Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry
Authors: Chen Chih-Hao , Lee Chung-Wei , Hsieh Yi-Chen , Lin Chun-Jen , Chen Yu-Wei , Lin Kuan-Hung , Sung Pi-Shan , Tang Chih-Wei , Chu Hai-Jui , Tsai Kun-Chang , Chou Chao-Liang , Lin Ching-Huang , Wei Cheng-Yu , Yen Shang-Yih , Chen Po-Lin , Yeh Hsu-Ling , Chan Lung , Sung Sheng-Feng , Lee Meng , Liu Hon-Man , Lin Yen-Heng , Lee I-Hui , Yeh Shin-Joe , Lien Li-Ming , Chiou Hung-Yi , Lee Jiunn-Tay , Tang Sung-Chun , Jeng Jiann-Shing , Tang Sung-Chun , Jeng Jiann-Shing , Lee Chung-Wen , Chen Chih-Hao , Lin Yen-Heng , Yeh Shin-Joe , Lee Bo-Ching , Chung Tai-Chun , Lin Chun-Jen , Lee I-Hui , Chi Nai-Fang , Hsu Li-Chi , Chung Chih-Ping , Liu Hung-Yu , Luo Chao-Bao , Chang Feng-Chi , Lin Chung-Jung , Wu Chia-Hung , Yu Kai-Wei , Hwang Hsuen-En , Lin Te-Ming , Chen Yu-Wei , Chen Chi-Jen , Wang Ching-Yi , Kuo Yeh-Lin , Lu Ping-Sheng , Chao Yen-Tung , Su Yi-Hsin , Lin Pei-Ju , Chen Yi-Chun , Fan Li-Ling , Yang Ju-Fang , Lin Kuan-Hung , Lin Chien-Jen , Yang Sheng-Hsiang , Yang Chun-Ming , Lin Huey-Juan , Yeh Poh-Shiow , Chang Chia-Yu , Cheng Tian-Junn , Lee Wei-Jia , Ko Ching-Chung , Tsui Yu-Kun , Shih Yun-Ju , Wu Te-Chang , Sung Pi-Shan , Chang Chun-Min Wang Yu-Ming , Huang Chih-Yuan , Chen Chih-Hung , Hsieh Meng-Tsang , Ou Chang-Hsien , Lin Wan-Ching , Chen Li-Ching , Ann Bi-Shin , Tang Chih-Wei , Lai Yen-Jun , Huang Lih-Wen , Kuo Ya-Ling , Peng Szu-Hsiang , Pai Lin Yi-Chun , Chu Hai-Jui , Lin Cheng-Huai , Sun Yu , Lu Chien-Jung , Lee Chun-Yu , Liu Chang-Hsiu , Tsai Kun-Chang , Chen Kuo-Wei , Tsai Li-Kai , Hsiue Yen-Chung , Cheng Ya-Wen , Fu Chuan-Hsiu , Chen Wen-Yu , Chou Chao-Liang , Po Helen L. , Lin Ya-Ju , Hwang Yung-Pin , Kuo Shu-Fan , Huang Chun-Chao , Jhou Zong-Yi , Yu Hui-Fen , Lin Hsiao-Chu , Wei Cheng-Yu , Chen Chih-Lin , Wu Pei-han , Tsai Yi-Ching , Yen Shang-Yih , Lee Jiunn-tay , Chou Chung-Hsing , Ko Chien-An , Chen Po-Lin , Tsuei Yuang-Seng , Chen Wen-Hsien , Liao Nien-Chen , Liaw Yeng-Fung , Yeh Hsu-Ling , Lien Li-Ming , Hsiao Chen-Yu , Lin Kuan-Yu , Yang Tsui-Hua , Chan Lung , Chen Jia-Hung , Yu Shun-Fan , Su I-Chang , Lu Yueh-Hsun , Sung Sheng-Feng , Yang Tzu-Hsien , Hsu Yung-Chu , Su Yu-Hsiang , Hung Ling-Chien , Lin Mao-Hsun , Su Chien-Yu , Liu Hon-Man , Huang Yung-Chuan , Wan Chih-Cheng , Lin Ching-Huang , Yen Cheng- Chang , Shih Ching-Sen , Lin Chun-Shien , Lee Meng , Tsai Yuan-Hsiung , Huang Yen-Chu , Hung Wei-Tse , Lee Jiann-Der 
Published: February 2024

BACKGROUND:
Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase).

METHODS:
We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician’s discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b–3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis.

RESULTS:
Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40–0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88–3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0–2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28–2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43–1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata.

CONCLUSIONS:
Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.