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Brain & Heart Advances in stroke treatment

The introduction of intravenous thrombolysis (IVT) 2. TNK in AIS
with alteplase (ALT) has been a cornerstone in AIS
management. Administered within a narrow 4.5-h TNK is a genetically modified form of ALT with enhanced
window from symptom onset, IVT has demonstrated resistance to plasminogen activator inhibitor-1, greater
substantial benefits in eligible patients. Recent advances in fibrin specificity and a longer half-life, allowing for single-
bolus administration, and enhancing practicality in AIS
imaging technologies, particularly computed tomography
(CT) and magnetic resonance imaging (MRI) perfusion thrombolysis. This could reduce door-to-needle times and
have enabled precise differentiation of salvageable simplify intra- and inter-hospital transfers for patients
ischemic penumbra from the irreversibly damaged infarct eligible for mechanical thrombectomy (MT). Several trials,
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core. Landmark studies, including ECASS IV, EXTEND , including TNK-S2B, TAAIS, ATTEST, EXTEND-IA
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and EPITHET, have validated the safety and efficacy of TNK, TRACE, TASTE-A and AcT, have compared
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extending the IVT treatment window up to 9 h in carefully TNK with ALT in AIS (Table 1).
selected patients, fundamentally altering the scope of Following a systematic review of these studies, the
thrombolytic therapy. European Stroke Organization (ESO) now recommends
Similarly, endovascular therapy (EVT) has transformed TNK at a dose of 0.25 mg/kg as a safe, effective alternative
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the treatment of large vessel occlusions (LVOs). Originally to ALT within 4.5 h from symptom onset. The TNK-S2B
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confined to a 6-h window, the therapeutic timeframe in and ATTEST trials demonstrated that TNK provides
pivotal trials such as DEFUSE-3 and DAWN has been similar functional outcomes to ALT while reducing the risk
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expanded to 16 – 24 h in select cases based on advanced of long-term disability. The AcT trial further confirmed
imaging criteria. These developments have emphasized TNK’s non-inferiority at 90 days, with similar adverse
tissue viability as a central tenet in clinical decision- event rates, including sICH.
making, replacing rigid time-based thresholds. However, the ESO strongly advises against using TNK
Despite these advancements, several complex scenarios at a dose of 0.4 mg/kg, on the basis of the results from
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remain inadequately addressed, including posterior the NOR-TEST 2A trial, which reported a significantly
circulation strokes, large infarct cores, distal medium vessel higher risk of sICH with this dosage.
occlusions (DMVOs), and mild-deficit LVO-related AIS. On regards of LVO-related AIS, the ESO favors TNK
Addressing these gaps necessitates innovative approaches over ALT within 4.5 h; indeed, EXTEND-IA TNK
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and ongoing research to refine patient selection and demonstrated TNK superiority in restoring perfusion
optimize outcomes. without delaying MT. For cases beyond 4.5 h, including
Emerging evidence on alternative thrombolytic agents, “wake-up” strokes, TNK is considered, based on expert
particularly tenecteplase (TNK), offers promise for consensus, a reasonable alternative to ALT when the
improving the efficiency and accessibility of reperfusion DWI-FLAIR or perfusion mismatch criteria apply (up to
therapies. Furthermore, the integration of intra-arterial 9 h). This indication is particularly supported by findings
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thrombolysis post-thrombectomy is gaining traction as a from TASTE-A, which showed TNK efficacy in lesion
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complementary approach in challenging clinical contexts. volume reduction, and TRACE, which confirmed its
safety in extended windows, with no increase in sICH or
Moreover, advanced imaging techniques continue adverse events. The European Medicines Agency (EMA)
to evolve, with new biomarkers and algorithms being has approved TNK (Metalyse, 25 mg) for AIS within 4.5 h,
developed to further refine patient selection criteria. These extending its indications beyond myocardial infarction,
tools aim to identify candidates who might benefit from while authorization from the Italian Medicines Agency
aggressive reperfusion therapies while minimizing the risk (AIFA) is still pending for AIS use.
of hemorrhagic complications. This personalized approach
seeks to balance the benefits and risks of treatment, ensuring 2.1. Pro-urokinase in AIS
optimal outcomes across diverse patient populations. Pro-urokinase (Pro-UK) is a fibrin-specific thrombolytic
This review critically examines recent advancements agent initially studied in the late 1990s, primarily through
in AIS revascularization therapies, highlighting the the PROACT I (1998) and PROACT II (1999) trials
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evolving role of IVT, EVT, and novel therapeutic agents. conducted in the United States. These studies demonstrated
By exploring these innovations, the review aims to provide its efficacy in recanalizing middle cerebral artery
a comprehensive overview of contemporary stroke occlusions, with improved functional outcomes compared
management and the ongoing efforts to expand therapeutic to standard therapy. However, concerns over elevated rates
opportunities for different patient populations. of sICH, the complexity of intra-arterial administration,

Volume 3 Issue 3 (2025) 2 doi: 10.36922/bh.6683