Abstract 158: Persisting Arterial Occlusion And Risk Of Symptomatic Intracranial Hemorrhage In Systemic Thrombolysis: A Pooled Analysis Of Randomized Sonothrombolysis Studies

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Georgios Tsivgoulis ◽  
Kristian Barlinn ◽  
Maher Saqqur ◽  
Robert Mikulik ◽  
Andrew M Demchuk ◽  
...  
Keyword(s):  
Intracranial Hemorrhage ◽  
Treatment Time ◽  
Arterial Occlusion ◽  
Pooled Analysis ◽  
Transcranial Ultrasound ◽  
Stroke Severity ◽  
Clinical Safety ◽  
Exact Test ◽  
Systemic Thrombolysis ◽  
Symptomatic Intracranial Hemorrhage

Background & Purpose: Recent observational data showed that delayed (>6 hours) recanalization in acute ischemic stroke (AIS) patients treated with systemic thrombolysis may be associated with a higher risk of symptomatic intracranial hemorrhage (sICH). We sought to investigate the relationship of persisting occlusion during the first two hours of iv-tPA and the likelihood of sICH using pooled data from three randomized sonothrombolysis studies. Subjects & Methods: We evaluated the risk of sICH among AIS patients randomized in the Combined Lysis of Thrombus in Brain Ischemia (CLOTBUST), Transcranial Ultrasound in Clinical Sonothrombolysis (TUCSON) and a pilot randomized clinical safety study of sonothrombolysis augmentation with ultrasound-activated perflutren-lipid microspheres (Definity study). Acute proximal arterial occlusions were identified in all patients at baseline using Trancranial Doppler (TCD). Patients underwent continuous or intermitted TCD-monitoring for a two-hour period following tPA-bolus. Persisting occlusion was defined as absence of improvement of baseline TIBI flow grade at the end of TCD-monitoring. sICH was defined using ECASS-2 definition as imaging evidence of ICH with clinical worsening (NIHSS≥4) within 72 hours from stroke onset. Results: A total of 176 AIS patients (mean age 68±14years, 57% men, median baseline NIHSS-score 16 points, interquartile range 11-20) were randomized in CLOTBUST (n=126), DEFINITY (n=15) and TUCSON (n=35). A total of 75 (43%) and 101 (57%) individuals were randomized to systemic thrombolysis and sonothrombolysis respectively. Persisting occlusion was identified at the end of TCD-monitoring in 65 patients (37%). Patients with persisting occlusion tended to have higher sICH rates compared to individuals with partial or complete recanalization (9.2% vs. 2.7%; p=0.078 by Fisher’s exact test). After adjusting for demographic characteristics, onset-to-treatment time, baseline stroke severity, baseline TIBI flow grade and treatment (sonothrombolysis vs. systemic thrombolysis) persisting occlusion was independently associated with a higher likelihood of sICH (OR:6.29, 95%CI:1.28-30.85; p=0.024). Conclusions: Failure to recanalize during the first two hours following tPA-bolus appears to increase sICH risk among AIS treated with standard systemic thrombolysis and sonothrombolysis. Possible mechanisms (elevated blood pressure with persistent occlusion and late, potentially harmful recanalization causing reperfusion injury to infracted brain tissue) are now subject of a prospective multicenter study (CLOTBUST-PRO).

Abstract 60: Outcomes Following Sonothrombolysis in Severe Acute Ischemic Stroke

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Kristian Barlinn ◽  
Georgios Tsivgoulis ◽  
Andrew D Barreto ◽  
Robert Mikulik ◽  
Maher Saqqur ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Brain Ischemia ◽  
Treatment Time ◽  
Favorable Outcome ◽  
Transcranial Ultrasound ◽  
Stroke Severity ◽  
Clinical Safety ◽  
Ultrasound Monitoring ◽  
Iv Tpa

Background&Purpose: A recent meta-analysis showed that sonothrombolysis is safe and can double the rate of early recanalization in acute ischemic stroke (AIS). We sought to explore whether patients with severe strokes could clinically benefit from ultrasound amplification of tPA-induced recanalization. Subjects&Methods: We compared functional outcomes at 3 months among randomized AIS patients with pre-treatment NIHSS scores >=10 in the Combined Lysis of Thrombus in Brain Ischemia (CLOTBUST), Transcranial Ultrasound in Clinical Sonothrombolysis (TUCSON) and pilot randomized clinical safety study of sonothrombolysis with microspheres (Definity study). Patients had proximal arterial occlusions identified by baseline TCD and received intravenous (IV) tPA or IV tPA plus continuous 2-hour TCD ultrasound monitoring (=sonothrombolysis). Favorable outcome was defined as modified Rankin Scale (mRS) 0-1 at 3 months. Sustained complete recanalization was defined as Thrombolysis in Brain Ischemia (TIBI) flow grades 4-5 assessed by TCD at 2 hours after tPA bolus. Symptomatic intracranial hemorrhage (sICH) was defined using ECASS-2 definition as imaging evidence of ICH with clinical worsening (NIHSS >=4) within 72 hours from stroke onset. Results: A total of 139 AIS patients with severe stroke due to proximal arterial occlusions (mean age 69±13years, 56% men, median NIHSS 17, interquartile range 14-21, range 10-34) were randomized in CLOTBUST (n=105), TUCSON (n=21) and Definity (n=13). A total of 60 (43%) and 79 (57%) patients were randomized to IV tPA and sonothrombolysis, respectively. Patients treated with IV tPA and sonothrombolysis did not differ in terms of age, baseline stroke severity, baseline TIBI grades and onset-to-treatment time. Symptomatic ICH rates were similar in patients treated with IV tPA and sonothrombolysis (5.0% vs. 5.1%; p=0.987). More patients achieved sustained complete recanalization in the sonothrombolysis than in the IV tPA group (38.0% vs. 18.3%; p=0.012). Favorable outcome (mRS 0-1) tended to be more prevalent in the sonothrombolysis than in the IV tPA group (36.6% vs. 23.2%; p=0.104). Conclusions: Our data point to a signal-of-efficacy and provide basis to determine the sample size of a phase 3 randomized trial of sonothrombolysis in patients with severe strokes ( NCT01098981 ).

scholarly journals Simple Estimates of Symptomatic Intracranial Hemorrhage Risk and Outcome after Intravenous Thrombolysis Using Age and Stroke Severity

2017 ◽  
Vol 19 (2) ◽  
pp. 229-231 ◽  
Author(s):  
Hye Jung Lee ◽  
Ji Sung Lee ◽  
Jay Chol Choi ◽  
Yong-Jin Cho ◽  
Beom Joon Kim ◽  
...  
Keyword(s):  
Intracranial Hemorrhage ◽  
Intravenous Thrombolysis ◽  
Stroke Severity ◽  
Hemorrhage Risk ◽  
Symptomatic Intracranial Hemorrhage

Abstract W P308: A Four-Year Experience of Symptomatic Intracranial Hemorrhage Rate Following Intravenous Tissue Plasminogen Activator at a Comprehensive Stroke Center

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Jeffrey C Wagner ◽  
Alessandro Orlando ◽  
Christopher V Fanale ◽  
Michelle Whaley ◽  
Kathryn L McCarthy ◽  
...  
Keyword(s):  
Intracranial Hemorrhage ◽  
High Volume ◽  
Stroke Severity ◽  
Chi Square ◽  
Arrival Times ◽  
Intravenous Tissue Plasminogen Activator ◽  
Symptomatic Intracranial Hemorrhage ◽  
Comprehensive Stroke Center ◽  
Stroke Center ◽  
Iv Tpa

OBJECTIVE: To describe the 4-year symptomatic intracranial hemorrhage (sICH) rate at a high-volume comprehensive stroke center. METHODS: This was a retrospective observational cohort study. All admitted adult (≥18 years) patients presenting with an ischemic stroke (IS) from 2010 to 2013 were included in this study. Chi-square, Wilcoxon rank-sum, Student’s t-tests and Cochran-Armitage trend tests were used to compare groups and analyze data. sICHs were defined by a 4-point increase in NIHSS within 36h with new ICH seen on CT; sICHs were included only if they were directly related to IV-tPA treatment. Favorable mRS outcome was defined as a score ≤2. In-patient stroke alerts were excluded from door-to-needle (DTN) times. RESULTS: 2673 patients were admitted with IS. Of these, 627 (23%) were treated with IV-tPA (90% <3h from symptom onset, 69% at an outside facility). There was a significant increase in the percentage of IS patients treated with IV-tPA over the four years (p-trend=0.02). Compared to patients not receiving IV/IA therapy, patients receiving IV-tPA had significantly higher NIHSS scores, higher prevalence of atrial fibrillation, hyperlipidemia, and cardioembolic etiology, and lower proportion of small vessel occlusive IS. The median (IQR) DTN was 41m (32-53). In the 627 IS patients treated with IV-tPA, 11 (1.8%) developed a sICH; in 2013, the sICH rate was 0.6% (1/158). IV-tPA patients who developed a sICH were similar to those who were sICH-free; however, sICH patients had a significantly higher proportion of coronary artery disease (p=0.04) and severe strokes (p=0.19), and higher median symptom to arrival times (237m vs 187m, p=0.19), but similar median DTN (40m vs 41m, p=0.84). The in-hospital mortality rate for the IV-tPA group was 11% (n=71), and 37% had favorable mRS discharge scores. CONCLUSIONS: These data show that expeditious care and careful selection of patients for IV-tPA treatment can lead to very low rates of sICHs. The few sICHs subsequent to IV-tPA are likely to be a consequence of long symptom-to-arrival times and stroke severity.

Symptomatic intracranial hemorrhage risk and functional outcome by age and stroke severity strata

2017 ◽  
Vol 26 (4) ◽  
pp. 899
Author(s):  
KyuYoon Chung ◽  
Hye Jung Lee ◽  
Jay Chol Choi ◽  
Ji Sung Lee ◽  
Tai Hwan Park ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Intracranial Hemorrhage ◽  
Stroke Severity ◽  
Hemorrhage Risk ◽  
Symptomatic Intracranial Hemorrhage

Abstract WMP85: Target Stroke Implementation: Best Practice Strategies Cut Thrombolysis Time to <30 minutes in a 1,550 Bed Academic Urban County Hospital

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Erika T Marulanda-Londoño ◽  
Nirav Bhatt ◽  
Kunakorn Atachaneeyasakul ◽  
Amer M Malik ◽  
Negar Asdaghi ◽  
...  
Keyword(s):  
Intracranial Hemorrhage ◽  
Best Practice ◽  
Medical Center ◽  
Academic Medical Center ◽  
Tertiary Care ◽  
Stroke Severity ◽  
Care Hospital ◽  
Ct Scanner ◽  
Improvement Program ◽  
Symptomatic Intracranial Hemorrhage

Introduction: Thrombolytic window for acute ischemic stroke is brief and crucial. The AHA/ASA Target: Stroke Best Practice Strategies (TSBPS) aim to help hospitals improve thrombolysis door-to-needle (DTN) time. We assessed long-term efficacy of TSBPS to reduce DTN in a tertiary care hospital. Methods: We initiated a quality improvement program across one regional academic medical center (1,550 beds, 900 annual stroke admissions) that serves a multi-ethnic population by establishing a multidisciplinary DTN committee to assess causes of delayed DTN and implement focused TSBPS. Strategies included stroke team pre-admission notification, direct transfer to CT scanner, storing and administering IV rt-PA at CT scanner, and immediate stakeholder feedback. Door-to-CT, DTN, CT to IV rt-PA and door-to-groin (DTG) times were analyzed prospectively in consecutive IV rt-PA treated patients over 27 months pre-implementation and 13 months post-implementation. Results: A total of 148 patients were included in the pre-implementation and 126 patients in the post-implementation group. The two groups had similar demographics, comorbidities, anticoagulation status, pre-thrombolysis hypertension treatment, stroke severity (median NIHSS 11 (6-18) vs. 11 (5-17), p= 0.483), arrival by EMS (96% vs. 97%, p=0.708), and arrival after hours. Post implementation, reductions in treatment times were observed for median DTN (IQR) 59 (52-80) to 28.5 (20-41) min (p<0.001), door-to-CT time 17 (14-21) to 16 (12-19) min (p=0.016), CT-to-IV rt-PA time 43 (31-59) to 13 (6-23) min (p<0.001), and DTG time 164 (136-188) min (n=37) to 86 (63-103) min (n=51) (p<0.001). Overall monthly IV r-tPA administration increased post-implementation (5.5 vs. 9.8, p<0.001). Rate of symptomatic intracranial hemorrhage (2.7% vs. 3.2%, p=0.817) and treatment of stroke mimics (9% vs. 13%, p=0.311) were similar pre- and post-implementation. Conclusions: In this study, delay in IV rt-PA administration was predominantly related to prolonged CT to IVrt-PA time. DTN committee implementation is a simple, low-cost intervention, that significantly reduced DTN and DTG with persistent effect and no increase in symptomatic intracranial hemorrhage or stroke mimic treatment rate.

Use of intravenous cangrelor and stenting in acute ischemic stroke interventions: a new single center analysis and pooled-analysis of current studies

2021 ◽  
pp. 159101992110144
Author(s):  
Alexandra R Paul ◽  
Pouya Entezami ◽  
Devin Holden ◽  
Nicholas Field ◽  
John Dalfino ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Case Series ◽  
Platelet Inhibition ◽  
Pooled Analysis ◽  
Thromboembolic Complication ◽  
Symptomatic Intracranial Hemorrhage ◽  
Neurointerventional Procedures ◽  
The Ideal

Introduction Emergent stenting of both extra- and intracranial occlusions during acute ischemic stroke procedures is complicated by the need for immediate platelet inhibition to prevent thromboembolic complications. IV cangrelor is a relatively new antiplatelet that was initially approved for coronary interventions. Five prior case series have been published evaluating the results of IV cangrelor in neurointerventional procedures. We sought to combine the data from all prior studies and analyze only ischemic stroke interventions. Methods A prospectively maintained database was reviewed to identify all cases of IV cangrelor administration during acute ischemic stroke intervention. Nine additional patients were identified who have not been previously published. In addition, a literature search was performed to identify five prior publications of cangrelor in neurointervention. The data from these was combined with our institution in a pooled-analysis. Results Overall, 129 patients who received IV cangrelor during an acute ischemic stroke intervention were identified. The asymptomatic intracranial hemorrhage rate was 12.6%(11/87). The symptomatic intracranial hemorrhage rate was 6.2% (8/129). The rate of retroperitoneal hematoma and gastrointestinal bleeding were also low (1.5% and 0.8%, 2/129 and 1/129). There was one case of intraprocedural thromboembolic complication (0.8%) and no cases of intraprocedural in-stent thrombosis(0%). Conclusions IV cangrelor during acute ischemic stroke intervention appears to be safe, with a symptomatic intracranial hemorrhage rate of 6.2%. More research is needed to determine the ideal dosing regimen.

scholarly journals Safety and Outcomes of Intravenous tPA in Acute Ischemic Stroke Patients With Prior Stroke Within 3 Months

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Shreyansh Shah ◽  
Li Liang ◽  
Andrzej Kosinski ◽  
Adrian F. Hernandez ◽  
Lee H. Schwamm ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Hospital Mortality ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Tissue Type ◽  
Stroke Severity ◽  
Stroke Patients ◽  
Symptomatic Intracranial Hemorrhage ◽  
Prior Stroke ◽  
Iv Tpa

Background Guidelines recommend against the use of intravenous tPA (tissue-type plasminogen activator; IV tPA) in acute ischemic stroke patients with prior ischemic stroke within 3 months. However, there are limited data on the safety of IV tPA in this population. Methods and Results A retrospective observational study of patients ≥66 years of age linked to Medicare claims and treated with IV tPA at Get With The Guidelines–Stroke hospitals (February 2009 to December 2015). We identified 293 patients treated with IV tPA who had a prior ischemic stroke within 3 months and 30 655 with no history of stroke. Patients with prior stroke had a higher stroke severity (median National Institutes of Health Stroke Scale, 11 [6–19] versus 11 [6–18]; absolute standardized difference, 11.2%) and a higher prevalence of cardiovascular comorbidities. Patients with prior stroke had a higher unadjusted risk for symptomatic intracranial hemorrhage (7.7% versus 4.8%) and in-hospital mortality (12.6% versus 8.9%), but these differences were not statistically significant after adjustment. When stratified by prespecified time epochs, the elevated risk for symptomatic intracranial hemorrhage was seen only within the first 14 days (16.3% versus 4.8%; adjusted odds ratio [aOR], 3.7 [95% CI, 1.62–8.43]) but not in other epochs (2.1% versus 4.8%; aOR, 0.38 [95% CI, 0.05–2.79] for 15–30 days and 7.4% versus 4.8%; aOR, 1.36 [95% CI, 0.77–2.40] for 31–90 days). In addition, patients with prior stroke were significantly more likely to have a combined outcome of in-hospital mortality or discharge to hospice (25.9% versus 17.0%; aOR, 1.70 [95% CI, 1.21–2.38]), less likely to be discharged to home (28.3% versus 32.3%; aOR, 0.72 [95% CI, 0.54–0.98]), or to have good functional outcomes at discharge (modified Rankin Scale, 0–1; 11.3% versus 20.0%; aOR, 0.46 [95% CI, 0.24–0.89]). Conclusions Stroke providers need to continue to be vigilant about the safety of IV tPA in patients with prior stroke, particularly those with an event in the previous 14 days.

scholarly journals Tenecteplase Thrombolysis for Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (11) ◽  
pp. 3440-3451
Author(s):  
Steven J. Warach ◽  
Adrienne N. Dula ◽  
Truman J. Milling
Keyword(s):  
Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Time Window ◽  
Large Vessel ◽  
Bolus Administration ◽  
Phase 2 ◽  
Qualitative Synthesis ◽  
Phase 3 ◽  
Symptomatic Intracranial Hemorrhage ◽  
Meta Analyses

Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment–elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.

Pre-procedural predictive factors of symptomatic intracranial hemorrhage after thrombectomy in stroke

2021 ◽  
Author(s):  
Laura Venditti ◽  
Olivier Chassin ◽  
Claire Ancelet ◽  
Nicolas Legris ◽  
Mariana Sarov ◽  
...  
Keyword(s):  
Intracranial Hemorrhage ◽  
Predictive Factors ◽  
Symptomatic Intracranial Hemorrhage
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