In patients with ST-segment elevation myocardial infarction (STEMI), esmolol treatment significantly decreased troponin T, creatine kinase (CK), CK isoenzyme (CK-MB), and n-terminal brain natriuretic peptide (NT-proBNP) release, according to results from the BEAT-AMI (Beta-Blocker Therapy in Acute Myocardial Infarction) trial.
“Although a generally elevated heart rate has been identified as a prognostic indicator in AMI, heart rate has not been evaluated as a potential therapeutic target,” the authors noted in the study, published in JACC: Cardiovascular Interventions. “The hypothesis of this research was whether heart rate modulation might influence the myocardial damage in the period of early PCI in AMI.”
Investigators randomly assigned 101 patients to receive either heart rate control with intravenous esmolol for 24 hours or placebo. The maximum change in troponin T from baseline to 48 hours served as the primary outcome. Secondary end points included CK, CK-MB, NT-proBNP concentrations at 48 hours and echocardiographic ejection fraction at 48 hours, 6 weeks, and 6 months. Researchers also evaluated safety end points including cardiogenic shock, symptomatic bradycardia or hypotension, and re-angina pectoris.
Patients who received sympathetic control with esmolol experienced a median serum troponin T concentration increase from 0.2 ng/mL (interquartile range [IQR]: 0.1-0.7 ng/mL) to 1.3 ng/mL (IQR: 0.6-4.7 ng/mL). Patients who received placebo increased concentrations from 0.3 ng/mL (IQR: 0.1-1.2 ng/mL) to 3.2 ng/mL (IQR: 1.5-5.3 ng/mL; P=.010 for all).
Peak CK, CK-MB, and NT-proBNP levels were lower in the esmolol group compared with placebo—CK: 619 U/L (IQR: 250-1701 U/L) vs 1309 U/L (IQR: 610-2324 U/L); P=.013; CK-MB: 73.5 U/L (IQR: 30-192 U/L) vs 158.5 U/L (IQR: 74-281 U/L); P=.005; NT-proBNP: 1048 pg/mL (IQR: 623-2062 pg/mL) vs 1497 pg/mL (IQR: 739-3318 pg/mL); P=.059.
As for safety end points, 3 patients in the placebo group had cardiogenic shock compared to 0 in the esmolol group. Nonsustained ventricular tachycardia occurred in 11 patients in the placebo group compared to 4 patients in the esmolol group (P=.091). Incidence of ventricular extrasystoles was significantly lower in the esmolol group (27/24 hours, IQR: 16-123 hours) compared to the placebo group (152/24 hours, IQR: 37-418 hours; P=.002).
Baseline serum troponin T was similar in both the esmolol group (0.2 ng/mL; IQR: 0.1-0.7 ng/mL) and placebo group (0.3 ng/mL; IQR: 0.1-1.2 ng/mL). Hypertension and coronary artery disease were common among all patients (54% and 12% respectively), and the baseline heart rate was similar in both groups (esmolol: 79.5 ± 14.7 beats/minute; placebo: 79.4 ± 14.6 beats/minute; P=.97). During the first 24 hours, 19 patients in the esmolol group received an oral beta-blocker compared to 10 patients in the placebo group. Within 48 hours, 45 patients in the esmolol group and 41 in the placebo group also received an oral beta-blocker, after percutaneous coronary intervention.
“The maximum troponin T release was weak, but positively associated with the mean heart rate,” researchers wrote. “In the fitted regression model without interaction term, the effect of esmolol-treatment on troponin T release was statistically significant (P=.011) after adjustment for baseline troponin T (P<.001) and meant heart rate (P=.012).” Furthermore, the troponin T level in the esmolol group was 34% reduced compared with the placebo group, independent of heart rate and baseline concentrations.
Finally, all 4 biomarkers—troponin, CK, CK-MB, and NT-proBNP—were significantly lowered by heart rate control with esmolol treatment. Further studies are needed to determine the effects of esmolol-induced infarct size limitation on clinical outcomes.
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. JACC Cardiovasc Interv. 2016;9(3):231-240. doi: 10.1016/j.jcin.2015.10.035.