Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis. Issue 3 (2nd February 2023)

• Record Type: Journal Article
• Authors: Yogendrakumar, Vignan; Churilov, Leonid; Guha, Prodipta; Beharry, James; Mitchell, Peter J.; Kleinig, Timothy J.; Yassi, Nawaf; Thijs, Vincent; Wu, Teddy Y.; Brown, Helen; Dewey, Helen M.; Wijeratne, Tissa; Yan, Bernard; Sharma, Gagan; Desmond, Patricia M.; Parsons, Mark W.; Donnan, Geoffrey A.; Davis, Stephen M.; Campbell, Bruce C.V.
• Other Names: Dowling Richard author non-byline.; Bush Steven author non-byline.; Scroop Rebecca author non-byline.; Brooks Mark author non-byline.; Asadi Hamed author non-byline.; Ang Timothy author non-byline.; Miteff Ferdinand author non-byline.; Levi Christopher author non-byline.; Zhao Henry author non-byline.; Ng Felix author non-byline.; Alemseged Fana author non-byline.; Rice Henry author non-byline.; de Villiers Laetitia author non-byline.; Redmond Kendal author non-byline.; Leggett David author non-byline.
• Is Part Of: Stroke. Volume 54:Issue 3(2023)
• Page Start: 706
• Page End: 714
• Publication Date: 2023-02-02
• Subjects: carotid artery -- reperfusion -- tenecteplase -- thrombus -- tomography; Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.122.041061
• Languages: English
• ISSNs: 0039-2499

Abstract

Abstract : Background: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). Methods: Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015–2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. Results: Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%], adjusted odds ratio [aOR], 2.18 [95% CI, 1.03–4.63]). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%], aOR, 3.93 [95% CI, 1.50–10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16–2.06]; P interaction =0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00–8.05] versus absent: aOR, 1.98 [95% CI, 0.65–6.03]; P interaction =0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%], aOR, 3.73 [95% CI, 1.25–11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01–3.83]; P interaction =0.16). Conclusions: Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.