Abstract 16: IV TPA in the 0-3 Hour Window: Quantitative Fragility-Robustness Assessment of the Strength of the RCT Evidence

Background: After 3 decades, the era of RCTs of IV tPA as a standalone therapy in acute ischemic stroke has now likely closed, with the completion of TESPI, PRISMS, and late, imaging-selection RCTs, and the advent of endovascular thrombectomy. Some non-expert contrarians questioned the accumulating evidence regarding tPA; the recently formulated fragility-robustness index (FRI) enables quantification of the actual rigor of evidence throughout the era of IV tPA investigation. Methods: The FRI summarizing the strength of the statistical evidence for clinical trial findings is the minimum nonevent to event changes needed to turn a statistically significant to non-significant result. The FRI was applied to disability-free (mRS 0-1) and independence (mRS 0-2) outcomes; cumulative meta-analyses delineated evidence strength after each successive RCT. FRI scores were classified: Not Robust (FRI 0-4), Somewhat Robust (5-12), Robust (13-33), and Highly Robust (>33). Results: Systematic search identified 8 RCTs (1960 patients) of IV tPA in the 0-3h window from 1995 - 2018. Study-level meta-analyses showed FRIs of 42 for mRS 0-1 and 40 for mRS 0-2; individual patient data meta-analyses showed FRIs of 40 for both mRS 0-1 and mRS 0-2, placing IV tPA in the highest quintile of FRIs among meta-analyses for all conditions. Evolution of RCT evidence over time is shown in Table 1. Strength of evidence for IV tPA superiority was already robust with publication of the initial 2 NINDS-tPA in 1995, remained robust through 2011 after 4 additional RCTs, increased to highly robust with the IST-3 mega-trial in 2012, and remains highly robust today after 1 additional trial. Conclusions: Intravenous tPA for acute ischemic stroke in 0-3h patients is one of the most robustly proven therapies in medicine. This therapy was already robustly supported with publication of the initial trials 25 years ago and advanced 9 years ago after additional trials to highly robust/non-fragile.

Download Full-text

Blood Pressure After Endovascular Thrombectomy and Outcomes in Patients With Acute Ischemic Stroke: An Individual Patient Data Meta-analysis

Neurology ◽

10.1212/wnl.0000000000013049 ◽

2021 ◽

pp. 10.1212/WNL.0000000000013049

Author(s):

Aristeidis H Katsanos ◽

Konark Malhotra ◽

Niaz Ahmed ◽

Georgios Seitidis ◽

Eva A. Mistry ◽

...

Keyword(s):

Blood Pressure ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Individual Patient Data ◽

Patient Data ◽

Neurological Deterioration ◽

Endovascular Thrombectomy ◽

Early Neurological Deterioration ◽

Symptomatic Intracranial Hemorrhage

Objective:To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO).Methods:A study was eligible if it enrolled AIS patients older than 18 years, with an LVO treated with either successful or unsuccessful EVT, and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed using a generalized linear mixed-effects model.Results:A total of 5874 patients (mean age: 69±14 years, 50% women, median NIHSS on admission: 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common OR=0.82, 95%CI:0.80-0.85; adjusted common OR=0.88, 95%CI:0.84-0.93) and modified Ranking Scale score≤2 (unadjusted OR=0.82, 95%CI:0.79-0.85; adjusted OR=0.87, 95%CI:0.82-0.93), and a higher odds of all-cause mortality (unadjusted OR=1.18, 95%CI:1.13-1.24; adjusted OR=1.15, 95%CI:1.06-1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurological deterioration (unadjusted OR=1.14, 95%CI:1.07-1.21; adjusted OR=1.14, 95%CI:1.03-1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR=1.20, 95%CI:1.09-1.29; adjusted OR=1.20, 95%CI:1.03-1.38) after EVT.Conclusion:Increased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurological deterioration, three-month mortality, and worse three-month functional outcomes.

Download Full-text

Abstract 4: Variation and Temporal Trends in the Characteristics of US Hospitals Treating Acute Ischemic Stroke Patients with IV-tPA: Findings from GWTG-Stroke

Stroke ◽

10.1161/str.44.suppl_1.a4 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Lee H Schwamm ◽

Syed F Ali ◽

Mathew J Reeves ◽

Eric E Smith ◽

Jeffrey L Saver ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Systems Of Care ◽

Team Building ◽

Temporal Trends ◽

High Volume ◽

Wilcoxon Test ◽

Chi Square ◽

Over Time ◽

Iv Tpa

Introduction: Utilization of IV tPA is challenging for many hospitals. Using data from the national Get With The Guidelines-Stroke program, we analyzed changes over time in the characteristics of the hospitals that treated patients with tPA. Methods: We analyzed patient-level data from 2003-2011 at 1600 GWTG hospitals that joined the program at any time during the study period and admitted any acute ischemic stroke (AIS) patients arriving ≤ 2 hr of onset and eligible for tPA. Descriptive trends by time were analyzed by chi-square or Wilcoxon test for continuous data. Results: IV tPA was given within 3 hr at 1394 sites to 50,798/ 75,115 (67.6%) eligible AIS patients arriving ≤ 2 hr; 206 (14.8%) sites had a least one eligible patients but no tPA use. IV tPA treatment rates varied substantially across hospitals (median 61.2%, range 0-100%), with > 200 hospitals providing tPA < 10% of the time (Figure). Over time, more patients and a larger proportion of patients were treated at smaller (median bed size 407 vs. 372, p< 0.001), non-academic, Southern hospitals, and those with lower annualized average ischemic stroke volumes (252.4 vs. 235.2, p< 0.001) (Table). While more than half of all tPA patients were treated at Primary Stroke Centers, this proportion did not change over time. The proportion of patients treated at high volume tPA treatment sites (average > 20/year) increased over time (31.9 vs. 34.5, p< 0.007). Conclusion: Over the past decade, while primary stroke centers still account for more than half of all treatments, tPA has been increasingly delivered in smaller, non-academic hospitals. These data support the continued emphasis on stroke team building and systems of care at US hospitals.

Download Full-text

Geographic dissemination of endovascular stroke thrombectomy in Catalonia within the 2011–2015 period

European Stroke Journal ◽

10.1177/2396987317696376 ◽

2017 ◽

Vol 2 (2) ◽

pp. 163-170 ◽

Cited By ~ 2

Author(s):

Sònia Abilleira ◽

Cristian Tebé ◽

Natalia Pérez de la Ossa ◽

Marc Ribó ◽

Pere Cardona ◽

...

Keyword(s):

Primary Care ◽

Ischemic Stroke ◽

Confidence Interval ◽

Acute Ischemic Stroke ◽

Care Service ◽

Primary Care Service ◽

Large Artery ◽

Endovascular Thrombectomy ◽

Service Areas ◽

Over Time

Introduction Endovascular thrombectomy was recently established as a new standard of care in acute ischemic stroke patients with large artery occlusions. Using small area health statistics, we sought to assess dissemination of endovascular thrombectomy in Catalonia throughout the period 2011–2015. Patients and methods We used registry data to identify all endovascular thrombectomies for acute ischemic stroke performed in Catalonia within the study period. The SONIIA registry is a government-mandated, population-based and externally audited data base that includes all reperfusion therapies for acute ischemic stroke. We linked endovascular thrombectomy cases identified in the registry with the Central Registry of the Catalan Public Health Insurance to obtain the primary care service area of residence for each treated patient, age and sex. We calculated age-sex standardized endovascular thrombectomy rates over time according to different territorial segmentation patterns (metropolitan/provincial rings and primary care service areas). Results Region-wide age-sex standardized endovascular thrombectomy rates increased significantly from 3.9 × 100,000 (95% confidence interval: 3.4–4.4) in 2011 to 6.8 × 100,000 (95% confidence interval: 6.2–7.6) in 2015. Such increase occurred in inner and outer metropolitan rings as well as provinces although highest endovascular thrombectomy rates were persistently seen in the inner metropolitan area. Changes in endovascular thrombectomy access across primary care service areas over time were more subtle, but there was a rather generalized increase of standardized endovascular thrombectomy rates. Discussion This study demonstrates temporal and territorial dissemination of access to endovascular thrombectomy in Catalonia over a 5-year period although variation remains at the completion of the study. Conclusion Mapping of endovascular thrombectomy is essential to assess equity and propose actions for access dissemination.

Download Full-text

Abstract 2268: Trends In Reasons For Non-eligibility For tPA

Stroke ◽

10.1161/str.43.suppl_1.a2268 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Xin Tong ◽

Mary G George

Keyword(s):

Ischemic Stroke ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

Advanced Age ◽

Stroke Patients ◽

Rapid Improvement ◽

Nihss Score ◽

Mild Stroke ◽

Over Time ◽

Iv Tpa

Background: Use of IV tPA has increased over time, as has the adherence to the NQF endorsed performance measure for receipt of IV tPA within 3 hours. Little is known about trends in the reasons for patient ineligibility for IV tPA. This study examines trends in reasons for not providing IV tPA over time and by race and gender among acute ischemic stroke patients in the Paul Coverdell National Acute Stroke Registry (PCNASR), a quality improvement program for acute stroke implemented by state health departments. Methods: There were 13,164 PCNASR patients enrolled from 2008- 2010 with a clinical diagnosis of acute ischemic stroke with documentation of LKW and who arrived within 2 hours of LKW. Cochran-Armitage tests were used to test for trend on accepted reasons for not providing IV tPA within 3 hours of time last known well (LKW). Chi-square tests were used to test for differences among reasons between men and women and between non-Hispanic whites and minorities. Multiple reasons for not giving tPA could be selected. Results: Among 13,164 acute ischemic patients admitted between 2008 and 2010 with documentation of LKW and who arrived within 2 hours of LKW, 3781 (28.7%) received IV tPA, 7284 (55.3%) had documented reasons for not receiving IV tPA, and 2099 (16.0%) did not receive IV tPA. Contraindications to IV tPA, advanced age, rapid improvement and inability to determine eligibility increased over time. Mild stroke decreased over time. Conditions with warning, advanced age, limited life expectancy and family refusal were more common in women; mild stroke and rapid improvement were more common in men. Contraindications were more common in minorities; advanced age, mild stroke and rapid improvement, and family refusal were more common in non-Hispanic whites. When advanced age was selected, 46.6% of patients were over age 90 and 3.4% were under age 80. When stroke too mild was selected, 44.8% of patients had missing NIHSS scores, 42.1% of scores were 0-4, 8.8% were 5-9, and 4.3% were ≥ 10. The three most common reasons for not providing tPA were rapid improvement (40.9%), mild stroke (33.0%), and contraindications (29.2%) in 2010. Conclusions: More than half of ischemic stroke patients arriving within 2 hours of LKW were ineligible to receive IV tPA. There was little use of advanced age for patients under age 80. Documentation of stroke too mild was not substantiated by an NIHSS score in nearly half of patients. Better documentation of NIHSS score should be provided.

Download Full-text

Direct endovascular thrombectomy and bridging strategies for acute ischemic stroke: a network meta-analysis

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2018-014260 ◽

2018 ◽

Vol 11 (5) ◽

pp. 443-449 ◽

Cited By ~ 4

Author(s):

Kevin Phan ◽

Adam A Dmytriw ◽

Declan Lloyd ◽

Julian M Maingard ◽

Hong Kuan Kok ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Mechanical Thrombectomy ◽

Meta Analysis ◽

Endovascular Thrombectomy ◽

Treatment Groups ◽

Randomized Controlled ◽

Improved Outcomes ◽

Significant Difference ◽

Meta Analyses

ObjectivesThe present Bayesian network meta-analysis aimed to compare the various strategies for acute ischemic stroke: direct endovascular thrombectomy within the thrombolysis window in patients with no contraindications to thrombolysis (DEVT); (2) direct endovascular thrombectomy secondary to contraindications to thrombolysis (DEVTc); (3) endovascular thrombectomy in addition to thrombolysis (IVEVT); and (4) thrombolysis without thrombectomy (IVT).MethodsSix electronic databases were searched from their dates of inception to May 2017 to identify randomized controlled trials (RCTs) comparing IVT versus IVEVT, and prospective registry studies comparing IVEVT versus DEVT or IVEVT versus DEVTc. Network meta-analyses were performed using ORs and 95% CIs as the summary statistic.ResultsWe identified 12 studies (5 RCTs, 7 prospective cohort) with a total of 3161 patients for analysis. There was no significant difference in good functional outcome at 90 days (modified Rankin Scale score ≤2) between DEVT and IVEVT. There was no significant difference in mortality between all treatment groups. DEVT was associated with a 49% reduction in intracranial hemorrhage (ICH) compared with IVEVT (OR 0.51; 95% CI 0.33 to 0.79), due to reduction in rates of asymptomatic ICH (OR 0.47; 95% CI 0.29 to 0.76). Patients treated with DEVT had higher rates of reperfusion compared with IVEVT (OR 1.73; 95% CI 1.04 to 2.94).ConclusionsTo our knowledge, this is the first network meta-analysis to be performed in the era of contemporary mechanical thrombectomy comparing DEVT and DEVTc. Our analysis suggests the addition of thrombolysis prior to thrombectomy for large vessel occlusions may not be associated with improved outcomes.

Download Full-text

Abstract 2545: Does Participation in a Stroke Registry Improve tPA Administration Rates?

Stroke ◽

10.1161/str.43.suppl_1.a2545 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Moges Ido ◽

Lydia Clarkson ◽

Deborah Camp ◽

Kerrie Krompf ◽

Michael Frankel

Keyword(s):

Quality Improvement ◽

Ischemic Stroke ◽

Length Of Stay ◽

Patient Care ◽

Acute Ischemic Stroke ◽

Stroke Patients ◽

Hospital Size ◽

Stroke Registry ◽

Over Time ◽

Iv Tpa

Background: The purpose of the Georgia Coverdell Acute Stroke Registry (GCASR) is to improve the quality of patient care. GCASR conducts regular quality improvement activities to educate hospital staff and improve systems and processes. Administration of intravenous tissue plasminogen activator (IV tPA) is standard treatment for eligible acute ischemic stroke patients and can dramatically improve outcomes. Purpose: To determine whether GCASR hospitals were more likely to administer tPA to acute ischemic stroke patients than non-GCASR hospitals. Methods: Hospitalization data from acute care hospitals in Georgia was provided by the Georgia Hospital Association for November 2005 through December 2009. Acute ischemic stroke patients receiving tPA were identified using ICD-9 codes (433 and 434), procedure codes (9910), and healthcare common procedure system codes (J2997). A hospital was defined as a GCASR facility if it was actively participating in the registry at the time of patient hospitalization. A generalized estimating equation with robust variance estimation was applied using the SAS GLIMMIX procedure. “Hospital” was treated as a random variable. Relative risks for receiving tPA were estimated and adjusted for demographics, co-morbidities, hospital size, urbanicity, and length of stay. Results: A total of 55,403 patients were admitted with a principal diagnosis of acute ischemic stroke during the study period, and two percent (1,231) received tPA. Three percent of patients (871) seen at registry facilities received tPA, compared to 1.4% (360) of those seen at non-GCASR facilities. Age, gender, race, length of stay, hospital size, and participation in the registry all predicted tPA administration, either at or near significant levels (p-values from <0.0001 to 0.0646). Although IV tPA administration has increased over time in both hospital groups, patients treated at GCASR facilities were more likely to receive tPA after controlling for confounders (OR=1.64; 95% CI: 0.97-2.78), which approached significance (p=0.0646). Approximately 340 fewer people would have received tPA had all study patients been treated at non-GCASR facilities. Conclusions: Although all Georgia hospitals have improved their rate of tPA administration over time, GCASR hospitals maintained a higher rate than non-GCASR hospitals. This may be due in part to the quality improvement activities that registry facilities participate in and the assistance they receive. These results support the stroke registry model as a method of improving stroke patient care and outcomes.

Download Full-text

Abstract TP81: Faster Start of IV tPA Does not Decrease the Need for Endovascular Thrombectomy in Acute Ischemic Stroke

Stroke ◽

10.1161/str.47.suppl_1.tp81 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Arun Chhabra ◽

Kristina Shkirkova ◽

Rodel Alfonso ◽

Manuel Buitrago Blanco ◽

Paul Vespa ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Imaging Modality ◽

Large Vessel ◽

Vessel Occlusion ◽

Endovascular Thrombectomy ◽

Academic Medical ◽

Vessel Imaging ◽

Recent Patient ◽

Iv Tpa

Background: Recent patient series have shown IV tPA to more often lyse cerebral thrombi when started sooner after symptom onset in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). This association has been attributed to less fibrin-cross-linking and less compaction of thrombi. We sought to determine if this phenomenon would make endovascular thrombectomy less often needed among AIS-LVO patients treated hyperacutely with IV tPA. Methods: In a prospectively maintained registry, we identified patients receiving IV tPA at 2 academic medical centers from March 2005 - May 2015. Inclusion criteria were: 1) LVO seen on CTA or MRA before (or early during) infusion of IV tPA and 2) follow-up vessel imaging within 6h of IV tPA initiation, using CT, MR or catheter angiogram. Degree of thrombus lysis with IV tPA alone was rated using the arterial occlusive lesion (AOL) Scale. Results: Among the 166 patients, average age was 72.4 (±13.4), 52.4% were female and pretreatment NIHSS was 13.9 (±8.4). Onset to needle time (OTN) was median 105 min (IQR 79-129) and door to needle time 44 min (27-65). Initial vessel imaging modality was MRA in 68.7% and CTA in 31.3%. Early post-tPA vessel imaging modality was catheter angiogram in 63.8%, MRA in 33.7% and CTA in 2.4%. Time from tPA initiation to recanalization assessment was faster when post-tPA vessel imaging was catheter angiogram vs MRA/CTA, 72 min (45.5-116.5) vs 232 min (185-283), p<0.001. In cases assessed with early post-treatment catheter angiogram, IV tPA yielded complete recanalization in 17%, partial in 6.6%, and none in 76.4%. In cases assessed with MRA/CTA, IV tPA yielded complete recanalization in 30%, partial in 35%, and none in 35%. Recanalization within the 6h window was visualized more often when imaged with later CTA/MRA than with earlier catheter angiogram (p<0.001). Among patients going directly to catheter angiography, OTN for IV tPA was not different between recanalizers and non-recanalizers, 106 vs 98 min, p = 0.53. Discussion: Among large vessel acute ischemic stroke patients, the rate of complete recanalization with IV tPA alone is only 1 in 6, and faster OTN time is not associated with increased recanalization. All AIS-LVO patients should proceed to thrombectomy as swiftly as possible.

Download Full-text

Abstract P215: Declining Gastrostomy Tube Utilization in Acute Ischemic Stroke

Stroke ◽

10.1161/str.52.suppl_1.p215 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Lee Pfaff ◽

Karen C Albright ◽

Julius Gene Latorre ◽

Fadar O Otite

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Age Groups ◽

Intravenous Thrombolysis ◽

International Classification Of Diseases ◽

Joinpoint Regression ◽

Peg Tube ◽

Demographic Subgroups ◽

Over Time ◽

Iv Tpa

Objective: To test the hypothesis that placement of percutaneous feeding tubes (PEG) in acute ischemic stroke (AIS) patients has declined following increased usage of intravenous thrombolysis (IV-tPA) and mechanical thrombectomy (MT) over the last decade. Methods: We identified all primary adult AIS admissions contained in the 2005-2017 National Inpatient Sample using International Classification of Diseases (ICD) codes. Age and sex-specific proportions of hospitalizations with coexisting ICD procedural codes for PEG were computed. Joinpoint regression was used to evaluate trends over time. Multivariable adjusted logistic regression was used to compare odds of PEG use between periods and demographic subgroups. Results: From 2005-2017, 4.3% of all AIS hospitalizations had coexisting codes for PEG but usage differed by age, with highest proportion of usage in patients >=80 year old (y.o) (5.2%) and lowest frequency of usage in adults 18-39 y.o (2.7%). On joinpoint regression, there was no significant change in PEG use from 2005-2009, usage declined annually by -3.0% from 2009-2015 (95%CI -4.2% to -1.8%) and then declined sharply by -9.2% (95%CI -13.4 to -4.8%) from 2015 to 2017 (figure 1). The pace of decline was faster in patients >=80y.o compared to other age groups. After multivariable adjustment for clinical and hospital level factors, patients hospitalized in the period 2014-2017 had 25% reduced odds of PEG when compared to admissions in the period 2005-2009 (OR 0.76, 95%CI 0.72-0.79). Female sex and white race were associated with lower odds of PEG compared to males and black patients, respectively. IV-tPA and MT usage increased over time with marked increase in usage after 2015. Conclusion: Overall the rate at which PEG tube have been utilized has decreased significantly over the last decade. This decrease is likely from multifactorial advances in acute stroke (IV-tPA and MT) and post stroke neuro critical care.

Download Full-text