You are here

Article Text

Article menu
Cerebrovascular disease
Original research
Bridging versus direct endovascular therapy in basilar artery occlusion
  1. Sergio Nappini1,
  2. Francesco Arba2,
  3. Giovanni Pracucci3,
  4. Valentina Saia4,
  5. Danilo Caimano3,
  6. Nicola Limbucci1,
  7. Leonardo Renieri1,
  8. Andrea Zini5,
  9. Domenico Inzitari3,
  10. Danilo Toni6,
  11. Salvatore Mangiafico1
  12. On behalf of the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) Study Group
  1. 1 Neurovascular Interventional Unit, University Hospital Careggi, Firenze, Italy
  2. 2 Stroke Unit, University Hospital Careggi, Firenze, Italy
  3. 3 NEUROFARBA Department, Universita degli Studi di Firenze Scuola di Scienze della Salute Umana, Firenze, Italy
  4. 4 Neurology and Stroke Unit, Hospital Santa Corona Pietra Ligure, Pietra Ligure, Italy
  5. 5 Department of Neurology and Stroke Center, IRCCS Istituto delle Scienze Neurologiche, Maggiore Hospital, Bologna, Italy
  6. 6 Neurological Sciences, University of Rome La Sapienza, Roma, Italy
  1. Correspondence to Dr Sergio Nappini, Neurovascular Interventional Unit, University Hospital Careggi, Firenze, Italy; nappini{at}gmail.com

Abstract

Background We evaluated safety and efficacy of intravenous recombinant tissue Plasminogen Activator plus endovascular (bridging) therapy compared with direct endovascular therapy in patients with ischaemic stroke due to basilar artery occlusion (BAO).

Methods From a national prospective registry of endovascular therapy in acute ischaemic stroke, we selected patients with BAO. We compared bridging and direct endovascular therapy evaluating vessel recanalisation, haemorrhagic transformation at 24–36 hours; procedural complications; and functional outcome at 3 months according to the modified Rankin Scale. We ran logistic and ordinal regression models adjusting for age, sex, National Institutes of Health Stroke Scale (NIHSS), onset-to-groin-puncture time.

Results We included 464 patients, mean(±SD) age 67.7 (±13.3) years, 279 (63%) males, median (IQR) NIHSS=18 (10–30); 166 (35%) received bridging and 298 (65%) direct endovascular therapy. Recanalisation rates and symptomatic intracerebral haemorrhage were similar in both groups (83% and 3%, respectively), whereas distal embolisation was more frequent in patients treated with direct endovascular therapy (9% vs 3%; p=0.009). In the whole population, there was no difference between bridging and direct endovascular therapy regarding functional outcome at 3 months (OR=0.79; 95% CI=0.55 to 1.13). However, in patients with onset-to-groin-puncture time ≤6 hours, bridging therapy was associated with lower mortality (OR=0.53; 95% CI=0.30 to 0.97) and a shift towards better functional outcome in ordinal analysis (OR=0.65; 95% CI=0.42 to 0.98).

Conclusions In ischaemic stroke due to BAO, when endovascular therapy is initiated within 6 hours from symptoms onset, bridging therapy resulted in lower mortality and better functional outcome compared with direct endovascular therapy.

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. All free text entered below will be published.

https://doi.org/10.1136/jnnp-2020-325328

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Introduction

    Endovascular treatment for acute ischaemic stroke gained wide acceptance for anterior ischaemic stroke caused by intracranial large vessel occlusion.1 More than 80% of patients enroled in major endovascular clinical trials received intravenous treatment with recombinant tissue Plasminogen Activator (rt-PA) before endovascular treatment,2 supporting the use of rt-PA before endovascular treatment.

    However, patients with ischaemic stroke and posterior circulation symptoms were excluded from the aforementioned clinical trials. Unlike the anterior circulation, the posterior circulation depends on the basilar artery, which supplies most of the brainstem, part of the cerebellum, thalamus and the occipital lobes.3 Ischaemic stroke in the posterior circulation stroke represents about 20% of all ischaemic strokes and is a major challenge due to the variability of clinical presentation, ranging from transient ischaemic attack or minor stroke to rapidly progressive brainstem dysfunction or coma at onset, as often seen in basilar artery occlusion (BAO). Although BAO is relatively rare, accounting for approximately 1% of all ischaemic strokes and 5%–10% of large vessel occlusion strokes, it is a subtype of ischaemic stroke with a rate of disability and mortality of almost 80%.3 4 Moreover, there is debate about the best acute treatment strategy (only rt-PA, direct endovascular, both) in BAO and evidence about the acute management for BAO is lacking. The per-protocol and the as-treated analysis of the recent BEST trial5 seemed to favour endovascular treatment, although the intention-to-treat analysis was neutral. A subgroup analysis of the recent BASICS trial suggested that endovascular treatment was effective in patients with moderate to severe neurological deficit, whereas rt-PA alone may be suited for patients with milder deficit.6 Previously, the BASICS registry did not provide evidence about superiority of a treatment strategy7 but confirmed the high rates of mortality and disability of BAO. The American Heart Association (AHA) Guidelines suggest that endovascular treatment of BAO within 6 hours from symptoms onset is reasonable.2

    Furthermore, there is no consensus about the treatment time window in BAO. Although AHA guidelines suggest that treatment could be reasonable within 6 hours,2 there is preliminary evidence that selected patients could benefit of treatment in extended time windows.8 9 Mainly based on empirical evidence, many centres with endovascular therapy service adopted revascularisation protocols for BAO with wider time windows than those recommended for endovascular therapy.10

    The aim of the present study, based on a prospective national registry of patients with ischaemic stroke receiving endovascular treatment, was to explore in those with BAO safety and efficacy of bridging (rt-PA plus endovascular) as compared with direct endovascular treatment, received within and beyond 6 hours of stroke onset.

    Methods

    We extracted patient-level data from the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS), from 2011 to 2017. The IRETAS is a prospective, observational multicentre internet-based registry (http:// www.registroendovascolare.it) running in Italy since 2010 and involving more than 50 academic and non-academic hospitals.11 All participating centres are required to include in the IRETAS anonymous data of consecutive patients with ischaemic stroke treated with endovascular procedures.

    We selected patients with isolated BAO, excluding BAO with concurrent vertebral artery or posterior cerebral artery occlusion. We acquired patient-level data about demographics, anamnestic, clinical and procedural data. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). All patients underwent brain CT and CT-angiography or magnetic resonance (MR) and MR-angiography (MRA) before treatment, to demonstrate BAO. Patients underwent direct endovascular treatment alone or after intravenous administration of rt-PA within 4.5 hours. Eligibility to rt-PA was assessed by local stroke physicians at each participating centre, according to national guidelines. Eligibility to endovascular treatment was assessed by both neurologist and neuroradiologist on duty on the basis of the neurological symptoms consistent with occlusion in the posterior circulation, evidence of occlusion of basilar artery at the CT or MRA, onset to treatment time no longer than 12 hours, absence of extensive ischaemic lesions involving the brainstem.

    Patients eligible for endovascular treatment that spontaneously recanalised (with or without previous rt-PA) and found without occlusion at the angio-suite were not included. The site of occlusion (proximal, middle and distal) was further detailed with angiographic study, and classified according to the segment of basilar artery as follows: (1) proximal: from vertebrobasilar junction up to anterior inferior cerebellar artery, which was not included in the proximal segment; (2) middle: from anterior inferior cerebellar artery up to superior cerebellar artery, which was not included in the middle segment; (3) distal: from superior cerebellar artery up to the origin of the posterior cerebral arteries (top-of-basilar occlusion).12 Endovascular procedures included mechanical thrombectomy, thrombus aspiration or both, according to the neurointerventionalist choice. Vessel recanalisation was assessed by the treating neurointerventionalist at each centre with the Thrombolysis In Cerebral Infarction (TICI) scale.13

    Patients underwent brain CT or MR within 24 hours after the procedure. Haemorrhagic transformation (HT) was rated according to the Second European Cooperative Acute Stroke Study (ECASS-II) criteria14; symptomatic intracerebral haemorrhage (sICH) was defined as any type of intracerebral haemorrhage with increase of four or more NIHSS points or death. Onset of symptoms was recorded as described by the patient or witness and onset- to-treatment (onset-to-groin-puncture) time, and was dichotomised into ≤6 hours and >6 hours.

    For the purposes of the present study, study population was divided into two groups: direct endovascular and bridging (intravenous thrombolysis with rt-PA + endovascular) treatment.

    Our study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology criteria.15

    Outcomes

    We investigated efficacy outcomes:

    1. Vessel recanalisation: we defined good recanalisation as TICI 2b/3.

    2. Functional status at 3 months assessed with the modified Rankin Scale (mRS), defined as excellent outcome (mRS=0–1), good outcome (mRS=0–2), death (mRS=6); mRS was assessed by local investigators at each site with outpatient visit or telephone call.

    As safety outcomes, we evaluated any HT at 24 hours according to the ECASS-II classification,14 sICH, vessel perforation (ie, subarachnoid haemorrhage), vessel dissection, thrombus fragmentation/distal embolisation (ie, evidence of unwanted occlusion of arterial segments distal to the occlusion and along the path of thrombectomy after endovascular manoeuvres).

    Statistical analysis

    We described general characteristics of the population with summary statistics, and used analysis of variance, Mann-Whitney U test and Pearson χ2 as appropriate, to test differences between the two groups. We therefore evaluated univariate associations between treatment strategy (bridging and endovascular alone) and study outcomes using logistic and ordinal regression for binary and ordinal outcomes, respectively. We retained in multivariate analysis explanatory variable with p<0.1 at the univariate analysis adjusting for age, sex, NIHSS and onset-to-treatment (onset-to-groin-puncture) time. We considered statistically significant a p value <0.05. We repeated the analysis after stratification in two groups according to onset-to-groin-puncture ≤6 hours and >6 hours. Statistical analysis was carried out using SPSS for Windows (V.25.0; SPSS, IBM Corp, Armonk, New York, USA).

    Results

    General characteristics

    In the study period, data about 728 patients with occlusion in the posterior circulation were available from the registry. A total of 61 (8%) patients had posterior cerebral artery occlusion and 49 (7%) patients had vertebral artery occlusion and were excluded, further 127 (17%) patients had no available relevant anamnestic/clinical data or had combined basilar + vertebral or basilar + posterior cerebral artery occlusions, and 25 (3%) had missing mRS at 3 months and were therefore excluded from the final analysis. Among the remaining 466 patients with isolated BAO treated with endovascular therapy, we had two missing data about type of treatment, which left 464 patients for the final analysis (figure 1).

    Figure 1
    Figure 1

    Flow diagram of study population. BAO, basilar artery occlusion; mRS, modified Rankin Scale; PCA, posterior cerebral artery; VA, vertebral artery.

    Baseline characteristics of the study population are summarised in table 1. Mean (±SD) age was 67.7 (±13.3) years, 303 (65%) patients were male, 166 (36%) received bridging and 298 (64%) direct endovascular therapy. Overall, 36 (8%) of patients had MR before endovascular treatment, the remaining patients had CT. BAO site was as follows: distal in 187 (40%) patients, proximal in 72 (16%), middle in 91 (20%), complete BAO in 40 (7%); 76 (16%) had mixed site of occlusion (proximal and middle; middle and distal); distribution of site of occlusion according to treatment is shown in figure 2. Overall, occlusion site was as follow: 185 (40%) top of the basilar, 91 (20%) middle segment, 72 (15%) inferior segment, 40 (9%) whole basilar, 43 (9%) middle and top of basilar segment, 33 (7%) inferior and middle segment. Median (IQR) NIHSS was 18 (10–30), and median (IQR) onset-to-groin puncture was 290 (210–401) minutes. Median (IQR) prestroke mRS was 0 (0–0). Patients treated with direct endovascular therapy had higher NIHSS (18 vs 17; p=0.038), were more likely to have atrial fibrillation (26% vs 13%; p<0.001) and were more frequently on therapy with antiplatelets (33% vs 24%; p=0.025) and anticoagulants (11% vs 7%; p=0.064) before stroke. There was no difference between bridging and direct endovascular regarding onset-to-groin-puncture (280 vs 300 min, respectively; p=0.175) and duration of endovascular treatment (80 vs 79 min, respectively; p=0.451). There were no other differences among general characteristics of the population. Characteristics of study population stratified by onset to endovascular treatment time (≤ and > 6 hours) are shown in online supplemental tables 1,2 A,B.

    Supplemental material

    Figure 2
    Figure 2

    Occlusion site according to treatment type. rt-PA, recombinant tissue Plasminogen Activator

    View this table:
    Table 1

    Baseline characteristics of study population

    Efficacy outcomes

    Good recanalisation (TICI 2b/3) of basilar artery was obtained in 375 (82%) patients, with no differences between bridging and endovascular treatment (83% vs 81%, respectively; p=0.857; online supplemental figure 1). At 3 months, a total of 115 (25%) patients had died, 176 (38%) had excellent (mRS=0–1) and 215 (46%) had good outcome (mRS=0–2). Patients treated with bridging therapy had more frequently excellent outcome (43% vs 35%; p=0.070) and good outcome (53% vs 43%; p=0.031); but the associations were not confirmed in multivariable logistic regression analysis (OR=1.21; 95% CI=0.78 to 1.87; OR=1.35; 95% CI=0.88 to 2.08; respectively; online supplemental table 3). Similarly, bridging therapy was associated with lower occurrence of death at 3 months (19% vs 28%; p=0.028), but the association was not confirmed after adjustment for confounders (OR=0.68; 95% CI=0.41 to 1.12) (table 2). In ordinal shift analysis, after adjustment for confounders, we did not find an association between type of treatment and functional outcome (common OR=0.79; 95% CI=0.55 to 1.13) (figure 3).

    Figure 3
    Figure 3

    Crude rates of mRS at 3 months after treatment. OR is from ordinal analysis adjusted for age, sex, National Institutes of Health Stroke Scale score and onset-to-groin puncture time. mRS, modified Rankin Scale.

    View this table:
    Table 2

    Functional outcomes at 3 months in the whole population and stratified by onset to groin puncture time

    We therefore stratified the study population according to the endovascular time window of 6 hours, and found 301 (65%) patients with onset-to-groin-puncture within 6 hours (116 bridging treatment, 185 direct endovascular) and 135 (29%) patients with onset-to-groin-puncture beyond 6 hours (43 patients with bridging and 92 with endovascular treatment), 28 (6%) patients had missing onset-to-groin-puncture time and two types of treatment data. Patients treated with endovascular therapy within 6 hours were older compared with patients treated after 6 hours, there were no other differences among baseline characteristics between the two groups online supplemental table 1. Patients treated with bridging therapy within 6 hours had higher but not statistically significant chances to achieve excellent outcome (43% vs 35%; p=0.139) and good outcome (55% vs 42%; p=0.028) compared with those treated with direct endovascular treatment. However, the latter association was not confirmed in multivariate analysis (OR=1.60; 95% CI=0.97 to 2.65). Similarly, patients treated with bridging therapy within 6 hours had reduced risk of death at 3 months (19% vs 30%; p=0.019), this association was confirmed after adjustment for confounders (OR=0.53; 95% CI=0.30 to 0.97) (table 2). In patients treated within 6 hours from symptoms onset, after adjustment for confounders in ordinal shift analysis, bridging therapy was associated with a shift towards better functional outcomes at 3 months (common OR=0.65; 95% CI=0.42 to 0.98) (figure 4A). We did not find any association in patients treated beyond 6 hours from symptoms onset (figure 4B). Further analyses are shown in online supplemental material. Further analyses showing functional outcomes at 3 months and recanalisation rate stratified by BAO occlusion site are shown in online supplemental tables 4 and 5.

    Figure 4
    Figure 4

    Crude rates of mRS at 3 months stratified by time of endovascular treatment (A: ≤6 hours; B: >6 hours). ORs are from ordinal analysis adjusted for age, sex, National Institutes of Health Stroke Scale score and onset-to-groin puncture time. mRS, modified Rankin Scale.

    Safety outcomes

    A total of 51 (12%) patients had HT of any type with higher frequency in patients treated with bridging therapy (17% vs 9%; p=0.011); whereas sICH occurred in 17 (4%) patients, with no difference between bridging and direct endovascular therapy (4% vs 4%; p=0.605) (table 3). There were no differences between the two groups in procedural complications, except higher rates of distal embolisation/thrombus fragmentation in patients treated with direct endovascular therapy (9% vs 3%; p=0.009) (table 4).

    View this table:
    Table 3

    Haemorrhagic transformation at 24 hours after treatment

    View this table:
    Table 4

    Procedural complications

    Discussion

    We found that in the whole series of patients with ischaemic stroke due to BAO, recanalisation rates and functional outcomes were similar in bridging and direct endovascular therapy groups. Patients treated with direct endovascular therapy had lower occurrence of HT but more frequently distal embolisation of the thrombus. However, patients treated with bridging therapy with onset-to-groin puncture within 6 hours had lower mortality and a shift towards better functional outcome compared with those treated with direct endovascular therapy. This association was not observed in patients with onset-to-groin puncture beyond 6 hours.

    Although BAO is a rare event, its natural history is associated with poor outcome16 17 and acute treatment is fundamental to reduce disability and mortality. Due to the lack of conclusive evidence from randomised controlled trials, there is still uncertainty about the best management of acute BAO. Prospective studies did not favour any specific acute treatment strategy,7 18 while a meta-analysis of cohort studies and a recent randomised trial would suggest a potential benefit of endovascular treatment (bridging or direct) over intravenous thrombolysis alone.5 19 Such finding is in keeping with a subgroup analysis of the BASICS trial that showed a benefit of endovascular therapy over best medical treatment in patients with NIHSS >10, although the trial was overall neutral.6 Moreover, a recent study showed a greater benefit of endovascular therapy over standard medical therapy.20 In line with these findings, our results suggest a greater efficacy in terms of functional outcome of bridging (rt-PA + endovascular) approach compared with direct endovascular strategy (endovascular only) in acute management of BAO. We found that recanalisation rate was similar to previous studies,18 21 22 with little difference between bridging and direct endovascular treatment, and the duration of the endovascular procedure was similar in both groups. However, the bridging group achieved better functional outcomes, which was statistically significant when endovascular treatment was initiated within 6 hours from symptoms onset.

    Some authors suggested that direct endovascular therapy could be possibly more effective compared with bridging therapy in patients with anterior large vessel occlusion23 due to higher haemorrhagic risk, distal thrombus migration and delay of endovascular therapy initiation in bridging therapy. A recent randomised controlled trial showed non-inferiority of direct endovascular compared with bridging treatment within 4.5 hours from symptoms onset, however, patients had occlusion in the anterior circulation.24 There are scarce data about comparison of bridging versus direct endovascular therapy in the posterior circulation, and our results did not advocate direct endovascular therapy in patients with BAO. Although there was an increase in HT in the bridging therapy group, sICH occurrence was similar in both groups and to that reported in previous studies.6 Interestingly, in the BASICS trial rt-PA was administered in around 80% of patients allocated to the endovascular group, and the reported occurrence of sICH was approximately the same with that of our study. We did not observe a longer time to treatment in patients treated with bridging therapy, and this does not support the issue of a delay of endovascular therapy initiation in patients treated with bridging therapy. However, around one-third of patients with onset-to-groin puncture beyond 6 hours received rt-PA, suggesting a delay of the in-hospital workflow of more than 1 hour from rt-PA to groin puncture in some patients. On the other hand, it should be noted that the onset-to-groin puncture was similar to other data on BAO.5 8 Conversely to previous observations,25 26 we found a higher occurrence of distal embolisation in the direct endovascular group, suggesting that rt-PA before endovascular therapy may help lysing thrombus, rather than facilitating migration in small distal arteries not accessible with endovascular procedures. Our findings are also in keeping with previous studies that demonstrated better functional outcomes of bridging therapy in anterior circulation stroke27 28 and reinforce the indication of rt-PA before endovascular treatment also in patients with BAO. While mortality was lower in bridging therapy within 6 hours from symptoms onset, beyond 6 hours it was approximately the same in the two groups. This supports previous studies that found that time to treatment is crucial also in posterior circulation stroke,29 30 suggesting that appropriate selection of patients eligible for recanalisation treatment beyond 6 hours may help to improve functional outcomes.8 9 30 Although our data suggest that bridging therapy is safe and improves functional outcomes compared with direct endovascular, it is still unknown whether administration of thrombolytic therapy beyond 4.5 hours in the posterior circulation, particularly BAO, is safe and effective.

    Our study has limitations. As an observational registry, patients were not randomised but were allocated according to eligibility to rt-PA or not, and this may have introduced a selection bias not detectable even with adjustment in the multivariable analysis. Furthermore, if patients with missing anamnestic, clinical and outcome data have had more severe strokes, we could expect another selection bias. Our findings are therefore hypothesis generating and add to the existing evidence from other observational studies, but need confirmation in external cohorts. Again, a detection bias in assessment of recanalisation and outcomes is also plausible, since were not blinded to treatment allocation. Moreover, our registry did not record prognostic radiological variables such as posterior circulation Alberta Stroke Programme Early CT Score, which has been shown to reliably predict outcomes in patients with stroke due to posterior occlusion.4 9 31 However, all such limitations could represent a reasonable trade-off for including a relevant sample size from a prospective national registry. We included patients treated in the context of a multicentre collaboration in a timeframe of 7 years, with a considerable proportion of patients treated before the publication of trials that demonstrated efficacy of endovascular therapy. As a consequence, some patients were likely treated with older endovascular devices and different procedures; in-hospital workflows may also vary, since from 2015 endovascular trials prompt implementation of strategies to reduce prehospital and in-hospital processes. However, we analysed a large sample size that reflects the real-world population and pragmatic treatment of acute stroke. We did not include in our analysis patients with BAO treated only with rt-PA that experienced an early improvement and were not treated with endovascular procedures, thus another selection bias is possible. However, this would have favoured the endovascular rather than the bridging approach group, since around 10% of candidates to endovascular treatment have an early vessel recanalisation and neurological improvement when treated with systemic thrombolysis that avoid further treatment.32 33

    In conclusion, our results suggest that patients with ischaemic stroke due to BAO bridging therapy have less thrombus fragmentation and distal embolisation compared with direct endovascular treatment, and when initiated within 6 hours from symptoms onset, is associated with reduced mortality and improved functional outcomes. Similar to indications for anterior circulation strokes, our results support early treatment and administration of intravenous thrombolysis prior to endovascular treatment for BAO. Further studies with appropriate design are warranted to replicate our findings and to clarify whether patients with appropriate selection may benefit from bridging or direct endovascular therapy with extended treatment time.

    Data availability statement

    Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. All free text entered below will be published.

    Ethics statements

    Ethics approval

    The patients in this study would still be treated, need for ethical approval or patient consent for participation in the Italian Registry of Endovascular Treatment in Acute Stroke varied among participating hospitals. Ethical approval and patient consent were obtained where required.

    References

    1. ↵
      2. Goyal M ,
      3. Menon BK ,
      4. van Zwam WH , et al
      . Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723–31.doi:10.1016/S0140-6736(16)00163-X pmid:http://www.ncbi.nlm.nih.gov/pubmed/26898852
      OpenUrlCrossRefPubMed
    2. ↵
      2. Powers WJ ,
      3. Rabinstein AA ,
      4. Ackerson T
      . Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American heart Association/American stroke association. 49, 2018.
    3. ↵
      2. Greving JP ,
      3. Schonewille WJ ,
      4. Wijman CAC , et al
      . Predicting outcome after acute basilar artery occlusion based on admission characteristics. Neurology 2012;78:1058–63.doi:10.1212/WNL.0b013e31824e8f40 pmid:http://www.ncbi.nlm.nih.gov/pubmed/22442438
      OpenUrlCrossRefPubMed
    4. ↵
      2. Wu L ,
      3. Zhang D ,
      4. Chen J , et al
      . Long-Term outcome of endovascular therapy for acute basilar artery occlusion. J Cereb Blood Flow Metab 2020:0271678X2095858. doi:10.1177/0271678X20958587 pmid:http://www.ncbi.nlm.nih.gov/pubmed/32955959
    5. ↵
      2. Liu X ,
      3. Dai Q ,
      4. Ye R , et al
      . Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (best): an open-label, randomised controlled trial. Lancet Neurol 2020;19:115–22.doi:10.1016/S1474-4422(19)30395-3 pmid:http://www.ncbi.nlm.nih.gov/pubmed/31831388
      OpenUrlCrossRefPubMed
    6. ↵
      2. Schonewille W et al
      . The basilar artery international collaboration study (basics): a randomized controlled trial of endovascular therapy in basilar artery occlusion. Int J Stroke 2020;15.
    7. ↵
      2. Schonewille WJ ,
      3. Wijman CAC ,
      4. Michel P , et al
      . Treatment and outcomes of acute basilar artery occlusion in the basilar artery international cooperation study (basics): a prospective registry study. Lancet Neurol 2009;8:724–30.doi:10.1016/S1474-4422(09)70173-5 pmid:http://www.ncbi.nlm.nih.gov/pubmed/19577962
      OpenUrlCrossRefPubMedWeb of Science
    8. ↵
      2. Alemseged F ,
      3. Van der Hoeven E ,
      4. Di Giuliano F , et al
      . Response to Late-Window endovascular revascularization is associated with collateral status in basilar artery occlusion. Stroke 2019;50:1415–22.doi:10.1161/STROKEAHA.118.023361
      OpenUrl
    9. ↵
      2. Ravindren J ,
      3. Aguilar Pérez M ,
      4. Hellstern V , et al
      . Predictors of outcome after endovascular thrombectomy in acute basilar artery occlusion and the 6hr time window to recanalization. Front Neurol 2019;10:1–13.doi:10.3389/fneur.2019.00923
      OpenUrlCrossRefPubMed
    10. ↵
      2. Lindsberg PJ ,
      3. Pekkola J ,
      4. Strbian D , et al
      . Time window for recanalization in basilar artery occlusion: Speculative synthesis. Neurology 2015;85:1806–15.doi:10.1212/WNL.0000000000002129 pmid:http://www.ncbi.nlm.nih.gov/pubmed/26574535
      OpenUrlCrossRefPubMed
    11. ↵
      2. Mangiafico S ,
      3. Pracucci G ,
      4. Saia V , et al
      . The Italian registry of endovascular treatment in acute stroke: rationale, design and baseline features of patients. Neurol Sci 2015;36:985–93.doi:10.1007/s10072-014-2053-5 pmid:http://www.ncbi.nlm.nih.gov/pubmed/25567080
      OpenUrlPubMed
    12. ↵
      2. Cross DT ,
      3. Moran CJ ,
      4. Akins PT , et al
      . Relationship between clot location and outcome after basilar artery thrombolysis. AJNR Am J Neuroradiol 1997;18:1221–8.pmid:http://www.ncbi.nlm.nih.gov/pubmed/9282845
      OpenUrlAbstract
    13. ↵
      2. Fugate JE ,
      3. Klunder AM ,
      4. Kallmes DF
      . What Is Meant by “TICI”? AJNR Am J Neuroradiol 2013;34:1792–7.doi:10.3174/ajnr.A3496
      OpenUrlAbstract/FREE Full Text
    14. ↵
      2. Hacke W ,
      3. Kaste M ,
      4. Fieschi C
      . Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). second European-Australasian acute stroke study Investigators. Lancet 1998;352:1245–51.doi:10.1016/s0140-6736(98)08020-9 pmid:http://www.ncbi.nlm.nih.gov/pubmed/9788453
      OpenUrlCrossRefPubMedWeb of Science
    15. ↵
      2. von Elm E ,
      3. Altman DG ,
      4. Egger M , et al
      . The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008;61:344–9.doi:10.1016/j.jclinepi.2007.11.008 pmid:http://www.ncbi.nlm.nih.gov/pubmed/18313558
      OpenUrlCrossRefPubMedWeb of Science
    16. ↵
      2. Schonewille WJ ,
      3. Algra A ,
      4. Serena J , et al
      . Outcome in patients with basilar artery occlusion treated conventionally. J Neurol Neurosurg Psychiatry 2005;76:1238–41.doi:10.1136/jnnp.2004.049924 pmid:http://www.ncbi.nlm.nih.gov/pubmed/16107358
      OpenUrlAbstract/FREE Full Text
    17. ↵
      2. Mattle HP ,
      3. Arnold M ,
      4. Lindsberg PJ , et al
      . Basilar artery occlusion. Lancet Neurol 2011;10:1002–14.doi:10.1016/S1474-4422(11)70229-0 pmid:http://www.ncbi.nlm.nih.gov/pubmed/22014435
      OpenUrlCrossRefPubMedWeb of Science
    18. ↵
      2. Singer OC ,
      3. Berkefeld J ,
      4. Nolte CH , et al
      . Mechanical recanalization in basilar artery occlusion: the ENDOSTROKE study. Ann Neurol 2015;77:415–24.doi:10.1002/ana.24336 pmid:http://www.ncbi.nlm.nih.gov/pubmed/25516154
      OpenUrlCrossRefPubMed
    19. ↵
      2. Shu L ,
      3. Salehi Ravesh M ,
      4. Jansen O , et al
      . Stent retriever thrombectomy potentially increases the recanalization rate, improves clinical outcome, and decreases mortality in acute basilar occlusion: a systematic review and meta-analysis. Cerebrovasc Dis Extra 2019;9:46–56.doi:10.1159/000499665 pmid:http://www.ncbi.nlm.nih.gov/pubmed/31167189
      OpenUrlPubMed
    20. ↵
      2. Zi W ,
      3. Qiu Z ,
      4. Wu D
      . Assessment of endovascular treatment for acute basilar artery occlusion via a nationwide prospective registry. JAMA Neurol 2020;30303:561–73.
      OpenUrl
    21. ↵
      2. Sun X ,
      3. Tong X ,
      4. Gao F , et al
      . Endovascular treatment for acute basilar artery occlusion: a single center retrospective observational study. BMC Neurol 2019;19:1–8.doi:10.1186/s12883-019-1551-8
      OpenUrl
    22. ↵
      2. Lindsberg PJ ,
      3. Sairanen T ,
      4. Nagel S , et al
      . Recanalization treatments in basilar artery occlusion-Systematic analysis. Eur Stroke J 2016;1:41–50.doi:10.1177/2396987316629889 pmid:http://www.ncbi.nlm.nih.gov/pubmed/31008266
      OpenUrlPubMed
    23. ↵
      2. Fischer U ,
      3. Kaesmacher J ,
      4. Mendes Pereira V , et al
      . Direct mechanical thrombectomy versus combined intravenous and mechanical thrombectomy in large-artery anterior circulation stroke: a topical review. Stroke 2017;48:2912–8.doi:10.1161/STROKEAHA.117.017208 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28887391
      OpenUrlFREE Full Text
    24. ↵
      2. Yang P ,
      3. Zhang Y ,
      4. Zhang L , et al
      . Endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med Overseas Ed 2020;382:1981–93.doi:10.1056/NEJMoa2001123
      OpenUrl
    25. ↵
      2. Kaesmacher J ,
      3. Boeckh-Behrens T ,
      4. Simon S , et al
      . Risk of thrombus fragmentation during endovascular stroke treatment. AJNR Am J Neuroradiol 2017;38:991–8.doi:10.3174/ajnr.A5105 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28279987
      OpenUrlAbstract/FREE Full Text
    26. ↵
      2. Kaesmacher J ,
      3. Maegerlein C ,
      4. Kaesmacher M , et al
      . Thrombus migration in the middle cerebral artery: incidence, imaging signs, and impact on success of endovascular thrombectomy. J Am Heart Assoc 2017;6:e005149. doi:10.1161/JAHA.116.005149 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28202431
      OpenUrlAbstract/FREE Full Text
    27. ↵
      2. Gamba M ,
      3. Gilberti N ,
      4. Premi E , et al
      . Intravenous fibrinolysis plus endovascular thrombectomy versus direct endovascular thrombectomy for anterior circulation acute ischemic stroke: clinical and infarct volume results. BMC Neurol 2019;19:4–9.doi:10.1186/s12883-019-1341-3
      OpenUrl
    28. ↵
      2. Casetta I ,
      3. Pracucci G ,
      4. Saletti A , et al
      . Combined intravenous and endovascular treatment versus primary mechanical thrombectomy. The Italian registry of endovascular treatment in acute stroke. Int J Stroke 2019;14:898–907.doi:10.1177/1747493019851279 pmid:http://www.ncbi.nlm.nih.gov/pubmed/31126218
      OpenUrlPubMed
    29. ↵
      2. Dorňák T ,
      3. Herzig R ,
      4. Kuliha M , et al
      . Endovascular treatment of acute basilar artery occlusion: time to treatment is crucial. Clin Radiol 2015;70:e20–7.doi:10.1016/j.crad.2015.01.008 pmid:http://www.ncbi.nlm.nih.gov/pubmed/25703459
      OpenUrlPubMed
    30. ↵
      2. Vergouwen MDI ,
      3. Algra A ,
      4. Pfefferkorn T , et al
      . Time is brain(stem) in basilar artery occlusion. Stroke 2012;43:3003–6.doi:10.1161/STROKEAHA.112.666867 pmid:http://www.ncbi.nlm.nih.gov/pubmed/22989501
      OpenUrlAbstract/FREE Full Text
    31. ↵
      2. Puetz V ,
      3. Khomenko A ,
      4. Hill MD , et al
      . Extent of hypoattenuation on CT angiography source images in basilar artery occlusion: prognostic value in the basilar artery international cooperation study. Stroke 2011;42:3454–9.doi:10.1161/STROKEAHA.111.622175 pmid:http://www.ncbi.nlm.nih.gov/pubmed/21960577
      OpenUrlAbstract/FREE Full Text
    32. ↵
      2. Tsivgoulis G ,
      3. Katsanos AH ,
      4. Schellinger PD , et al
      . Successful reperfusion with intravenous thrombolysis preceding mechanical thrombectomy in large-vessel occlusions. Stroke 2018;49:232–5.doi:10.1161/STROKEAHA.117.019261 pmid:http://www.ncbi.nlm.nih.gov/pubmed/29212743
      OpenUrlAbstract/FREE Full Text
    33. ↵
      2. Campbell BCV ,
      3. Mitchell PJ ,
      4. Churilov L , et al
      . Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med 2018;378:1573–82.doi:10.1056/NEJMoa1716405 pmid:http://www.ncbi.nlm.nih.gov/pubmed/29694815
      OpenUrlCrossRefPubMed

    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Footnotes

    • SN and FA contributed equally.

    • Collaborators Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) Study Group: Antonio Laiso; Carolina Capirossi; Enrico Fainardi; Patrizia Nencini; Fabrizio Sallustio; Daniele Morosetti; Stefano Vallone; Guido Bigliardi; Sergio Vinci; Paolino La Spina; Tommaso Casseri; Rosanna Tassi; Mauro Bergui; Paolo Cerrato; Andrea Saletti; Ilaria Casetta; Roberto Gasparotti; Mauro Magoni; Ciro Princiotta; Maria Ruggiero; Enrico Maria Lotti; Lucio Castellan; Laura Malfatto; Roberto Menozzi; Umberto Scoditti; Mirco Cosottini; Michelangelo Mancuso; Alessio Comai; Enrica Franchini; Iacopo Valente; Fabio Pilato; Edoardo Puglielli; Alfonsina Casalena; Giacomo Cester; Claudio Baracchini; Chiara Comelli; Alessandra Giai Via; Mauro Plebani; Manuel Cappellari; Luigi Chiumarulo; Marco Petruzzellis; Giuseppina Sanfilippo; William Boadu; Nicola Cavasin; Adriana Critelli; Alessandra Briatico Vangosa; Angela Pesare; Alberto Terrana; Elisa Candeloro; Umberto Silvagni; Carmen Gaudiano; Francesco Biraschi; Ettore Nicolini; Valeria Ledda; Maurizio Melis; Valentina Caldiera; Tiziana Tassinari; Nunzio Paolo Nuzzi; Simona Marcheselli; Simona Sacco; Marco Pavia; Paolo Invernizzi; Ivan Gallesio; Delfina Ferrandi; Maria Cristina Fancello; Alessandro Mela; Pietro Amistà; Monia Russo; Claudio Fabio; Antonello Caddeo; Giuseppe Craparo; Marina Mannino.

    • Contributors SN and FA conceived and planned the study, gaining access to the IRETAS database. SN, FA, GP, NL, LR and DC performed data analysis and interpretation. SN, FA and DC drafted the manuscript. SM, DT, DI, NL, GP and VS took care of the critical review of the manuscript, constantly providing ideas that allowed its development. AL, CC, EF, PN, FS, DM, SV, GB, SV, PLS, TC, RT, MB, PC, AS, IC, RG, MM, CP, MR, EML, LC, LM, RM, US, MC, MM, AC, EF, IV, FP, EP, AC, GC, CB, CC, AGV, MP, MC, LC, MP, GS, WB, NC, AC, ABV, AP, AT, EC, US, CG, FB, EN, VL, MM, VC, TT, NPN, SM, SS, MP, PI, IG, DF, MCF, AM, PA, MR, CF, AC, GC and MM collected data.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests AZ is the national coordinator for Italy for BASICS trial and received speaker and consulting fees from Boehringer-Ingelheim, Medtronic, Cerenovus and advisory board from Boehringer-Ingelheim and Stryker. Other authors report no conflict of interests relevant to this paper.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.