Bridging thrombolysis in atrial fibrillation stroke is associated with increased hemorrhagic complications without improved outcomes

2021 ◽  
pp. neurintsurg-2021-017954
Author(s):  
Feras Akbik ◽  
Ali Alawieh ◽  
Laurie Dimisko ◽  
Brian M Howard ◽  
C Michael Cawley ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Functional Outcomes ◽  
Propensity Score Analysis ◽  
Intravenous Thrombolysis ◽  
Patient Characteristics ◽  
Bridging Therapy ◽  
Vessel Occlusion ◽  
Improved Outcomes ◽  
Score Analysis ◽  
Hemorrhagic Complications

BackgroundAtrial fibrillation (AF) associated ischemic stroke is associated with worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Conversely, AF is not associated with hemorrhagic complications or functional outcomes in patients undergoing mechanical thrombectomy (MT). This differential effect of MT and IVT in AF associated stroke raises the question of whether bridging thrombolysis increases hemorrhagic complications in AF patients undergoing MT.MethodsThis international cohort study of 22 comprehensive stroke centers analyzed patients with large vessel occlusion (LVO) undergoing MT between June 1, 2015 and December 31, 2020. Patients were divided into four groups based on comorbid AF and IVT exposure. Baseline patient characteristics, complications, and outcomes were reported and compared.Results6461 patients underwent MT for LVO. 2311 (35.8%) patients had comorbid AF. In non-AF patients, bridging therapy improved the odds of good 90 day functional outcomes (adjusted OR (aOR) 1.29, 95% CI 1.03 to 1.60, p=0.025) and did not increase hemorrhagic complications. In AF patients, bridging therapy led to significant increases in symptomatic intracranial hemorrhage and parenchymal hematoma type 2 (aOR 1.66, 1.07 to 2.57, p=0.024) without any benefit in 90 day functional outcomes. Similar findings were noted in a separate propensity score analysis.ConclusionIn this large thrombectomy registry, AF patients exposed to IVT before MT had increased hemorrhagic complications without improved functional outcomes, in contrast with non-AF patients. Prospective trials are warranted to assess whether AF patients represent a subgroup of LVO patients who may benefit from a direct to thrombectomy approach at thrombectomy capable centers.

Abstract P20: Bridging Therapy Increases Hemorrhagic Complications Without Improving Functional Outcomes in Atrial Fibrillation Associated Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Feras Akbik ◽  
Ali Alawieh ◽  
C. Michael Cawley ◽  
Brian Howard ◽  
Frank Tong ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Outcomes ◽  
Functional Outcomes ◽  
Randomized Trials ◽  
Mechanical Thrombectomy ◽  
Intravenous Thrombolysis ◽  
Bridging Therapy ◽  
Anterior Circulation ◽  
Hemorrhagic Complications ◽  
Baseline Characteristics

* on behalf of the Stroke Thrombectomy and Aneurysm Registry (STAR) Collaborators Introduction: Intravenous thrombolysis complications are enriched in AF associated stroke, as these patients have worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications. These data suggest that AF patients may be at particularly high risk for complications of bridging therapy for large vessel occlusions treated with mechanical thrombectomy (MT). Here we determine whether clinical outcomes differ in AF associated stroke treated with MT and bridging therapy. Methods: We performed a retrospective cohort study of the Stroke and Aneurysm Registry (STAR) from January 2015 to December 2018 and identified 4,169 patients who underwent MT for an anterior circulation stroke, 1,517 (36.4 %) of which had comorbid AF. Prospectively defined baseline characteristics and clinical outcomes were compared. Results: Hemorrhagic complications after MT were similar in patients with or without AF. In patients without AF, bridging therapy improved 90-day outcomes (aOR 1.32, 1.02-1.74, p<0.05) without increasing hemorrhagic complications. In patients with AF, bridging therapy independently predicted hemorrhagic complications in AF patients (aOR 2.08, 1.06-4.06, p<0.033) without improving functional outcomes. Conclusions: Bridging therapy in AF patients undergoing thrombectomy independently increased the odds of intracranial hemorrhage and did not improve functional outcomes. AF patients may represent a high-risk subgroup for thrombolytic complications. Randomized trials are warranted to determine whether patients with AF associated stroke may benefit by deferring bridging therapy at thrombectomy-capable centers.

Abstract 130: Is Intravenous Thrombolysis Far From Obsolete in the Era of Endovascular Thrombectomy? A Hint From a Meta-analysis of Randomized Clinical Trials

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Georgios Tsivgoulis ◽  
Aristeidis H Katsanos ◽  
Dimitris Mavridis ◽  
Anne W Alexandrov ◽  
Georgios Magoufis ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Intravenous Thrombolysis ◽  
Functional Independence ◽  
Bridging Therapy ◽  
Vessel Occlusion ◽  
Endovascular Thrombectomy ◽  
Systemic Thrombolysis ◽  
Shift Analysis ◽  
Ordinal Logistic Regression Analysis

Background & Purpose: Current AHA recommendations advocate that pretreatment with intravenous thrombolysis (IVT) should first be offered to all eligible acute ischemic stroke (AIS) patients with emergent large vessel occlusion (ELVO) before an endovascular thrombectomy (ET) procedure. Nevertheless, recent single-center observational studies question the utility of IVT pretreatment in ELVO patients eligible for systemic thrombolysis and advocate ET monotherapy. We sought to evaluate the comparative efficacy between ET and bridging therapy (IVT&ET) in AIS due to ELVO. Methods: We performed mixed-effects subgroup analyses, according to IVT pretreatment status of both functional independence [modified Rankin Scale (mRS) of 0-2)] and death/dependency (mRS of 5-6) at 90 days using available RCTs that evaluated the safety and efficacy of ET with stent-retrievers in comparison to standard therapy. We additionally performed an ordinal logistic regression analysis of individual patient data on the distribution of 3-month mRS scores (shift analysis) between the two groups. Results: We identified 7 eligible RCTs including 1764 ELVO patients (53% men), and 108 patients randomized to ET without IVT pretreatment. Patients receiving bridging therapy (BT) had lower rates (p=0.041) of 90-day death/dependency (19%, 95%CI: 14%-25%) compared to patients receiving only ET (31%, 95%CI: 21%-43%; Figure). Similarly, shift-analysis favored a trend for BT over ET in terms of better 90-day functional outcome (common OR=0.78, 95%CI: 0.53-1.10; p=0.155). Conclusion: Our findings indicate that pretreatment with IVT prior ET in ELVO patients may be associated with lower rates of three-month death/dependency and a trend towards more favorable functional outcomes. Until the results from head-to-head RCTs comparing BT to ET monotherapy become available, our findings support AHA guidelines recommending delivery of tPA to appropriate ELVO candidates undergoing ET.

Abstract TP28: Intravenous Thrombolysis is Associated With Better Functional Outcomes in Endovascular Thrombectomy Patients Requiring Multiple-Passes to Achieve Reperfusion

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Christopher Blair ◽  
Cecilia Cappelen-Smith ◽  
Dennis Cordato ◽  
Leon Edwards ◽  
Amer Mitchelle ◽  
...  
Keyword(s):  
Functional Outcomes ◽  
Intravenous Thrombolysis ◽  
Functional Independence ◽  
Independent Effect ◽  
Large Vessel Occlusion ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Endovascular Thrombectomy ◽  
Multiple Pass ◽  
First Pass

Introduction: In patients with anterior circulation stroke with large vessel occlusion (LVO), recent data suggest that successful reperfusion (mTICI≥2b) after a single device pass results in more favourable functional outcomes in comparison to patients requiring multiple passes. It is unclear if this effect represents an epiphenomenon or a true independent effect. Methods: A prospectively maintained database of EVT was interrogated for patients presenting with anterior circulation LVO with onset to groin puncture times of ≤ 6 hours from January 2016 to March 2019. Three-month functional outcomes were compared between first-pass reperfusion and multiple-pass reperfusion patients using logistic regression. Results: A total of 169 patients were identified (mean age 71 yrs, 44% female, median NIHSS 17, intravenous thrombolysis (IVT) in 47%). Successful reperfusion (mTICI≥2b) was achieved with the first-pass (FP) in 80 patients (47%) and multiple-passes (MP) in 89 patients (53%). First pass patients had better outcomes when compared to MP patients (mRS 0-2 71% vs 31%, p < 0.001). No difference in functional outcomes was seen between FP patients who received IVT and those that did not (mRS 0-2 68% vs 75%, p = 0.459). Multiple-pass patients who received IVT achieved higher rates of functional independence than those who did not (mRS 0-2 40% vs 27%, p = 0.035). Conclusion: Intravenous thrombolysis may improve functional recovery in EVT patients requiring multiple-passes to achieve reperfusion. Prospective studies should be considered.

Abstract P345: Perfusion-Guided Bridging Therapy in Strokes With Unknown Time of Onset and Large Vessel Occlusion

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Jose Bernardo Escribano Paredes ◽  
Julian Klug ◽  
Elisabeth Dirren ◽  
Nicolae Sanda ◽  
Maria Vargas ◽  
...  
Keyword(s):  
Intravenous Thrombolysis ◽  
Stroke Onset ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Bridging Therapy ◽  
Vessel Occlusion ◽  
Intracerebral Bleeding ◽  
Interhospital Transfer ◽  
Symptom Recognition ◽  
Increased Risk

Introduction: Endovascular treatment (EVT) is the therapy of choice, in patients with unknown stroke onset (unwitnessed and wake-up strokes) and large vessel occlusion (LVO) with a favorable perfusion pattern. Whether bridging therapy (intravenous thrombolysis (IVT) and EVT) is superior to EVT alone remains unknown. Material and Methods: We retrospectively included all patients admitted to the Geneva University Hospital from 01.2016 to 06.2020 with i) stroke of unknown onset, due to ii) anterior circulation occlusion, with iii) favorable CT perfusion pattern based on the DEFUSE criteria (ischemic core volume< 70ml; mismatch ratio >= 1.8 and mismatch volume >= 15ml), and iv) treated < 4.5 hours after symptom recognition. As a standard of care, the patients fulfilling these inclusion criteria were treated with EVT and IVT or EVT alone when IVT was contraindicated. Outcome measures were any intracerebral bleeding (symptomatic or asymptomatic), mortality and favorable outcome (mRS 0-1) at three months. Results: 32 patients were included (17 treated with EVT alone and 15 with EVT and IVT). Mean age was 69±18 yo. Median NIHSS was 16 (IQR 12-20) and median time from symptom recognition to treatment was 184 (146-226) minutes. Median hypoperfused tissue volume (Tmax > 6s) was 119 ml (80-151) and infarcted core (CBF ratio <30%) 8 ml (0-27). After propensity score weighting, bridging therapy was not associated with an increased risk of intracerebral bleeding (p=0.72) or mortality (p=0.55). The proportion of favorable outcomes at three months was similar between treatment groups (p=0.78). Conclusion: These results suggest that IVT before EVT is a safe therapeutic option in patients with unknown stroke onset selected on perfusion imaging and treated <4.5 hours after symptom recognition. Early administration of IVT may be particularly relevant before interhospital transfer to a comprehensive stroke center for EVT.

Abstract TMP8: Predictors of Large Vessel Occlusion in Kaiser Stroke EXPRESS Program

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jeffrey G Klingman ◽  
Anne C Kim ◽  
Meghan Hatfield ◽  
Benjamin Wilson ◽  
Lauren Klingman ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Patient Characteristics ◽  
Stroke Care ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Acute Stroke Care ◽  
Kaiser Permanente ◽  
Vessel Occlusion ◽  
Stroke Treatment ◽  
Improved Outcomes

Background: In 2015, trials showed that rapid endovascular stroke treatment (EST) of qualified patients with large vessel occlusion (LVO) resulted in improved outcomes over treatment with IV tPA alone. In 2015, Kaiser Permanente Northern California (KPNC) redesigned its acute stroke care work flow for its 21 stroke centers, which included expedited IV t-pa treatment, rapid CTA investigation, expedited transfer of appropriate patients for EST. We assessed for predictors of LVO post-implementation. Methods: The KPNC Stroke EXPRESS program was live in all centers by January 2016. Using clinical data for 1/1/16 - 7/10/16, we evaluated the frequency and locations of LVO, and patient characteristics of those with LVO. Multivariate logistic regression was used to examine whether age, gender, race, or an NIHSS ≥ 8 are predictors of LVO. Results: There were 2,204 tele-stroke alert cases from the ED. Among 993 (39.3%) that proceeded as likely acute stroke, 812 (81.8%) were evaluated with CTA. Out of those who had a CTA, 152 (18.7%) were found to have LVO as followed: 27 (17.8%) ICA, 87 (57.2%) M1, 24 (15.8%) M2, 6 (4.0%) basilar, 5 (3.3%) PCA, and 3 (2.0%) vertebral. Of those with LVO, 97 (63.8%) were treated with EST. Patients with LVO had a higher median NIHSS (15 vs. 5 in those without LVO). Neglect (27% vs. 7%) and gaze deviation (16% vs. 1%) were more likely to be seen among those with LVO and treated with EST compared to those without LVO. In multivariate analysis, age (OR=1.02, 95% CI 1.00 - 1.03, p=0.01) and NIHSS ≥8 (OR = 4.99, 95% CI 3.32- 7.49, p < 0.001) were associated with LVO. PPV for NIHSS ≥8 was 75.7%. Conclusions: In our large multi-ethnic population of acute stroke patients, a relatively small percentage (19%) was found to have LVO and only a subset qualified for EST. Predictors of LVO included NIHSS ≥8, increasing age, and presence of neglect and gaze preference. Given the low numbers of patients brought in for acute stroke treatment who ended up with a LVO requiring EST, further research is needed to assess a given system’s ability to rapidly evaluate and transfer as appropriate for EST rather than paramedic based diversion.

Impact of Strategy on Clinical Outcome in Large Vessel Occlusion Stroke Successfully Reperfused: ETIS Registry Results

Stroke ◽  
2021 ◽  
Author(s):  
Marian Douarinou ◽  
Benjamin Gory ◽  
Arturo Consoli ◽  
Bertrand Lapergue ◽  
Maeva Kyheng ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Therapy Group ◽  
Intravenous Thrombolysis ◽  
Large Vessel ◽  
Favorable Outcome ◽  
Modified Rankin Scale ◽  
Large Vessel Occlusion ◽  
Bridging Therapy ◽  
Anterior Circulation ◽  
Vessel Occlusion

Background and Purpose: Approximately half of the patients with acute ischemic stroke due to anterior circulation large vessel occlusion do not achieve functional independence despite successful reperfusion. We aimed to determine influence of reperfusion strategy (bridging therapy, intravenous thrombolysis alone, or mechanical thrombectomy alone) on clinical outcomes in this population. Methods: From ongoing, prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke registry in France, all patients with anterior circulation large vessel occlusion who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3) following reperfusion therapy were included. Primary end point was favorable outcome, defined as 90-day modified Rankin Scale score ≤2. Patient groups were compared using those treated with bridging therapy as reference. Differences in baseline characteristics were reduced after propensity score-matching, with a maximum absolute standardized difference of 14% for occlusion site. Results: Among 1872 patients included, 970 (51.8%) received bridging therapy, 128 (6.8%) received intravenous thrombolysis alone, and the remaining 774 (41.4%) received MT alone. The rate of favorable outcome was comparable between groups. Excellent outcome (90-day modified Rankin Scale score 0–1) was achieved more frequently in the bridging therapy group compared with the MT alone (odds ratio after propensity score-matching, 0.70 [95% CI, 0.50–0.96]). Regarding safety outcomes, hemorrhagic complications were similar between the groups, but 90-day mortality was significantly higher in the MT alone group compared with the bridging therapy group (odds ratio, 1.60 [95% CI, 1.09–2.37]). Conclusions: This real-world observational study of patients with anterior circulation large vessel occlusion demonstrated a similar rate of favorable outcome following successful reperfusion with different therapeutic strategies. However, our results suggest that bridging therapy compared with MT alone is significantly associated with excellent clinical outcome and lower mortality. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03776877.

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