Efficacy of intravenous thrombolysis bridging endovascular thrombectomy on functional outcome of patients with acute cardioembolic stroke_West China Medical Journal

Authors：

LI Jingjing ¹ , LIU Meng ¹ , HUA Xing ¹ , HUANG Linrui ¹ ,  WU Simiao ^1,2

1. Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Center of Cerebrovascular Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

WU Simiao, Email: simiao.wu@hotmail.com

Keywords：

Cardioembolic stroke; endovascular thrombectomy; intravenous thrombolysis; bridging therapy; outcome

DOI：

10.7507/1002-0179.202403307

Video：

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Objective To investigate the clinical efficacy and safety of intravenous thrombolysis bridging endovascular thrombectomy (EVT) in patients with acute cardioembolic stroke. Methods We retrospectively included patients with cardioembolic stroke who were admitted within 24 h after onset of stroke symptoms and had received EVT in the Department of Neurology, West China Hospital of Sichuan University between January 2017 and December 2021. Based on whether they had received intravenous thrombolysis, the patients were divided into bridging therapy group and direct EVT group. The primary outcome was unfavorable outcome by 3 months, defined as a modified Rankin Scale (mRS) score of 3 to 6. The secondary outcomes included intracranial hemorrhage during hospitalization and 3-month death. Multivariable logistic regression was performed to assess the treatment effect on the primary outcome after adjusting for confounding factors. Results A total of 285 patients were enrolled. Among them, 174 (61.1%) were female, the median age was 74 years (interquartile range 64-80 years), and the median time from stroke onset to admission was 4.0 h (interquartile range 3.0-5.0 h). Compared to patients in the direct EVT group (n=202), patients in the bridging therapy group (n=83) had a lower rate of unfavorable functional outcome (55.4% vs 68.3%, P=0.039) by 3 months, while the incidences of intracranial hemorrhage (47.0% vs. 39.6%, P=0.251) and 3-month death (20.5% vs. 30.7%, P=0.080) were comparable between the two groups. After adjusting for confounding factors, the bridging therapy improved 3-month functional outcomes over direct EVT [odds ratio=0.482, 95% confidence interval (0.249, 0.934), P=0.031]. Conclusion In patients with acute cardioembolic stroke, intravenous thrombolysis bridging endovascular treatment can significantly improve 3-month functional outcomes without increasing the risk of intracranial hemorrhage.

Citation： LI Jingjing, LIU Meng, HUA Xing, HUANG Linrui, WU Simiao. Efficacy of intravenous thrombolysis bridging endovascular thrombectomy on functional outcome of patients with acute cardioembolic stroke. West China Medical Journal, 2024, 39(5): 684-691. doi: 10.7507/1002-0179.202403307 Copy

1.	Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke, 1993, 24(1): 35-41.
2.	O’Carroll CB, Barrett KM. Cardioembolic stroke. Continuum (Minneap Minn), 2017, 23(1, Cerebrovascular Disease): 111-132.
3.	National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med, 1995, 333(24): 1581-1587.
4.	Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med, 2015, 372(1): 11-20.
5.	Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med, 2015, 372(11): 1009-1018.
6.	Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med, 2015, 372(11): 1019-1030.
7.	Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med, 2015, 372(24): 2285-2295.
8.	Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med, 2015, 372(24): 2296-2306.
9.	Yang P, Zhang Y, Zhang L, et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med, 2020, 382(21): 1981-1993.
10.	Suzuki K, Matsumaru Y, Takeuchi M, et al. Effect of mechanical thrombectomy without vs with intravenous thrombolysis on functional outcome among patients with acute ischemic stroke: the SKIP randomized clinical trial. JAMA, 2021, 325(3): 244-253.
11.	Bogiatzi C, Hackam DG, McLeod AI, et al. Secular trends in ischemic stroke subtypes and stroke risk factors. Stroke, 2014, 45(11): 3208-3213.
12.	Bjerkreim AT, Khanevski AN, Thomassen L, et al. Five-year readmission and mortality differ by ischemic stroke subtype. J Neurol Sci, 2019, 403: 31-37.
13.	Chen Z, Shi F, Zhang M, et al. Prediction of the multisegment clot sign on dynamic CT angiography of cardioembolic stroke. AJNR Am J Neuroradiol, 2018, 39(4): 663-668.
14.	Zaidat OO, Yoo AJ, Khatri P, et al. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke, 2013, 44(9): 2650-2663.
15.	中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组, 中华医学会神经病学分会神经血管介入协作组. 中国急性缺血性卒中早期血管内介入诊疗指南 2022. 中华神经科杂志, 2022, 55(6): 565-580.
16.	中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性缺血性脑卒中诊治指南 2018. 中华神经科杂志, 2018, 51(9): 666-682.
17.	Van Swieten JC, Koudstaal PJ, Vissee MC, et al. Interobserver agreement for the assessment of handicap in stroke patients. Stroke, 1988, 19(5): 604-607.
18.	Zi W, Qiu Z, Li F, et al. Effect of endovascular treatment alone vs intravenous alteplase plus endovascular treatment on functional independence in patients with acute ischemic stroke: the DEVT randomized clinical trial. JAMA, 2021, 325(3): 234-243.
19.	LeCouffe NE, Kappelhof M, Treurniet KM, et al. A randomized trial of intravenous alteplase before endovascular treatment for stroke. N Engl J Med, 2021, 385(20): 1833-1844.
20.	Fischer U, Kaesmacher J, Strbian D, et al. Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial. Lancet, 2022, 400(10346): 104-115.
21.	Mitchell PJ, Yan B, Churilov L, et al. Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4.5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial. Lancet, 2022, 400(10346): 116-125.
22.	Majoie CB, Cavalcante F, Gralla J, et al. Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials. Lancet, 2023, 402(10406): 965-974.
23.	Kaesmacher J, Cavalcante F, Kappelhof M, et al. Time to treatment with intravenous thrombolysis before thrombectomy and functional outcomes in acute ischemic stroke: a meta-analysis. JAMA, 2024, 331(9): 764-777.
24.	Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet, 2014, 384(9958): 1929-1935.
25.	Friedrich B, Gawlitza M, Schob S, et al. Distance to thrombus in acute middle cerebral artery occlusion: a predictor of outcome after intravenous thrombolysis for acute ischemic stroke. Stroke, 2015, 46(3): 692-696.
26.	Ryu JC, Kwon B, Song Y, et al. Effect of intravenous thrombolysis prior to mechanical thrombectomy according to the location of M1 occlusion. J Stroke, 2024, 26(1): 75-86.
27.	Bilgic AB, Gocmen R, Arsava EM, et al. The effect of clot volume and permeability on response to intravenous tissue plasminogen activator in acute ischemic stroke. J Stroke Cerebrovasc Dis, 2020, 29(2): 104541.
28.	Cao J, Xing P, Zhu X, et al. Mild and moderate cardioembolic stroke patients may benefit more from direct mechanical thrombectomy than bridging therapy: a subgroup analysis of a randomized clinical trial (DIRECT-MT). Front Neurol, 2022, 13: 1013819.
29.	Vemmos KN, Tsivgoulis G, Spengos K, et al. Association between 24-h blood pressure monitoring variables and brain oedema in patients with hyperacute stroke. J Hypertens, 2003, 21(11): 2167-2173.
30.	Goyal N, Tsivgoulis G, Iftikhar S, et al. Admission systolic blood pressure and outcomes in large vessel occlusion strokes treated with endovascular treatment. J Neurointerv Surg, 2017, 9(5): 451-454.
31.	Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol, 2019, 18(4): 394-405.
32.	Whiteley WN, Slot KB, Fernandes P, et al. Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies. Stroke, 2012, 43(11): 2904-2909.
33.	Mazya MV, Lees KR, Collas D, et al. IV thrombolysis in very severe and severe ischemic stroke: results from the SITS-ISTR Registry. Neurology, 2015, 85(24): 2098-2106.

1. Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke, 1993, 24(1): 35-41.
2. O’Carroll CB, Barrett KM. Cardioembolic stroke. Continuum (Minneap Minn), 2017, 23(1, Cerebrovascular Disease): 111-132.
3. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med, 1995, 333(24): 1581-1587.
4. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med, 2015, 372(1): 11-20.
5. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med, 2015, 372(11): 1009-1018.
6. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med, 2015, 372(11): 1019-1030.
7. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med, 2015, 372(24): 2285-2295.
8. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med, 2015, 372(24): 2296-2306.
9. Yang P, Zhang Y, Zhang L, et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med, 2020, 382(21): 1981-1993.
10. Suzuki K, Matsumaru Y, Takeuchi M, et al. Effect of mechanical thrombectomy without vs with intravenous thrombolysis on functional outcome among patients with acute ischemic stroke: the SKIP randomized clinical trial. JAMA, 2021, 325(3): 244-253.
11. Bogiatzi C, Hackam DG, McLeod AI, et al. Secular trends in ischemic stroke subtypes and stroke risk factors. Stroke, 2014, 45(11): 3208-3213.
12. Bjerkreim AT, Khanevski AN, Thomassen L, et al. Five-year readmission and mortality differ by ischemic stroke subtype. J Neurol Sci, 2019, 403: 31-37.
13. Chen Z, Shi F, Zhang M, et al. Prediction of the multisegment clot sign on dynamic CT angiography of cardioembolic stroke. AJNR Am J Neuroradiol, 2018, 39(4): 663-668.
14. Zaidat OO, Yoo AJ, Khatri P, et al. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke, 2013, 44(9): 2650-2663.
15. 中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组, 中华医学会神经病学分会神经血管介入协作组. 中国急性缺血性卒中早期血管内介入诊疗指南 2022. 中华神经科杂志, 2022, 55(6): 565-580.
16. 中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性缺血性脑卒中诊治指南 2018. 中华神经科杂志, 2018, 51(9): 666-682.
17. Van Swieten JC, Koudstaal PJ, Vissee MC, et al. Interobserver agreement for the assessment of handicap in stroke patients. Stroke, 1988, 19(5): 604-607.
18. Zi W, Qiu Z, Li F, et al. Effect of endovascular treatment alone vs intravenous alteplase plus endovascular treatment on functional independence in patients with acute ischemic stroke: the DEVT randomized clinical trial. JAMA, 2021, 325(3): 234-243.
19. LeCouffe NE, Kappelhof M, Treurniet KM, et al. A randomized trial of intravenous alteplase before endovascular treatment for stroke. N Engl J Med, 2021, 385(20): 1833-1844.
20. Fischer U, Kaesmacher J, Strbian D, et al. Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial. Lancet, 2022, 400(10346): 104-115.
21. Mitchell PJ, Yan B, Churilov L, et al. Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4.5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial. Lancet, 2022, 400(10346): 116-125.
22. Majoie CB, Cavalcante F, Gralla J, et al. Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials. Lancet, 2023, 402(10406): 965-974.
23. Kaesmacher J, Cavalcante F, Kappelhof M, et al. Time to treatment with intravenous thrombolysis before thrombectomy and functional outcomes in acute ischemic stroke: a meta-analysis. JAMA, 2024, 331(9): 764-777.
24. Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet, 2014, 384(9958): 1929-1935.
25. Friedrich B, Gawlitza M, Schob S, et al. Distance to thrombus in acute middle cerebral artery occlusion: a predictor of outcome after intravenous thrombolysis for acute ischemic stroke. Stroke, 2015, 46(3): 692-696.
26. Ryu JC, Kwon B, Song Y, et al. Effect of intravenous thrombolysis prior to mechanical thrombectomy according to the location of M1 occlusion. J Stroke, 2024, 26(1): 75-86.
27. Bilgic AB, Gocmen R, Arsava EM, et al. The effect of clot volume and permeability on response to intravenous tissue plasminogen activator in acute ischemic stroke. J Stroke Cerebrovasc Dis, 2020, 29(2): 104541.
28. Cao J, Xing P, Zhu X, et al. Mild and moderate cardioembolic stroke patients may benefit more from direct mechanical thrombectomy than bridging therapy: a subgroup analysis of a randomized clinical trial (DIRECT-MT). Front Neurol, 2022, 13: 1013819.
29. Vemmos KN, Tsivgoulis G, Spengos K, et al. Association between 24-h blood pressure monitoring variables and brain oedema in patients with hyperacute stroke. J Hypertens, 2003, 21(11): 2167-2173.
30. Goyal N, Tsivgoulis G, Iftikhar S, et al. Admission systolic blood pressure and outcomes in large vessel occlusion strokes treated with endovascular treatment. J Neurointerv Surg, 2017, 9(5): 451-454.
31. Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol, 2019, 18(4): 394-405.
32. Whiteley WN, Slot KB, Fernandes P, et al. Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies. Stroke, 2012, 43(11): 2904-2909.
33. Mazya MV, Lees KR, Collas D, et al. IV thrombolysis in very severe and severe ischemic stroke: results from the SITS-ISTR Registry. Neurology, 2015, 85(24): 2098-2106.

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Efficacy of intravenous thrombolysis bridging endovascular thrombectomy on functional outcome of patients with acute cardioembolic stroke

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