Endovascular Thrombectomy Versus Intravenous Thrombolysis of Posterior Cerebral Artery Occlusion Stroke

Article information

J Stroke. 2024;26(2):290-299

Publication date (electronic) : 2024 May 30

doi : https://doi.org/10.5853/jos.2024.00458

Silja Räty^,1, Thanh N. Nguyen^2,3, Simon Nagel^4,5, Davide Strambo⁶, Patrik Michel⁶, Christian Herweh⁷, Muhammad M. Qureshi², Mohamad Abdalkader², Pekka Virtanen⁸, Marta Olive-Gadea⁹, Marc Ribo⁹, Marios Psychogios¹⁰, Anh Nguyen¹⁰, Joji B. Kuramatsu¹¹, David Haupenthal¹¹, Martin Köhrmann¹², Cornelius Deuschl¹³, Jordi Kühne Escol๲, Jelle Demeestere¹⁴, Robin Lemmens¹⁴, Lieselotte Vandewalle¹⁴, Shadi Yaghi¹⁵, Liqi Shu¹⁵, Volker Puetz^16,17, Daniel P.O. Kaiser^17,18, Johannes Kaesmacher¹⁹, Adnan Mujanovic¹⁹, Dominique Cornelius Marterstoc²⁰, Tobias Engelhorn²⁰, Anne Berberich⁴, Piers Klein², Diogo C. Haussen²¹, Mahmoud H. Mohammaden²¹, Hend Abdelhamid²¹, Isabel Fragata²², Bruno Cunha²², Michele Romoli²³, Wei Hu²⁴, Jianlon Song²⁴, Johanna T. Fifi²⁵, Stavros Matsoukas²⁵, Sunil A. Sheth²⁶, Sergio A. Salazar-Marioni²⁶, João Pedro Marto²⁷, João Nuno Ramos²⁸, Milena Miszczuk²⁹, Christoph Riegler³⁰, Sven Poli³¹, Khouloud Poli³¹, Ashutosh P. Jadhav³², Shashvat Desai³², Volker Maus³³, Maximilian Kaeder³³, Adnan H. Siddiqui³⁴, Andre Monteiro³⁴, Tatu Kokkonen⁸, Francesco Diana³⁵, Hesham E. Masoud³⁶, Neil Suryadareva³⁶, Maxim Mokin³⁷, Shail Thanki³⁷, Pauli Ylikotila³⁸, Kemal Alpay³⁹, James E. Siegler⁴⁰, Italo Linfante⁴¹, Guilherme Dabus⁴¹, Dileep Yavaghal⁴², Vasu Saini⁴², Christian H. Nolte³⁰, Eberhart Siebert²⁹, Markus A. Möhlenbruch⁷, Peter A. Ringleb⁵, Raul G. Nogueira⁴³, Uta Hanning⁴⁴, Lukas Meyer⁴⁴, Urs Fischer^45,46, Daniel Strbian¹

¹Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

²Department of Radiology, Boston Medical Center, Boston, MA, USA

³Department of Neurology, Boston Medical Center, Boston, MA, USA

⁴Department of Neurology, Klinikum Ludwigshafen, Ludwigshafen, Germany

⁵Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany

⁶Department of Neurology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

⁷Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany

⁸Department of Radiology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

⁹Department of Neurology, University Hospital Vall d’Hebron, Barcelona, Spain

¹⁰Department of Neuroradiology, University Hospital Basel, University of Basel, Basel, Switzerland

¹¹Department of Neurology, University of Erlangen, Erlangen, Germany

¹²Department of Neurology, Universitätsklinikum Essen, Essen, Germany

¹³Department of Radiology, Universitätsklinikum Essen, Essen, Germany

¹⁴Department of Neurology, UZ Leuven, Leuven, Belgium

¹⁵Department of Neurology, Rhode Island Hospital, Providence, RI, USA

¹⁶Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

¹⁷Dresden Neurovascular Center, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

¹⁸Institute of Neuroradiology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

¹⁹Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, University of Bern, Bern, Switzerland

²⁰Department of Neuroradiology, University of Erlangen, Erlangen, Germany

²¹Department of Neurology, Grady Memorial Hospital, Atlanta, GA, USA

²²Department of Neuroradiology, Centro Hospitalar Universitario de Lisboa Central, Lisbon, Portugal

²³Neurology and Stroke Unit, Department of Neuroscience, Bufalini Hospital, Cesena, Italy

²⁴Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

²⁵Department of Neurosurgery, Mount Sinai Hospital, New York, NY, USA

²⁶Department of Neurology, UT Health McGovern Medical School, Houston, TX, USA

²⁷Department of Neurology, Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal

²⁸Department of Neuroradiology, Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal

²⁹Department of Neuroradiology, Charité - Universitätsmedizin Berlin, and Berlin Institute of Health (BIH), Freie Universität Berlin and Humboldt-Universität, Berlin, Germany

³⁰Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, and Berlin Institute of Health (BIH), Freie Universität Berlin and Humboldt-Universität, Berlin, Germany

³¹Hertie-Institute for Clinical Brain Research, Tübingen University, Tübingen, Germany

³²Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA

³³Department of Radiology, Neuroradiology and Nuclear Medicine, University Hospital Knappschaftskrankenhaus Bochum, Bochum, Germany

³⁴Department of Neurosurgery, University of Buffalo, Buffalo, NY, USA

³⁵Department of Interventional Neuroradiology, University Hospital Vall d’Hebron, Barcelona, Spain

³⁶Department of Neurology, New York Upstate Medical University, Syracuse, NY, USA

³⁷Department of Neurosurgery, University of South Florida, Tampa, FL, USA

³⁸Department of Neurology, Turku University Hospital and University of Turku, Turku, Finland

³⁹Department of Radiology, Turku University Hospital and University of Turku, Turku, Finland

⁴⁰Department of Neurology, University of Chicago, Chicago, IL, USA

⁴¹Miami Neuroscience Institute, Miami, FL, USA

⁴²Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA

⁴³Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

⁴⁴Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

⁴⁵Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland

⁴⁶Department of Neurology, University Hospital Bern, University of Bern, Bern, Switzerland

Correspondence: Silja Räty Department of Neurology, Helsinki University Hospital, Haartmaninkatu 4, 00290 Helsinki, Finland Tel: +358-9-47172662 E-mail: silja.raty@hus.fi

Received 2024 February 1; Revised 2024 April 4; Accepted 2024 April 17.

Abstract

Introduction

Endovascular thrombectomy (EVT) has become the standard of care for patients with large vessel occlusion (LVO) of the proximal anterior and posterior circulations in recent years [1-3]. However, there are no data from randomized controlled trials (RCTs) on EVT for patients with medium or distal vessel occlusion. Patients with posterior cerebral artery occlusion (PCAo) may present with severe neurological symptoms and harbor significant long-term disability, especially in more proximal occlusions [4,5]. Observational studies comparing EVT and best medical management (BMM) have not found a difference in 3-month functional outcome, yet their sample sizes have been mostly modest [6-10].

Our previous report from the international multicenter Posterior cerebraL ArTery Occlusion (PLATO) study comprising 1,023 patients with acute isolated PCAo revealed that patients treated with EVT experienced more often early neurological improvement (ENI) and excellent 3-month functional outcome compared to BMM despite an increased risk of symptomatic intracranial hemorrhage (sICH) and mortality [11]. However, BMM included intravenous thrombolysis (IVT) in only 45.5% of the patients, even though IVT is the guideline-based treatment in this indication [12,13]. A study from the Swiss Stroke Registry (n=136 in the propensity score matched cohort) compared EVT with or without bridging to IVT alone and observed no significant difference in functional outcome, sICH, or mortality but did not have data on ENI [14]. In recent meta-analyses, patients undergoing EVT for isolated PCAo had higher odds for ENI, but other clinical or safety outcomes did not differ significantly from patients treated with IVT, even though there was a trend for excellent functional outcome after EVT [15,16].

Due to the inconclusive results, our aim was to further investigate the clinical outcomes and safety of EVT versus IVT in acute PCAo. We compared the outcomes of patients treated with EVT +/- bridging IVT to those of patients treated with IVT alone from the updated multicenter PLATO cohort of isolated PCAo patients. We hypothesized that the functional recovery at 3 months would not differ based on reperfusion strategy.

Methods

Results

Baseline characteristics

The PLATO cohort included altogether 1,357 patients. After excluding patients treated with medical management only (n=557), other exclusion criteria (n=54), or missing covariate data (n=22), the final cohort comprised 724 patients (Figure 1): 400 patients treated with EVT with or without IVT and 324 patients treated with IVT alone.

Figure 1.

Flowchart of the study cohort. PCA, posterior cerebral artery; IVT, intravenous thrombolysis; EVT, endovascular thrombectomy; mRS, modified Rankin Scale; pc-ASPECTS, posterior circulation Acute Stroke Prognosis Early CT Score; ENI, early neurological improvement; sICH, symptomatic intracranial hemorrhage.

In the overall cohort, the median (IQR) age was 74 (64–82) years, and 57.7% were men (Table 1). The occlusion site was the P1 segment in 43.9%, P2 in 48.3%, P3 or P4 in 6.1%, posterior communicating artery in 0.7%, and bilateral PCA in 1.0%. The median baseline NIHSS score was 7 (4–11), and 449 of 641 patients (70.0%) had a visual field deficit on admission. The median onset-to-treatment time was 2.9 (1.8–4.7) hours. The patients treated with EVT were more often on oral anticoagulation before stroke (16.8% vs. 7.2%, P<0.01), had a higher baseline median (IQR) NIHSS score (8 [5–12] vs. 6 [3–10], P<0.01), were less frequently imaged with computed tomography, had more proximal occlusions (P1: 54.3% vs. 31.2%, P<0.01), lower baseline pc-ASPECTS, and different etiological distribution (more large artery atherosclerosis and less cardioembolic strokes) (Table 1). In addition, they had longer median (IQR) onset-to-treatment times (3.8 [2.4–7.2] h vs. 2.3 [1.5–3.3] h, P<0.01) and more often wake-up stroke.

Table 1.

Baseline characteristics, metrics, and outcomes of patients with PCA occlusion treated with EVT with or without IVT versus IVT alone

During EVT, the most frequently used first-pass technique was contact aspiration (51.4%), followed by combined aspiration and stent retriever use (32.9%) and stent retriever alone (12.7%). The median number of passes was 1 (IQR 1–2), and 79.6% achieved TICI 2b-3 recanalization. Of patients treated with EVT, 41.0% received bridging IVT.

Outcomes

The primary outcome data were available for 655 patients (90.5%). Median 3-month mRS was 2 (1–4) in the EVT+/-IVT group and 2 (1–3) in the IVT-alone group (P=0.27) (Figure 2). Excellent outcome was observed in 31.8% of the EVT+/-IVT and 28.4% of the IVT-alone group (P=0.39) and independent outcome in 50.4% and 55.7% (P=0.18), respectively. ENI occurred more often after EVT+/-IVT than after IVT alone (64.7% vs. 53.2%, P<0.01) (Table 2). Data on visual fields at 1 to 3 months were available for 162 of the 449 patients (36.1%) with visual field defect at baseline; there was no difference in the vision field recovery between the groups (Table 1). Mortality at 3 months was higher in the EVT+/-IVT group than in the IVT group (16.2% vs. 10.1%, P=0.03), as was the sICH rate (6.1% vs. 2.5%, P=0.03).

Figure 2.

Distribution of the 3-month modified Rankin Scale (mRS) in patients with isolated posterior cerebral artery occlusion by endovascular therapy (EVT) with or without intravenous thrombolysis (IVT) versus IVT alone.

Table 2.

Univariable logistic regression and doubly robust regression analyses of outcomes according to treatment (EVT+/-IVT vs. IVT alone)

According to the IPWRA analyses, there was no difference in the distribution of 3-month functional outcome (adjusted common OR 1.07 [95% CI 0.79–1.43]) between the treatment groups (Table 2). The patients treated with EVT+/-IVT were more likely to achieve ENI (adjusted OR 1.49 [95% CI 1.05–2.12]) compared to those receiving only IVT but had higher odds for mortality (adjusted OR 1.77 [95% CI 1.07–2.95]) and sICH (adjusted OR 2.87 [95% CI 1.23–6.72]). There was a trend for more frequent excellent 3-month functional outcome after EVT+/-IVT (adjusted OR 1.39 [95% CI 0.96–2.02]), but odds for independent outcome did not differ between the treatments (adjusted OR 1.07 [95% CI 0.73–1.58]).

There was no interaction between the treatment group and onset-to-treatment time ≤4.5 hours (P=0.48), occlusion of the P1 segment (P=0.13), or baseline NIHSS as a binary (NIHSS<10) (P=0.52) or ordinal variable (P=0.34) in the primary outcome model. In the sensitivity analysis adjusted for onset-to-treatment time, the results on the primary outcome remained unchanged (Supplementary Table 1). However, unlike in the main analysis including the whole cohort, the EVT+/-IVT group had significantly higher odds for excellent outcome (adjusted OR 1.66 [95% CI 1.10–2.50]), and mortality no longer differed between the groups (adjusted OR 1.33 [95% CI 0.75–2.35]).

The distribution of 3-month mRS of the patients treated with EVT only, IVT+EVT, and IVT alone are presented in Supplementary Figure 1. The patients treated with direct EVT had lower odds for a 1-point shift towards more favorable mRS (adjusted OR 0.65 [95% CI 0.44–0.96], for mRS 0–1 (adjusted OR 0.60 [95% CI 0.37–0.98]), and mRS 0–2 (adjusted OR 0.55 [95% CI 0.34–0.89]) compared to the patients receiving EVT+/-IVT, whereas the safety outcomes and ENI did not differ between these groups (Supplementary Table 2). Of note, when we compared the safety outcomes of EVT and IVT alone, EVT alone had higher mortality (adjusted OR 2.06 [95% CI 1.18–3.61]) and a trend for an increased sICH rate (adjusted OR 2.43 [95% CI 0.97–6.09]) compared to IVT alone.

Discussion

In this multicenter cohort of 724 patients with isolated PCAo, there was no difference in the 3-month functional outcome according to treatment either with EVT with or without bridging IVT or with IVT alone. EVT increased the odds for early improvement in the NIHSS score to the detriment of an increased risk of sICH and mortality. There was also a trend for more frequent excellent 3-month functional outcome after EVT.

Several prior observational studies have implied that EVT may promote ENI [7,11], vision recovery [8,11], and recanalization [8] in patients with isolated PCAo in comparison to BMM. Yet they have not shown a robust effect on functional recovery [6-8,10,14], the only exception being the more frequent excellent functional outcome (mRS 0–1) after EVT in the previous analysis from our registry [11]. Some studies have also observed an increased risk of sICH [6,11], mortality [11], or early neurological deterioration [6] after EVT. However, BMM in the previous studies has included either IVT or no reperfusion therapy. As IVT is the guideline-recommended treatment for acute ischemic stroke within 4.5 hours irrespective of the occlusion location [12], we focused on the question of whether EVT improves the outcome in addition to or in lieu of this standard of care.

Two previous observational studies compared EVT+/-IVT to IVT alone and found no difference in functional outcome, ENI, mortality, or sICH—potentially due to small sample sizes [9,14]. A subgroup analysis of the earlier PLATO cohort (n=613) did not detect a significant difference in ENI or mortality between patients receiving EVT+/-IVT versus IVT only, even though there were higher odds for excellent functional outcome and sICH in the EVT group [11]. On the other hand, a meta-analysis combining the previous observational data reported more frequent ENI after EVT, whereas other outcomes did not differ between the treatments [15]. However, the analysis was heavily driven by the previous results from the PLATO cohort and used unadjusted data with significant baseline imbalances, including higher baseline NIHSS in the EVT group. Thus, the results are susceptible to confounding.

Taken together, our results are largely in line with prior reports, strengthening the notion that EVT could increase the odds for early and excellent recovery at the potential cost of an increased risk of bleeding complications and mortality, neutralizing the effect on the distribution of mRS at 3 months. Our findings are also compatible with outcomes reported for PCAo patients who did not receive reperfusion therapy. As 43% of conservatively treated patients (IVT rate 3.8%) with isolated PCA stroke achieve mRS 0–1 and 69% mRS 0–3 at 1 month [4], there is less potential for a significant mRS shift with EVT compared to patients with anterior circulation LVO [1] or basilar artery occlusion [20,21]. Moreover, early recanalization after IVT is more likely with smaller vessel size, narrowing the gap of possible benefit of EVT in addition to IVT [22]. The same applies to the low mortality (0% to 8%) of PCA stroke patients at 1 month [4,23,24]. Therefore, it is important to weigh the bleeding risk against the potential benefit and consider EVT primarily for patients with reasonable probability for significant recovery, e.g., patients presenting with high severity of NIHSS.

The current data also suggest that if EVT is opted for PCAo, optimizing procedural safety is of uttermost importance. The sICH rate of 6.1% in the EVT+/-IVT group of our study was slightly higher than in the anterior circulation LVO [1] and approximately equal to reports in basilar artery occlusion [20,21,25,26]; however, different sICH definitions across studies hinder direct comparisons. Smaller vessel diameter, thinner vessel wall, and more distal and tortuous access to medium- or distal-vessel occlusions might increase the risk of complications, including perforation, dissection, and vasospasm [27,28]. However, a study on distal PCAo (P2 and P3 segments) observed an overall low frequency of procedural complications after EVT and no difference in the frequency of sICH or mortality compared to BMM [10]. Regardless, targeting increasingly distal and small arteries challenges interventionalists and device manufacturers to realize the potential benefit of EVT.

Interestingly, when we examined the patients treated with EVT according to whether they received bridging IVT or not, the poorest outcome was discovered after direct EVT. This contrasts the previous analysis from the Swiss stroke registry, where the outcomes did not differ depending on the bridging IVT [14], but is in line with the observational data on reperfusion treatment of basilar artery occlusion [29]. Although our data do not reveal the reasons for withholding IVT, some of which may be associated with poorer outcomes, this observation underlines the benefits of IVT as the first-line treatment for eligible patients undergoing EVT with isolated PCAo–similar to the current guideline recommendations for EVT in anterior circulation LVO [30]. Furthermore, there was no significant difference in the sICH rate between patients who received bridging IVT and those who received EVT alone.

Our large multicenter cohort builds upon the previous observational data on reperfusion therapies in isolated PCAo, as there are yet no available RCTs on the topic. The cohort is composed of patients treated after 2015, so it represents the era of EVT as the routine stroke treatment with modern catheter technology. The baseline pc-ASPECTS of both treatment groups was high, reflecting little established ischemic changes within the posterior circulation that could have affected the outcome despite successful recanalization.

However, there were some limitations. As the study design was non-randomized, the treatment decisions were based on the treating physician’s discretion, which resulted in patients with more severe symptoms and proximal occlusions being treated with EVT more frequently. We used the robust IPWRA method to account for the baseline differences but acknowledge the risk of remaining confounding. Due to missing time metric data, we did not adjust the analyses for time in the overall cohort. However, there was no interaction of treatment strategy and onsetto-treatment time within 4.5 hours. Our primary outcome measure, mRS, is not ideal to assess non-motor disability that often dominates after PCA stroke [31]. Indeed, a previous study found better cognitive outcome after EVT in PCAo, even though there was no difference in mRS [8]. The assessment of radiological data was not centralized but performed in each participating center following instructions in the data collection sheet. Furthermore, visual field recovery was available only for a minority of patients and was assessed with variable methods, including contrast perimetry that may miss smaller defects [32]. Finally, there were 19 (2.6%) patients whose stroke etiology was recorded as small vessel disease, potentially reflecting concomitant stroke mechanisms in the same patient. However, we acknowledge this classification may be a limitation.

Conclusions

In our large, observational multicenter cohort, there was no difference in functional outcome at 3 months as measured by the distribution of mRS scores in patients treated with either EVT+/- IVT or IVT alone for isolated PCAo. EVT increased the likelihood of ENI but at the cost of an increased risk of sICH and mortality. Ongoing RCTs on medium- and distal-vessel occlusion may shed light on the best treatment strategy for these patients in the future [33-35].

Supplementary materials

Article information Continued