Off-hour effect is not significant in endovascular treatment for anterior circulation large vessel occlusion in a multicentre registry

Patient selection

This study was a retrospective analysis of the acute anterior circulation ischaemic stroke registry (ACTUAL). Between January 2014 and June 2016, 698 consecutive AC-LVO patients were enrolled from 21 comprehensive stroke centres in China. Detailed descriptions on this registry have been published previously.27 Patients were enrolled after fulfilling the inclusion criteria: (1) age ≥18 years; (2) were diagnosed as acute ischaemic stroke; (3) had angiographically proven (CT angiography/magnetic resonance angiography/digital subtraction angiography) AC-LVO; (4) underwent EVT. Patients treated with intra-arterial thrombolysis alone or diagnosed with a concomitant aneurysm, arteriovenous malformation or posterior circulation occlusion were excluded to maintain the homogeneity. The ACTUAL study was approved by the ethics committee of each participating centre.

Treatment protocol

Neurointerventional teams in all participating centres were capable of providing potential EVTs across the 7-day week including nights and national holidays. All enrolled patients were treated following contemporary guidelines. Patients received intravenous thrombolysis within 4.5 hours since stroke onset after excluding contradictions. Thrombectomy was performed with a stent-like retriever (Solitaire, Covidien, Irvine, California, USA) in most patients via a transfemoral approach, with other devices permitted. Rescue therapies including balloon angioplasty, stenting, intraarterial thrombolysis and intraarterial tirofiban administration were performed at the discretions of neurointerventionalists.

Definitions and group divisions

Off-hour was defined as weekends, Chinese national holidays and 18:00–7:59 on weekdays. On-hour was defined as regular working hours between 8:00 and 17:59 on weekdays except for holidays.21 Patients were categorised into the off-hour group and the on-hour group, and off-hour was defined according to arrival time (arrival mode) and groin-puncture time (puncture mode), respectively. Some patients presented during off-hour but were treated during on-hour, and some vice versa. The true off-hour group was defined when patients arrived and treated both during off-hour. Patients who arrived and got punctured both during on-hour were defined as the true on-hour group. Comparisons between the true off-hour group and the true on-hour group were performed to explore the off-hour effect thoroughly.

Data collection

Demographics, medical histories, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline Alberta Stroke Program Early CT Score (ASPECTS), time metrics, and clinical outcomes were collected. Time metrics were calculated according to medical records and automatic time stamps on images and digital subtraction angiography documents. Onset to door time (OTD) was defined as the time interval from stroke symptom onset to emergency department arrival. Door to imaging (DTI) time was defined as the time interval between patient arrival and imaging results acquired. Onset to puncture (OTP) time and door to puncture (DTP) were defined as the time interval from symptom onset to groin-puncture and patient-arrival to groin-puncture, respectively. Puncture to reperfusion (PTR) was referred to the time interval between groin-puncture and successful reperfusion. If reperfusion failed, PTR was regarded as the time interval from groin-puncture to the ending of EVT. Time from symptom onset to reperfusion (OTR) was also calculated.

Clinical outcomes

Reperfusion status was evaluated according to the modified Thrombolysis In Cerebral Infarction (mTICI) Scale, and successful reperfusion was defined as a mTICI score of 2b-3.28 Post-EVT intracranial haemorrhages (ICH) were recorded and analysed. Symptomatic ICH (sICH) and asymptomatic ICH (aICH) were evaluated according to the Heidelberg criteria.29 Collateral flow grading was estimated through the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading system.30 All angiographic data were sent to a core laboratory in Jinling Hospital. The size of ICH, collateral flow grading and preprocedure and postprocedure mTICI were evaluated blindly by two physicians/interventionists with advice from the third experienced physician/interventionist in case of disagreement.27 Modified Rankin Scale (mRS) scores at 90 days were followed up by the outpatient clinic or telephone. The primary outcome was 90-day mRS score. Secondary outcomes included favourable outcome (mRS 0–2 at 90 days), successful reperfusion, time metrics, sICH, aICH, mortality in hospital and mortality at 90 days.

Statistical analyses

Multiple imputations with chain equations were performed to account for missing values (glucose level: 7.02%; atrial fibrillation: 0.14%; ASPECTS: 3.72%; ASITN/SIR grade: 0.86%; DTI time: 1.29%; PTR: 1.00%; OTR: 0.86%). Categorical variables were expressed as numbers (percentages). Continuous variables were displayed as means (SD) or medians (IQR) according to the normality of data distributions. Univariate analysis was performed between the off-hour group and the on-hour group by using t-test, Mann-Whitney U test, χ² test or Fisher exact test as appropriate.

The on-hour group was set as the reference in multivariable regressions. Ordinary logistic regression (shift analysis) was taken to analyse differences in the 90-day mRS score between the off-hour group and the on-hour group. Linear regression and binary logistic regression were taken to compare time metrics and binary clinical outcomes between the two groups, respectively.2 In different off-hour modes, time metrics were adjusted for baseline variables with statistical trends (p<0.1 on univariate analyses). Other clinical outcomes were adjusted for baseline variables with statistical trends, OTD time and other time metrics with statistical trends. A two-sided p<0.05 was considered statistically significant. Analyses were performed using the SPSS software package, V.22.0 (IBM) and R V.3.6.3 (R Core Team (2020). R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/).

Overview

Of all 698 patients enrolled in the ACTUAL registry, the median (IQR) age was 66 (57–74) years old, and men accounted for 60.6% (423/698). The median (IQR) admission NIHSS score and ASPECTS were 16.0 (12.0–21.0) and 9.0 (8.0–10.0), respectively. Two hundred and twenty-nine (32.8%) patients received intravenous thrombolysis. The median OTD, DTI, DTP, PTR, OTP and OTR time metrics were 125.0, 23.0, 125.0, 100.0, 271.5 and 380.5 min, respectively. Four hundred and thirty-five (62.3%) patients were categorised into the off-hour group and 263 (37.7%) patients into the on-hour group in the arrival mode. Four hundred and fifty-six (65.3%) patients were categorised into the off-hour group and 242 (34.7%) patients were into the on-hour group in the puncture mode. Arrival and puncture times across all days are illustrated in figure 1. Patients who arrived or were treated in the afternoon/evening were more prevalent than those in the morning in both modes. A total of 579 (83.0%) patients reached successful reperfusion. Two hundred and eighteen (31.2%) patients were diagnosed as aICH and 108 (15.5%) as sICH. The median (IQR) mRS score at 90 days was 3 (1–6). At 90 days, 304 (43.6%) patients had favourable outcomes.

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Baseline characteristics

Table 1 shows comparisons on the baseline characteristics and clinical outcomes between the off-hour group and the on-hour group in different modes. Male sex was much more prevalent in the off-hour arrival group (64.8% vs 53.6%, p=0.003). Admission glucose level was significantly higher in the off-hour puncture group (median: 6.8 mmol/L vs 6.4 mmol/L, p=0.024). No other statistical difference in baseline characteristics was noted between the off-hour group and the on-hour group.

Clinical outcomes

In univariate analysis, mRS scores at 90 days were comparable between the off-hour arrival group and the on-hour arrival group (median: 3 vs 3; p=0.624). The OTD time was significantly shorter in the off-hour arrival group (120.0 min vs 140.0 min, p=0.047). Other EVT-related time metrics and clinical outcomes including successful reperfusion, favourable outcome, sICH, aICH, mortality in hospital and mortality at 90 days were comparable between the two groups (table 1). In the puncture mode, there was no significant difference concerning all clinical outcomes between the off-hour and on-hour presentations. Figure 2 illustrates distributions of mRS scores in different modes.

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In multivariable analyses, OTD was significantly shorter in the off-hour arrival group after adjusting for covariates (adjusted ß coefficient: −21.56 min; 95% CI −39.96 to −3.16 min; p=0.022). Ordinary logistic regression indicated that the 90-day mRS scores remained comparable between the two groups in arrival mode (common OR: 0.98; 95% CI 0.74 to 1.29; p=0.881) and puncture mode (common OR: 0.96; 95% CI 0.72 to 1.28; p=0.792). No significant difference was found regarding other time metrics and clinical outcomes between the off-hour group and the on-hour group in both arrival and puncture modes (table 2).

Subgroup analysis

Of 595 patients who presented and were treated during the same period (both during off-hour or during on-hour), 394 patients were categorised into the true off-hour group and 201 into the true on-hour group. Baseline characteristics between the two groups were shown in online supplemental table 1. A trend towards a longer DTP time metric was witnessed in the true off-hour group (median: 125.0 min vs 116.0 min; adjusted ß coefficient: 12.17 min; 95% CI −1.20 to 25.55; p=0.074). No significant difference in other time metrics and clinical outcomes was noted between the two groups (table 3). The summary of this research is illustrated in figure 3.

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