Papamichalis P, Papathanasiou SK, Skoura AL, Oikonomou KG, Xanthoudaki M, Papadogoulas A, Valsamaki A, Plageras D, Papamichalis M, Katsiafylloudis P, Papapostolou E, Mantzarlis K, Koukoulis A, Koukoulis GD, Parisi K, Papapostolou G, Siokas V, Dardiotis E, Chovas A. Correlation between esmolol usage in the acute phase of ischemic stroke and outcomes of patients undergoing intravenous thrombolysis. World J Clin Cases 2026; 14(8): 117167 [DOI: 10.12998/wjcc.v14.i8.117167]
Corresponding Author of This Article
Panagiotis Papamichalis, MD, PhD, Intensive Care Unit, General Hospital of Larissa, 1 Tsakalof, Larissa 41221, Thessaly, Greece. ppapamih@med.uth.gr
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Neurosciences
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Retrospective Study
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Mar 16, 2026 (publication date) through Mar 28, 2026
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World Journal of Clinical Cases
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Papamichalis P, Papathanasiou SK, Skoura AL, Oikonomou KG, Xanthoudaki M, Papadogoulas A, Valsamaki A, Plageras D, Papamichalis M, Katsiafylloudis P, Papapostolou E, Mantzarlis K, Koukoulis A, Koukoulis GD, Parisi K, Papapostolou G, Siokas V, Dardiotis E, Chovas A. Correlation between esmolol usage in the acute phase of ischemic stroke and outcomes of patients undergoing intravenous thrombolysis. World J Clin Cases 2026; 14(8): 117167 [DOI: 10.12998/wjcc.v14.i8.117167]
Panagiotis Papamichalis, Katerina G Oikonomou, Maria Xanthoudaki, Antonios Papadogoulas, Periklis Katsiafylloudis, Evangelia Papapostolou, Kyriaki Parisi, Achilleas Chovas, Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Thessaly, Greece
Sophia K Papathanasiou, Dimitrios Plageras, Department of Internal Medicine, General Hospital of Larissa, Larissa 41221, Thessaly, Greece
Apostolia Lemonia Skoura, Department of Transfusion Medicine, University Hospital of Larissa, Larissa 41110, Thessaly, Greece
Asimina Valsamaki, Konstantinos Mantzarlis, Department of Critical Care, University Hospital of Larissa, Larissa 41110, Thessaly, Greece
Michail Papamichalis, Department of Cardiology, University Hospital of Larissa, Larissa 41110, Thessaly, Greece
Athanasios Koukoulis, Faculty of Medicine, University of Thessaly, Larissa 41500, Thessaly, Greece
Georgios D Koukoulis, Department of Surgery, General Hospital of Larissa, Larissa 41221, Greece
Grigorios Papapostolou, Department of Neurology, General Hospital of Larissa, Larissa 41221, Thessaly, Greece
Vasileios Siokas, Efthimios Dardiotis, Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Mezourlo Hill, Larissa 41110, Thessaly, Greece
Author contributions: Papamichalis P, Papathanasiou SK, Skoura AL, and Oikonomou KG designed the article; Skoura AL, Xanthoudaki M, Papadogoulas A, Valsamaki A, Plageras D, Papamichalis M, Katsiafylloudis P, Papapostolou E, Koukoulis A, Koukoulis GD, Parisi K, Papapostolou G, and Siokas V assisted in data gathering; Papamichalis P, Papathanasiou SK, Skoura AL, and Oikonomou KG wrote the final version of the manuscript; Oikonomou KG performed English editing; Papamichalis P and Papathanasiou SK performed statistical analysis; Mantzarlis K, Siokas V, Dardiotis E, and Chovas A critically reviewed the paper; All authors have read and approve the final manuscript.
Institutional review board statement: The study was approved by the Institutional Review Board of General Hospital of Larissa, approval number 234 (February 5, 2025).
Informed consent statement: Due to the retrospective nature of the study and in accordance with the Institutional review board statement, informed consent statement was waived.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
Data sharing statement: Data that support the findings of this study will be available upon request at the e-mail address of the corresponding author (ppapamih@med.uth.gr) for research purposes.
Corresponding author: Panagiotis Papamichalis, MD, PhD, Intensive Care Unit, General Hospital of Larissa, 1 Tsakalof, Larissa 41221, Thessaly, Greece. ppapamih@med.uth.gr
Received: December 1, 2025 Revised: January 31, 2026 Accepted: February 25, 2026 Published online: March 16, 2026 Processing time: 106 Days and 9.2 Hours
Abstract
BACKGROUND
Arterial blood pressure (ABP) management is critical in the acute phase of an ischemic stroke, especially during intravenous thrombolysis (IT). Esmolol is one of the commonly prescribed antihypertensive agents for managing ABP.
AIM
To examine a possible neuroprotective activity of esmolol in patients with acute ischemic stroke (AIS) undergoing IT.
METHODS
This study retrospectively examined data from the thrombolysis database of General Hospital of Larissa. The National Institutes of Health Stroke Scale (NIHSS) score, predisposing factors, length of stay (LOS), need for advanced critical/neurocritical care, primary adverse events, mortality, functional outcomes, and 3-month survival rates of 26 patients [mean NIHSS score: 11 (range: 3-23)] who underwent IT with alteplase for AIS and esmolol therapy for control of heart rate and/or ABP management at the acute phase (within the first 72 hours from AIS onset) were compared with those of 123 patients [mean NIHSS score: 11 (range: 2-28)] who underwent alteplase but not esmolol therapy during the same time period for AIS. Subgroup analysis was performed with the following patient groups: Patients without arrhythmia-atrial fibrillation (AF) (n = 95): Esmolol-treated (n = 8) and esmolol-untreated subgroups (n = 87); patients with AF (n = 54): Esmolol-treated (n = 18) and esmolol-untreated subgroups (n = 36); patients with a history of hypertension (n = 97): Esmolol-treated (n = 22) and esmolol-untreated subgroups (n = 75); patients without a history of hypertension (n = 52): Esmolol-treated (n = 4) and esmolol-untreated subgroups (n = 48).
RESULTS
In the overall cohort, the AF (69.2% vs 29.3%; P < 0.001) and hypertension (84.6% vs 61%; P = 0.022) incidence rates at baseline in the esmolol-treated group were higher than those in the esmolol-untreated group. The esmolol-treated group exhibited increased LOS, need for advanced critical/neurocritical care and incidence of poor functional outcome rates (P = 0.001, P = 0.003, and P = 0.023, respectively). Subgroup analysis revealed similar outcomes for patients without AF who underwent IT and esmolol therapy [increased LOS (P = 0.006), need for advanced critical/neurocritical care (P = 0.026), incidence of primary adverse events (P = 0.034), and 3-month mortality rates (P = 0.048)] and those without a history of hypertension who underwent IT and esmolol therapy [increased LOS (P = 0.03), need for advanced critical/neurocritical care (P = 0.003), incidence of primary adverse events (P = 0.013), and poor functional outcome rates (P = 0.019)]. Esmolol usage was not correlated with the clinical outcomes in patients with AF. In patients with a history of hypertension, esmolol usage was correlated only with LOS (P = 0.013).
CONCLUSION
Our study found that esmolol therapy was correlated with worse outcomes, worse survival rates and more complications in the whole study group, and these effects were more apparent in the subgroups of esmolol-treated patients without AF and without a history of hypertension, while patients with AF presented no differences and patients with a history of hypertension presented minimal differences in outcomes that could be associated with esmolol. Further studies are needed to investigate the role of esmolol at the acute phase of ischemic strokes.
Core Tip: Various drugs, including esmolol, are used for managing elevated arterial blood pressure before intravenous thrombolysis for acute ischemic stroke. This study evaluated baseline characteristics and outcomes of 149 patients with a focus on esmolol-treated and esmolol-untreated groups. Sub-group analysis was performed to compare the outcomes between the esmolol-treated and esmolol-untreated subgroups among the following patient groups: Patients with atrial fibrillation (AF); patients without AF; patients with a history of hypertension; patients without a history of hypertension. Esmolol usage resulted in poor outcomes for the overall cohort, patients without AF, and patients without a history of hypertension but not for patients with AF and patients with a history of hypertension.
Citation: Papamichalis P, Papathanasiou SK, Skoura AL, Oikonomou KG, Xanthoudaki M, Papadogoulas A, Valsamaki A, Plageras D, Papamichalis M, Katsiafylloudis P, Papapostolou E, Mantzarlis K, Koukoulis A, Koukoulis GD, Parisi K, Papapostolou G, Siokas V, Dardiotis E, Chovas A. Correlation between esmolol usage in the acute phase of ischemic stroke and outcomes of patients undergoing intravenous thrombolysis. World J Clin Cases 2026; 14(8): 117167
Maintaining arterial blood pressure (ABP) within the range that international guidelines recommend before the initiation of intravenous thrombolysis (IT) is a prerequisite for starting the administration of the thrombolytic agent and influences outcome in acute ischemic strokes (AISs)[1,2]. Previous studies have revealed that the correlation curve between ABP levels and poor outcomes in AIS is U-shaped. This is mainly attributed to several mechanisms, such as cerebral autoregulation and recanalization status[3-5]. Aberrantly elevated levels of systolic and/or diastolic blood pressure (BP) in the acute phase of ischemic strokes in patients undergoing thrombolytic therapy are associated with increased rates of intracranial hemorrhage[2,6]. Thus, a strict 24-hour monitoring of ABP must be implemented during stroke thrombolysis (every 15 minutes during alteplase infusion and for the first 2 hours, every 30 minutes for 6 hours, and every 60 minutes for 16 hours). Previous studies have examined the effects of ABP variations on the clinical outcomes of stroke for up to 72 hours post-IT[7,8].
However, a specific strategy for managing ABP that improves the outcomes in AIS has not been established. Apart from the well-defined upper acceptable limits of systolic BP (185 mmHg), or diastolic BP (110 mmHg) before IT initiation[1], other relative issues still remain under investigation such as the rate with which elevated ABP should decline, the desired cut-off point of the decrease, the pharmacological agents that are more efficient for this purpose. Esmolol, a cardioselective beta 1 receptor blocker, is one of the commonly prescribed intravenous antihypertensive agents.
This study aimed to evaluate the effect of esmolol on the clinical outcomes of patients with AIS who underwent IT.
MATERIALS AND METHODS
Study design
This retrospective single-center (Intensive Care Unit of General Hospital of Larissa) study analyzed prospectively collected medical data of 149 consecutive patients. Patients’ characteristics were as follows: Median age: 69 years (range: 30-88 years); median National Institutes of Health Stroke Scale (NIHSS) score at admission: 11 (range: 2-28). All patients underwent IT with alteplase for AIS fulfilling the international inclusion and exclusion criteria[1,9]. The baseline data, including demographic characteristics, AIS predisposing factors [diabetes mellitus, arrhythmia-atrial fibrillation (AF), hypertension, smoking status, hyperlipidemia, vascular disease, and previous ischemic stroke occurrence], stroke neurological severity score (NIHSS score at admission), and the therapeutic window (symptom-to-needle time) were recorded. This study compared the clinical characteristics and outcomes of patients who received esmolol during IT or within the first 72 hours from the onset of symptoms (n = 26) (esmolol-treated group) with those patients who did not receive esmolol during the same period (n = 123) (esmolol-untreated group). The time frame of 72 hours was selected as it represents the acute phase of an ischemic stroke and is based on the findings of previous studies on the correlation of ABP with clinical outcomes[8]. The following safety and efficacy outcomes were evaluated: Length of stay (LOS), need for advanced critical/neurocritical care [intubation, mechanical ventilation, hemodynamic inotropic support, surgical interventions (craniectomy, positioning of an intracranial pressure or a multimodal brain monitoring catheter)], primary adverse events [symptomatic intracranial hemorrhage (n = 1), and/or death (n = 5), and/or serious systemic bleeding and/or new stroke (n = 1)], mortality at 3 months, and performance/disability status at 3 months [evaluated with assessment of modified Rankin Scale (mRS)]. The mRS was assessed either after patients’ visit and examination or by telephone estimation when in person assessment was not possible. It was recorded both as an absolute value and a categorical variable [favorable (mRS ≤ 2) and unfavorable (mRS > 2)]. The cut-off value for the mRS score was based on previous studies[10]. The Kaplan-Meier curve for 3-month survival was plotted.
The correlation of esmolol usage with poor clinical outcomes can be misleading due to the increased frequency of esmolol use among patients with AF or those with a history of hypertension, who receive esmolol often for rate or hypertension control respectively. Additionally, patients with AF and/or hypertension are susceptible to severe strokes, which are associated with worse outcomes[11-13]. Thus, this study performed subgroup analyses. In particular, the baseline characteristics and outcomes of the following patient groups were analyzed based on esmolol usage: Patients with AF (n = 54): Esmolol-treated (n = 18) and esmolol-untreated subgroups (n = 36); patients without AF (n = 95): Esmolol-treated (n = 8) and esmolol-untreated subgroups (n = 87); patients with a history of hypertension (n = 97): Esmolol-treated (n = 22) and esmolol-untreated subgroups (n = 75); patients without a history of hypertension (n = 52): Esmolol-treated (n = 4) and esmolol-untreated subgroups (n = 48).
The Kaplan-Meier survival curves of patients in different subgroups for 3-month survival were plotted.
This study was approved by the institutional review board of General Hospital of Larissa [Approval number: 234 (February 5, 2025)].
Statistical analysis
All statistical analyses were performed using the SPSS (version 26) package (IBM Corp., Armonk, NY, United States). Data are expressed as median (range) or n (%), where applicable. Chi-square (χ²) test with Yates’ correction, Fisher’s exact test, and Mann-Whitney U-test were used to compare the data, where applicable. The survival probability was determined using Kaplan-Meier analysis. Differences were considered significant at P < 0.05 (two-sided test).
RESULTS
The demographic characteristics of the study population (n = 149) are presented in Table 1.
Table 1 Clinical characteristics of the study cohort (n = 149), n (%)/median (range).
Regarding baseline characteristics, the incidence rates of hypertension [84.6% (n = 22) vs 61% (n = 75); P = 0.022] and arrhythmia-AF [69.2% (n = 18) vs 29.3% (n = 36); P < 0.001] in the esmolol-treated group were higher than those in the esmolol-untreated group. Regarding outcomes, increased LOS [5 days (range: 1-52 days) vs 3 days (range: 1-52 days); P = 0.001], need for advanced critical/neurocritical care [30.8% (n = 8) vs 7.3% (n = 9); P = 0.003], mRS score [3.5 (range: 0-6) vs 1 (range: 0-6); P = 0.023], and frequency of unfavorable functional outcomes (mRS > 2) [57.7% (n = 15) vs 30.1% (n = 37); P = 0.007] in the esmolol-treated group relative to the esmolol-untreated group, were positively correlated with esmolol use (Table 2).
Table 2 Clinical characteristics of the esmolol-untreated (n = 123) and esmolol-treated (n = 26) groups and the safety and efficacy assessments of esmolol, n (%)/median (range).
The baseline characteristics of the esmolol-treated subgroup (n = 22) were not significantly different from those of the esmolol-untreated subgroup (n = 75) in patients with a history of hypertension (n = 97). Among the evaluated outcomes, only LOS in the esmolol-treated subgroup was significantly higher than that in the esmolol-untreated subgroup [4 days (range: 1-52 days) vs 3 days (1-52 days); P = 0.013] (Table 3).
Table 3 Clinical characteristics of the esmolol-treated (n = 22) and esmolol-untreated (n = 75) subgroups among patients with hypertension (n = 97) and the safety and efficacy assessments of esmolol, n (%)/median (range).
In patients without a history of hypertension (n = 52), the baseline characteristics of the esmolol-treated subgroup (n = 4) were not significantly different from those of the esmolol-untreated subgroup (n = 48). Additionally, the esmolol-treated group exhibited increased LOS [26 days (range: 2-39 days) vs 2 (range: 1-36 days); P = 0.03], need for advanced critical/neurocritical care [75% (n = 3) vs 6.2% (n = 3); P = 0.003], rates of primary adverse events [50% (n = 2) vs 2.1% (n = 1); P = 0.013], and mRS scores [5 (range: 0-6) vs 1 (range: 0-6); P = 0.019] when compared with the esmolol-untreated subgroup (Table 4).
Table 4 Clinical characteristics of the esmolol-untreated (n = 48) and esmolol-treated (n = 4) subgroups among patients without hypertension (n = 52) and the safety and efficacy assessments of esmolol, n (%)/median (range).
Regarding baseline characteristics, in patients without arrhythmia-AF (n = 95), the incidence of previous ischemic stroke in the esmolol-treated subgroup (n = 8) was significantly higher than that in the esmolol-untreated subgroup (n = 87) [50% (n = 4) vs 11.5% (n = 10); P = 0.015]. Regarding outcomes, the esmolol-treated subgroup exhibited increased LOS [9 days (range: 1-52 days) vs 2 days (range: 1-52 days); P = 0.006], need for advanced critical/neurocritical care [37.5% (n = 3) vs 6.9% (n = 6); P = 0.026], incidence of primary adverse events [25% (n = 2) vs 2.3% (n = 2); P = 0.034], and 3-month mortality rate [37.5 % (n = 3) vs 9.2% (n = 8); P = 0.048] when compared with the esmolol-untreated subgroup (Table 5). When the abovementioned outcomes were compared at patients with and without a history of former ischemic stroke, no statistically significant differences were found: The LOS [3 days (1-52 days) vs 2 days (1-52 days); P = 0.14], the need for advanced critical/neurocritical care [14.3% (n = 2) vs 8.6% (n = 2); P = 0.62], the occurrence of primary adverse events [7.1% (n = 1) vs 3.7% (n = 3); P = 0.48], and 3-month mortality rate [21.4% (n = 3) vs 9.9% (n = 8); P = 0.2] in patients with a history of previous ischemic stroke were not significantly different from those in patients without a history of previous ischemic stroke.
Table 5 Clinical characteristics of the esmolol-untreated (n = 87) and esmolol-treated (n = 8) subgroups among patients without arrythmia (n = 95) and the safety and efficacy assessments of esmolol, n (%)/median (range).
In patients with AF (n = 54), the baseline characteristics and clinical outcomes were not significantly different between the esmolol-treated (n = 18) and esmolol-untreated subgroups (n = 36) (Table 6).
Table 6 Clinical characteristics of the esmolol-untreated (n = 36) and esmolol-treated (n = 18) subgroups among patients with arrhythmia-atrial fibrillation (n = 54) and the safety and efficacy assessments of esmolol, n (%)/median (range).
Kaplan-Meier survival analysis was performed to assess the 90-day survival rates of the esmolol-treated and esmolol-untreated groups and subgroups.
In the overall cohort, the 90-day survival rates were not significantly different between the esmolol-treated (76%) and esmolol-untreated groups (88%) (log-rank test; P = 0.077) (Figure 1A).
Figure 1 Kaplan-Meier 90-day survival curves.
A: Kaplan-Meier 90-day survival curves for all patients undergoing intravenous thrombolysis (IT) for acute ischemic stroke (AIS). The 90-day survival rates in the esmolol-treated subgroup (76%) were non-significantly lower than those in the esmolol-untreated group (88%) (log-rank test; P = 0.077); B: Kaplan-Meier 90-day survival curves of the esmolol-treated and esmolol-untreated subgroups among patients without atrial fibrillation who underwent IT for AIS. The survival rates in the esmolol-treated subgroup (62%) were significantly lower than those in the esmolol-untreated subgroup (88%) (log-rank test; P = 0.009).
In patients without AF, the 90-day survival rate in the esmolol-treated subgroup (62%) was significantly lower than that in the esmolol-untreated subgroup (88%) (log-rank test; P = 0.009) (Figure 1B).
The 90-day survival rates were not significantly different between the esmolol-treated and esmolol-untreated subgroups in patients with AF, with a history of hypertension, or without a history of hypertension (log-rank test; P = 0.807, 0.23, or 0.13, respectively) (Figure 2).
Figure 2 Kaplan-Meier 90-day survival curves.
A: Kaplan-Meier 90-day survival curves of the esmolol-treated and esmolol-untreated subgroups among patients with atrial fibrillation who underwent intravenous thrombolysis (IT) for acute ischemic stroke (AIS). The survival rates were not significantly different between the esmolol-treated and esmolol-untreated subgroups (log-rank test; P = 0.807); B: Kaplan-Meier 90-day survival curves of the esmolol-treated and esmolol-untreated subgroups among patients with a history of hypertension who underwent IT for AIS. The survival rates were not significantly different between the esmolol-treated and esmolol-untreated subgroups (log-rank test; P = 0.23); C: Kaplan-Meier 90-day survival curves of the esmolol-treated and esmolol-untreated subgroups among patients without a history of hypertension who underwent IT for AIS. The survival rates were not significantly different between the esmolol-treated and esmolol-untreated subgroups (log-rank test; P = 0.13).
DISCUSSION
Esmolol, a beta-blocker with antiarrhythmic and antihypertensive activities, is indicated for the management of several hypertensive emergencies, such as acute aortic dissection, preeclampsia, Hemolysis-Elevated Liver enzymes-Low Platelets syndrome, eclampsia, acute heart failure, pulmonary edema, and acute coronary syndrome[14]. It is reported to exert neuroprotective effects against brain ischemia in animal models or anti-immunosuppressive effects in humans. Thus, the therapeutic effects of esmolol in AISs can be attributed to its anti-inflammatory and antioxidative properties and its inhibitory effects on sympathetic nervous system activation[15-18]. Characteristics derived from its pharmacokinetic and pharmacodynamics profile are: Rapid onset of action, easy titration, and quick cessation of action after withdrawal or dose reduction, resulting in an ideal safety profile for critically ill patients[19,20]. Therefore, esmolol is the preferred therapeutic agent for refractory hypertension. Similar to other intravenous antihypertensive drugs, esmolol requires close ABP and preferably electrocardiographic monitoring. The contraindications of esmolol usage include preexisting systolic heart failure, asthma, second-degree or third-degree atrioventricular heart block, and sick sinus syndrome. Meanwhile, its rare adverse effects include hypotension, bradycardia, cardiac arrest, heart block, lower limb ischemia, dizziness, skin site reaction, and bronchospasm[21].
Limited studies have reported the usage of esmolol in the acute phase of ischemic strokes, especially in patients who are candidates for reperfusion therapies[22,23]. Compared with other antihypertensive agents, esmolol was demonstrated to be safe for patients with AIS and similarly effective. These findings are not consistent with those of this study. Patients who received esmolol during the first 72 hours of stroke occurrence exhibited poor functional outcomes, increased LOS and need for advanced critical/neurocritical care. Meta-analyses or randomized controlled studies have not been performed to evaluate the role of esmolol in AIS management. Labetalol is the most commonly used and well-studied beta-blocker for AIS management[14]. Although the administration of beta-blockers has been associated with decreased mortality in patients with AIS[24,25], a meta-analysis by Balla et al[26] revealed that the use of beta-blockers was not associated with beneficial effects in these patients. Since the administration of beta-blockers can indicate underlying severe vascular disease, it may not be a direct cause of adverse outcomes. Further studies are needed to clarify the effect of beta-blockers, especially esmolol, on AIS outcomes.
In this study, the frequency of esmolol usage was higher in patients with AF and those with a medical history of hypertension. Consistently, previous studies have reported that AF and hypertension are major predisposing factors for AIS and esmolol is one of the most commonly used medications for AIS management. In patients with AF, the outcomes (LOS, need for advanced critical/neurocritical care, rates of primary adverse events, and 3-month mortality) in the esmolol-treated subgroup were not significantly different from those in the esmolol-untreated subgroup. Thus, frequent esmolol usage did not result in worse outcomes in these patients. This is the first study to report preferable esmolol usage in selective groups, indicating that esmolol is a safe and effective medication when administered according to its main indications (rate control and management of hypertension in patients with AF who are undergoing IT). For patients without AF who are undergoing IT, an alternative antihypertensive agent can be chosen. This targeted approach based on the characteristics of patients (such as co-morbidities) and the indications and side-effect profiles of the drugs can yield improved outcomes.
The effect of esmolol in patients without AF cannot be attributed to ABP decline, since ABP is closely monitored in patients undergoing IT. Similarly, it cannot be attributed to the frequent incidence of previous ischemic stroke, since the outcomes of patients with previous ischemic stroke were similar to those of patients without former ischemic stroke. It may involve more complex hemodynamic actions: Esmolol is a cardioselective beta-1 receptor inhibitor. In sinus rhythm it affects both heart rate (HR) and contractility, finally decreasing cardiac output (CO) [CO = HR × stroke volume (SV)]. Both HR and SV decrease in patients without AF when esmolol is applied. On the other hand, in most patients (up to 70%) with recent-onset (< 72 hours) AF, spontaneous conversion to sinus rhythm occurs[27]. Beta-blockers are the first-line therapeutic agents for the prevention of early recurrence of AF[28]. After cardioversion and maintenance of sinus rhythm, esmolol-treated patients with prior recent-onset AF present similar or even increased CO due to the enhancement of left ventricular filling. In particular, the atrial kick is restored, improving SV. The impact of CO variations on the outcomes of AIS is well documented. CO is elevated after AIS in individuals with intact cerebrovascular compensatory mechanisms[29]. Furthermore, an enhanced SV index is associated with early neurological improvement in patients with AIS, and this association is attributed to mechanisms such as the preservation of autoregulation, collateral blood flow, and brain-penumbra perfusion[5,30]. Left ventricular ejection fraction, a major factor influencing SV, is associated with long-term outcomes after AIS[31,32]. These findings indicate that esmolol is a potential ideal antihypertensive agent for patients with recent-onset AF due to the enhancement of CO after cardioversion, favoring the maintenance of sinus rhythm. On the other hand, esmolol is not the preferred therapeutic agent for patients without AF due to the subsequent reduction of CO. These fluctuations of CO can determine the outcomes of AIS.
Sub-group analysis in patients with, and patients without a history of hypertension, found worse results in the subgroup of patients without a history of hypertension that were esmolol-treated (increased LOS, need for advanced critical/neurocritical care, occurrence of primary adverse events, worse functional outcome), while only LOS was elevated at the subgroup of esmolol-treated patients with a history of hypertension. A possible explanation for these findings could arise from the fact that a significant proportion of hypertensive patients presents refractory hypertension, leading to more difficult to treat elevations of ABP during hypertensive emergencies[14]. Under these conditions, esmolol, due to its excellent pharmacokinetic and pharmacodynamic properties may be proven more efficient, active and beneficial[33] for ABP control. In that way, esmolol should be considered a very good therapeutic choice for patients with a history of hypertension and AIS who are undergoing IT, while its effectiveness is questioned for patients without a history of hypertension undergoing IT for AIS.
This retrospective and single-center study presents additional limitations: It examined the effect of a single intervention (esmolol) on the clinical outcomes of AIS. However, the clinical outcomes of acute cerebrovascular diseases post-treatment are dependent on multiple factors[9,34]. Furthermore, although every effort has been made to perform an objective and accurate analysis minimizing the risk of bias, the retrospective study design did not allow blinded data analysis. Thus, caution must be exercised while interpreting the results of this study. However, subgroup analysis was performed to examine the differential baseline factors, allowing the extraction of statistically powerful results and minimizing the influence of confounding factors.
CONCLUSION
The findings of this study indicate that a single antihypertensive is not suitable for all hypertensive emergencies or patients. Personalization is critical for treating patients with emergencies, such as AIS. Esmolol may benefit patients with AF or those with a history of hypertension, but not patients without AF or without a history of hypertension. The identification of the clinical characteristics of patients and the properties (side effects and interactions) of the drug can aid in improving the efficacy of the interventions and consequently enable the safe management of AIS.
ACKNOWLEDGEMENTS
This paper is dedicated to the memory of a great doctor and friend, Tilemachos Zafeiridis (1974-2021), as a 5-year tribute to his premature death.
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