Comparing mismatch strategies for patients being considered for ischemic stroke tenecteplase trials

Background Currently there are multiple variations of imaging-based patient selection mismatch methods in ischemic stroke. In the present study, we sought to compare the two most common mismatch methods and identify if there were different effects on the outcome of a randomized clinical trial depending on the mismatch method used. Aims Investigate the effect of clinical and imaging-based mismatch criteria on patient outcomes of a pooled cohort from randomized trials of intravenous tenecteplase versus alteplase. Methods Baseline clinical and imaging scores were used to categorize patients as meeting either the DAWN mismatch (baseline NIHSS ≥ 10, and age cut-offs for ischemic core volume) or DEFUSE 2 mismatch criteria (mismatch volume > 15 mL, mismatch ratio > 1.8 and ischemic core < 70 mL). We then investigated whether tenecteplase-treated patients had favorable odds of less disability (on modified Rankin scale, mRS) compared to those treated with alteplase, for clinical and imaging mismatch, respectively. Results From 146 pooled patients, 71 received alteplase and 75 received tenecteplase. The overall pooled group did not show improved patient outcomes when treated with tenecteplase (mRS 0-1 OR 1.77, 95% CI 0.89–3.51, p = 0.102) compared with alteplase. A total of 39 (27%) patients met both clinical and imaging mismatch criteria, 25 (17%) patients met only imaging criteria, 36 (25%) met only clinical mismatch criteria and, finally, 46 (31%) did not meet either of imaging or mismatch criteria. Patients treated with tenecteplase had more favorable outcomes when they met either imaging mismatch (mRS 0–1, OR 2.33, 95% CI 1.13–5.94, p = 0.032) or clinical mismatch criteria (mRS 0–1, OR 2.15, 95% CI 1.142, 8.732, p = 0.027) but with differing proportions. Conclusion Target mismatch selection was more inclusive and exhibited in a larger treatment effect between tenecteplase and alteplase.

[1]  C. Levi,et al.  The independent predictive utility of computed tomography angiographic collateral status in acute ischaemic stroke. , 2009, Brain : a journal of neurology.

[2]  Bruce C V Campbell,et al.  Cerebral Blood Flow Is the Optimal CT Perfusion Parameter for Assessing Infarct Core , 2011, Stroke.

[3]  C. Levi,et al.  Perfusion computer tomography: imaging and clinical validation in acute ischaemic stroke. , 2011, Brain : a journal of neurology.

[4]  G. Donnan,et al.  A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. , 2012, The New England journal of medicine.

[5]  C. Levi,et al.  Perfusion CT in acute stroke: a comprehensive analysis of infarct and penumbra. , 2013, Radiology.

[6]  Mark W Parsons,et al.  Comparison of Computed Tomographic and Magnetic Resonance Perfusion Measurements in Acute Ischemic Stroke: Back-to-Back Quantitative Analysis , 2014, Stroke.

[7]  I. Ford,et al.  Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study , 2015, The Lancet Neurology.

[8]  M. Krause,et al.  Endovascular therapy for ischemic stroke with perfusion-imaging selection. , 2015, The New England journal of medicine.

[9]  G. Donnan,et al.  Tenecteplase in ischemic stroke offers improved recanalization , 2017, Neurology.

[10]  G. Donnan,et al.  Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials , 2016, Circulation.

[11]  M. Parsons,et al.  Tissue is more important than time: insights into acute ischemic stroke from modern brain imaging , 2017, Current opinion in neurology.

[12]  M. Chen,et al.  Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct , 2018, The New England journal of medicine.

[13]  A. Demchuk,et al.  Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging , 2018, The New England journal of medicine.