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Impact of Prior Antiplatelet Therapy on Outcomes After Endovascular Therapy for Acute Stroke: Endovascular Treatment in Ischemic Stroke Registry Results

and for the ETIS Registry Investigators*
Originally publishedhttps://doi.org/10.1161/STROKEAHA.121.034670Stroke. 2021;52:3864–3872

Abstract

Background and Purpose:

The influence of prior antiplatelet therapy (APT) uses on the outcomes of patients with acute ischemic stroke treated with endovascular therapy is unclear. We compared procedural and clinical outcomes of endovascular therapy in patients on APT or not before stroke onset.

Methods:

We analyzed 2 groups from the ongoing prospective multicenter Endovascular Treatment in Ischemic Stroke registry in France: patients on prior APT (APT+) and patients without prior APT (APT−) treated by endovascular therapy, with and without intravenous thrombolysis. Multilevel mixed-effects logistic models including center as random effect were used to compare angiographic (rates of reperfusion at the end of procedure, procedural complications) and clinical (favorable and excellent outcome, 90-day all-cause mortality, and hemorrhagic complications) outcomes according to APT subgroups. Comparisons were adjusted for prespecified confounders (age, admission National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, intravenous thrombolysis, and time from onset to puncture), as well as for meaningful baseline between-group differences.

Results:

A total of 2939 patients were analyzed, of whom 877 (29.8%) were on prior APT. Patients with prior APT were older, had more frequent vascular risk factors, cardioembolic stroke mechanism, and prestroke disability. Rates of complete reperfusion (37.9% in the APT− group versus 42.7 % in the APT+ group; aOR, 1.09 [95% CI, 0.88–1.34]; P=0.41) and periprocedural complication (16.9% versus 13.3%; aOR, 0.90 [95% CI, 0.7–1.2]; P=0.66) did not differ between the two groups. Symptomatic intracerebral hemorrhage (aOR, 0.93 [95% CI, 0.63–1.37]; P=0.73), 3 months favorable clinical outcome (modified Rankin Scale score of 0–2; aOR, 0.98 [95% CI, 0.77–1.25]; P=0.89), and mortality (aOR, 0.95 [95% CI, 0.72–1.26]; P=0.76) at 90 days did not differ between the groups.

Conclusions:

Prior APT does not influence angiographic and functional outcomes following endovascular therapy and should not be taken into account for acute revascularization strategies.

Introduction

Endovascular treatment (EVT), with or without prior intravenous thrombolysis (IVT), is the most efficient treatment for patients with acute ischemic stroke (AIS) caused by a large vessel occlusion (LVO) in the anterior circulation.1 Successful recanalization in a timely manner is the most critical determinant underlying the functional outcome following EVT and is achieved in >70%.2,3 Unfortunately, more than one-third of these patients do not recover to functional independence despite early and successful recanalization.4,5 Two main factors may hamper the benefit of acute revascularization strategies. First, the incomplete microvascular reperfusion in venules and arterioles which is observed in approximately one-quarter of patients with successful recanalization and leads to unfavorable brain tissue outcome.6,7 Second, the occurrence of hemorrhagic transformation, either symptomatic, which is a common source of early neurological deterioration8 or asymptomatic as recently highlighted by several studies.9,10

Antiplatelet therapy (APT), such as aspirin, may be able to improve the quality of recanalization following EVT11,12 and restore microvascular reperfusion,13 but one of its main drawback is to potentially increase the risk of hemorrhagic transformation.14 According to the literature, 30 to 40% of AIS patients are under APT at admission.15 Following IVT, most recent meta-analysis reported a higher risk of antiplatelet-associated symptomatic intracerebral hemorrhage (sICH) but with an increased rate of favorable functional outcome and early recanalization in prior APT users.16,17 Data in the recent era of EVT still support uncertainty about the efficacy and safety in patients under APT, some studies highlighting a higher risk of sICH, with an expected risk between 6% and 17%, whereas other reported better rates of recanalization without clear influence on functional outcome.13 Most of the discrepancies between studies rely on their small sample size or monocentric design.

We tested in the prospective multicenter Endovascular Treatment in Ischemic Stroke registry the hypothesis that prior APT is associated with better 90-day functional outcomes following EVT combined to the best medical treatment for AIS patients related to anterior circulation LVO. We also tested secondary hypotheses that prior APT is associated with a higher incidence of secondary hemorrhage and higher rate of recanalization.

Methods

All the data used in this study were anonymized. Requests for access to the data reported in this article will be considered by the Endovascular Treatment in Ischemic Stroke Scientific Committee.

Study Population

Data were recorded in the Endovascular Treatment in Ischemic Stroke registry (NCT03776877)—an ongoing French prospective multicenter database from comprehensive stroke centers that included consecutive patients with AIS treated with EVT between October 2015 and May 2020. We included patients with anterior circulation AIS treated with EVT for LVO proven on cerebral imaging (magnetic resonance imaging or computed tomography [CT] with angiographic sequences) and effectively treated. Patients were considered effectively treated with APT (whatever the number of agents) before the onset of AIS when they declared that they used to take APT on a daily basis without recent interruption. The source of information was the patient himself or his relative when the patient had impaired consciousness or severe speech disorders. Exclusion criteria were the following: patient <18 years of age, baseline modified Rankin Scale (mRS) score ≥3, unknown delay of onset, posterior circulation strokes, isolated extracranial internal carotid artery occlusion and distal occlusion (beyond M2 segment), unknown APT status, not treated with EVT, unknown initial and final modified Thrombolysis in Cerebral Infarction (mTICI), and unknown 90-day mRS (Figure 1).

Figure 1.

Figure 1. Flowchart. DAO indicates direct oral anticoagulant; ETIS, Endovascular Treatment in Ischemic Stroke; and VKA, vitamin K antagonist.

Data Recorded

The following variables were recorded: baseline characteristics such as age and sex, baseline mRS, cardiovascular risk factors (diabetes, hypertension, smoking, dyslipidemia), medical history (prior ischemic heart disease and atrial fibrillation), use of APT (single or dual) at the time of stroke onset, stroke severity assessed by the National Institutes of Health Stroke Scale score before EVT, arterial systolic and diastolic pressure, Trial of ORG 10172 in Acute Stroke Treatment etiologic classification of ischemic stroke, Alberta Stroke Program Early CT Score, occlusion site (divided into 4 groups: distal internal carotid artery, M1 and M2 portion of the middle cerebral artery, and tandem occlusion), as well as times from symptom onset to groin puncture and from symptom onset to revascularization. In addition to the investigation of the supra-aortic ipsilateral vessels during endovascular procedure, the full stroke diagnosis workup was up to the decision of the clinician and not similar at all centers but at least included an ECG, a 48-hour cardiac rhythm recording in the acute stroke unit, a transthoracic echocardiography, and a standard biological evaluation.

All patients underwent noncontrast CT scan brain imaging within 24 hours post-treatment; additional noncontrast CT scan imaging could be performed at any time in case of neurological deterioration. Intracranial hemorrhages (ICHs) on post-treatment imaging were also studied. We used both the radiological classification of ICH18 and the National Institute of Neurological Disorders and Stroke criteria of sICH defined by any new ICH on follow-up imaging with any clinical deterioration within the first 7 days.19 mTICI at the end of the procedure, the number of passes, and procedural complications were also recorded. Radiographic outcome measures were adjudicated by individual site investigators.

Outcomes

The primary study outcome was the percentage of patients who achieved a favorable 90-day outcome, defined as an mRS score of 0 to 2 or equal to prestroke mRS score. Secondary outcomes included clinical outcomes (excellent 90-day outcome defined as an mRS score of 0–1 or equal to prestroke mRS score, the degree of disability assessed by the overall distribution of 90-day mRS [shift analysis], 24-hour change in the National Institutes of Health Stroke Scale score, 90-day all-cause mortality, any hemorrhagic complications, parenchymal hematoma, sICH and procedural outcomes [reperfusion rates at the end of endovascular procedure: successful reperfusion (mTICI score 2b/3), near-to-complete reperfusion (mTICI score 2c/3), complete reperfusion (mTICI score 3)], >2 passes, procedural complications [defined as arterial perforation, arterial dissection, embolization in a new territory, and subarachnoid hemorrhage]).

Statistical Analysis

Quantitative variables are expressed as mean (SD) in case of normal distribution or median (interquartile range) otherwise. Categorical variables are expressed as numbers (percentage). Patients were divided into 4 groups according to their medication (no APT, at least 1 APT, 1 APT, and 2 APTs) before EVT. Baseline characteristics were compared between the no APT and at least 1 APT study groups, as well as between the 1 APT and 2 APT study groups using the Student t test for gaussian continuous variables, the Mann-Whitney U test for nongaussian continuous variables, or the χ2 test (or Fisher exact test when the expected cell frequency was <5) for categorical variables, as appropriate. Between-group imbalances in baseline characteristics were also assessed by calculating absolute standardized differences; an absolute standardized difference >20% was interpreted as a meaningful difference. Comparison in binary outcomes (rates of reperfusion at the end of procedure, number of passes >2, procedural complications, favorable outcome, excellent outcome, 90-day all-cause mortality, and hemorrhagic complications) between groups was made using multilevel mixed-effects logistic models by including center as random effect, and odds ratios were calculated. Comparison in the overall distribution of mRS (shift analysis) was performed with multilevel mixed-effects ordered logistic models adjusted for center; common odds ratio for 1-point improvement was derived from this model as effect size. Comparisons in outcomes were further adjusted for prespecified confounders (age, admission National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score, IVT, and time from symptom onset to groin puncture), as well as for meaningful differences in baseline characteristics between the no APT and at least 1 APT group after handling missing values by multiple imputation procedure. Missing data were imputed under the missing at random assumption by using a regression-switching approach (chained equation with m=10 imputations) using baseline characteristics and the study outcomes with a predictive mean matching method for continuous variables and a multinomial or binary logistic regression model for categorical variables. Estimates obtained in the different imputed data sets were combined using the Rubin rules. Statistical testing was conducted at the 2-tailed α-level of 0.05. Data were analyzed using the STATA software, version 16.1.

Standard Protocol Approvals, Registration, and Patient Consent

A local ethics committee and the French Data Protection Agency approved the use of patient data for this research protocol. In accordance with French legislation, informed patient consent was not required because this study used analysis of only anonymized data collected prospectively as part of routine clinical care. From the Endovascular Treatment in Ischemic Stroke registry, the trial number is NCT03776877.

Results

A total of 2939 patients were analyzed, of whom 877 (29.8%) were on APT. Seventy-seven patients were on dual APT (2.61%). Patients on APT were older, were more likely to have hypertension, hypercholesterolemia, diabetes, a history of ischemic stroke, ischemic heart disease, more frequent cardioembolic stroke mechanism, and higher prestroke mRS score (Table 1; Table I in the Data Supplement). Both populations showed differences in the location of occlusions while there were no differences in thrombectomy time metrics and stroke mechanisms.

Table 1. Baseline Characteristics

No APT (n=2072)At least 1 APT (n=867)Total (n=2939)P valueASDMissing
Demographics
Age, y; mean (SD)66 (15)73 (12)69 (15)0.00049.93 (0.10)
Women1072 (51.8)370 (42.9)1442 (49.2)0.00017.99 (0.31)
Hypertension980 (48.2)676 (78.8)1656 (57.3)0.0006747 (1.60)
Hypercholesterolemia397 (19.7)432 (50.5)829 (28.9)0.00068.266 (2.25)
Smoking471 (24.1)169 (20.9)640 (23.2)0.0777.4175 (5.95)
Diabetes224 (11.1)227 (26.5)451 (15.7)0.0004058 (1.97)
Prior stroke116 (6.0)237 (29.2)353 (12.9)0.00063.7205 (6.98)
Ischemic heart disease98 (5.1)317 (38.8)415 (15.2)0.00088.9206 (7.01)
Initial Rankin Scale score 0–21893 (94.6)766 (93.5)2659 (94.3)0.2874.3118 (4.01)
Initial systolic BP, mean (SD)146 (26)149 (26)147 (26)0.02210.1502 (17.08)
Initial diastolic BP, mean (SD)83 (17)80 (17)82 (17)0.00313.1509 (17.32)
Glycemia, mean (SD)7 (2)8 (3)7 (3)0.00023.6727 (24.74)
NIHSS16 (9)17 (9)16 (9)0.0489.273 (2.48)
ASPECTS7 (3)7 (3)7 (3)0.2882.1216 (7.35)
Cardioembolic etiology (yes), n (%)675 (37.8)378 (48.8)1053 (41.1)0.00022.5377 (12.83)
Occlusion site
 M11071 (51.7)478 (55.1)1549 (52.7)
 M2377 (18.2)173 (20.0)550 (18.7)
 ICA T307 (14.8)135 (15.6)442 (15.0)
 Tandem317 (15.3)81 (9.3)398 (13.5)0.00013.50 (0.00)
Procedural data
 Intravenous thrombolysis1255 (60.7)509 (58.9)1764 (60.2)0.3633.68 (0.27)
 General anesthesia362 (17.6)145 (16.8)507 (17.3)0.6421.816 (0.54)
 First line thrombectomy strategy
  Stentriever244 (11.9)132 (15.4)376 (12.9)
  Aspiration934 (45.5)353 (41.1)1287 (44.2)
  Stentriever and aspiration875 (42.6)372 (43.3)1247 (42.8)
  Other1 (0.0)2 (0.2)3 (0.1)0.0153.426 (0.88)
 Stenting
  No stent1916 (97.8)814 (98.8)2730 (98.1)
  Cervical24 (1.2)7 (0.8)31 (1.1)
  Intracranial19 (1.0)3 (0.4)22 (0.8)0.1758.3156 (5.31)
 Time from onset to puncture, min, median (IQR)256 (140)244 (135)252 (137)0.01313.2280 (9.53)
 Time from puncture to recanalization, min, median (IQR)42 (39)40 (35)41 (38)0.1206.1300 (10.21)
 Time from onset to recanalization, min, median (IQR)305 (143)293 (140)300 (142)0.00912.6330 (11.23)

Values are expressed as n/total n (%) unless otherwise indicated. APT indicates antiplatelet therapy; ASD, absolute standardized difference; ASPECTS, Alberta Stroke Program Early CT Score; BP, blood pressure; ICA, intracranial carotid artery; IQR, interquartile range; M1, M1 segment of the middle cerebral artery; M2, M2 segment of the middle cerebral artery; and NIHSS, National Institutes of Health Stroke Scale.

Angiographic Outcomes

As shown in Table 2, on multivariate analysis no significant difference in recanalization rates, number of passes and periprocedural complication was found between patients with and without APT. When patients were further divided according to previous administration of IVT (Table II in the Data Supplement), no difference in reperfusion rates was observed in the IVT group. Prior APT was not associated with complete recanalization conversely to history of ischemic heart disease, cardioembolic stroke, IVT, and time from onset to puncture (Table III in the Data Supplement).

Table 2. Comparison of Outcomes Between Patients Treated With No Antithrombotics and Those Treated With at Least 1 Antithrombotic Before Thrombectomy

No APT (n=2072)At least 1 APT (n=867)Missing on (n=2939)OR (95% CI)*P valueOR (95% CI)P value
Angiographic outcomes
 First-pass recanalization216 (14.3)105 (16.7)804 (27.36)1.23 (1.07–1.4)0.0020.93 (0.67–1.29)0.661
 mTICI score 2b-31732 (84.9)741 (86.8)45 (1.53)1.21 (0.98–1.5)0.0641.07 (0.80–1.44)0.612
 mTICI score 2c-31162 (57.0)505 (59.1)45 (1.53)1.17 (1.008–1.35)0.0380.97 (0.78–1.19)0.776
 mTICI score 3774 (37.9)365 (42.7)45 (1.53)1.31 (1.2–1.43)<0.0011.09 (0.88–1.34)0.414
 Total passes ≤≤2705 (55.3)305 (59)1146 (38.99)1.15 (1.04–1.26)0.0051.11 (0.88–1.4)0.355
 Complication348 (16.9)115 (13.3)11 (0.37)1.66 (1.41–1.932)0.0760.93 (0.7–1.24)0.662
Clinical outcomes
 Early neurological improvement996 (48.1)404 (46.6)0 (0.00)0.95 (0.84–1.08)0.4640.98 (0.80–1.21)0.856
 mRS score 0–2862 (47.6)306 (39.4)350 (11.91)0.70 (0.62–0.8)<0.0010.98 (0.77–1.25)0.896
 mRS score 0–1562 (31.0)202 (26)350 (11.91)0.76 (0.64–0.92)0.0050.90 (0.70–1.16)0.439
 mRS score 6328 (18.1)192 (24.7)350 (11.91)1.46 (1.15–1.85)0.0020.95 (0.72–1.26)0.762
 PH213 (12.9)119 (16.9)587 (19.97)1.35 (1.05–1.715)0.0201.02 (0.76–1.37)0.855
 sICH130 (7.8)77 (10.8)558 (18.99)1.39 (1.04–1.85)0.0220.93 (0.63–1.37)0.736

Values are expressed as n/total n (%), unless otherwise stated. APT indicates antiplatelet therapy; ASPECTS, Alberta Stroke Program Early CT Score; mRS, modified Rankin Scale; mTICI, modified Thrombolysis in Cerebral Infarction; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; PH, parenchymal hematoma; and sICH, symptomatic intracranial hemorrhage.

* Calculated using the no antithrombotic group as reference after adjustment for center.

† Calculated using the no antithrombotic group as reference after adjustment for center, age, hypertension, hypercholesterolemia, diabetes, previous stroke, ischemic heart disease, glycemia, admission NIHSS score, admission ASPECT score, intravenous thrombolysis, stroke etiology, time from symptom onset to puncture, and multiple imputation procedure to handle missing values (m=10).

Clinical Outcomes

On fully adjusted shift analysis and multivariate analysis of binary outcome variables after imputation, patients on single or dual APT had similar clinical outcome and similar rates of mortality, sICH, and parenchymal hematoma (Figure 2; Table 2; Table IV in the Data Supplement). Similarly, no difference in clinical outcome categories was detected when dividing patients according to prior thrombolysis status (Table II in the Data Supplement).

Figure 2.

Figure 2. Distribution of the modified Rankin Scale (mRS) scores at 90 d. Odds ratio calculated for 1-point improvement in mRS score for patients not on antiplatelet therapy (APT) vs patients on single (a) or dual (b) APT calculated using a mixed ordinal logistic regression model including center as random effect, age, hypertension, hypercholesterolemia, diabetes, previous stroke, ischemic heart disease, glycemia, admission National Institutes of Health Stroke Scale score, admission Alberta Stroke Program Early CT Score, intravenous thrombolysis, stroke etiology, time from symptom onset to puncture, and multiple imputation procedure to handle missing values (m=10). aOR indicates adjusted odds ratio.

Discussion

This large prospective multicenter cohort study assessing the safety and efficacy of EVT combined to best medical treatment in AIS patients related to anterior LVO according to the prior chronic exposure to APT emphasized 2 main results: (1) there are major baseline differences in the population of patients with prior APT versus no prior APT and (2) after adjusting for those differences, the apparent difference in rates of recanalization, hemorrhagic complications, and 90-day functional outcomes becomes nonsignificant.

In vitro studies have previously demonstrated that APT is responsible of smoother endothelial surface, decreases tissue factor expression, and impaired clot structure, which might, therefore, contribute to easier removal of clot.20,21 In addition, some studies have reported earlier and better recanalization among patients chronically receiving APT.16 In the setting of EVT, 2 studies have reported prior APT as an independent predictor of good recanalization,11,12 but these studies suffered from methodological issues. Conversely, secondary analysis from the MR-CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) randomized multicenter trial reported no difference of recanalization rates between patients chronically treated by APT and others.22 Interestingly while between-group comparisons identified a better recanalization rate in the APT+ group, APT was not a predictor of mTICI 2b/3 in univariate analysis. This result suggests that additional clinical, biological, or pharmacological parameters that characterize the APT+ group support this difference. In line with this hypothesis, statins, which are frequently coprescribed with APT, were associated with a better recanalization rate,23 which might explain the positive association observed between the presence of ischemic heart disease and a better recanalization rate. The higher frequency of vascular risk factors in the APT+ group might have contributed to the development of good collaterals that could also partly explain this result.24 Finally, cardioembolic stroke mechanism, which was more frequent among APT+ patients, was also a predictor of good reperfusion, suggesting that clot composition might partly explain the better reperfusion rate in this population.25,26

Conversely to Pandhi et al11 we did not observe a better recanalization rate among patients treated by EVT plus IVT compared with EVT alone. However IVT is a strong predictor of recanalization, and we cannot exclude a potential molecular interaction between APT and IVT that could support the more frequent recanalization observed in the APT+ group.27

The main drawback of APT on top of recanalization strategies is the increased risk of sICH. Indeed, the ARTIS trial was prematurely interrupted due to an increased rate of hemorrhagic complications in the group receiving aspirin on top of IVT.28 The same concern has been raised for patients chronically treated by APT prior recanalization. To date, most recent meta-analysis demonstrated a trend toward a higher risk of sICH among patients treated by IVT, but most of the studies in the era of EVT did not identify an increased risk of sICH among patients chronically treated by APT.11,12,22 Herein, no increased risk was observed in the APT+ group, even in the subgroup that was treated by bridging therapy. The discrepancy in term of sICH observed between patients chronically receiving APT in cohort studies of those from the ARTIS trial may partly rely on the high loading dose of aspirin used in the randomized trial (300 mg). This result reinforces the current practice that does not exclude patients with AIS related to LVO despite prior APT from the optimal recanalization strategy, including IVT. Beside sICH, the deleterious role of asymptomatic ICH on poststroke functional outcome was recently emphasized by several studies.9,10 Herein, prior APT was not associated with a higher rate of asymptomatic ICH following EVT, highlighting the safety of the procedure in this population.

Finally, according to the absence of difference in terms of recanalization and sICH rates, we did not observe between-group differences in functional outcome. Patients chronically treated by APT had a higher frequency of vascular risk factors, prestroke physical disability and cardioembolic stroke, a strong predictor of severe stroke, and hemorrhagic transformation29; differences that might support their worse functional outcome observed in univariate analysis. Conversely to previous studies evaluating the benefit/risk ratio of APT regimen in patients treated by IVT who reported a better functional outcome despite an increased risk of sICH, most of the EVT studies failed to confirm a difference in functional outcome according to a baseline APT. This result does not support the hypothesis of a better microcirculatory reperfusion related to antiplatelet drug or lower risk of reocclusion. Also it does not support a better outcome related to other pharmacological agents such as antihypertensive drugs or statins.30

Altogether, the present results suggest a neutral effect of prestroke chronic APT exposure and do not support an individual adaption of the recanalization strategies according to this treatment. These results raise the question of the biological efficacy of APT at admission. Indeed, patients with aspirin resistance have previously been reported to have more severe stroke and larger infarcts31,32 suggesting more frequent proximal occlusion. To date, no study has investigated the rate of APT resistance among patients with LVO and their influence on stroke outcome in large cohort studies; this point will have to be clarified in future studies.

The main strength of the present study is its large sample size in multicenter design, but the results should be interpreted cautiously due to several limits. First, despite the prospective recruitment of the patients, the rate of missing data (Figure 1; Table 1) was high, and many patients had to be dropped from the final analysis. Second, several parameters that might have influenced the rate of sICH and the functional outcome such as the periprocedure blood pressure variation or blood glucose variability or the reocclusion rates were not assessed in the present study. Third, radiographic outcome measures were adjudicated by individual site investigators while a blinded-centralized evaluation would have improved the reliability of the analyses. Fourth, APT use before admission was self-reported by patients or families. Nevertheless, medication compliance was not systematically evaluated, and this concern should be considered when interpreting our study findings. Similarly, we did not evaluate the biological efficacy of APT while at least 20 % of stroke patients are unresponsive to aspirin. Interestingly, we did not observe outcome differences between patients treated by single or dual APT, which does not support the hypothesis of residual confounding or misclassification of patients. Finally, we did not assess the role of clot composition of retrieved thrombi on the rate of reperfusion according to the use of APT.

To conclude, this large prospective study strongly supports the neutral effect of prior APT on main outcome parameters in AIS patients with LVO. To date, the decisional algorithm about the best recanalization strategy to be used at the individual level should not include the notion of chronical APT exposure.

Article Information

Supplemental Materials

Online Tables I–IV

List of Endovascular Treatment in Ischemic Stroke Investigators

Nonstandard Abbreviations and Acronyms

AIS

acute ischemic stroke

APT

antiplatelet therapy

EVT

endovascular treatment

ICH

Intracranial hemorrhage

IVT

intravenous thrombolysis

LVO

large vessel occlusion

mRS

modified Rankin Scale

mTICI

modified Thrombolysis in Cerebral Infarction

sICH

symptomatic intracranial hemorrhage

Footnotes

*A list of ETIS Registry Investigators is given in the Data Supplement.

The Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.121.034670.

For Sources of Funding and Disclosures, see page 3871.

Correspondence to: Igor Sibon, MD, PhD, Stroke Unit, Pellegrin Hospital, CHU Bordeaux, Pl Amélie Raba Léon, 33076 Bordeaux Cedex, France. Email

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