TY - JOUR
T1 - Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke
T2 - A Post Hoc Analysis of the EXTEND-IA TNK Trials
AU - Yogendrakumar, Vignan
AU - Churilov, Leonid
AU - Mitchell, Peter J.
AU - Kleinig, Timothy J.
AU - Yassi, Nawaf
AU - Thijs, Vincent
AU - Wu, Teddy
AU - Shah, Darshan
AU - Bailey, Peter
AU - Dewey, Helen M.
AU - Choi, Philip M.C.
AU - Ma, Alice
AU - Wijeratne, Tissa
AU - Garcia-Esperon, Carlos
AU - Cloud, Geoffrey
AU - Chandra, Ronil V.
AU - Cordato, Dennis J.
AU - Yan, Bernard
AU - Sharma, Gagan
AU - Desmond, Patricia M.
AU - Parsons, Mark W.
AU - Donnan, Geoffrey A.
AU - Davis, Stephen M.
AU - Campbell, Bruce C.V.
AU - for the EXTEND-IA TNK Investigators
N1 - Funding Information:
This study did not receive study-specific funding. The EXTEND-IA TNK trials received funding from the National Health and Medical Research Council Australia (GNT1113352, GNT1111972). V. Yogendrakumar is supported by a Canadian Institute of Health Research Fellowship Award, a University of Melbourne Research Scholarship, and a Detweiler Travelling Fellowship.
Funding Information:
V. Yogendrakumar, L. Churilov, and P.J. Mitchell reports no disclosures relevant to the manuscript. T.J. Kleinig receives educational meeting supports from Boehringer Ingelheim. N. Yassi reports no disclosures relevant to the manuscript. V. Thijs receives personal compensation from Pfizer, Boehringer Ingelheim, Medtronic, BMS, Bayer, Allergan, Amgen, Biotronik and Abbott. D. Shah has received speakers honoraria from Boehringer Ingelheim and Bayer. P. Bailey, H.M. Dewey, P.M.C. Choi, A. Ma, and T. Wijeratne report no disclosures relevant to the manuscript. C. Garcia-Esperon received funding from Boehringer Ingelheim and Bayer for conference travel. G. Cloud, R.V Chandra, D.J. Cordato, B. Yan, and G. Sharma report no disclosures relevant to the manuscript. M. Parsons is on the Global Metalyse (TNK) Advisory Board for Boehringer Ingelheim. G.A. Donnan, S.M. Davis, B.C.V. Campbell, T. Wu, and P. Desmond report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© American Academy of Neurology.
PY - 2023/5/2
Y1 - 2023/5/2
N2 - Background and ObjectivesThe safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients with TLs.MethodsWe first compared the treatment effect of TNK and alteplase in patients with TLs using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day modified Rankin scale (mRS) with ordinal logistic and Firth regression models. Because 2 key outcomes, mortality and symptomatic intracranial hemorrhage (sICH), were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving TNK.ResultsSeventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a TL. In patients with TLs, intracranial reperfusion was observed in 11/56 (20%) of TNK-treated patients vs 1/15 (7%) alteplase-treated patients (adjusted odds ratio 2.19; 95% CI 0.28-17.29). No significant difference in 90-day mRS was observed (adjusted common odds ratio 1.48; 95% CI 0.44-5.00). A pooled study-level proportion of alteplase-associated mortality and sICH was 0.14 (95% CI 0.08-0.21) and 0.09 (95% CI 0.04-0.16), respectively. Compared with a mortality rate of 0.09 (95% CI 0.03-0.20) and an sICH rate of 0.07 (95% CI 0.02-0.17) in TNK-treated patients, no significant difference was observed.DiscussionFunctional outcomes, mortality, and sICH did not significantly differ between patients with TLs treated with TNK and those treated with alteplase.Classification of EvidenceThis study provides Class III evidence that TNK is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and sICH compared with alteplase in patients with acute stroke due to TLs. However, the CIs do not rule out clinically important differences.
AB - Background and ObjectivesThe safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients with TLs.MethodsWe first compared the treatment effect of TNK and alteplase in patients with TLs using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day modified Rankin scale (mRS) with ordinal logistic and Firth regression models. Because 2 key outcomes, mortality and symptomatic intracranial hemorrhage (sICH), were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving TNK.ResultsSeventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a TL. In patients with TLs, intracranial reperfusion was observed in 11/56 (20%) of TNK-treated patients vs 1/15 (7%) alteplase-treated patients (adjusted odds ratio 2.19; 95% CI 0.28-17.29). No significant difference in 90-day mRS was observed (adjusted common odds ratio 1.48; 95% CI 0.44-5.00). A pooled study-level proportion of alteplase-associated mortality and sICH was 0.14 (95% CI 0.08-0.21) and 0.09 (95% CI 0.04-0.16), respectively. Compared with a mortality rate of 0.09 (95% CI 0.03-0.20) and an sICH rate of 0.07 (95% CI 0.02-0.17) in TNK-treated patients, no significant difference was observed.DiscussionFunctional outcomes, mortality, and sICH did not significantly differ between patients with TLs treated with TNK and those treated with alteplase.Classification of EvidenceThis study provides Class III evidence that TNK is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and sICH compared with alteplase in patients with acute stroke due to TLs. However, the CIs do not rule out clinically important differences.
UR - http://www.scopus.com/inward/record.url?scp=85158820686&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000207138
DO - 10.1212/WNL.0000000000207138
M3 - Article
C2 - 36878701
AN - SCOPUS:85158820686
SN - 0028-3878
VL - 100
SP - e1900-e1911
JO - Neurology
JF - Neurology
IS - 18
ER -