Combined Intravenous Thrombolysis Research Articles

Thrombectomy versus combined thrombolysis and thrombectomy in patients with large vessel occlusion and chronic kidney disease

BackgroundWhether intravenous thrombolysis (IVT) should be bridged before mechanical thrombectomy (MT) remains uncertain in patients with large vessel occlusion (LVO) and chronic kidney disease (CKD). MethodsThis research systematically enrolled every patient with both acute ischemic stroke (AIS) and CKD who received MT and fulfilled the criteria for IVT from January 2015 to December 2022. According to whether they underwent IVT, the patients were categorized into two cohorts: MT and combined IVT + MT. A binary logistic regression model was used to adjust for potential confounders, and propensity score matching analysis was used to assess the efficacy and safety of IVT in AIS patients with CKD who underwent MT. ResultsA total number of 406 patients were ultimately included in this study, with 236 patients in the MT group and 170 in the combined group. After PSM, there were 170 patients in the MT group and 170 in the combined group, and the clinical characteristics between the two groups were well balanced. The MT + IVT group had better long-term functional outcomes than the MT group (35.9% versus 21.2%, P = 0.003) and more modified thrombolysis in cerebral infarction (mTICI) (2b-3) (94.1% versus 87.6%, P = 0.038), while no significant difference was found regarding symptomatic intracranial hemorrhage (sICH). In line with the results observed in the in the postmatched population, the logistic regression revealed that patients in the IVT + MT group demonstrated superior clinical outcomes (adjusted OR 0.440 [95% CI (0.267–0.726)], P = 0.001) in the prematched population. ConclusionFor LVO patients with CKD and indications for IVT, IVT bridging MT improves their prognosis compared with direct MT.

Abstract TP192: Combined Intra-Venous and Intra-Arterial Thrombolysis versus Intra-Venous Thrombolysis Alone in Stroke Patients Undergoing Mechanical Thrombectomy for Large Vessel Occlusion: A Propensity-Matched Analysis

Introduction: The combination of intravenous or intra-arterial thrombolysis with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) has been thoroughly investigated. However, no study has explored the outcomes of combining both intravenous and intra-arterial thrombolysis with MT. Methods: Data from Stroke Thrombectomy and Aneurysm Registry (STAR) from 2013 to 2023 was utilized. We compared AIS patients with LVO who underwent MT with combined intra-venous and intra-arterial thrombolysis (IV+IA) and with intra-venous thrombolysis alone (IV). We performed propensity score (PS) matching between the two groups using age, sex, premorbid mRS, admission NIHSS, occluded vessel, ASPECTS score, time from symptoms onset to arterial puncture, and frontline technique. Primary outcomes were any intracranial hemorrhage (ICH) and symptomatic ICH (sICH). Secondary outcomes included successful recanalization (mTICI ≥2C), early neurological improvement (defined as 4 or more points improvement in NIHSS score in 24 hours), 90-day modified Rankin Scale (mRS) 0-2, mRS 0-1, and mortality. Results: A total of 2495 LVO-related AIS patients were included, consisting of the IA+IV group (n = 266) and the IV group (n = 2228). Propensity matching yielded 192 well-matched patients in each group. No significant differences were observed between the groups in either ICH or sICH (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.61-1.52, p = 0.60; OR: 0.92, 95% CI: 0.42-2.03, p > 0.90, respectively). The IA+IV group had a significantly lower proportion of successful recanalization (OR: 0.41, 95% CI: 0.27-0.62, p < 0.001), and early neurological improvement (OR: 0.55, 95% CI: 0.30-1.00). However, 90-day mRS 0-2, mRS 0-1, and mortality rates showed no significant differences between the two groups. Conclusion: The findings of this study suggest that the combined use of IA and IV thrombolysis in AIS patients undergoing MT is safe. Although the IA+IV group demonstrated lower rates of recanalization and early neurological improvement, long-term functional outcomes and mortality rates were comparable to the IV-thrombolysis group, indicating a potential delayed benefit of additional IA thrombolysis therapy.

Endovascular thrombectomy for posterior cerebral artery strokes in the national inpatient sample (EaT PeCANpIeS) study.

Posterior cerebral arteries with acute ischemic strokes (PCA-AISs) comprise around 2% of all acute ischemic strokes and may result in significant long-term deficits. Current guidance regarding endovascular thrombectomy (EVT) for PCA-AIS is insufficient as no published randomized trials exist. An analysis of the National Inpatient Sample database compared medical management versus EVT for PCA-AIS. Propensity score matching was applied to adjust for nonrandomization. The study included 19,655 patients. Before matching, the EVT cohort had significantly higher National Institutes of Health Stroke Scale (NIHSS) (10.21 vs. 4.67, p < 0.001), had lower rates of favorable functional outcomes, functional independence, and higher rates of intracranial hemorrhage (ICH) and inpatient mortality. After matching, no differences in functional outcomes were identified, but revealed a higher proportion of ICH in the EVT group (17.45% vs. 8.98%, p < 0.001). However, NIHSS subgroup analysis identified improved functional outcomes associated with the EVT group who presented with an NIHSS between 10 and 19 both in terms of rates of favorable functional outcomes (35.56% vs. 12.09%, p < 0.001) and rates of functional independence (26.67% vs. 9.34%, p < 0.01). On further investigation, the clinical benefit, in the NIHSS 10-19 subgroup, was driven by patients receiving EVT in combination with intravenous thrombolysis (IVT). This analysis shows that current national practices utilize EVT for more severe PCA strokes. Clinical benefit was only detected in patients with moderate stroke severity (NIHSS 10-19) who were treated with combined EVT and IVT. Further work is needed to investigate the features of PCA-AIS that might benefit from EVT the most.

Hemorheology and Inflammatory Marker Changes in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis with Mechanical Thrombectomy.

To investigate hemorheology and inflammatory marker changes after treatment for acute ischemic stroke (AIS) using intravenous thrombolysis (IVT) with mechanical thrombectomy (MT). We retrospectively reviewed clinical records of patients with AIS (n=83) treated in The First Affiliated Hospital of Bengbu Medical College between January 2021 and December 2022 (n=83). The control group consisted of 38 patients who underwent IVT alone and the observation group consisted of 45 patients who underwent IVT with MT. We compared differences in mean variables related to hemorheology, inflammatory markers, and total efficacy between the two groups. We found that hemorheology values (plasma viscosity [PV], whole blood viscosity [WBV], fibrinogen [FIB], and hematocrit [HCT]), and the levels of inflammatory markers (tumor necrosis factor ɑ [TNF-ɑ] and interleukin-6 [IL-6]) were higher in the control group than in the observation group after treatment (P<0.05). In addition, the total efficacy of the observation group (93.3%) was higher than that in the control group (76.3%; P=0.016). The clinical efficacy of combined IVT and MT in the treatment of AIS is superior to IVT alone, improving levels of hemorheology and inflammatory markers in patients with AIS.

Effect of mechanical thrombectomy with and without intravenous thrombolysis on the functional outcome of patients with different degrees of thrombus perviousness.

This study aimed to investigate the long-term functional outcome of patients with different degrees of thrombus perviousness (TP) undergoing mechanical thrombectomy alone and those undergoing combined intravenous thrombolysis (IVT) plus mechanical thrombectomy. We conducted a retrospective analysis of consecutive patients with acute ischemic stroke due to large vessel occlusion who underwent mechanical thrombectomy alone or bridging therapy between January 2016 and October 2020. TP was quantified by thrombus attenuation increase (TAI) on admission computed tomography angiography compared with non-contrast computed tomography. After dichotomization of TAI as higher or lower perviousness, Fisher exact tests were performed to estimate the associations of different therapies with favorable functional outcomes [Modified Ranking Scale score at 90days (90-day mRS) of 0 to 2]. A total of 73 patients were included in our study. 35 (47.9%) thrombi were classified as higher-perviousness clots with TAI of ≥ 24 HU, and the other 38 thrombi were lower-perviousness clots. A favorable outcome with a 90-day mRS of 0 to 2 was observed in 32 patients. In patients with thrombi of lower perviousness, favorable outcome was more common in the bridging therapy group than in the thrombectomy-alone group (p = 0.013), whereas in patients with thrombi of higher perviousness, the long-term neurological outcome did not significantly differ between two therapy groups (p = 0.094). Patients with thrombi of lower perviousness were recommended to undergo intravenous alteplase followed by endovascular thrombectomy, and those with thrombi of higher perviousness could undergo thrombectomy alone.

Ultra-early rt-PA administration should improve patient outcome on mechanical thrombectomy: Post hoc analysis of SKIP

BackgroundTo investigate whether ultra-early recombinant tissue-plasminogen activator (rt-PA) administration can improve patient outcomes on mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO). MethodsParticipants comprised rt-PA-eligible 204 patients with internal carotid artery or middle cerebral artery occlusion in the SKIP trial, who were randomly assigned to receive mechanical thrombectomy alone or combined intravenous thrombolysis (rt-PA: alteplase at 0.6 mg/kg) plus mechanical thrombectomy. We assessed associations between onset-to-puncture time and onset-to-rt-PA administration time and frequency of favorable outcome at 90 days and any intracerebral hemorrhage (ICH) at 36 h after onset. ResultsAs a cut-off onset-to-puncture time for favorable outcome, receiver operating characteristic curves defined 2.5 h (57% sensitivity, 62% specificity). For onset-to-puncture times ≤2.5 h and > 2.5 h, frequencies of favorable outcomes were 72% and 63% (p = 0.402) in patients with rt-PA therapy and 44% and 58% (p = 0.212) in patients without rt-PA therapy, respectively. In terms of onset-to-rt-PA administration time, frequencies of favorable outcomes among patients with ultra-early rt-PA administration at ≤100, >100 min after onset, and without rt-PA therapy with onset-to-puncture time ≤ 2.5 h, and with and without rt-PA therapy with onset-to-puncture time > 2.5 h were 84% and 64%, 63%, and 44% and 58%, respectively (p = 0.025). Frequencies of any ICH among those patients were 37% and 32%, 32%, and 63% and 40%, respectively (p = 0.006). ConclusionUltra-early rt-PA administration should improve patient outcomes on mechanical thrombectomy among patients with LVO. Relatively late rt-PA administration might increase the frequency of any ICH.

Clinical trials in stroke in 2022: new answers and questions

In 2022, several clinical trials have answered important research questions about revascularisation, and about the indications for endovascular thrombectomy, but their answers have raised additional questions. For example, two multicentre, open-label, randomised trials (DIRECT-SAFE and SWIFT-DIRECT)1,2 compared endovascular thrombectomy alone with combined intravenous thrombolysis and endovascular thrombectomy to find out if intravenous alteplase could be withheld in patients with large vessel occlusion who present directly to a hospital at which endovascular thrombectomy can be done (referred to as mothership patients).

High glycemic variability: An underestimated determinant of stroke functional outcome following large vessel occlusion

Background and purposeEarly glycemic variability (GV) in diabetic patients is a poor prognosis factor following cardiovascular events. However, its influence on the course of acute ischemic stroke (AIS) with large vessel occlusion remains unclear. We investigated the relationship between high GV during acute stroke and three-month functional outcome among patients treated with combined intravenous thrombolysis and endovascular therapy for large vessel occlusion. MethodsA single-center retrospective analysis of AIS patients with proximal intracranial occlusion who underwent thrombolysis and mechanical thrombectomy between January 2015 and May 2017. Early GV was assessed using standard deviation (SD) of blood glucose levels for the first 24hours. The main outcome was functional status at three months as defined by the modified Rankin scale (mRS). Secondary outcomes were change in NIHSS score from baseline to 24hours and occurrence of severe hemorrhagic transformation. Multivariate logistic regression analyses including GV, admission glycemia and mean glycemia were performed. ResultsAmong the 93 patients evaluated, 26 had early high GV (≥20.9mg/dl). High GV was associated with poor functional outcome (OR=8.00; 95%CI [1.34–47.89]; P=0.02) unlike admission glycemia and mean glycemia (OR=2.92; 95%CI [0.51–16.60]; P=0.23 and OR=0.36; 95%CI [0.05-2.6]; p=0.31, respectively). High GV was not associated with NIHSS at 24hours or hemorrhagic transformation. ConclusionAcute high GV contributes to poorer functional outcome following AIS related to large vessel occlusion and should be considered as a new target in acute stroke management.

Predicting Poststroke Pneumonia in Patients With Anterior Large Vessel Occlusion: A Prospective, Population-Based Stroke Registry Analysis.

ObjectiveTo assess predictive factors for poststroke pneumonia (PSP) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) of the anterior circulation, with special regard to the impact of intravenous thrombolysis (IVT) and endovascular treatment (EVT) on the risk of PSP. As a secondary goal, the validity of the A2DS2, PNEUMONIA, and ISAN scores in LVO will be determined.MethodsAnalysis was based on consecutive data for the years 2017 to 2019 from the prospective inpatient stroke registry covering the entire federal state of Hesse, Germany, using the Kruskal-Wallis test and binary logistic regression.ResultsData from 4,281 patients with LVO were included in the analysis (54.8% female, median age = 78 years, range = 18–102), of whom 66.4% (n = 2,843) received recanalization therapy (RCT). In total, 19.4% (n = 832) of all LVO patients developed PSP. Development of PSP was associated with an increase in overall in-hospital mortality of 32.1% compared with LVO patients without PSP (16.4%; p < 0.001). Incidence of PSP was increased in 2132 patients with either EVT (n = 928; 25.9% PSP incidence) or combined EVT plus IVT (n = 1,204; 24.1%), compared with 2,149 patients with IVT alone (n = 711; 15.2%) or conservative treatment only (n = 1,438; 13.5%; p < 0.001). Multivariate analysis identified EVT (OR 1.5) and combined EVT plus IVT (OR 1.5) as significant independent risk factors for PSP. Furthermore, male sex (OR 1.9), age ≥ 65 years (OR 1.7), dysphagia (OR 3.2) as well as impaired consciousness at arrival (OR 1.7) and the comorbidities diabetes (OR 1.4) and atrial fibrillation (OR 1.3) were significantly associated risk factors (each p < 0.001). Minor stroke (NIHSS ≤ 4) was associated with a significant lower risk of PSP (OR 0.5). Performance of risk stratification scores varied between A2DS2 (96.1% sensitivity, 20.7% specificity), PNEUMONIA (78.2% sensitivity and 45.1% specificity) and ISAN score (98.0% sensitivity, 20.0% specificity).ConclusionNearly one in five stroke patients with LVO develops PSP during acute care. This risk of PSP is further increased if an EVT is performed. Other predictive factors are consistent with those previously described for all AIS patients. Available risk stratification scores proved to be sensitive tools in LVO patients but lack specificity.

Abstract TP163: Effect Of Renal Impairment On Clinical Outcomes Among Acute Ischemic Stroke Patients Treated With Endovascular Therapy- A Bi-center Study.

Objective: To investigate the effect of renal impairment on clinical outcomes among acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT). Methods: We performed a retrospective analysis from January to December 2020 involving AIS patients with CKD and premorbid modified Rankin Scale (mRS) ≤2, undergoing EVT in two large academic comprehensive stroke centers. Our primary efficacy outcome of interest was mRS at 90 days. Secondary outcomes included: inpatient mortality, length of hospitalization and reperfusion status based on Thrombolysis in Cerebral Infarction (TICI) score. CKD was defined as estimated glomerular filtration rate (eGFR) ranging from mild (eGFR 60-89 mL/min), moderate (eGFR 30-59 mL/min) or severe (eGFR 15-29 mL/min). We performed ordinal regression, multinomial logistic regression and binomial logistic regression analyses. In our subgroup analysis, we compared outcomes among AIS patients diagnosed with mild, moderate and severe CKD. We additionally performed a sensitivity analysis comparing patients with treated with combined intravenous thrombolysis (IVT) and EVT vs EVT only. Results: A total of 484 AIS patients underwent EVT at both stroke centers during the study period. After excluding patients for missing data and baseline mRS &gt;2, total of 300 AIS patients who underwent EVT (176 CKD and 124 patients with normal renal function) were included. Patients with CKD was associated with worse clinical outcomes [4 (2-6) vs 3 (1-6)]; adjusted odds ratio [aOR] 1.70, 95% confidence interval [CI] 1.10 - 2.61, p =0.02] based on 90-day mRS shift analysis and increased odds of in-hospital mortality (aOR 2.63, 95% CI; 1.08-6.38, p =0.03). Rates of TICI 2b/3 reperfusion ( p =0.84) and length of stay ( p =0.42) were similar between the two groups. Subgroup analyses found no difference between CKD and normal renal function groups for primary and secondary outcomes (all p &gt;0.05). Similarly, sensitivity analyses demonstrated no difference in clinical outcomes between patients receiving combined IVT and EVT compared to EVT only (all p &gt;0.05). Conclusion: Among AIS patients undergoing EVT, renal impairment was independently associated with worsening functional outcomes at 90 days and a higher rate of inpatient mortality.

Bridging Thrombolysis versus Direct Mechanical Thrombectomy in Stroke Due to Basilar Artery Occlusion.

Background and Purpose Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT. Methods This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0–3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH). Results Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not as Comorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013). Conclusions Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.

SWIFT DIRECT: Solitaire™ With the Intention For Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire™ Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke: Methodology of a randomized, controlled, multicentre study.

Whether treatment with intravenous alteplase prior to mechanical thrombectomy (MT) in acute ischemic stroke patients with large vessel occlusion is beneficial remains unclear. To determine whether patients experiencing acute ischemic stroke due to occlusion of the intracranial internal carotid artery or the M1 segment of the middle cerebral artery who are referred to an endovascular stroke center and who are candidates for intravenous alteplase will have non-inferior functional outcome at 90 days when treated with MT alone (direct MT) with stent retrievers compared to patients treated with combined intravenous thrombolysis (IVT) with alteplase plus MT (IVT + MT) with stent retrievers. To randomize 404 patients 1:1 to direct MT or combined IVT+MT. A multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial utilizing an adaptive statistical design. The primary efficacy endpoint is functional independence (modified Rankin Scale 0-2) at 90 days. Secondary clinical efficacy outcomes include change in National Institutes of Health Stroke Scale score from baseline to day 1 and health-related quality of life at 90 days. Secondary technical efficacy outcomes include successful reperfusion prior to start of MT and time from randomization to successful reperfusion. Safety outcomes include all serious adverse events, symptomatic intracranial hemorrhage, and mortality up to 90 days. SWIFT DIRECT will inform physicians whether direct MT in acute ischemic stroke patients with large vessel occlusion is equally or more efficacious than combined treatment with intravenous alteplase and MT. ClinicalTrials.gov Identifier: NCT03192332.

Bridging thrombolysis versus direct mechanical thrombectomy in stroke due to basilar artery occlusion

Mechanical thrombectomy (MT) is an effective treatment basilar artery occlusion (BAO) acute ischaemic stroke (AIS) patients. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers benefit. This study compared the outcomes of patients with BAO AIS who were treated with direct MT versus combined IVT plus MT.

Antiplatelet therapy increases symptomatic ICH risk after thrombolysis and thrombectomy.

The influence of chronic treatment by antiplatelet drug (APD) at stroke onset on the outcomes of patients with acute ischemic stroke (AIS) treated with combined intravenous thrombolysis (IVT) and endovascular therapy (EVT) is unclear. We investigated whether prior APD use influences the risk of symptomatic intracranial hemorrhage (sICH) and functional outcome in AIS patients treated with combined reperfusion therapy. A single-center retrospective analysis of AIS patients with proximal intracranial occlusion who underwent IVT and EVT between January 2015 and May 2017. The main outcomes were the incidence of sICH using the Heidelberg Bleeding Classification and patients' functional status at 90days, as defined by the modified Rankin scale (mRS). Outcomes were evaluated according to daily exposure to APD, and associations were assessed using multivariate logistic regression analysis. This study included 204 patients: 71 (34.8%) were taking APD before AIS. Patients with chronic treatment by APD at stroke onset had a higher rate of sICH (26.7% vs. 3.7%; p<.001) and worse functional outcome (mRS >2) at 90days (69% vs. 36.8%; p<.001). Prior APD use was associated with an increased likelihood of sICH (OR 9.8; 95%CI [3.6-31.3], p<.05) and of functional dependence at 90days (OR 5.72; 95%CI [2.09-1.72], p<.001), independent of confounders on multivariate analysis. Chronic treatment by APD at stroke onset in AIS patients with proximal intracranial occlusion treated using IVT and EVT increases the risk of sICH and worsens the functional prognosis. Further investigation to refine acute revascularization strategies in this population might be required.

Thrombectomy Versus Combined Thrombolysis and Thrombectomy in Patients With Acute Stroke: A Matched-Control Study.

A recent randomized controlled trial DIRECT-MT (Direct Intra-Arterial Thrombectomy to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals) compared the safety and efficacy of mechanical thrombectomy (MT) versus combined intravenous thrombolysis (IVT) and MT for acute large vessel occlusion. The current study utilized a prospective, nationwide registry to validate the results of the DIRECT-MT trial in a real-world practice setting. Subjects were selected from a prospective cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals from 26 provinces in China (ANGEL-ACT registry [Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke]) between November 2017 and March 2019. All patients eligible for IVT and receiving MT were reviewed and then grouped according to whether prior IVT or not (MT and combined IVT+MT). After a 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale, successful recanalization, door-to-puncture time, symptomatic intracranial hemorrhage, and intraprocedural embolization were compared. A total of 1026 patients, 600 in the MT group and 426 in the combined group, were included. Among 788 patients identified after matching, there were no significant differences in the 90-day modified Rankin Scale (median, 3 versus 3 points; P=0.82) and successful recanalization (86.6% versus 89.3%; P=0.23) between the two groups; however, patients of the MT group had a shorter door-to-puncture time (median, 112 versus 136 minutes; β=−45.02 [95% CI, −68.31 to −21.74]), lower rates of symptomatic intracranial hemorrhage (5.5% versus 10.1%; odds ratio, 0.52 [95% CI, 0.30–0.91]), and embolization (4.6% versus 8.1%; odds ratio, 0.54 [95% CI, 0.30–0.98]) than those of the combined group. This matched-control study largely confirmed the findings of the DIRECT-MT trial in a real-world practice setting, suggesting that MT may carry similar effectiveness to combined IVT+MT for acute large vessel occlusion patients, despite MT alone seems to be associated with a shorter in-hospital delay until procedure, lower risks of symptomatic intracranial hemorrhage, and embolization. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939

Effect of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional Outcome Among Patients With Acute Ischemic Stroke

Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear. To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome. Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019. Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103). The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours. Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, -11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞]; P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, -0.8% [95% CI, -9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43]; P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, -16.8% [95% CI, -32.1% to -1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88]; P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, -1.8% [95% CI, -9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24]; P = .78). Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority. umin.ac.jp/ctr Identifier: UMIN000021488.

Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke

<h3>Importance</h3> For patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes. <h3>Objective</h3> To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke. <h3>Design, Setting, and Participants</h3> Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020). <h3>Interventions</h3> A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group. <h3>Main Outcomes and Measures</h3> The primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was −10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. <h3>Results</h3> The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, −5.1% to ∞)<i>P</i>for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, −0.8%; 95% CI, −7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, −0.5%; 95% CI, −10.3% to 9.2%). <h3>Conclusions and Relevance</h3> Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold. <h3>Trial Registration</h3> Chinese Clinical Trial Registry:ChiCTR-IOR-17013568

Safety of Mechanical Thrombectomy with Combined Intravenous Thrombolysis in Stroke Treatment 4.5 to 9 Hours from Symptom Onset

BackgroundAn extended time window for intravenous thrombolysis (IVT) for acute stroke patients up to 9 hours from symptom onset has been established in recent trials, excluding patients who received mechanical thrombectomy (MT). We therefore investigated whether combined therapy with IVT and MT (IVT+MT) is safe in patients with ischemic stroke and large vessel occlusion (LVO) in an extended time window. MethodsWe retrospectively analyzed patients with anterior circulation ischemic stroke and LVO who were treated within 4.5 to 9 hours after symptom onset using MT with or without IVT. Primary endpoint was the occurrence of any intracranial hemorrhage (ICH). Multivariable logistic regression was used to adjust for potential confounders. ResultsIn total, 168 patients were included in the study, 44 (26%) were treated with IVT+ MT. 133 (79%) patients had a M1-/distal carotid artery occlusion. Median ASPECT-Score was 8 (IQR 7-10) and complete reperfusion (mTICI 2b-3) was achieved in 132 (79%) patients. 18 (41%) of the patients in the IVT+MT group developed any ICH vs. 45 (36%) patients in the direct MT group (p=0.587). Symptomatic ICH occurred in 5 (11%) patients with IVT+MT vs. 8 (6%) patients receiving direct MT (p=0.295). In multivariable analysis, IVT+MT was not an independent predictor of ICH (adjusted for NIHSS, degree of reperfusion, symptom-onset-to-treatment time and therapy with tirofiban; OR 0.95 [95% CI 0.43-2.08], p=0.896). ConclusionMechanical thrombectomy in stroke patients seems to be safe with combined intravenous thrombolysis within 4.5 to 9 hours after onset as it did not significantly increase the risk for intracranial hemorrhage.

Bridging therapy is associated with improved cognitive function after large vessel occlusion stroke \u2013 an analysis of the German Stroke Registry

BackgroundThe targeted use of endovascular therapy (EVT), with or without intravenous thrombolysis (IVT) in acute large cerebral vessel occlusion stroke (LVOS) has been proven to be superior compared to IVT alone. Despite favorable functional outcome, many patients complain about cognitive decline after EVT. If IVT in addition to EVT has positive effects on cognitive function is unclear.MethodsWe analyzed data from the German Stroke Registry (GSR, an open, multicenter and prospective observational study) and compared cognitive function 90 days after index ischemic stroke using MoCA in patients with independent (mRS ≤ 2 pts) and excellent (mRS = 0 pts) functional outcome receiving combined EVT and IVT (EVT + IVT) vs. EVT alone (EVT-IVT).ResultsOf the 2636 GSR patients, we included 166 patients with mRS ≤ 2 at 90 days in our analysis. Of these, 103 patients (62%) received EVT + IVT, 63 patients (38%) were treated with EVT alone. There was no difference in reperfusion status between groups (mTICI ≥ 2b in both groups at 95%, p = 0.65). Median MoCA score in the EVT + IVT group was 20 pts. (18–25 IQR) vs. 18 pts. (16–21 IQR) in the EVT-IVT group (p = 0.014). There were more patients with cognitive impairment (defined as MoCA < 26 pts) in the EVT-IVT group (54 patients (86%)) compared to the EVT + IVT group (78 patients (76%)). EVT + IVT was associated with a higher MoCA score at 90 days (mRS ≤ 2: p = 0.033, B = 2.39; mRS = 0: p = 0.021, B = 4.38).ConclusionsIn Patients with good functional outcome after LVOS, rates of cognitive impairment are lower with combined EVT and IVT compared to EVT alone.Trial registrationClinicalTrials.gov Identifier: NCT03356392.

Safety and efficacy of tirofiban in acute ischemic stroke patients not receiving endovascular treatment: a systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis was to analyze the safety and efficacy of tirofiban when used for acute ischemic stroke (AIS) patients not undergoing endovascular treatment. An electronic search was performed for English-language studies on PubMed, Scopus, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases up to 31st July 2019. All types of studies comparing tirofiban monotherapy or combined intravenous (IV) thrombolysis and tirofiban therapy with controls for AIS patients were included. Six studies were included in the review. Three evaluated tirofiban monotherapy while three compared IV thrombolysis and tirofiban therapy with controls. Meta-analysis indicates that tirofiban monotherapy does not significantly increase the incidence of intracerebral hemorrhage (ICH) (Odds Ration [OR] 1.14, 95% CI 0.72-1.82, p = 0.57; I2 = 0%), symptomatic intracerebral hemorrhage (sICH) (OR 0.52, 95% CI 0.09-3.03, p = 0.46; I2 = 0%) and mortality (OR 0.53, 95% CI 0.13-2.07, p = 0.36; I2 = 63%) in AIS patients. Similarly, our analysis indicates no significant increase in the rates of ICH (OR 0.82, 95% CI 0.33-2.07, p = 0.68; I2 = 0%), sICH (OR 0.91, 95% CI 0.16-5.16, p = 0.91; I2 = 0%) and mortality (OR 1.50, 95% CI 0.42-5.38, p= 0.54; I2 = 0%) in AIS patients treated with combined IV thrombolysis and tirofiban therapy. Meta-analysis for functional outcome was not possible. To conclude, tirofiban appears to be safe when used following IV thrombolysis or as monotherapy in AIS patients. Conclusions regarding improvement in functional improvement cannot be drawn. Further trials are needed to strengthen the evidence on this topic.