blocker use in the acute phase of acute MI is supported by European and US guidelines, “routine use of intravenous beta-blockade is not recommended,” Fikret Er, MD, of the University Hospital Münster (Gütersloh, Germany), and colleagues write. “This reservation is on the basis of historical trials, which demonstrated risk for cardiogenic shock in patients with severe myocardial infarction, reflected by higher Killip classes.”

Treatment Targets Heart Rate Control

For the single-blind BEAT-AMI trial, the investigators enrolled only patients within 6 hours of symptom onset who had Killip class I or II STEMI. A total of 101 patients were randomly allocated to receive heart rate control with IV esmolol for 24 hours (target of 60 bpm) or placebo. Treatment began within 60 minutes of PCI, after patient transfer from the cath lab to the ICU.

Maximum change in troponin T release, the primary endpoint, was significantly less in the esmolol group, as were levels of peak CK and CK-MB. There also was a trend toward lower peak NT-proBNP with esmolol.

Median Levels Within 48 Hours in STEMI Patients Post-PCI

Cardiogenic shock requiring IV catacholaminergic therapy occurred in 3 patients in the placebo group (1 of whom died) and none in the esmolol group. More patients in the placebo group than in the esmolol group experienced ventricular tachycardia, though the difference did not reach statistical significance.

Two-Pronged Approach to Acute MI

As to what motivated the approach, Er told TCTMD in an email that attempts to influence post-reperfusion recovery is often neglected by physicians. “I think we have a chance to limit myocardial injury by actively controlling the post-PCI phase,” he said, noting this can be done  by controlling sympathetic drive in the very early hours of acute MI. “In our daily ICU visits, we see that heart rate is elevated in post-MI patients,” he added.

This sort of approach is not without precedent, Er stressed. “First-generation cardiologists acted in necessity and were probably right when they administered sedatives for MI,” he said. “We now have the chance to [both achieve] timely reperfusion and control the sympathetic activity with esmolol.”

Er noted no downsides to IV esmolol. “The costs are very low,” he reported. “Few Euros for 24 hours are well invested.”

That the study did not find any difference in clinical outcome is to be expected, Er noted, given that its participants were at low risk. Better understanding of differences would require a larger sample size or higher risk patients, such as those with NSTEMI or subacute MI being treated beyond 6 hours, he said.

Jan J. Piek, MD, PhD, and Martijn A. van Lavieren, MSc, both of Academic Medical Center, University of Amsterdam in the Netherlands, are quick to point out in their editorial numerous limitations to BEAT-AMI. Not only was magnetic resonance imaging not used to quantify final infarct size but there was no exploration of exactly how esmolol might be working. In addition, the study population involved both anterior and nonanterior MIs, they say. “As a result, the present study should be considered a pilot study that warrants further evaluation in a larger randomized, controlled multicenter trial with a focus on elucidating the mechanisms behind the effects of early administration of beta-blockers,” they write.

Like the investigators, the editorialists note that the current findings dovetail with those of METOCARD-CNIC, despite differences in the timing of beta-blocker administration between the 2 studies.

“Rapid reperfusion remains the cornerstone of contemporary STEMI care,” Piek and van Lavieren conclude. Yet in terms of adjunctive therapies, “evidence is accumulating that early administration of beta-blockers is a safe, promising, low-cost therapeutic strategy to further improve clinical outcome in patients with acute coronary syndromes.”


Sources: 
1. Er F, Dahlem KM, Nia AM, et al. Randomized control of sympathetic drive with continuous intravenous esmolol in patients with acute ST-segment elevation myocardial infarction: the BEtA-blocker Therapy in Acute Myocardial Infarction (BEAT-AMI) trial. J Am Coll Cardiol Intv. 2016;9:231-240.
2. Piek JJ, van Lavieren MA. Accelerate and decelerate in primary percutaneous coronary intervention [editorial]. J Am Coll Cardiol Intv. 2016;9:241-243.

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Disclosures
  • The trial was funded by Baxter Healthcare Corporation (Deerfield, Illinois).
  • Er, Piek, and van Lavieren report having no relevant conflicts of interest.

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