Intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) are described in this review as the foundational treatments for acute ischemic stroke. The authors note that most patients eligible for IVT have medium or distal arterial occlusions, whereas EVT is used primarily for large artery occlusions. Despite these established therapies, both IVT and EVT frequently do not achieve sustained recanalization, complete microvascular reperfusion, or optimal clinical outcomes.
The review emphasizes that improving reperfusion at both the macrovascular and microvascular levels is necessary to translate vessel opening into better functional recovery. Failure to sustain recanalization or to restore microvascular perfusion after initial success remains a clinical challenge.
The article reviews alternative fibrinolytic agents tested as substitutes for alteplase. In particular, tenecteplase is discussed; available evidence suggests tenecteplase provides, at best, a marginal improvement in outcome compared with alteplase. The authors convey that substituting lytic agent alone has not produced a clear, consistent advantage in clinical outcomes across studies summarized in the review.
The review also notes that supplementing IVT with antithrombotic therapies has not demonstrated consistent benefit. Details of specific trials, doses, or quantitative results are not presented in the PubMed abstract and therefore are not reported here.
A central focus of the review is the concept of multiple dosing strategies for IVT. This includes repeat administration of IVT in patients who are not EVT candidates and sequential dosing approaches intended to maintain or re-establish fibrinolysis when initial therapy does not produce durable reperfusion.
Physiologic and pharmacokinetic rationales are outlined as reasons to consider sequential or repeat IVT. The review frames these approaches as aimed at enhancing fibrinolytic effectiveness over time, addressing clot composition or rethrombosis, and potentially reaching microvascular territories not reopened by a single dose. Specific pharmacokinetic parameters and mechanistic data are discussed in the full text but are not detailed in the PubMed abstract.
The review summarizes strategies that combine systemic IVT or targeted intra-arterial thrombolytics with EVT. Combining modalities is proposed to address incomplete reperfusion after mechanical thrombectomy and to improve microvascular flow beyond the site of large vessel recanalization.
Adjunct intra-arterial thrombolysis administered during or after EVT is highlighted as a potentially promising tactic to augment reperfusion in regions not fully reached by mechanical devices. The authors present this combined-modality approach as a logical extension of current practice when EVT alone does not secure optimal tissue reperfusion.
The authors review key clinical trials evaluating alternative lytics, adjunctive antithrombotics, repeat IVT dosing, and intra-arterial thrombolysis combined with EVT. While the abstract indicates that some approaches have shown emerging supportive data, it also makes clear that broad, consistent clinical benefit has not yet been established for many adjunct strategies.
Specific trial names, patient numbers, and quantitative outcomes are discussed in the full review text; the PubMed abstract does not provide those granular results, so such details are not included here.
Safety is a recurrent theme in the review: any strategy to intensify or repeat fibrinolysis must preserve an acceptable safety profile. The authors state that emerging strategies aim to enhance reperfusion and functional recovery while maintaining safety, implying that hemorrhagic complications and other adverse events are important endpoints in ongoing evaluations.
The abstract notes that supplementing IVT with antithrombotic therapies has not produced consistent benefit, which indirectly underscores safety and efficacy trade-offs that remain unsettled.
The review identifies persistent knowledge gaps and calls for further research to define optimal agents, dosing regimens, and combinations with EVT. Areas highlighted as promising—novel fibrinolytic agents, sequential IVT dosing, and adjunct intra-arterial thrombolysis—require additional study to determine whether they can reliably improve sustained recanalization, microvascular reperfusion, and functional outcomes without unacceptable harm.
This is a review article published in Neurology (2026 Aug 25;107(4):e218285), authored by Mahan Shahrivari and James C. Grotta, with affiliations to the Department of Neurology at McGovern Medical School, University of Texas Health Science Center at Houston, and a Mobile Stroke Unit at Memorial Hermann Hospital, Houston, TX. PubMed identifier (PMID) is 42525907 and DOI is 10.1212/WNL.0000000000218285.
Note: The present summary is based on the PubMed abstract and article metadata. The abstract indicates that the full review discusses physiologic, pharmacokinetic, and clinical rationales and highlights results from key clinical trials; however, granular trial data and detailed dosing protocols are reported in the full text and are not provided in the PubMed abstract.