Abstract WMP1: Complications Of Intravenous Tenecteplase For The Treatment Of Acute Ischemic Stroke: A Systematic Review And Meta-Analysis

Abstract

Introduction: Prior systematic reviews have focused on a comparison of efficacy endpoints between tenecteplase (TNK) and alteplase. The objectives of this study are to determine whether the rate of treatment complications differs between patients treated with the two agents. Methods: This systematic review (CRD42022303835) was performed according to PRISMA guidelines. We included prospective, interventional studies and prospective and retrospective observational studies. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science and the ClinicalTrials.gov registry from inception through June 3 rd 2022. The primary endpoint was symptomatic intracranial hemorrhage (sICH) and secondary endpoints included any ICH, mortality, angioedema, gastrointestinal hemorrhage and other extracranial hemorrhage. We performed separate random effects meta analyses for each endpoint. Evidence was synthesized as relative risks, comparing subjects exposed to TNK versus alteplase as well as absolute risks in those treated with TNK. Results: Of 2,226 records identified, 26 were eligible for inclusion including 7,921 patients. Seventeen studies included alteplase as a comparator group and 10 were non-comparative. The relative risk of sICH in patients treated with TNK compared with alteplase was 0.93 (95% CI: 0.68-1.28). Across those treated with low, medium and high doses of TNK, the relative risks were 0.78 (95% CI: 0.22-2.82), 0.84 (95% CI: 0.58-1.20) and 2.31 (0.69-7.75) respectively. The unadjusted rate of sICH, including comparative and non-comparative studies, was 1%, 2% and 4% within the low, medium and high dose groups. Discussion: To-date, this is the most comprehensive systematic review examining relative complications of TNK and alteplase. The rate of treatment harms is broadly comparable between those treated with the two agents. We present evidence that the rate of sICH may be increased in those treated with higher doses of TNK.

CNS Drug Delivery in Stroke: Improving Therapeutic Translation From the Bench to the Bedside

“…8–10 Currently approved clinical treatments for stroke (ie, alteplase or surgical endovascular thrombectomy) and off-label use of TNKase (ie, tenecteplase, a fibrinolytic drug used for the treatment of acute myocardial infarction) are limited by short therapeutic windows following patient presentation to the clinic. 11 While recent advances in neuroimaging allow for improved determination of stroke causation and progression, aiding in more precise treatment options, few therapeutic agents are available to improve patient outcomes. Research into acute and subacute changes within the neurovascular unit (NVU) poststroke has identified several drug candidates and therapeutic agents that have failed in their clinical effectiveness due to the aforementioned challenges presented by limited CNS penetration.…”

Angioedema After Use of Recombinant Tissue-Type Plasminogen Activators in Stroke

“…In patients with stroke, angioedema (AE) without concomitant urticaria is a feared complication of treatment with the recombinant tissue-type plasminogen activator (r-tPA) alteplase and its genetically modified variant tenecteplase (0.4%–5.1%). 1–5 Angioedema is a nonpitting, nonitching vasogenic swelling of the skin or mucosa caused by temporarily increased vasopermeability. r-tPA-induced angioedema is primarily located in the head and neck region, where it can cause airway obstruction with a potentially lethal outcome.…”