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Endovascular treatment for acute ischemic stroke in patients with versus without atrial fibrillation: a matched-control study

Abstract

Background and objective

The effect of atrial fibrillation (AF) on outcomes of endovascular treatment (EVT) for acute ischemic stroke (AIS) is controversial. This study aimed to investigate the association of AF with outcomes after EVT in AIS patients.

Methods

Subjects were selected from ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) - a prospective consecutive cohort of AIS patients undergoing EVT at 111 hospitals in China between November 2017 and March 2019, and then grouped according to having a history of AF or not. After 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale (mRS) score, successful recanalization after final attempt, symptomatic intracranial hemorrhage (ICH) within 24 h, and death within 90 days were compared.

Results

A total of 1755 patients, 550 with AF and 1205 without AF, were included. Among 407 pairs of patients identified after matching, no significant differences were found in the mRS score (median: 3 vs. 3 points; P = 0.29), successful recanalization (87.2 vs. 85.3%; P = 0.42), symptomatic ICH (9. 4 vs. 9.1%; P = 0.86) and death (16.3 vs. 18.4%; P = 0.44) between patients with and without AF.

Conclusion

The findings of this matched-control study show comparable outcomes of EVT in Chinese AIS patients with and without AF, which do not support withholding EVT in patients with both AIS and AF.

Trial registration

NCT03370939

First registration date: 28/09/2017

First posted date: 13/12/2017

Peer Review reports

Introduction

Atrial fibrillation (AF), as the most common cause of cardioembolic stroke, is associated with a 4-5 times increased risk of acute ischemic stroke (AIS) and accounts for approximately 30–40% of all acute large vessel occlusion (LVO) [1,2,3,4,5,6,7,8]. Patients with AF-related stroke are older, have greater burden of comorbidities and worse neurological deficits, thus have a higher probability of disability or mortality after usual care [9,10,11,12]. Furthermore, intravenous thrombolysis (IVT) is less effective on both recanalization and clinical outcome but also increases the risk of intracranial hemorrhage (ICH) in patients with AF. The poor response to IVT could be partly explained by the pathophysiology of AF-related stroke, such as the gaps between patients with and without AF in terms of embolic size and components, collateral status, infarct core volume, and stroke progression [13, 14].

Endovascular treatment (EVT) represented by mechanical thrombectomy with stent-retriever or aspiration catheter has become the standard treatment for selected patients with AIS due to intracranial proximal LVO [15]. However, limited data and conflicting results exist regarding the role of AF on procedural and clinical outcomes after EVT [16,17,18,19,20,21]. To address this issue and on the hypothesis that the modification of AF was attributed to the effect of case mix; in other words, AF might not independently affect any outcome in EVT-treated patients after adjusting for possible confounders. We therefore performed a matched-control analysis based on a prospective nationwide registry database to assess whether the technical success and functional outcomes differ in LVO patients with and without AF after receiving EVT.

Methods

Study population

Data were extracted from ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke), a prospective nationwide registry of 1793 consecutive patients with AIS caused by LVO undergoing EVT in 111 hospitals in China between November 2017 and March 2019. Full methods of the registry, such as inclusion/exclusion criteria and data collection standards, have been reported earlier [22]. The protocol was approved by the ethics committees of all centers, and all participants (or legal representatives) provided written informed consent. The study procedures were in accordance with the 1964 Helsinki declaration and its later amendments.

In this analysis, patients with missing baseline or procedure data in Table 1 were excluded, and the remainder cases were divided into two groups based on whether they had pre-existing AF, identified by previous medical records.

Table 1 Baseline and procedure characteristics of patients with AF versus without AF

Outcome measures

The primary outcome was the 90-day modified Rankin Scale (mRS) score assessed by trained and independent investigators. The secondary outcomes included successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] of 2b-3) after first and final attempt, complete recanalization (mTICI of 3) after final attempt, [23] the proportions of mRS 0–1, 0–2 and 0–3 at 90 days. The safety outcomes were intra-procedural complications (e.g., new territorial embolization, arterial perforation, arterial dissection, vasospasm requiring treatment and in-stent thrombosis), any ICH, parenchymal hematoma type 2 (PH2) and symptomatic ICH within 24 hours according to the Heidelberg Bleeding Classification, [24] and death within 90 days.

Statistical analysis

Data were displayed as median (interquartile range [IQR]) or frequency (percentage). Univariable comparisons of baseline characteristics between patients with and without AF were performed using Mann-Whitney or Pearson’s chi-square tests. To improve the comparability between the two groups, a 1:1 propensity score matching (PSM) was performed by using a caliper distance of 0.05 [25]. For comparing the outcomes between both groups, the odds ratios (OR) or common OR with their 95% confidence intervals (CI) were calculated using a binary or ordinal logistic regression model, if applicable. Significance level was set to α = 0.05 (2-sided). Statistical analyses were conducted with SAS software version 9.4 (SAS Institute Inc., Cary, NC).

Results

Among 1793 patients enrolled in the ANGEL-ACT registry, 38 patients were excluded due to missing baseline or procedure information, a total of 1755 patients were included in this analysis, including 550 cases with AF and 1205 without AF. After PSM, 814 patients were identified (Fig. 1).

Fig. 1
figure1

Flow chart of patient selection. Abbreviations: AF = atrial fibrillation, ANGEL-ACT = Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke

As shown in Table 1, there were significant differences in many baseline and procedure characteristics between pre-matched patients with and without AF. For example, patients with AF were 8 years older, had 3 points higher NIHSS scores, were more frequently given anticoagulants before stroke onset, and received more passes of thrombectomy than those without AF; while patients with AF had lower proportions of male, current smoker, and vertebro-basilar artery occlusion, were less often given tirofiban during the procedure and emergency angioplasty/stenting, and experienced 65 min shorter onset-to-puncture time than those without AF (all P-values < 0.01). After PSM, all baseline and procedure characteristics between groups were well-balanced (Table 1).

Comparisons of outcome measures between patients with and without AF were presented in Table 2. Before matching, there was no significant difference in recanalization rates between the two groups, but patients with AF had a higher 90-day mRS score (P < 0.01) and higher risks of intra-procedural complications (P = 0.02), hemorrhagic transformations within 24 hours (all P < 0.01), and death within 90 days (P = 0.01), whereas they had lower proportions of mRS 0–1, 0–2, and 0–3 points at 90 days (all P < 0.01). After matching, the difference in the primary outcome - 90-day mRS score no longer existed between patients with and without AF (median: 3 vs. 3 points; P = 0.29). In addition, all differences in secondary and safety outcomes that differed between both groups before matching also disappeared.

Table 2 Outcome measures of patients with AF versus without AF

Discussion

This real-world registry study in China found that patients with AF were older, had more severe symptoms on admission, a lower proportion of posterior circulation occlusions, and a shorter time from onset to puncture. After matching for baseline characteristics using propensity scores, AF was not independently associated with 90-day functional outcomes, recanalization rates, and intra-procedural complications.

A subgroup analysis of the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) showed a trend towards a decreased treatment effect of EVT in patients with AF. However, the sample size of AF patients in their study was rather small, thus no definite conclusion could be drawn [16]. A subsequent meta-analysis from the HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) demonstrated no interaction between AF and functional outcomes after EVT, but found a trend towards a lower rate of symptomatic ICH in AIS patients with AF (3.4% in AF patients vs. 4.5% in non-AF patients), which might be related to the lower percentage of pre-treatment with IVT (76.3% in AF patients vs. 90.6% in non-AF patients). This is probably mainly due to the fact that patients with AF are more likely to taking oral anticoagulants, which is a contraindication for the administration of tPA [17]. Conversely, a post-hoc analysis of a multi-center head-to-head clinical trial revealed that AF was an independent risk factor for any ICH in AIS patients undergoing stent-retriever thrombectomy, which was partly attributable to the adjusted anticoagulation status and more retrieval attempts by mediation analyses [18]. Furthermore, a national registry study assessing post-thrombectomy outcomes found no difference in either in-hospital or discharge outcomes between matched patients with or without AF, [19] whereas two other studies suggested faster procedural time, fewer passes, higher rates of first pass effect, successful reperfusion and good functional outcome with AF-related stroke [20, 21].

Previous observations found patients with AIS caused by AF tend to have more bleedings and worse outcomes after EVT than those without AF [16, 18]. However, special cautions should be taken when interpreting these results, such a statement could lead to misconclusions to suspecting or even denying EVT to patients with AF. We may expect that AIS caused by a sudden embolus from the cardiovascular circulation can progress faster than AIS caused by progressive carotid or intracranial artery stenosis, where there may be time for development of collaterals [26]. In this study, patients with AF were treated about 1 hour earlier (median time from onset to puncture: 260 min vs. 325 min) compared to those without AF, suggesting a faster infarct growth rate and a stronger time dependence of reperfusion therapy in AF-related stroke.

Strengths of this study were the large sample size of enrolled patients (n = 1755) and the high prevalence of AF (31. 3%), resulting in more reliable estimations. Also, comparison of outcomes after PSM was a strength. Finally, all radiological and clinical outcomes in this analysis were centrally adjudicated by the independent imaging core laboratory or clinical events committee, except those intra-procedural complications were locally scored by site investigators. Nevertheless, our study has some limitations. First, the collateral status has been shown to be an excellent predictor of stroke outcomes, [27] so a major limitation of this study is the lack of assessment of collateral status, which has been postulated as a possible reason for difference in functional outcomes post-EVT of LVO patients with vs. without AF [28, 29]. Second, this study was conducted in Chinese population, where the prevalence of intracranial atherosclerotic disease (ICAD) is very high [30]. In this context, an underlying ICAD stenotic lesion is often cited as a possible reason for immediate re-occlusion after thrombectomy that results in bailout intracranial angioplasty or stenting, thus potentially having an impact on the outcomes [31]. Our findings should be interpreted with caution and could not easily be extrapolated to other populations. Third, patients with AF may have more comorbidities (e.g., decreased ejection fraction, valvular heart disease, other organ failure), larger infarct core, and different texture of thrombus compared to those without AF. However, these variables were not collected in the ANGEL-ACT registry, so their confounding effects could not be ruled out. Finally, no information on antithrombotic therapy from post-procedure to discharge, treatment adherence and rehabilitation training after discharge was recorded, therefore limiting comments on the association between them and functional outcomes.

Conclusion

The present study found no difference in the radiological and clinical outcomes following EVT between Chinese AIS patients with and without AF, implying AF status should not hamper the decision making to proceed to EVT. Furthermore, our results were in contrast to the increased hemorrhage rates and worse functional outcomes observed in AF-related stroke treated with supportive care or IVT. It is known that thrombolysis is less used in patients with AF-related LVO and, if used, has only limited effect. Thus, the fact is EVT might be the best chance for these patients.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author Dapeng Mo (bjttmodp@163.com) or Zhongrong Miao (zhongrongm@163.com) upon reasonable request.

Abbreviations

AF:

Atrial fibrillation

AIS:

Acute ischemic stroke

ANGEL-ACT:

Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke

ASPECTS:

Alberta Stroke Program Early CT Score

CI:

Confidence interval

EVT:

Endovascular treatment

HERMES:

Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials

ICH:

Intracranial hemorrhage

IQR:

Interquartile range

IVT:

Intravenous thrombolysis

LVO:

Large vessel occlusion

MR CLEAN:

Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands

mRS:

Modified Rankin Scale

mTICI:

Modified Thrombolysis in Cerebral Infarction

NIHSS:

National Institutes of Health Stroke Scale

OR:

Odds ratio

pc-ASPECTS:

Posterior circulation Alberta Stroke Program Early CT Score

PH2:

Parenchymal hematoma type 2

PSM:

Propensity score matching

SD:

Standardized difference

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Acknowledgements

We thank all participating hospitals, relevant clinicians, statisticians, and imaging and laboratory technicians.

The ANGEL-ACT study group

Zhongrong Miao1; Liqiang Gui8; Cunfeng Song9; Ya Peng10; Jin Wu11; Shijun Zhao12; Junfeng Zhao13; Zhiming Zhou14; Yongli Li15; Ping Jing16; Lei Yang17; Yajie Liu18; Qingshi Zhao19; Yan Liu20; Xiaoxiang Peng21; Qingchun Gao22; Zaiyu Guo23; Wenhuo Chen24; Weirong Li25; Xiaojiang Cheng26; Yun Xu27; Yongqiang Zhang28; Guilian Zhang29; Yijiu Lu30; Xinyu Lu31; Dengxiang Wang32; Yan Wang33; Hao Li34; Yang Hua35; Deqin Geng36; Haicheng Yuan37; Hongwei Wang38; Haihua Yang39; Zengwu Wang40; Liping Wei41; Xuancong Liufu42; Xiangqun Shi43; Juntao Li44; Wenwu Yang45; Wenji Jing46; Xiang Yong47; Leyuan Wang48; Chunlei Li49; Yibin Cao50; Qingfeng Zhu51; Peng Zhang52; Xiang Luo53; Shengli Chen54; WenWu Peng55; Lixin Wang56; Xue Wen57; Shugui Shi58; Wanming Wang59; Wang Bo60; Pu Yuan61; Dong Wang62; Haitao Guan63; Wenbao Liang64; Daliang Ma65; Long Chen66; Yan Xiao67; Xiangdong Xie68; Zhonghua Shi69; Xiangjun Zeng70; Fanfan Su71; MingZe Chang72; Jijun Yin73; Hongxia Sun74; Chong Li75; Yong Bi76; Gang Xie77; Yuwu Zhao78; Chao Wang79; Peng Zhang80; Xianjun Wang81; Dongqun Li82; Hui Liang83; Zhonglun Chen84; Yan Wang85; Yuxin Wang86; Lin Yin87; HongKai Qiu88; Jun Wei89; Yaxuan Sun90; Xiaoya Feng91; Weihua Wu92; Lianbo Gao93; Zhibing Ai94; Lan Tan95; Li Ding96; Qilong Liang97; Zhimin Wang98; Jianwen Yang99; Ping Xu100; Wei Dong101; Quanle Zheng102; Zhenyun Zhu103; Liyue Zhao104; Qingbo Meng105; Yuqing Wei106; Xianglin Chen107; Wei Wang108; Dong Sun109; Yongxing Yan110; Guangxiong Yuan111; Yadong Yang112; Jianfeng Zhou113; Zhi Yang114; Zhenzhong Zhang115; Ning Guan116; Huihong Wang117

1Beijing Tiantan Hospital, Beijing, China

8Langfang Changzheng Hospital, Hebei, China

9Liaocheng Third People’s Hospital, Shandong, China

10The First People’s Hospital of Changzhou, Jiangsu, China

11The Second Affiliated Hospital of Nanjing Medical University, Jiangsu, China

12Fengrun District People’s Hospital of Tangshan City, Hebei, China

13SiPing Central People’s Hospital, Jilin, China

14Yijishan Hospital of Wannan Medical College, Anhui, China

15The 2nd Affiliated Hospital of Harbin Medical University, Heilongjiang, China

16The Central Hospital of Wuhan, Hubei, China

17The First Hospital of Shijiazhuang, Hebei, China

18Shenzhen Hospital of Southern Medical University, Guangdong, China

19The People’s Hospital of Longhua, Guangdong, China

20Jingjiang People’s Hospital, Jiangsu, China

21The Third People’s Hospital of Hubei Province, Hubei, China

22The Second Affiliated Hospital of Guangzhou Medical University, Guangdong, China

23Tianjin TEDA Hospital, Tianjin, China

24Zhangzhou Affiliated Hospital of Fujian Medical University, Fujian, China

25Taiyuan Central Hospital, Shanxi, China

26The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China

27Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu, China

28The First People’s Hospital of Wenling, Zhejiang, China

29The Second Affiliated Hospital of Xi’an Jiaotong University, Shaanxi, China

30The First People’s Hospital of Yulin, Guangxi, China

31Zhenjiang First People’s Hospital, Jiangsu, China

32Qitaihe Coal General Hospital Heilongjiang, China

33People’s Hospital of Tangshan City, Hebei, China

34Affiliated Hospital of Guilin Medical University, Guangxi, China

35The Affiliated Hospital of Guizhou Medical University, Guizhou Province, China

36The Affiliated Hospital of Xuzhou Medical University, Jiangsu, China

37Qingdao Central Hospital, Shandong, China

38The Fourth People’s Hospital of Langfang City, Hebei, China

39Beijing Daxing hospital, Beijing, China

40Weifang People’s Hospital, Shandong, China

41Luoyang General Hospital Affiliated to Zhengzhou University, Henan, China

42Dongguan Kanghua Hospital, Guangdong, China

43Shunde Hospital of Southern Medical University, Guangdong, China

44Handan Central Hospital, Hebei, China

45The 981 hospital of the Chinese People’s Liberation Army, Hebei, China

46Linfen people’s Hospital, Shanxi, China

47Anshun people’s Hospital of Guizhou, China

48Changle People’s Hospital, Shandong, China

49The Second People’s Hospital of Dongying, Shandong, China

50Tangshan Gongren hospital, Hebei, China

51PLA 985 Hospital of the Joint Logistics Support Force, Shanxi, China

52Gaomi People’s Hospital, Shandong, China

53Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China

54Chongqing Sanxia Center Hospital, Chongqing, China

55Hospital of Traditional Chinese Medicine of Qiannan, Guizhou, China

56Guangdong Hospital of Chinese Medicine, Guangdong, China

57People’s hospital of Yangjiang, Guangdong, China

58The Third Affiliated Hospital of CQMU, Chongqing, China

59General Hospital of The Yangtze River Shipping, Hubei, China

60First People’s Hospital of Bijie City, Guizhou, China

61Suqian People’s Hospital of Nanjing Drum-Tower Hospital Group, Jiangsu, China

62Weifang TCM Hospital, Shandong, China

63The Third Affiliated Hospital of Guangzhou Medical University, Guangdong, China

64Karamay Central hospital, Xinjiang, China

65The third people’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, China

66Wulanchabu City Central Hospital, Inner Mongolia, China

67Hospital of Xinjiang Production & Construction Corps, Xinjiang, China

68Jiaozuo Second people’s hospital, Henan, China

69The 904 Hospital of Joint Logistic Support Force of PLA, Jiangsu, China

70Ganzhou People’s Hospital, Jiangxi, China

71The 967 Hospital of the Joint Logistics Support Force of PLA, Liaoning, China

72The Affiliated Hospital of Northwest University Xi’an No.3 Hospital, Shaanxi, China

73The Second Hospital of Liao Cheng, Shandong, China

74Jilin Province People’s Hospital, Jilin, China

75People’s Hospital of Huanghua City, Hebei, China

76Shanghai Forth People’s Hospital, Shanghai, China

77Wanbei Coal-electricity Group General Hospital, Anhui, China

78Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

79Binzhou Medical University Hospital, Shandong, China

80The 988 hospital of the people’s liberation army, Henan, China

81Linyi People’s Hospital, Shandong, China

82Yingkou City Central Hospital, Liaoning, China

83Yantaishan Hospital, Shandong, China

84Mianyang Central hospital, Sichuan, China

85Chengdu Fifth People’s Hospital, Sichuan, China

86Hengshui Fifth Hospital of Heng shui City, Hebei, China

87Second Hospital of Dalian Medical University, Liaoning, China

88Boai Hospital of Zhongshan, Guangdong, China

89The First People’s Hospital of Yibin, Sichuan, China

90Shanxi provincial people’s hospital, Shanxi, China

91Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Shandong, China

92Chuxiong State People’s Hospital, Chuxiong, Yunnan, China

93The Fourth Affiliated Hospital of China Medical University, Liaoning, China

94Taihe Hospital, Shiyan, Hubei, China

95Qingdao Municipal Hospital, Shandong, China

96The First People’s Hospital of Yunnan Province, Yunnan, China

97The NO.2 People’s Hospital of Lanzhou, Gansu, China

98Taizhou First People’s Hospital, Zhejiang, China

99Hunan Provincial People’s Hospital, Hunan, China

100First People’s Hospital of Changde City, Hunan, China

101Zhejiang Yuyao People’s Hospital, Zhejiang, China

102Aidebao Hospital, Hebei, China

103The First Hospital of Fangshan District, Beijing, China

104Tianjin Xiqing Hospital, Tianjin, China

105People’s Hospital of Zunhua, Hebei, China

106Xingtai Third Hospital, Hebei, China

107Qingyuan People’s Hospital, Guangdong, China

108Fengcheng City Central Hospital, Liaoning, China

109People’s Hospital of Hejian City, Hebei, China

110Hangzhou Third People’s Hospital, Zhejiang, China

111Xiangtan Central Hospital, Hunan, China

112People’s Hospital of Nanpi Country, Hebei, China

113Liuzhou Railway Central Hospital, Guangxi, China

114Maoming People’s Hospital, Guangdong, China

115Tongde Hospital of Zhejiang Province, Zhejiang, China

116The First Affiliated Hospital of Jinzhou Medical University, Liaoning, China

117Xishan coal electricity group worker general hospital, Shaanxi, China

Funding

This study was funded by the National Key Research and Development Program of China (2018YFC1312801, 2016YFC1301500), China Postdoctoral Science Foundation (2019 M650773). The funding body did not play any role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

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Contributions

XT, DM and ZM designed the study; XT, SL and WL wrote the main manuscript text and prepared figures; ZR and RL made the critical revision of manuscript; AW performed the statistical analysis; BJ, XZ, XH, GL and GM conducted the study and acquired the data; YW, YW and ZM supervised the study; DM and ZM analyzed and interpreted the data. All authors reviewed the manuscript. The author(s) read and approved the final manuscript

Corresponding authors

Correspondence to Zhongrong Miao or Dapeng Mo.

Ethics declarations

Ethics approval and consent to participate

The protocol was approved by the ethics committees of Beijing Tiantan Hospital and each participating site. Each participant or his/her representative gave written informed consent before being enrolled in the study. The study procedures were in accordance with the 1964 Helsinki declaration and its later amendments.

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Not applicable.

Competing interests

The authors have no financial conflicts of interest.

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Tong, X., Li, S., Liu, W. et al. Endovascular treatment for acute ischemic stroke in patients with versus without atrial fibrillation: a matched-control study. BMC Neurol 21, 377 (2021). https://doi.org/10.1186/s12883-021-02386-3

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Keywords

  • Atrial fibrillation
  • Endovascular treatment
  • Ischemic stroke
  • Propensity score matching