TY - JOUR
T1 - Effect of Occlusion Site on the Safety and Efficacy of Intravenous Alteplase before Endovascular Thrombectomy
T2 - A Prespecified Subgroup Analysis of DIRECT-MT
AU - Zhou, Yu
AU - Xing, Pengfei
AU - Li, Zifu
AU - Zhang, Xiaoxi
AU - Zhang, Lei
AU - Zhang, Yongxin
AU - Zhang, Yongwei
AU - Hong, Bo
AU - Xu, Yi
AU - Huang, Qinghai
AU - Li, Qiang
AU - Zhao, Kaijun
AU - Zou, Chao
AU - Yu, Ying
AU - Zuo, Qiao
AU - Liu, Shen
AU - Zhang, Liyong
AU - Majoie, Charles B. L. M.
AU - Roos, Yvo B. W. E. M.
AU - Treurniet, K. M.
AU - Ye, Xiaofei
AU - DIRECT-MT Investigators
AU - Peng, Ya
AU - Yang, Pengfei
AU - Liu, Jianmin
N1 - Funding Information: The trial was funded by the Stroke Prevention Project of the National Health Commission of the People’s Republic of China and the Wu Jieping Medical Foundation; The analysis of this subgroup analysis was partially funded by SanHang Program of the Naval Military Medical University, “Climbing” program of Changhai hospital, and National Health Commission of the People’s Republic of China (GN-2017R0001). The design and data collection were performed by members of the executive committee and the local investigators of each participating center. The steering committee had the final responsibility for the decision to submit the article for publication. The study sponsors were not involved in the study design, study conduct, protocol review, or article preparation or review. Funding Information: Dr Majoie reports grants from CVON/Dutch Heart Foundation, grants from European Commission, grants from Dutch Health Evaluation Program, grants from Stryker, and grants from TWIN Foundation outside the submitted work; and is shareholder of Nico-lab. Dr Roos is also shareholder of Nico-lab. The other authors report no conflicts. Publisher Copyright: © 2021 American Heart Association, Inc.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - BACKGROUND AND PURPOSE: Recent trials showed thrombectomy alone was comparable to bridging therapy in patients with anterior circulation large vessel occlusion eligible for both intravenous alteplase and endovascular thrombectomy. We performed this study to examine whether occlusion site modifies the effect of intravenous alteplase before thrombectomy. METHODS: This is a prespecified subgroup analysis of a randomized trial evaluating risk and benefit of intravenous alteplase before thrombectomy (DIRECT-MT [Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals]). Among 658 randomized patients, 640 with baseline occlusion site information were included. The primary outcome was the score on the modified Rankin Scale at 90 days. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by occlusion location (internal carotid artery versus M1 versus M2). We report the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after thrombectomy alone compared with combination treatment adjusted for age, the National Institutes of Health Stroke Scale score at baseline, the time from stroke onset to randomization, the modified Rankin Scale score before stroke onset, and collateral score per the DIRECT-MT statistical analysis plan. RESULTS: The overall adjusted common odds ratio was 1.08 (95% CI, 0.82–1.43) with thrombectomy alone compared with combination treatment, and there was no significant treatment-by-occlusion site interaction (P=0.47). In subgroups based on occlusion location, we found the following adjusted common odds ratios: 0.99 (95% CI, 0.62–1.59) for internal carotid artery occlusions, 1.12 (95% CI, 0.77–1.64) for M1 occlusions, and 1.22 (95% CI, 0.53–2.79) for M2 occlusions. No treatment-by-occlusion site interactions were observed for dichotomized modified Rankin Scale distributions and successful reperfusion (extended thrombolysis in Cerebral Infarction score ≥2b) before thrombectomy. Differences in symptomatic hemorrhage rate were not significant between occlusion locations (internal carotid artery occlusion: 7.02% in bridging therapy versus 7.14% for thrombectomy alone, P=0.97; M1 occlusion: 5.06% versus 2.48%, P=0.22; M2 occlusion: 9.09% versus 4.76%; P=0.78). CONCLUSIONS: In this prespecified subgroup of a randomized trial, we found no evidence that occlusion location can inform intravenous alteplase decisions in endovascular treatment eligible patients directly presenting at endovascular treatment capable centers. Future studies are needed to confirm our findings.
AB - BACKGROUND AND PURPOSE: Recent trials showed thrombectomy alone was comparable to bridging therapy in patients with anterior circulation large vessel occlusion eligible for both intravenous alteplase and endovascular thrombectomy. We performed this study to examine whether occlusion site modifies the effect of intravenous alteplase before thrombectomy. METHODS: This is a prespecified subgroup analysis of a randomized trial evaluating risk and benefit of intravenous alteplase before thrombectomy (DIRECT-MT [Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals]). Among 658 randomized patients, 640 with baseline occlusion site information were included. The primary outcome was the score on the modified Rankin Scale at 90 days. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by occlusion location (internal carotid artery versus M1 versus M2). We report the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after thrombectomy alone compared with combination treatment adjusted for age, the National Institutes of Health Stroke Scale score at baseline, the time from stroke onset to randomization, the modified Rankin Scale score before stroke onset, and collateral score per the DIRECT-MT statistical analysis plan. RESULTS: The overall adjusted common odds ratio was 1.08 (95% CI, 0.82–1.43) with thrombectomy alone compared with combination treatment, and there was no significant treatment-by-occlusion site interaction (P=0.47). In subgroups based on occlusion location, we found the following adjusted common odds ratios: 0.99 (95% CI, 0.62–1.59) for internal carotid artery occlusions, 1.12 (95% CI, 0.77–1.64) for M1 occlusions, and 1.22 (95% CI, 0.53–2.79) for M2 occlusions. No treatment-by-occlusion site interactions were observed for dichotomized modified Rankin Scale distributions and successful reperfusion (extended thrombolysis in Cerebral Infarction score ≥2b) before thrombectomy. Differences in symptomatic hemorrhage rate were not significant between occlusion locations (internal carotid artery occlusion: 7.02% in bridging therapy versus 7.14% for thrombectomy alone, P=0.97; M1 occlusion: 5.06% versus 2.48%, P=0.22; M2 occlusion: 9.09% versus 4.76%; P=0.78). CONCLUSIONS: In this prespecified subgroup of a randomized trial, we found no evidence that occlusion location can inform intravenous alteplase decisions in endovascular treatment eligible patients directly presenting at endovascular treatment capable centers. Future studies are needed to confirm our findings.
KW - Carotid artery, internal
KW - Intravenous
KW - Ischemic stroke
KW - Odds ratio
KW - Thrombectomy
UR - http://www.scopus.com/inward/record.url?scp=85122391343&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/STROKEAHA.121.035267
DO - https://doi.org/10.1161/STROKEAHA.121.035267
M3 - Article
C2 - 34915738
SN - 0039-2499
VL - 53
SP - 7
EP - 16
JO - Stroke
JF - Stroke
IS - 1
ER -