The results of this study ran parallel to the previous studies which reported that PCS was associated with a lower risk of hemorrhagic transformations.[15–18] Older age, hyperglycemia, and high NIHSS score are related to poor outcome of post-IVT in all parameters (intracranial hemorrhage, mortality, and independence). High systolic blood pressure and atrial fibrillation are additional predictors of intracranial hemorrhage. In this study, the age, baseline NIHSS score, and systolic blood pressure were similar between ACS and PCS groups. Blood glucose level was higher in the PCS group, whereas atrial fibrillation was less frequent in the PCS patients, potentially affecting the incidence of hemorrhagic transformations in favor of ACS patients. Because the infarction volume on baseline imaging could predict the risk of post-IVT intracranial hemorrhage,[20,21] the smaller infarction volume in PCS compared with ACS might also contribute to the lower rate of hemorrhagic transformations in PCS patients. In addition, the collateral supply in posterior circulation territory might be better than that of anterior circulation. Patients with better collaterals were not prone to having hemorrhagic complications after acute reperfusion therapy.[24,25] Moreover, the brain histopathological changes after stroke onset may be different between both circulation territories. Previous studies have suggested a delayed blood–brain barrier disruption in posterior circulation compared with anterior circulation.[26,27] The greater ischemic tolerance in posterior circulation may partly explain the decreased risk of hemorrhagic complications in PCS.
Inconsistent with previous studies,[16,29–31] our results showed that PCS patients had better responses to alteplase and thereby they had higher odds of excellent recovery and functional independence at 90 days than ACS patients. Possible reasons are as follows: the most devastating stroke—basilar artery occlusion—is seldom seen, only accounting for 8% of PCS. Often PCS locates in the cerebellum, hippocampus, or occipital lobe, whereas the brain stem or thalamus is spared. These patients with vertigo, ataxia, impaired vision, cognitive decline, or mental disorder may not have obvious neurological deficits after medical treatment and rehabilitation. On the other hand, because PCS patients had less often hemorrhagic complications in this cohort, they were more likely to be treated by antiplatelet agents or anticoagulants after IVT without fear of bleeding expansion. The subsequent antithrombotic therapies could consolidate the thrombolytic effect and have a positive impact on the outcome.
Our study had several limitations. Firstly, the design of this study is prospective observational cohort by nature. We presented adjusted OR as final results in multivariate logistic regression analyses. However, the confounding factors may not be completely removed by using the multivariate model. In addition, there may be some hidden confounders (e.g., volume of infarction and collateral circulation) we did not collect in this study. We should be careful to interpret the results. Secondly, the sample size was relatively small, especially in the PCS group, which could have reduced the power of test. Thirdly, we had no information about fetal origin of posterior cerebral artery. These patients could have a stroke from the anterior circulation. And finally, this study was conducted in Chinese population. However, ethnic differences may have an impact on the outcomes observed in this analysis. Our findings should be interpreted with caution and could not easily be extrapolated to other populations.
To the best of our knowledge, this was the first multicenter observational study comparing the safety and efficacy of IVT for ACS and PCS in Chinese population. Our study suggested that PCS patients treated with IVT had a lower risk of developing hemorrhagic transformation within 7 days and better chance of having no major disability at 90 days than ACS patients. In short, IVT might be more safe and effective for PCS. Our results will provide reassurance to the clinicians in using intravenous alteplase to treat all kinds of stroke patients with confidence, including those with PCS.
We thank all participating hospitals, relevant clinicians, statisticians, and imaging and laboratory technicians.
The TIMS-China Co-investigators include: Qi Bi, MD (Beijing Anzhen Hospital, Site investigator); Liying Cui, MD, PhD (Peking Union Medical College Hospital of Peking University, Site investigator); Yuheng Sun, MD (Beijing Jishuitan Hospital, Site investigator); Maolin He, MD (Beijing Shijitan Hospital, Site investigator); Dongsheng Fan, MD, PhD (Peking University Third Hospital, Site investigator); Xiaojun Zhang, MD, PhD (Beijing Tongren Hospital, Site investigator); Yansheng Li, MD, PhD (Shanghai Renji Hospital, Site investigator); Shaoshi Wang, MD (Shanghai First Municipal People's Branch hospital, Site investigator); Wei Fan, MD (Zhongshan Hospital of Fudan University, Site investigator); Chuancheng Ren, MD (The Fifth People's Hospital of Shanghai Affiliated to Fudan University, Site investigator); Zhenguo Liu, MD (Xinhua Hospital Affiliated to Shanghai Jiaotong University, Site investigator); Xiaojiang Sun, MD (The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Site investigator); Xu Chen, MD (Shanghai 8th People's Hospital, Site investigator); Qingke Bai, MD (Pudong New Area People's Hospital, Site investigator); Dexiang Gu, MD (Shanghai Yangpu Area Shidong Hospital, Site investigator); Chunmei Hu, MD (Shanghai Baoshan Area Center Hospital, Site investigator); Xin Li, MD (Shanghai Yangpu Area Center Hospital, Site investigator); Qiang Dong, MD, PhD (Huashan Hospital of Fudan University, Site investigator); Yan Cheng, MD, PhD (Tianjin Medical University General Hospital, Site investigator); Bin Li, MD (Dagang Oilfield General Hospital, Site investigator); Chen Li, MD (Tianjin Fifth Center Hospital, Site investigator); Tongyu Wang, MD (Bohai Oilfield Hospital, Site investigator); Liping Wang, MD (Ninghe County People's Hospital of Tianjin, Site investigator); Kun Zhao, MD (Baodi District People's Hospital of Tianjin, Site investigator); Dingbo Tao, MD, PhD (The First Afflicated Hospital of Dalian Medical University, Site investigator); Fang Qu, MD (Dalian Second People's hospital, Site investigator); Jingbo Zhang, MD (Dalian Third People's hospital, Site investigator); Jianfeng Wang, MD, PhD (Dalian Central hospital, Site investigator); Ying Lian, MD (Dalian Economic and Technological Development District Hospital, Site investigator); Fang Qu, MD (Shenyang Military District General hospital of Chinese People's Liberation Army, Site investigator); Ying Gao, MD (National Traditional Chinese Medicine Thrombus Treatment Center of Liaoning Province, Site investigator); Huashan Sun, MD (Jilin Chemical Industrial Group General Hospital, Site investigator); Jinying Li, MD (Jilin Oilfield General Hospital, Site investigator); Guozhong Li, MD (The First Clinical College of Harbin Medical University, Site investigator); Yulan Zhu, MD (The Second Clinical College of Harbin Medical University, Site investigator); Zichao Yang, MD (The Fourth Clinical College of Harbin Medical University, Site investigator); Jun Zhou, MD (Mudan Jiang Second hospital, Site investigator); Minxia Guo, MD (Shanxi Provincial People's Hospital, Site investigator); Qilin Ma, MD (The First Hospital of Xiamen, Site investigator); Xiaoping Gao, MD (Hunan Provincial People's Hospital, Site investigator); Renbin Huang, MD (Chenzhou First People's Hospital, Site investigator); Bo Xiao, MD, PhD (Xiangya Hospital of Centre-South University, Site investigator); Kangning Chen, MD (Southwest Hospital, Site investigator); Li Gao, MD (Chengdu Third Municipal People's Hospital, Site investigator); Anding Xu, MD, PhD (The First Affiliated Hospital of Jinan University, Site investigator); Ming Shao, MD (The First Affiliated Hospital of Guangzhou Medical University, Site investigator); En Xu, MD (The Second Affiliated Hospital of Guangzhou Medical University, Site investigator); Xiaoping Pan, MD (Guangzhou First Municipal People's Hospital, Site investigator); Yefeng Cai, MD (Guangdong Provincial Hospital of Traditional Chinese Medicine, Site investigator); Yun Xu, MD, PhD (Drum Tower Hospital Affiliated to Nanjing Medical University, Site investigator); KaiFu Ke, MD (The Affiliated Hospital of Nantong University, Site investigator); Yuenan Kong, MD (Wuxi Second People's Hospital, Site investigator); Liangcai Ding, MD (The Third Affiliated Hospital of Suzhou University, Site investigator); Yumin Liu, MD (Zhongnan Hospital of Wuhan University, Site investigator); Kang Xu, MD (Hubei Xinhua Hospital, Site investigator); Chengming Xing, MD (Qingdao Municipal Hospital Group, Site investigator); Shaohua Su, MD (Dezhou People's Hospital, Site investigator); Guiru Zhang, MD (Penglai People's Hospital, Site investigator); Rongyuan Zheng, MD (The First Affiliated Hospital of Wenzhou Medical University, Site investigator); Ming Zhai, MD (The First People's Hospital of Yunnan Province, Site investigator); Yi Zhu, MD (The Xinjiang Autonomous Region People's Hospital, Site investigator); Yuanxin Liu, MD (Autonomous Region Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Site investigator); Xiaoying Zhang, MD (Hospital of Xinjiang Production and Construction Corps, Site investigator); Shizheng Wu, MD (Qinghai Provincial People's Hospital, Site investigator); Jinfeng Liu, MD (Yangquan Coalmine Group General hospital, Site investigator).
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