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February 2, 2026Journal of Stroke5 citationsOpen Access

Mechanism-Oriented Treatment of Early Neurologic Deterioration in Acute Ischemic Stroke

JHJi Hoe HeoKLKee Ook LeeJHJoonNyung Heo

Key Result

Argatroban use is associated with a lower risk of early neurologic deterioration compared to dual antiplatelet therapy within 48 hours after stroke onset.

Key Points

  • The aim is to differentiate between recurrence and progression of early neurologic deterioration after ischemic stroke to optimize treatment.
  • Reviewed clinical and experimental studies on early neurologic deterioration.
  • Focused on epidemiology, mechanisms, and treatment strategies.
  • Examined interventions including antiplatelet therapy and induced hypertension.
  • Early recurrence is linked to thrombus growth and new ischemic events.
  • Progression correlates with infarct growth due to impaired perfusion.
  • Distinct therapeutic approaches are necessary for recurrence and progression.

Structured PICO

Do mechanism-oriented treatments (antiplatelets, direct thrombin inhibitors, induced hypertension) prevent or improve early neurologic deterioration in patients with acute ischemic stroke?

P
Population
Patients with acute ischemic stroke at risk of or experiencing early neurologic deterioration (END).
I
Intervention
Mechanism-oriented treatments including antiplatelet therapy, direct thrombin inhibition (e.g., argatroban), and induced hypertension.

Differentiating early neurologic deterioration into recurrence and progression is essential for tailoring mechanism-oriented treatments such as antithrombotics or induced hypertension in acute ischemic stroke.

Main Result

Effect estimate: HR 0.55 (95% CI 0.33-0.91)

Absolute Event Rate: 3.1% vs 5.6%

p-value: p=0.034

Limitations

  • Variability in definitions of END across studies
  • Lack of randomized controlled trials
  • Potential confounding factors in observational studies
  • Most previous studies did not differentiate between END due to recurrence and END due to progression
  • Most previous studies on argatroban were conducted in Chinese cohorts with heterogeneous stroke populations, making efficacy and safety uncertain in other populations

Abstract

Early neurologic deterioration (END) is common and occurs within a few hours to days after an ischemic stroke. Traditionally, END has been treated as a collective entity, including the occurrence of new deficits (recurrence) and the aggravation of pre-existing neurologic deficits (progression). END arises from distinct mechanisms that require different therapeutic approaches. We reviewed clinical and experimental studies addressing the epidemiology, mechanisms, and treatment of END, focusing on differentiating END due to recurrence from END due to progression and on interventions including antiplatelet therapy, direct thrombin inhibition, and induced hypertension. Early recurrence is closely associated with thrombus growth and new ischemic events, particularly in atherothrombotic disease. Early recurrence is also common in patients with cancer-associated stroke. Thrombin and platelet activation play central roles under both conditions. In contrast, progression is mainly driven by infarct growth, that is, the evolution from incomplete infarction to complete infarction due to impaired perfusion, especially in lesions involving the subcortical fiber tracts. Therapeutic implications differ accordingly. Recurrence may respond to potent antithrombotic strategies, including combined antiplatelet and direct thrombin inhibition, whereas progression may benefit from induced hypertension. However, recurrence and progression often occur simultaneously, making clinical differentiation challenging. END should be conceptualized as a spectrum of clinical presentations arising from distinct mechanisms. Recognizing recurrence and progression as separate processes is essential for mechanism-oriented treatments. Future trials should adopt this framework to develop individualized strategies and improve outcomes in patients with acute stroke.

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Cite This Study

Heo et al. (2026) conducted a review in Early Neurologic Deterioration (n=4,299). Argatroban vs. DAPT (Dual Antiplatelet Therapy) was evaluated on Incidence of Early Neurologic Deterioration (END) as defined by a ≥2-point increase in NIHSS score (HR 0.55, 95% CI 0.33-0.91, p=0.034). Argatroban use is associated with a lower risk of early neurologic deterioration compared to dual antiplatelet therapy within 48 hours after stroke onset.

synapsesocial.com/papers/6980fd18c1c9540dea80ed78https://doi.org/10.5853/jos.2025.05120
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