Abstract MP5: Intravenous Thrombolysis With Tenecteplase in Patients With Large Vessel Occlusions: Systematic Review and Meta-Analysis

Abstract

Background: Accumulating evidence from randomized-controlled clinical trials (RCTs) suggest that tenecteplase may represent an effective treatment alternative to alteplase for acute ischemic stroke (AIS). In the present systematic review and meta-analysis we sought to compare the efficacy and safety outcomes of intravenous tenecteplase to intravenous alteplase administration for AIS patients with large vessel occlusions (LVO). Methods: We searched MEDLINE and Scopus for published RCTs providing outcomes of AIS with confirmed LVO receiving intravenous thrombolysis with either tenecteplase at different doses or alteplase at standard dose 0.9mg/kg. The primary outcome was the odds of modified Rankin Scale (mRS) score of 0-2 at 3 months. Results: We included 4 RCTs including a total of 433 patients. Patients with confirmed LVO receiving tenecteplase had higher odds of successful recanalization (OR=3.05, 95%CI: 1.73-5.40; Figure A), mRS scores of 0-2 [odds ratio (OR)=2.06, 95%CI: 1.15-3.69; Figure B], and functional improvement defined as 1-point decrease across all mRS grades (common OR=1.84, 95%CI: 1.18-2.87; Figure C) at 3 months compared to patients with confirmed LVO receiving alteplase. There was little or no heterogeneity between the results provided from included studies regarding the aforementioned outcomes (I 2 ≤20%). No difference in the outcomes of early neurological improvement, symptomatic intracranial hemorrhage (ICH), any ICH and the rates of mRS 0-1 or all-cause mortality at 3 months were detected between patients with LVO receiving intravenous thrombolysis with either tenecteplase or alteplase. Conclusion: AIS patients with LVO receiving intravenous thrombolysis with tenecteplase have significantly better recanalization and clinical outcomes compared to patients receiving intravenous alteplase.

Intravenous Thrombolysis with Tenecteplase for the Treatment of Acute Ischemic Stroke

“…[25][26][27][28][29] The 2-fold increase in the odds of 3-month good functional outcome found in the present report has previously been reported in a systematic review and meta-analysis from our group analyzing data from patients with confirmed acute LVOs enrolled in randomized-controlled clinical trials comparing intravenous tenecteplase to intravenous alteplase for the treatment of AIS. 7 The association between intravenous tenecteplase and a lower risk for all-cause mortality at 3 months compared to intravenous alteplase uncovered in the present study is in accordance with the reduction in all-cause mortality at 3 months found in the Tenecteplase versus Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial. 30 In the EXTEND-IA TNK trial, pretreatment with tenecteplase before endovascular thrombectomy was associated with a 50% reduction in the adjusted risk ratio of all-cause mortality at 3 months.…”

“…In the unmatched analysis, the rate of patients receiving endovascular thrombectomy after IVT was twice as high for patients receiving alteplase as for those receiving tenecteplase. It is unclear whether this difference in the endovascular thrombectomy rates between the two groups could be attributed to the 2‐fold higher probability of successful recanalization of LVOs with tenecteplase compared to alteplase, 7,30 amending the need for subsequent endovascular treatment, 35 or whether it indicates the presence of unmeasured confounders at the participant, institutional level, or both. Results from TASTE‐A (Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance) lend further support to the hypothesis that ultraearly IVT with tenecteplase can lead to higher rates of early reperfusion and early clinical recovery, when compared to alteplase 36 .…”

Prospective Observational Cohort Study Of Tenecteplase Versus Alteplase In Routine Clinical Practice

“…17 Overall, these results from routine clinical practice are consistent with the results of randomized trials and meta-analysis and are supportive of tenecteplase as an alternative to alteplase for stroke thrombolysis. [4][5][6][7][8][9][10][11][12] Our results for tenecteplase are also similar in magnitude and difference to the experience reported from New Zealand. 13,14 Currently American Heart Association clinical practice guidelines give a Class IIb recommendation of tenecteplase as an alternative to alteplase 15 but recommend different doses for large vessel occlusions for whom thrombectomy is planned (0.25 mg/kg; EXTEND IA TNK Part1 11 ) and for milder strokes (0.4mg/kg NORTEST 12 ).…”

Direct mechanical thrombectomy without intravenous thrombolysis versus bridging therapy for acute ischemic stroke: A meta-analysis of randomized controlled trials

“…Sixth, only alteplase was used for IVT, which precludes comparisons to potentially more effective or safer thrombolytics, such as tenecteplase. 28 Finally, to fully understand the impact of treatment on clinical outcomes an ordinal shift mRS analysis should be performed on individual patient data. 29…”