Endovascular thrombectomy with and without preceding thrombolysis in posterior circulation stroke – insights from STAR

Endovascular thrombectomy with and without preceding thrombolysis in posterior circulation stroke – insights from STAR | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Endovascular thrombectomy with and without preceding thrombolysis in posterior circulation stroke – insights from STAR View ORCID Profile Ev-Christin Heide , View ORCID Profile Sami Al Kasab , Ali Alawieh , Adam Arthur , View ORCID Profile Waleed Brinjikji , View ORCID Profile Shakeel Chowdhry , View ORCID Profile Roberto Crosa , View ORCID Profile Hugo Cuellar , View ORCID Profile Reade De Leacy , Travis Dumont , Marielle Ernst , View ORCID Profile Mohamad Ezzeldin , View ORCID Profile Isabel Fragata , Brian Howard , View ORCID Profile Pascal Jabbour , View ORCID Profile Peter Kan , View ORCID Profile Joon-Tae Kim , View ORCID Profile Michael R. Levitt , Justin Mascitelli , View ORCID Profile Charles Matouk , Mark Moss , View ORCID Profile Pedro Navia , View ORCID Profile Joshua Osbun , Min S. Park , View ORCID Profile Adam Polifka , View ORCID Profile Marios-Nikos Psychogios , View ORCID Profile Ansaar Rai , Daniele G. Romano , View ORCID Profile Amir Shaban , Robert M. Starke , Omar Tanweer , Richard Williamson Jr. , View ORCID Profile Stacey Q. Wolfe , View ORCID Profile Shinichi Yoshimura , Alejandro M. Spiotta , View ORCID Profile Ilko L. Maier STAR Investigators doi: https://doi.org/10.1101/2024.02.22.24303230 Ev-Christin Heide 1 Department of Neurology, University Medical Center , Goettingen, Germany MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ev-Christin Heide For correspondence: christin-heide{at}med.uni-goettingen.de Sami Al Kasab 2 Department of Neurosurgery and Department of Neurology, Medical University of South Carolina , Charleston, South Carolina MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sami Al Kasab Ali Alawieh 3 Department of Neurosurgery, Emory University School of Medicine , Atlanta, Georgia MD PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Adam Arthur 4 Department of Neurosurgery, Semmes-Murphey Neurologic and Spine Clinic, University of Tennessee Health Science Center , Memphis, Tennessee MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Waleed Brinjikji 5 Department of Radiology, Mayo Clinic , Rochester, Minnesota MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Waleed Brinjikji Shakeel Chowdhry 6 North Shore University Health System , Evanston, Illinois MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Shakeel Chowdhry Roberto Crosa 7 Department of Neurosurgery, Endovascular Neurological Center , Montevideo, Uruguay MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Roberto Crosa Hugo Cuellar 8 Department of Neurosurgery, Louisiana State University Health , Shreveport, Louisiana MD PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Hugo Cuellar Reade De Leacy 9 Department of Neurosurgery, Mount Sinai Health System , New York, New York Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Reade De Leacy Travis Dumont 10 Department of Neurosurgery, University of Arizona , Tuscon, Arizona MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marielle Ernst 11 Department of Neuroradiology, University Medical Center , Goettingen, Germany MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mohamad Ezzeldin 12 Department of Clinical Sciences, College of Medicine, University of Houston , Houston, Texas MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mohamad Ezzeldin Isabel Fragata 13 Neuroradiology Department, Centro Hospitalar Universitário de Lisboa Central , Lisboa, Portugal MD PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Isabel Fragata Brian Howard 14 Department of Neurosurgery, Emory University School of Medicine , Atlanta, Georgia MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Pascal Jabbour 15 Department of Neurosurgery, Thomas Jefferson University Hospitals , Philadelphia, Pennsylvania MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Pascal Jabbour Peter Kan 16 Department of Neurosurgery, University of Texas Medical Branch , Galveston, Texas MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Peter Kan Joon-Tae Kim 17 Department of Neurology, Chonnam National University Medical School, Chonnam National University Hospital , Gwangju, Korea MD PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Joon-Tae Kim Michael R. Levitt 18 Department of Neurosurgery, University of Washington , Seattle, Washington MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Michael R. Levitt Justin Mascitelli 19 Department of Neurosurgery, University of Texas Health Science Center , San Antonio, Texas MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Charles Matouk 20 Department of Neurosurgery, Yale School of Medicine , New Haven, Connecticut MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Charles Matouk Mark Moss 21 Department of Interventional Neuroradiology, Washington Regional Medical Center , Fayetteville, Arkansas MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Pedro Navia 22 Interventional and Diagnostic Neuroradiology, Hospital Universitario La Paz , Madrid, Spain MD PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Pedro Navia Joshua Osbun 23 Department of Neurosurgery, Washington University of School of Medicine , St. Louis, Missouri MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Joshua Osbun Min S. Park 24 Department of Neurosurgery, University of Virginia , Charlottesville, Virginia MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Adam Polifka 25 Department of Neurosurgery, University of Florida , Gainesville, Florida MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Adam Polifka Marios-Nikos Psychogios 26 Department of interventional and diagnostical Neuroradiology, University of Basel , Basel, Switzerland MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marios-Nikos Psychogios Ansaar Rai 27 Department of Radiology, West Virginia School of Medicine , Morgantown, West Virginia MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ansaar Rai Daniele G. Romano 28 University Hospital of Siena , Siena, Italy MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Amir Shaban 29 Department of Neurology, University of Iowa Hospitals and Clinics , Iowa City, Iowa MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Amir Shaban Robert M. Starke 30 Department of Neurosurgery, University of Miami Health System , Miami, Florida MD MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Omar Tanweer 31 Department of Neurosurgery, Baylor College of Medicine , Houston, Texas MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Richard Williamson Jr. 32 Department of Neurosurgery, Allegheny Health Network , Pittsburgh, Pennsylvania MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Stacey Q. Wolfe 33 Department of Neurosurgery, Wake Forest School of Medicine , Winston-Salem, North Carolina MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Stacey Q. Wolfe Shinichi Yoshimura 34 Department of Neurosurgery, Hyogo College of Medicine , Nishinomiya, Hyogo, Japan MD PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Shinichi Yoshimura Alejandro M. Spiotta 35 Department of Neurological Surgery, Medical University of South Carolina , Charleston, South Carolina MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ilko L. Maier 1 Department of Neurology, University Medical Center , Goettingen, Germany MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ilko L. Maier Abstract Full Text Info/History Metrics Preview PDF Abstract Background Multiple randomized trials could not establish the non-inferiority of endovascular thrombectomy (EVT) alone without preceding intravenous thrombolysis (IVT) or superiority of IVT followed by EVT in anterior circulation large vessel occlusion (LVO) stroke. The role of prior IVT in posterior circulation LVO remains controversial. Methods In this multicenter, retrospective study, stroke patients with LVO in the posterior circulation who received EVT alone or with IVT were selected from the stroke thrombectomy and aneurysm registry (STAR) between 2013 to 2022. Effects of IVT followed by thrombectomy on favorable functional outcome (defined as modified Rankin scale ≤ 3 at 90 days) and safety were investigated using multivariable logistic and linear regression models. Results Of the 588 included patients, 67 % (n = 394) were treated with EVT alone and 29% (n = 170) with EVT after IVT and 4% (n = 24) have missing values on this variable. Controlling for multiple confounding factors, IVT was not associated with a higher likelihood of favorable functional outcome at 90 days (odds ratio 1.04, 95 % CI 0.52-2.09, p = 0.901). Thrombectomy alone did not show any safety advantages compared with those receiving IVT. Conclusions Similar functional outcomes and complication rates were seen in patients with posterior circulation LVO treated with EVT alone vs EVT after IVT. Further prospective studies are required to determine the utility of IVT in posterior circulation stroke, especially in patients being directly admitted to thrombectomy centers. Introduction Endovascular thrombectomy (EVT) in combination with best medical treatment has been shown to improve functional outcomes and reduce mortality rates compared with medical treatment alone in acute basilar artery (BA) occlusion stroke. 1 , 2 However, the effect of EVT with prior intravenous thrombolysis (IVT) versus EVT alone in stroke from large vessel occlusion (LVO) of the posterior circulation (PC) remains unclear. IVT prior to EVT may improve recanalization rates and functional outcomes, but may also increase the risk of clot fragmentation with distal embolization, delay interventional treatment, add costs, and increase the risk of intracranial hemorrhage. 3 , 4 The non-inferiority of IVT followed by thrombectomy for anterior circulation LVO has been evaluated in six multicenter, randomized controlled clinical trials: Two trials showed non-inferiority of EVT alone 5 , 6 , while four trials failed to demonstrate non-inferiority. 7 – 10 A recent meta-analysis of these six studies could neither establish superiority of IVT plus EVT nor non-inferiority of EVT alone in patients presenting directly at endovascular treatment centers with anterior circulation LVO. Differences in functional outcomes between treatment groups were small and not significant. 11 On the basis of this meta-analysis, the loss of a clinically relevant effect when omitting IVT before EVT in patients presenting directly at centers capable of endovascular treatment cannot be excluded. However, the benefit of IVT in this setting seems to be small. In contrast, in patients with secondary transfers to thrombectomy centers (‘drip-and-ship scenari’) randomized trials on the benefit of IVT before EVT are missing likely due to a real equipoise. To date, no randomized trials have investigated the role of IVT followed by thrombectomy in PC-LVO. In a retrospective study of 322 patients with acute BA occlusion, functional outcomes were similar in patients treated with IVT versus EVT alone. 12 However, in patients with underlying large-artery atherosclerosis, a significant beneficial treatment effect of IVT followed by thrombectomy was observed. Conversely, a meta-analysis of 1096 patients demonstrated that IVT followed by thrombectomy was associated with lower mortality rates at 90 days compared with EVT alone in patients with acute BA occlusion, while no differences have been observed concerning functional outcomes or rates of intracranial hemorrhages. 13 The aim of this study is to investigate the effect of IVT prior to EVT in patients with PC-LVO compared to EVT alone using a large, international ‘real world’ stroke database. Given the retrospective nature of this study, the results are purely observational and to be interpreted as hypotheses-generating to encourage further prospective studies. Methods Patient cohort Patients with acute PC-LVO who underwent EVT with or without systemic thrombolysis between 2013 and 2022 were identified using a multicenter, international database. The Stroke Thrombectomy and Aneurysm Registry (STAR) includes a diverse cohort of individuals who have undergone EVT, reflecting real-world clinical practice. 14 STAR comprises 85 stroke centers worldwide, in which EVT is performed on a regular basis following highest standards. Data from this registry contains preinterventional, intrainterventional, and postinterventional, prospectively documented information of treatment periods, prestroke functional status, medical history, interventional strategy, and used materials as well as functional outcome using the National Institutes of Health Stroke Scale (NIHSS; baseline and at discharge) and modified Rankin scale (mRS; at discharge and at 90 days). For this study, we selected patients with following inclusion criteria: (1) BA occlusion with or without extension into one or both posterior cerebral arteries, (2) no acute intracranial stenting performed, (3) no treatment with intraarterial tissue-type plasminogen activator (IA-tPA). All patients with other occlusions than BA or basilar-posterior artery occlusion in the primary/first vessels for which thrombectomy was attempted, or patients with intracranial stenosis that needed intervention (Percutaneous transluminal angioplasty, stenting, or acute surgery) and intra-arterial (IA) thrombolysis or spontaneous reperfusion without EVT were excluded. The primary outcome was favorable functional outcome defined as modified Rankin scale [mRS] ≤ 3 at 90 days. Secondary outcomes included mortality by 90 days, mRS ≤ 3 at discharge, successful reperfusion (defined as good final modified Thrombolysis in Cerebral Infarction score [mTICI ≥ 2b]), number of recanalization attempts, NIHSS at discharge, change in NIHSS between presentation and discharge and complications. The data that support the findings of this study are available from the corresponding author upon reasonable request. This study was approved by institutional review boards at each study center, and there was no need for written informed consent given the retrospective design of the study. The study follows the “Strengthening the Reporting of Observational Studies in Epidemiology” statement. 15 The data that support the findings of this study are available from the corresponding author on reasonable request. Statistical analysis Statistical analyses were performed using Stata 17.0. (StataCorp., College Station, Texas). Characteristics of all patients are shown as mean ± standard deviation (SD), if normally distributed, and as median with interquartile range for non-parametric data. P-values < 0.05 were considered statistically significant. The analysis of interest is a comparison of outcomes by cohort (EVT alone vs IVT + EVT). Multiple imputation was used to address missingness prior to analysis. Multiple imputation was performed using the chained equations approach. 16 Forty imputations were used for this analysis. The N for all analyses is 588. For the analysis model, logistic regression was used to estimate analysis models for binary outcomes (mRS at 90 days, mortality by 90 days, mRS ≤ 3 at discharge, successful reperfusion, and complications). Final mTICI and mRS at 90 days were analyzed using ordered logistic regression. Based on the nature of the variables and their distributions negative binomial models were used for number of total recanalization attempts, length of stay and time to successful reperfusion. Results of all analyses that used logistic, ordered logistic, or negative binomial regression are reported both as average marginal effects, and/or exponentiated coefficients (odds ratios [OR] or incidence-rate ratios). Linear models were used for outcomes NIHSS at discharge and 90 days, and change in NIHSS between admission and discharge. Results of analyses that used linear models are reported as linear regression coefficients. Variables that are associated with both exposure (IVT) and outcome, but do not lie on the causal path from exposure to outcome, were defined as confounders. For all the analyses, the following confounders were included: age, sex, race, history of prior stroke, history of hypertension, history of diabetes, history of atrial fibrillation, history of hyperlipidemia, former smoker, current smoker, history of congestive heart failure. The confounders are displayed in the Supplemental Material. Due to the observational nature of this study, they cannot be interpreted as describing causal effects. Results Characteristics of patients and time metrics 588 patients with PC-LVO treated with EVT were identified from the STAR database. Of these patients, 67 % (n = 394) were treated with EVT alone and 29% (n = 170) with IVT followed by EVT and in 4% (n = 24) IVT status was unknown. The characteristics of the patients at baseline are presented in Table 1 . The proportion of missing values for variables in this study ranged from 0 % to 65 % (Supplemental Table 1). There were no differences in age, sex, vascular risk factors, history of prior stroke, type of occlusion (basilar occlusion alone, or basilar occlusion with additional posterior cerebral artery occlusion) between groups. The median NIHSS on admission was 17 (IQR 8-26) in the EVT alone group and 19 (IQR 11-26) in the IVT group. In the EVT alone group, the median time from puncture to recanalization was 39 (IQR 22-68) minutes (min) compared to 36 (IQR 26-60) min in the IVT group. The median time from symptom onset or last known well to puncture differed by 245 min between the groups (EVT alone: 503 [288-850] min and IVT: 258 [180-340] min). View this table: View inline View popup Table 1: Baseline characteristics of patient with posterior circulation large vessel occlusion with- and without intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT). Primary outcomes There was no difference in rates of favorable functional outcome between groups at 90 days (OR 1.02, 95% confidence interval [CI] 0.57-1.82; Figure 1 and Table 2 ). The primary outcome was reached in 45.66 % of patients in the EVT alone group and in 46.50 % of the patients in the IVT group. Download figure Open in new tab Figure 1: Shift plot of modified Rankin scale (mRS) at 90 days. The primary endpoint (mRS ≤3) was reached in 45.66 % and 46.50 % of the patients in the endovascular thrombectomy alone group and the intravenous thrombolysis group, respectively (odds ratio 1.02, 95% confidence interval 0.57-1.82, p = 0.957). View this table: View inline View popup Download powerpoint Table 2: Multivariable logistic regression for favorable functional outcome (mRS † at 90 days) in patients with posterior circulation large vessel occlusion with and without intravenous thrombolysis prior to thrombectomy. Secondary and safety outcomes Secondary clinical and technical efficacy outcomes are shown in Table 3 . There was no significant difference between the groups in successful reperfusion, 90-day mortality, mRS ≤ 3 at discharge, NIHSS at discharge, or successful reperfusion rate after completion of thrombectomy (≥ mTICI2b). The median number of recanalization attempts was significantly higher in the EVT alone group (2 [1-3] attempts) compared to the IVT group (1 [1-2] attempts; incidence-rate ratio 0.84, 95 % CI 0.72-0.98, p = 0.023). There was a trend towards a greater reduction in NIHSS between admission and discharge in the IVT group (EVT alone: reduction of 5 points [0-12]; IVT: reduction of 7 points [1-17] points, linear regression coefficient −2.805, 95 % CI −6.05-0.44, p = 0.089). View this table: View inline View popup Table 3: Regression of secondary outcome parameters in patients with posterior circulation large vessel occlusion with- and without intravenous thrombolysis prior to thrombectomy. Complications are shown in Table 4 . The risks for symptomatic intracranial hemorrhage (sICH) were inconclusive. Whereas the average marginal effect (AME) was significantly different with higher rates in the EVT alone group (5.79 %) compared to the IVT group (2.78 %; AME −0.04, 95 % CI −0.07 - <0.01, p = 0.043), the OR was without significant differences between the two groups (OR 0.37, 95 % CI 0.12-1.16, p = 0.088). There was no significant difference in overall complications, hemorrhage or distal embolization between the two groups. View this table: View inline View popup Download powerpoint Table 4: Logistic regression of safety outcome parameters in patients with posterior circulation large vessel occlusion with- and without intravenous thrombolysis prior to thrombectomy. Discussion This large, international, multicenter study compared EVT alone to IVT followed by thrombectomy in a cohort of patients with posterior circulation LVO. There was no significant difference in the 90-day mRS between the two groups. There are no randomized controlled studies on the effect of IVT followed by EVT in posterior circulation LVO; three multicenter studies, one cohort study and multiple meta-analyses have reported equivocal results. To our knowledge, our study is the largest (n = 588). In accordance with our study, Siow et al. found similar overall functional outcomes and mortality in BA occlusion patients treated with EVT alone or IVT followed by EVT. 12 However, in patients with underlying BA atherosclerosis, IVT conferred significant benefit. One limitation of our study is the lack of stroke etiology, so this subgroup could not be analyzed in our cohort. Similarly, Nappini et al. studied 464 patients from a national prospective registry and found no difference in successful reperfusion (mTICI ≥ 2b), functional outcomes and mortality between EVT alone and IVT followed by EVT. 17 In contrast, Nie et al. found improved functional outcomes without differences in reperfusion or mortality in patients with IVT followed by EVT compared to EVT alone. 18 In a meta-analysis of these three existing but conflicting studies and one additional retrospective institutional study, IVT followed by thrombectomy was associated with significantly higher odds of superior functional outcomes at 90 days and lower mortality rates than EVT alone. 19 In our study, we could not find a significant difference in the functional outcome at 90 days between the two treatment groups. Thus, our study questions the benefit of IVT followed by thrombectomy. All these retrospective studies did not differentiate between mothership and drip-and-ship-patients, which might explain the varying results. Nevertheless, in our cohort, a potential beneficial effect of IVT followed by thrombectomy did not seem to be strong. Despite an earlier treatment and no underlying contraindications for IVT we could not find a significant difference in the functional outcome. In a meta-analysis of six randomized clinically trials, the non-inferiority of IVT followed by thrombectomy for anterior circulation LVO was studied. 11 The loss of a clinically relevant effect when omitting IVT before EVT in patients presenting directly at centers capable of endovascular treatment cannot be excluded. However, the benefit of IVT followed by thrombectomy in this setting also seems to be small. The trend for a greater reduction in NIHSS between admission and discharge in the IVT group was not significant and might be of less importance in the light of similar long-term outcomes. In addition, the change in NIHSS could be explained by the significantly shorter interval between stroke symptom onset and puncture time in the IVT group and thus is most likely a selection bias. Previous studies reported a significantly longer interval between stroke symptom onset and puncture time in patients treated with EVT alone compared to IVT followed by thrombectomy as well (Siow et al.: 330 min vs. 240 min [mean] and Kohli et al.: 711 min vs. 313 min [median]). 13 , 19 Multiple regression models cannot fully account for the longer time interval between stroke onset and puncture in the EVT alone group, which might have influenced the outcomes and is a limitation of this study. Interestingly, Nie et al. 18 reported an improved functional outcome in the IVT group despite the highest median onset to puncture time of 510 min in the IVT group (IQR 378-763). Concerning the onset to puncture time of the IVT group in our study (median and IQR: 258 min [180-340 min]), it was similar in comparison with Siow et al. (mean and SD: 240 ± 60 min) and Nappini et al. (median and IQR: 280 min [208-370 min]). 12 , 17 The time from puncture to recanalization was smaller in our cohort compared to Siow et al. (mean ± SD: EVT group 60 min ± 30 min vs. IVT group 60 min ± 30 min) and to Nie et al. (median [IQR]: EVT group 122 min [85-175 min] vs. IVT group 122 min [60-185 min]). Most importantly, the puncture to recanalization time was not significantly different between the two treatment groups in our study and all referenced studies. 12 , 17 , 18 Our results were inconclusive concerning the rate of sICH between the groups. Whereas AME was significantly different with slightly higher rates of sICH in the EVT group, the OR was without significant difference between the treatment groups. One could speculate that a higher rate of sICH could be explained by the significantly higher number of recanalization attempts in the sole EVT group in our cohort, raising the risk of vessel wall injury and rupture. In any case, IVT followed by thrombectomy was not associated with a higher sICH rate. In line with this, sICH rates were similar among the treatment groups in the above-mentioned studies. 12 , 17 , 18 It is assumed that IVT leads to an improved and earlier recanalization due to clot softening and to an improved microvascular reperfusion due to dissolving of distal emboli, that are inaccessible to thrombectomy devices. 4 We found a significantly reduced number of recanalization attempts in the IVT group in our cohort with an effect size of one attempt. This is in contrast to reported drawbacks of IVT including distal embolization, sICH, and delayed EVT. 4 , 20 However, a similar safety outcome would not justify a treatment without differences in mortality or long-term outcome. The lower number of recanalization attempts could also be attributed to other factors like stroke etiology (e.g. Intracranial Atherosclerotic Disease or cardiac embolism) or the shorter time from onset to recanalization in the IVT group. 21 Our study has several limitations. First, the retrospective design introduces selection bias, and radiographic and clinical results were self-adjudicated. Multivariable analyses cannot adjust completely for systematic differences between treatment groups without a randomized trial design. In addition, other comorbidities and information on contraindications for IVT such as anticoagulants and blood pressure levels or detailed imaging data were not listed in the registry and thus could not be accounted for. However, comorbidities often represent a contraindication to IVT and might have biased the results. Furthermore, there was no information on stroke etiology in our study, precluding subgroup analysis of patients with underlying atherosclerosis. Second, the time from stroke onset to puncture was higher in the EVT alone group which could have reduced the reversibility of the clinical symptoms. However, we chose a multivariable analysis which accounted for this variable. Although the inclusion criteria for EVT are likely to be dependent on the individual centers, it is very likely that in late time windows the dawn and defuse criteria have been used, also identifying patients likely to experience favorable outcomes even when presenting in the late time window. The point of individual inclusion and exclusion criteria based on the SOPs of every individual center on the one hand can be a limitation, but on the other also represents current practice in multiple centers worldwide and therefore real word data. Third, there was no information if the patients received thrombolytic treatment in mothership, drip-and-ship, or ship-only paradigms. Most probably, patients from all paradigms were included. However, patients receiving the mothership protocol are probably the most interesting cohort regarding this question. Therefore, there is a need for prospective randomized controlled clinical trials investigating the effect of IVT in patients with posterior circulation LVO receiving mothership protocol only. Finally, there was a certain missingness of values. Multiple imputation was used to address missingness prior to analysis. Nevertheless, this might have influenced the results. In conclusion, our large multicenter study of EVT alone compared to IVT followed by thrombectomy in patients with posterior circulation LVO showed similar long-term functional outcomes and complication rates. Given the retrospective study design, we cannot rule out possible beneficial effects of IVT in a subgroup of patients (drip-and-ship-patients). However, our study generally questions the benefit of IVT in patients before EVT and underlines the need of randomized clinical trials to answer this question. Maybe investigating superiority of thrombolysis might be the better trial design compared to a non-inferiority design. Source of Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Disclosures Dr Arthur: personal fees from Balt, Cerenovus, Medtronic, Microvention, Penumbra, Perfuze, Siemens, and Stryker; consulting fees from Arsenal, Balt, Johnson & Johnson, Medtronic, Microvention, Penumbra, Scientia, Siemens, and Stryker; and being a shareholder at Bendit, Cerebrotech, Magneto, Vastrax, and VizAI outside the submitted work. Dr Jabbour: consulting fees from Balt, Cerus Endovascular, MicroVention, and Medtronic outside the submitted work. Dr Kan: personal fees from Stryker Neurovascular Consulting, Imperative Care Consulting, Cerenovus Consulting, and Microvention Consulting outside the submitted work. Dr Levitt: unrestricted educational grants from Medtronic and Stryker; consulting agreement with Medtronic, Aeaean Advisers, and Metis Innovative; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, and Hyperion Surgical; editorial boards of Journal of NeuroInterventional Surgery and Frontiers in Surgery. Dr Mascitelli: consulting fees from Stryker outside the submitted work. Dr Osbun: personal fees from Medtronic, Stryker, Terumo, Microvention, Penumbra, and InNeuroCo outside the submitted work. Dr Polifka: consulting fees from Stryker and Depuy Synthes outside the submitted work. Dr Rai: personal fees from Stryker Neurovascular and Cerenovus outside the submitted work. Dr Romano: consulting fees from Penumbra INC, Microvention Europe, Balt International, and Balt Italy outside the submitted work. Dr Spiotta: Stroke Thrombectomy and Aneurysm Registry financial and nonfinancial support from RapidAI, Medtronic, Stryker Neurovascular, Penumbra, and Avail; research grants from Medtronic, Stryker Neurovascular, and Penumbra; and consulting services from Stryker Neurovascular, Penumbra, RapidAI, and Terumo outside the submitted work. Dr Starke: grants from the National Institutes of Health; and consulting fees from Medtronic, Penumbra, Cerenovus, Balt, InNeuroCo, Optimize Vascular, and Abbott outside the submitted work. Dr Yoshimura: personal fees from Stryker, Medtronic, Johnson & Johnson, Kaneka Medics, Terumo, and Biomedical Solutions during the conduct of the study; personal fees from Boehringer-Ingelheim, Daiichi Sankyo, Bayer, and Bristol-Myers Squibb outside the submitted work. No other disclosures were reported. Data availability The data that support the findings of this study are available from the corresponding author upon reasonable request. Author Contributions Conception and design of the study: IM, ECH; Analysis of data: ECH, IM; Drafting of the manuscript: ECH and IM; Drafting of the figures: ECH, IM; all authors critically revised and approved the final version of the manuscript. Supplemental Material Supplemental Methods: Tables S1-S13 Acknowledgments We thank R. A. Medeiros (engaged by STAR) for her statistical support. Nonstandard abbreviations and acronyms AME Average marginal effect BA Basilar artery CI Confidence interval IA Intra-arterial IA-tPA Intraarterial tissue-type plasminogen activator IQR Interquartile range IVT Intravenous thrombolysis LVO Large vessel occlusion mRS Modified Rankin scale EVT Endovascular thrombectomy NIHSS National institutes of health stroke scale OR Odds ratio PC Posterior circulation SD Standard deviation sICH Symptomatic intracranial hemorrhage STAR The stroke thrombectomy and aneurysm registry mTICI Modified Thrombolysis in Cerebral Infarction References 1. ↵ Zi W , Qiu Z , Wu D , Li F , Liu H , Liu W , Huang W , Shi Z , Bai Y , Liu Z , et al. Assessment of Endovascular Treatment for Acute Basilar Artery Occlusion via a Nationwide Prospective Registry . JAMA Neurol . 2020 ; 77 : 561 – 573 . OpenUrl 2. ↵ Zhao Y , Zhao W , Guo Y , Li Y . Endovascular thrombectomy versus standard medical treatment for stroke patients with acute basilar artery occlusion: a systematic review and meta-analysis . J Neurointerv Surg . 2022 ; 14 : 1173 – 1179 . OpenUrl Abstract / FREE Full Text 3. ↵ Desilles JP , Loyau S , Syvannarath V , Gonzalez-Valcarcel J , Cantier M , Louedec L , Lapergue B , Amarenco P , Ajzenberg N , Jandrot-Perrus M , et al. Alteplase Reduces Downstream Microvascular Thrombosis and Improves the Benefit of Large Artery Recanalization in Stroke . Stroke . 2015 ; 46 ( 11 ): 3241 – 8 . OpenUrl Abstract / FREE Full Text 4. ↵ Fischer U , Kaesmacher J , Mendes Pereira V , Chapot R , Siddiqui AH , Froehler MT , Cognard C , Furlan AJ , Saver JL , Gralla J . Direct Mechanical Thrombectomy Versus Combined Intravenous and Mechanical Thrombectomy in Large-Artery Anterior Circulation Stroke: A Topical Review . Stroke . 2017 ; 48 : 2912 – 2918 . OpenUrl FREE Full Text 5. ↵ Yang P , Zhang Y , Zhang L , Zhang Y , Treurniet KM , Chen W , Peng Y , Han H , Wang J , Wang S , et al. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke . N Engl J Med . 2020 ; 382 : 1981 – 1993 . OpenUrl CrossRef PubMed 6. ↵ Zi W , Qiu Z , Li F , Sang H , Wu D , Luo W , Liu S , Yuan J , Song J , Shi Z , et al. Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial . JAMA . 2021 ; 325 : 234 – 243 . OpenUrl CrossRef PubMed 7. ↵ Suzuki K , Matsumaru Y , Takeuchi M , Morimoto M , Kanazawa R , Takayama Y , Kamiya Y , Shigeta K , Okubo S , Hayakawa M , et al. Effect of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional Outcome Among Patients With Acute Ischemic Stroke: The SKIP Randomized Clinical Trial . JAMA . 2021 ; 325 : 244 – 253 . OpenUrl CrossRef PubMed 8. LeCouffe NE , Kappelhof M , Treurniet KM , Rinkel LA , Bruggeman AE , Berkhemer OA , Wolff L , van Voorst H , Tolhuisen ML , Dippel DWJ , et al. A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke . N Engl J Med . 2021 ; 385 : 1833 – 1844 . OpenUrl CrossRef PubMed 9. Fischer U , Kaesmacher J , Strbian D , Eker O , Cognard C , Plattner PS , Bütikofer L , Mordasini P , Deppeler S , Pereira VM , et al. Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial . Lancet . 2022 ; 400 : 104 – 115 . OpenUrl PubMed 10. ↵ Mitchell PJ , Yan B , Churilov L , Dowling RJ , Bush S , Nguyen T , Campbell BCV , Donnan GA , Miao Z , Davis SM . DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval versus Standard Bridging Therapy . J Stroke . 2022 ; 24 : 57 – 64 . OpenUrl CrossRef PubMed 11. ↵ Majoie CB , Cavalcante F , Gralla J , Yang P , Kaesmacher J , Treurniet KM , Kappelhof M , Yan B , Suzuki K , Zhang Y , et al. Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials . Lancet . 2023 ; 402 ( 10406 ): 965 – 974 . OpenUrl 12. ↵ Siow I , Tan BYQ , Lee KS , Ong N , Toh E , Gopinathan A , Yang C , Bhogal P , Lam E , Spooner O , et al. Bridging Thrombolysis versus Direct Mechanical Thrombectomy in Stroke Due to Basilar Artery Occlusion . J Stroke . 2022 ; 24 : 128 – 137 . OpenUrl PubMed 13. ↵ Lee KS , Siow I , Zhang JJ , Syn NL , Gillespie CS , Yuen LZ , Anil G , Yang C , Chan BP , Sharma VK , et al. Bridging thrombolysis improves survival rates at 90 days compared with direct mechanical thrombectomy alone in acute ischemic stroke due to basilar artery occlusion: a systematic review and meta-analysis of 1096 patients . J Neurointerv Surg . 2022 . 14. ↵ Alawieh AM , Spiotta AM. The Stroke Thrombectomy and Aneurysm Registry: Inception, Present, and Future . World Neurosurg . 2020 ; 138 : 562 – 564 . OpenUrl PubMed 15. ↵ Elm E von , Altman DG , Egger M , Pocock SJ , Gøtzsche PC , Vandenbroucke JP . The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies . Lancet . 2007 ; 370 : 1453 – 1457 OpenUrl CrossRef PubMed Web of Science 16. ↵ Little RJA , Rubin DB . Statistical analysis with missing data . 2019 . 3rd ed . Hoboken, NJ : Wiley . 17. ↵ Nappini S , Arba F , Pracucci G , Saia V , Caimano D , Limbucci N , Renieri L , Zini A , Inzitari D , Toni D , et al. Bridging versus direct endovascular therapy in basilar artery occlusion . J Neurol Neurosurg Psychiatry . 2021 ; 92 : 956 – 962 . OpenUrl Abstract / FREE Full Text 18. ↵ Nie X , Wang D , Pu Y , Wei Y , Lu Q , Yan H , Liu X , Zheng L , Liu J , Yang X , et al. Endovascular treatment with or without intravenous alteplase for acute ischaemic stroke due to basilar artery occlusion . Stroke Vasc Neurol . 2022 ; 7 : 190 – 199 . OpenUrl Abstract / FREE Full Text 19. ↵ Kohli GS , Schartz D , Whyte R , Akkipeddi SM , Ellens NR , Bhalla T , Mattingly TK , Bender MT . Endovascular thrombectomy with or without intravenous thrombolysis in acute basilar artery occlusion ischemic stroke: A meta-analysis . J Stroke Cerebrovasc Dis . 2022 ; 31 : 106847 . 20. ↵ Ren Y , Churilov L , Mitchell P , Dowling R , Bush S , Yan B . Clot Migration Is Associated With Intravenous Thrombolysis in the Setting of Acute Ischemic Stroke . Stroke . 2018 ; 49 : 3060 – 3062 . OpenUrl PubMed 21. ↵ de Havenon A , Alexander MD , Nogueira RG , Haussen DC , Castonguay AC , Linfante I , Johnson MA , Nguyen TN , Mokin M , Zaidat OO . Duration of symptomatic stroke and successful reperfusion with endovascular thrombectomy for anterior circulation large vessel occlusive stroke . J Neurointerv Surg . 2021 ; 13 : 1128 – 1131 . OpenUrl Abstract / FREE Full Text View the discussion thread. Back to top Previous Next Posted February 27, 2024. Download PDF Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Endovascular thrombectomy with and without preceding thrombolysis in posterior circulation stroke – insights from STAR Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Endovascular thrombectomy with and without preceding thrombolysis in posterior circulation stroke – insights from STAR Ev-Christin Heide , Sami Al Kasab , Ali Alawieh , Adam Arthur , Waleed Brinjikji , Shakeel Chowdhry , Roberto Crosa , Hugo Cuellar , Reade De Leacy , Travis Dumont , Marielle Ernst , Mohamad Ezzeldin , Isabel Fragata , Brian Howard , Pascal Jabbour , Peter Kan , Joon-Tae Kim , Michael R. Levitt , Justin Mascitelli , Charles Matouk , Mark Moss , Pedro Navia , Joshua Osbun , Min S. Park , Adam Polifka , Marios-Nikos Psychogios , Ansaar Rai , Daniele G. Romano , Amir Shaban , Robert M. Starke , Omar Tanweer , Richard Williamson Jr. , Stacey Q. Wolfe , Shinichi Yoshimura , Alejandro M. Spiotta , Ilko L. Maier medRxiv 2024.02.22.24303230; doi: https://doi.org/10.1101/2024.02.22.24303230 Share This Article: Copy Citation Tools Endovascular thrombectomy with and without preceding thrombolysis in posterior circulation stroke – insights from STAR Ev-Christin Heide , Sami Al Kasab , Ali Alawieh , Adam Arthur , Waleed Brinjikji , Shakeel Chowdhry , Roberto Crosa , Hugo Cuellar , Reade De Leacy , Travis Dumont , Marielle Ernst , Mohamad Ezzeldin , Isabel Fragata , Brian Howard , Pascal Jabbour , Peter Kan , Joon-Tae Kim , Michael R. Levitt , Justin Mascitelli , Charles Matouk , Mark Moss , Pedro Navia , Joshua Osbun , Min S. Park , Adam Polifka , Marios-Nikos Psychogios , Ansaar Rai , Daniele G. Romano , Amir Shaban , Robert M. Starke , Omar Tanweer , Richard Williamson Jr. , Stacey Q. Wolfe , Shinichi Yoshimura , Alejandro M. Spiotta , Ilko L. 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