Use Of tPA Research Articles

Fibrinolysis With TPA Alone Is Only One Third As Effective As It Should Be

Therapeutic fibrinolysis has used tissue Plasminogen Activator (tPA) alone since 1987,when tPA was first approved for the treatment of Acute Myocardial Infarction (AMI). The use of Tpa was based on the belief that it was responsible for fibrinolysis. However, this assumption should have been put into question from the outset when tPA was found to have the same efficacy as Streptokinase (SK). This was unexpected, since SK has an indirect, less efficient mechanism of action and SK has no fibrin clot affinity, in contrast to tPA. Nevertheless, the 30-day AMI mortality with tPA and SK were identical in the first two trials.

Increased brain plasmin levels following experimental ischemic stroke in male mice.

Many coagulation factor proteases are increased in the brain during ischemic stroke. One of these proteases is plasmin. In this study we established a novel method for direct quantitative measurement of plasmin activity in male mouse brain slices using a sensitive fluorescent substrate in the presence of specific protease inhibitors. In both the ischemic and contralateral hemispheres, plasmin activity increased 3, 6, and 24hr following stroke in comparison to healthy mice (F(3, 72)=39.5, p<0.0001, repeated measures ANOVA) after the induction of permanent middle cerebral artery occlusion (PMCAo). Plasmin activity was higher in the ischemic hemisphere (F(1,36)=9.1, p=0.005) and there was a significant interaction between time and ischemic hemisphere (F(3,36)=4.4, p=0.009). Plasmin activity was correlated with infarct volume (R2 =0.5289, p=0.0009 by Spearman). The specificity of the assay was verified utilizing tissue-type plasminogen activator (tPA)-deficient mice which, as expected, had significantly lower levels of plasmin 24hr following ischemia compared to wild-type mice (ischemic (0.6±0.23 and 1.94±0.5, respectively), p=0.049 and contralateral hemispheres (0.13±0.14 and 0.75±0.10, respectively), p=0.018 by t test). There is a time-dependent increase in plasmin levels and an association of higher levels of plasmin with larger infarct volumes in an experimental stroke model. This suggests caution in the use of recombinant tPA (rtPA) and that plasmin inhibition in the brain may be a therapeutic target in acute ischemic stroke.

M168 RECURRENT OROLINGUAL ANGIOEDEMA (OAE) IN THE SETTING OF STROKE

OAE has been described in patients with stroke after tissue plasminogen activator (tPA) use. Here, we discuss a case that occurred without the use of tPA.

Thrombolytic Refusal Over Telestroke.

Tissue plasminogen activator (tPA) refusal is 4%-6% for acute ischemic stroke (AIS) in the emergency department. Telestroke (TS) has increased the use of tPA for AIS but is accompanied by barriers in communication that can affect tPA consent. We characterized the incidence of tPA refusal in our TS network and its associated reasons. Patients with AIS who were offered tPA within 4.5 hours from symptom onset according to American Heart Association guidelines were identified within our Lone Star Stroke Consortium Telestroke Registry from September 2015 to December 2018. We compared baseline characteristics and clinical outcomes between patients who refused tPA and patients who accepted tPA. Among the 1,242 patients who qualified for tPA and were offered treatment, 8% refused tPA. Female and non-Hispanic Black patients and patients with a prior history of stroke were more likely to decline tPA. Patients who refused tPA presented with a lower NIHSS and were associated with a final diagnosis of stroke mimic (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.15-0.36). Good outcome (90-day modified Rankin Scale 0-2) was the same among patients who received tPA and those who refused (OR 0.80; 95% CI 0.42-1.54). The most common reasons for refusal were rapidly improving and mild/nondisabling symptoms and concern for potential side effects. tPA refusal over TS is comparable to previously reported rates; there was no difference in outcomes among patients who received tPA compared with those who refused. Sex and racial differences associated with an increased tPA refusal warrant further investigation in efforts to achieve equity/parity in tPA decisions.

Intrapleural Fibrinolytic Therapy Improves Results With Talc Slurry Pleurodesis.

ObjectiveTalc slurry pleurodesis (TSP) can lead to permanent small loculations. Intrapleural tissue plasminogen activator (tPA) breaks down loculations, and therefore may improve results but may also inhibit pleurodesis. tPA was given with and after talc slurry to promote more uniform talc distribution and eliminate loculations.MethodsCharts were reviewed for patients treated with TSP with or without tPA. Chest x-rays after TSP were compared to chest x-rays before and graded as “worse”, “same”, or “better”. Incidence of need for repeat TSP was recorded.ResultsThere were 52 patients, eight with bilateral effusions, for a study cohort of 60 effusions. One-third of the effusions were malignant. No patients experienced significant bleeding. Results were better than baseline for 14 (26%) patients given tPA, but not for patients that never received tPA. The addition of tPA 4-6 mg with talc slurry resulted in no patients requiring repeat TSP. When tPA was given after talc slurry, a delay of three days was associated with the lowest incidence of repeat TSP (3/14, 21%).ConclusionsThere were no significant complications from tPA use to supplement TSP, and tPA may improve results without interfering with pleurodesis. A prospective trial is warranted.

YiQiFuMai Lyophilized Injection ameliorates tPA-induced hemorrhagic transformation by inhibiting cytoskeletal rearrangement associated with ROCK1 and NF-κB signaling pathways

Ethnopharmacological relevanceThrombolytic therapy with tissue plasminogen activator (tPA) after ischemic stroke exacerbates blood–brain barrier (BBB) breakdown and leads to hemorrhagic transformation (HT). YiQiFuMai Lyophilized Injection (YQFM) is a modern preparation derived from Sheng-mai San (a traditional Chinese medicine). YQFM attenuates the BBB dysfunction induced by cerebral ischemia–reperfusion injury. However, whether YQFM can suppress tPA-induced HT remains unknown. Aim of the studyWe investigated the therapeutic effect of YQFM on tPA-induced HT and explored the underlying mechanisms in vivo and in vitro to improve the safety of tPA use against stroke. MethodsMale C57BL/6J mice were subjected to 45 min of ischemia and 24 h of reperfusion. tPA (10 mg/kg) were infused 2 h after occlusion and YQFM (0.671 g/kg) was injected 2.5 h after occlusion. The in vitro effect of YQFM (100, 200, 400 μg/mL) on tPA (60 μg/mL)-induced dysfunction of the microvascular endothelial barrier in the brain following oxygen-glucose deprivation/reoxygenation (OGD/R) was observed in bEnd.3 cells. ResultsYQFM suppressed tPA-induced high hemoglobin level in the brain, mortality, neurologic severity score, BBB permeability, expression and activation of matrix metalloproteinase (MMP)-9 and MMP-2, and degradation of tight-junction proteins. Furthermore, YQFM significantly blocked tPA-induced brain microvascular endothelial permeability and phosphorylation of Rho-associated kinase (ROCK)1, myosin light chain (MLC), cofilin and p65 in vivo and in vitro. ConclusionYQFM suppressed tPA-induced HT by inhibiting cytoskeletal rearrangement linked with ROCK-cofilin/MLC pathways and inhibiting the nuclear factor-kappa B pathway to ameliorate BBB damage caused by tPA.

Use of Tissue Plasminogen Activator as a Surrogate Measure for Central Venous Catheter Dysfunction and Survival Outcome in Children with Cancer: A Population-Based Retrospective Cohort Study

Central venous catheter (CVC) dysfunction is often associated with thrombosis, which in turn has been linked with poorer survival outcomes in cancer patients. Our objective was to examine the association of tissue plasminogen activator (tPA) administration as a surrogate measure of CVC dysfunction with survival in pediatric cancer patients. The present study uses data from a population-based retrospective cohort of pediatric oncology patients from the Canadian Maritime provinces treated between 2000 and 2017 at the IWK Health Centre, Halifax, NS. Demographics, diagnosis, date of death or date of last visit, and tPA use for CVC dysfunction were obtained from clinical databases and the provincial Cancer in Young People in Canada registry. The association between tPA administration and survival was examined using a Cox regression model adjusted for sex, age at diagnosis, cancer type, thrombosis, CVC duration, diagnosis era, and treatment modalities. Out of 821 patients, 206 received one or more doses of tPA during upfront therapy. The death rate was 21% and 15% respectively in patients who did and did not receive tPA. In the adjusted regression model, after receiving one or more doses of tPA, children had significantly poorer survival as compared to those that did not receive tPA (HR: 1.496, 95% CI: 1.019, 2.197). CVC dysfunction may be associated with a poorer prognosis in pediatric cancer patients. Future studies should corroborate these findings in other populations, examine the influence of other potential confounders, and determine the role of CVC dysfunction in prognostic models of cancer survival.

Is there a role for tissue plasminogen activator as a novel treatment for refractory COVID-19 associated acute respiratory distress syndrome?

Is there a role for tissue plasminogen activator as a novel treatment for refractory COVID-19 associated acute respiratory distress syndrome?

Use of Tissue Plasminogen Activator in Abdominal Abscesses in Children-A Single-Center Randomized Control Trial.

To establish the efficacy of once-per-day intracavitary tissue plasminogen activator (tPA) in the treatment of pediatric intra-abdominal abscesses. A single-center prospective, double-blinded, randomized controlled trial of the use of intracavitary tPA in abdominal abscesses in children. Patients were randomized to either tPA-treatment or saline-treatment groups. Primary outcome was drainage catheter dwell (hours). Secondary outcomes were length of hospital stay, times to discharge, clinical and sonographic resolution, and adverse events (AEs). Twenty-eight children were randomized to either group (n = 14 each). Demographics between groups were not significantly different (age P = .28; weight P = .40; gender P = .44). There were significantly more abscesses in the tPA-treated group (P = .03). Abscesses were secondary to perforated appendicitis (n = 25) or postappendectomy (n = 3). Thirty-four abscesses were drained, 4 aspirated, 3 neither drained/aspirated. There was no significant difference in number of drains (P = .14), drain size (P = .19), primary outcome (P = .077), or secondary outcomes found. No procedural or intervention drug-related AEs occurred. No patient in the saline-treated group required to be switched/treated with tPA. No significant difference in the length of catheter dwell time, procedure time to discharge, or time to resolution was found. Intracavitary tPA was not associated with morbidity or mortality. The results neither support nor negate routine use of tPA in the drainage of intra-abdominal abscess in children. It is possible that a multicentre study with a larger number of patients may answer this question more definitively.

Mobile stroke units: taking stroke care to the patient.

Since the development of intravenous tissue plasminogen activator (tPA) for acute ischemic stroke (AIS), functional outcome has improved when treatment occurs within 4.5 h of stroke onset and treatment benefits are greater with earlier treatment. Endovascular revascularization also is better the sooner it is delivered. The Get with the Guidelines Stroke registry found that less than one-third of treatment-eligible AIS patients receive intravenous tPA within 60 min of hospital arrival. Initiatives have tried to improve public education and awareness of stroke symptoms to decrease time to presentation. The mobile stroke unit (MSU) facilitates earlier computed tomography scans, delivery of tPA, proper triage and on-scene goal-directed care. MSUs reduce time from stroke alarm to treatment by 25-40 min and increase the rate of intravenous tPA use without an increase in hemorrhage risk. In addition, three-month favorable outcome is increased. MSUs likely will evolve further and be used for other acute neurologic disorders, help triage patients for endovascular therapy, and be incorporated into systems of care in remote areas. Further studies are awaited to fully understand the overall medical and health-economic benefit of MSUs.

An in vitro Model System for Evaluating Remote Magnetic Nanoparticle Movement and Fibrinolysis.

BackgroundThrombotic events continue to be a major cause of morbidity and mortality worldwide. Tissue plasminogen activator (tPA) is used for the treatment of acute ischemic stroke and other thrombotic disorders. Use of tPA is limited by its narrow therapeutic time window, hemorrhagic complications, and insufficient delivery to the location of the thrombus. Magnetic nanoparticles (MNPs) have been proposed for targeting tPA delivery. It would be advantageous to develop an improved in vitro model of clot formation, to screen thrombolytic therapies that could be enhanced by addition of MNPs, and to test magnetic drug targeting at human-sized distances.MethodsWe utilized commercially available blood and endothelial cells to construct 1/8th inch (and larger) biomimetic vascular channels in acrylic trays. MNP clusters were moved at a distance by a rotating permanent magnet and moved along the channels by surface walking. The effect of different transport media on MNP velocity was studied using video photography. MNPs with and without tPA were analyzed to determine their velocities in the channels, and their fibrinolytic effect in wells and the trays. ResultsMNP clusters could be moved through fluids including blood, at human-sized distances, down straight or branched channels, using the rotating permanent magnet. The greatest MNP velocity was closest to the magnet: 0.76 ± 0.03 cm/sec. In serum, the average MNP velocity was 0.10 ± 0.02 cm/sec. MNPs were found to enhance tPA delivery, and cause fibrinolysis in both static and dynamic studies. Fibrinolysis was observed to occur in 85% of the dynamic MNP + tPA experiments.ConclusionMNPs hold great promise for use in augmenting delivery of tPA for the treatment of stroke and other thrombotic conditions. This model system facilitates side by side comparisons of MNP-facilitated drug delivery, at a human scale.

What Interventional Radiologists Need to Know About Managing Severe Frostbite: A Meta-Analysis of Thrombolytic Therapy.

OBJECTIVE. The purpose of this study is to review the various techniques and clinical management paradigms using tissue plasminogen activator (tPA) to treat severe frostbite injuries, which are relevant to the interventional radiologist. MATERIALS AND METHODS. A literature search yielded 157 citations, which were manually screened for inclusion criteria of case reports, case series, cohort studies, and randomized prospective studies that reported the use of tPA to treat severe frostbite injuries, of which 16 qualified for review. Data extracted from the studies included authors, journal, year of publication, initial assessment and management of severe frostbite injuries, inclusion and exclusion criteria for tPA therapy, treatment and control group size, different imaging modalities used in evaluation of severe frostbite injuries, tPA treatment protocols, outcomes, and side effects or complications. RESULTS. The analyzed series included 209 patients with 1109 digits at risk of amputation who were treated with intraarterial (IA) or IV tPA (116 and 77 patients, respectively). A total of 926 digits at risk were treated with IA tPA and resulted in amputation of 222 digits, for a salvage rate of 76%. Twenty-four of 63 patients underwent amputation after IV tPA, resulting in a salvage rate of 62%. Both digital subtraction angiography and triple-phase bone scan were used for initial imaging evaluation. Additional concurrent treatment included therapeutic heparin, warfarin, nonsteroidal antiinflammatory drugs, pain management, and light dressings with topical antimicrobial agents. CONCLUSION. Severe frostbite injuries can lead to devastating outcomes with loss of limbs and digits, yet clinical management continues to consist primarily of tissue rewarming, prolonged watchful waiting, and often delayed amputation. Recent studies have shown promising results using both IA and IV tPA to reduce amputation after severe frostbite injuries. Through a meta-analysis of thrombolytic therapy in the management of severe frostbite, this article provides a useful guideline for interventional radiologists including a suggested protocol, inclusion and exclusion criteria, and potential complications.

Abstract WMP10: The Role of Intravenous Thrombolysis Before Mechanical Thrombectomy: A Subgroup Analysis of the RESILIENT Trial

Background: Mechanical thrombectomy (MT) in addition to intravenous thrombolysis (IVT) is now the recommended treatment for acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). The positive trials also demonstrated that MT alone among patients ineligible for IVT is an effective therapy for AIS. Whether MT alone is as effective, worse, or better than pretreatment with IVT before MT among IVT-eligible AIS patients with LVO is debatable. We aimed to assess the effect of IVT on the clinical outcome of MT in the RESILIENT trial. Methods: RESILIENT was a randomized, prospective, multicenter, controlled trial evaluating the safety, efficacy, and cost-effectiveness of thrombectomy versus medical treatment alone. A total of 221 patient were enrolled. The trial showed a strong benefit to thrombectomy (90-day mRS ordinal shift, OR 95%CI). All eligible patients received intravenous tPA within the 4.5-hour-window. The primary end-point was the common odds ratio (cOR) of mRs at 90 days (shift analysis) and the main secondary endpoint was the rate of functional independence (mRS 0-2) at 90 days. Ordinal logistic and binary regression analyses with the use of intravenous tPA as an interaction term were performed with adjustments for potential confounders including age, baseline NIHSS score, occlusion site, IV tPA use and ASPECTS. A p value &lt; 0.05 was considered statistically significant. Results: Among 221 randomized patients (median NIHSS, 18 IQR [14-21]), 155 (70%) were treated with IV tPA. The frequency of good recanalization (TICI 2b&gt; ) and of hemorrhagic transformation was not affected by IVT. There was no significant difference in the treatment effect size across patients who received intravenous tPA versus those who did not in terms of overall functional disability (ordinal mRS shift: aOR: 2.63, 95%CI [1.48-4.69] vs. 1.54, 95%CI [0.63-3.74]; p=0.42) or functional independence (mRS 0-2: aOR: 3.06, 95%CI [1.37-6.48] vs. 1.71 95%CI [0.55-5.33], p=0.40) at 90 days. Conclusions: The large effect size of MT on LVO outcomes was not significantly affected by IVT. Further studies directly evaluating the role of IVT before MT are of utmost importance.

Abstract 5: CT Perfusion is Not a Treatment Effect Modifier for Mechanical Thrombectomy in the 0-8-Hour-Window: A Pre-Planned Analysis of the RESILIENT Trial

Background: CT perfusion has been increasingly used as a selection tool in acute reperfusion therapies. However, it remains unknown whether its use is associated with a higher treatment benefit in patients undergoing thrombectomy. We sought to evaluate the interaction between imaging selection modalities and treatment effect in the RESILIENT Trial. Methods: RESILIENT was a randomized, prospective, multicenter, controlled trial evaluating the safety, efficacy, and cost-effectiveness of thrombectomy versus medical treatment alone in Brazil. A total of 221 patient were enrolled. The trial showed a strong benefit of thrombectomy (90-day mRS ordinal shift, OR 2.28 95%CI [1.41-3.70]; p=0.001). Key imaging selection criteria included ASPECTS ≥6 on non-contrast CT (NCCT) and the exclusion of malignant collateral profile on CT angiography. The use of automated CT perfusion software (RAPID, IschemaView) was optional but was made available in some centers with the pre-specified plan to compare imaging selection modalities. The primary end-point was the common odds ratio (cOR) of mRs at 90 days (shift analysis) and the main secondary endpoint was the rate of functional independence (mRS 0-2) at 90 days. Ordinal logistic and binary regression analyses with imaging selection modality (NCCT versus CTP) as an interaction term were performed with adjustments for potential confounders including age, baseline NIHSS score, occlusion site, IV tPA use and ASPECTS. A p value &lt; 0.05 was considered statistically significant. Results: CTP was performed in 41% of the thrombectomy group and 45% in the control group. There was no significant difference in the treatment effect size for patients selected on the basis of NCCT and CTA only versus those submitted to CTP in terms of overall functional disability (ordinal mRS shift: aOR: 2.87, 95%CI [1.47-5.61] vs. 2.10, 95%CI [1.01-4.36]; p=0.390) or functional independence (mRS 0-2: aOR: 3.16, 95%CI [1.32-7.57] vs. 2.54 95%CI [0.86-7.49], p=0.40) at 90 days. Conclusion: In a randomized clinical trial of thrombectomy within 8 hours of stroke onset, there was no evidence of difference in the treatment effect size across patients selected with NCCT and CTA alone versus automated CT perfusion software.

Abstract TMP14: Contemporary Use of IV Alteplase in Acute Ischemic Stroke Beyond 4.5 Hours of Stroke Onset in Clinical Practice is Rare

Introduction: Two RCTs conducted from 2010-2018 showed benefit in ischemic stroke (IS) of IV tPA &gt;4.5 h from last known well (LKW) using advanced imaging selection. Many subjects were wakeup strokes treated &lt; 4.5 h of symptom discovery (SxD). We assessed the frequency of IV tPA &gt; 4.5 h in the national GWTG-Stroke clinical registry during the same period as the RCTs were performed. Methods: We analyzed all IS hospitalizations between 1/1/09 - 10/1/18 at fully participating GWTG-Stroke sites to identify 219,565 patients at 1919 sites who received IV tPA (no thrombectomy) and had valid LKW, SxD and treatment times recorded. Table shows significant covariates (standardized differences &gt;10%) Results: Treatment beyond 4.5 h from LKW was rare, occurring in 2.19% (n=4798) of all tPA cases, and 50% of those treated were still within 4.5 h from SxD. The distribution of time to treatment in minutes was similar when stroke onset was defined by LKW compared to SxD (median (IQR) 134 (100-174) vs. 125 (94-163)) (Fig). The use of IV tPA at &gt;4.5 h from LKW as a proportion of all tPA cases treated varied substantially across sites (median (IQR) 1.7% (0-3.1%)) but fewer than ~10% of sites had more than 5% of their tPA use occurring beyond 4.5 h. Compared to &lt; 4.5 h, patients treated &gt;4.5 h differed in age, AF, arrival mode/time, stroke severity and hospital region (Table). Conclusions: During the past decade and prior to published RCT evidence that extended window IV tPA was effective, US sites in GWTG-Stroke rarely treated patients beyond the guideline-approved window of 4.5 h. It will be important to monitor adoption of extended window thrombolysis in the US, and determine if additional RCT data are required to change practice.

Abstract 103: Intravenous Thrombolysis for In-Hospital Ischemic Stroke in the Endovascular Era: Findings From the National Get With the Guidelines-Stroke Registry

Introduction: A significant proportion of acute ischemic strokes occur while patients are hospitalized for other reasons. Limited data exist on the utilization of intravenous alteplase (IV tPA) for in-hospital stroke, particularly in the endovascular era. We compared temporal trends of IV tPA use, patient characteristics, process measures of quality, and outcomes for in-hospital versus community onset strokes in a national registry. Methods: We performed a retrospective cohort study of Get With The Guidelines-Stroke (GTWG-Stroke) from January 2008 to June 2018 from 2,333 participating sites that included 2,428,178 patients with acute ischemic stroke. In-hospital onset was reported in 67,493 patients. We examined the association between stroke onset location, patient characteristics, comorbidities, treatment with IV tPA and unadjusted and adjusted functional outcomes (Table, standardized differences &gt;10% for significance). Results: Of 67,493 patients with in-hospital onset stroke, 11,123 received IV tPA. The rate of IV tPA administration steadily increased, from 9.5% in 2008 to 20.7% in 2017 (p&lt;0.001). Compared with patients with community-onset strokes who were treated with IV tPA, patients with in-hospital onset stroke had longer times to cranial imaging and administration of IV tPA. Patients with in-hospital onset stroke were less likely to be treated within 60 minutes of recognition, and at discharge, ambulate independently or go directly home. They were more likely to die or be discharged to hospice after adjusting for patient and hospital characteristics. Conclusions: In this national cohort, in-hospital onset strokes are increasingly treated with intravenous tPA in a period that spans the endovascular era. Compared with community-onset stroke, patients with in-hospital onset stroke had longer intervals to thrombolysis and worse outcomes. These data highlight opportunities to improve inpatient systems of stroke care further.

Abstract WP346: Factors Associated With TPA Refusal via Telestroke

Introduction: tPA refusal occurs 4-8% when offered in-person for acute ischemic stroke (AIS). Telestroke (TS) has increased tPA use for AIS, but entails non-traditional patient-physician interaction. Refusal accounts for 16-18% of reasons patients do not receive tPA via TS. We report tPA refusal incidence and associated factors in our TS network. Methods: We identified patients in our TS registry (9/2015-12/2018) who were offered tPA for suspected AIS within 4.5 hrs of symptom onset. We compared demographics, clinical characteristics, and outcomes associated with tPA refusal. Results: Of 1242 patients offered tPA in our TS network, 101 (8%) refused. Of 1376 patients that did not receive tPA, refusal accounted for 7% (101/1376). Patients refusing tPA were younger than those that accepted (median age 61 vs 66, p=0.01) (Table 1). Male patients were less likely to decline tPA (OR 0.65, CI 0.43-0.98), and non-Hispanic black patients were more likely (OR 1.86, CI 1.18-2.93). tPA refusal was associated with mild stroke (median NIHSS 3 vs 7, p&lt;0.0001) and prior ischemic stroke (OR 1.66, CI 1.06-2.60). Patients with final diagnosis of stroke vs stroke mimic were less likely to refuse tPA (OR 0.23, CI 0.15-0.36). Insurance status and baseline functional status were similar among patients who accepted and refused tPA. Patients who accepted tPA were more likely discharged to inpatient rehab. tPA was primarily refused for risk of adverse effects and mild/improving symptoms. Conclusion: Refusal contributes to lower utilization of tPA. Our incidence of refusal was comparable to historical data in non-TS settings. While some factors associated with tPA refusal via TS are consistent with historical data on tPA refusal in-person, differences in patient age, gender, and race/ethnicity still warrant further investigation. Specifically, studies are needed to understand if tPA refusal is related to care delivered via TS, or if patients are more reluctant due to perceived risks of tPA via TS.

Abstract WP42: Stroke Severity and Size Modify the Association Between IV Thrombolysis and Outcomes Following Endovascular Thrombectomy

Background: Whether IV tPA has adjunctive benefit to endovascular thrombectomy (EVT) is unclear. Methods: In a prospective multicenter cohort study of imaging selection for EVT (SELECT), patients who received IV tPA vs. no IV tPA were compared stratified by stroke severity and ischemic core size (rCBF&lt;30%). Results: Of 361 enrolled, 285 received EVT; 226 presented within 4.5 hrs, 162 (72%) received IV tPA. IV tPA patients had lower median ASPECTS (8 vs 9, p=0.007) and larger ischemic core size (11.4 (1.5-37) vs 3.9 (0-32.15), p=0.042, otherwise similar at baseline. There were no delays in EVT delivery associated with tPA: median time (IQR) from arrival to groin puncture 95.0 min (66.0, 118.0) tPA vs 81.5 (63.5, 107.5) no tPA, p=0.21. IV tPA use was associated with higher mRS 0-2 rates (57% vs 44%), aOR 2.02 (95% CI 1.01-4.03, p=0.046) after adjustment for baseline differences with a shift towards better outcomes on all mRS levels (cOR 2.06, 95% CI 1.18-3.59, p=0.01) with lower mortality (11% vs 22%, p=0.026) and similar sICH rates (and 6% vs 6%, p=1.0). In patients with NIHSS &lt;15, IV tPA was associated with higher mRS 0-2 (tPA 83% vs no tPA 50%, aOR 4.53, 95%CI 1.48-13.80, p=0.008) with a shift towards better outcomes (adj cOR 5.44, 95% CI 2.16-13.70, p&lt;0.001) while with NIHSS≥15 there was no adjunctive benefit of IV tPA (tPA 42% vs no tPA 38%, aOR 1.05, 95%CI 0.40-2.74, p=0.92) or shift (adj cOR: 1.32, 95% CI 0.61-2.86, p=0.48) with an interaction between IV tPA effect on EVT outcome with NIHSS (p=0.04) Fig A. Similarly, in ischemic core &lt; 50 cc (62% vs. 46%, aOR 1.96, 95%CI 0.96-3.99, p=0.06; adj cOR 2.03, 95% CI 1.13-3.66, p=0.018) as compared to core ≥ 50cc (tPA 26% vs no tPA 25% P=1.0) with an interaction between IV tPA effect on EVT outcome with core size (p=0.037) Fig B. Conclusion: IV tPA did not result in thrombectomy delivery delays and may result in better outcomes. Patients with less severe strokes and smaller infarct size had a stronger association between the use of IV tPA and favorable outcomes.

Quality of Acute Stroke Care at Primary Stroke Centers Before and After Certification in Comparison to Never-Certified Hospitals.

Background and Purpose: Primary stroke center (PSC) certification is associated with improvements in stroke care and outcome. However, these improvements may reflect a higher baseline level of care delivery in hospitals eventually achieving certification. This study examines whether advancements in acute stroke care at PSCs are due to certification or factors intrinsic to the hospital.Methods: Data was obtained from the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial with participation of 40 Emergency Medical System agencies, 315 ambulances, and 60 acute receiving hospitals in Los Angeles and Orange Counties. Subjects were transported to one of three types of destinations: PSC certified hospitals (PSCs), hospitals that were not PSCs at time of enrollment but would later become certified (pre-PSCs), and hospitals that would never be certified (non-PSCs). Metrics of acute stroke care quality included time arrival to imaging, use of intravenous tPA, and arrival to treatment.Results: Of 1,700 cases, 856(50%) were at certified PSCs, 529(31%) were at pre-PSCs, and 315 (19%) were at non-PSCs. Mean (SD) was 33min (±76.1) at PSCs, 47(±86.6) at pre-PSCs, and 49(±71.7) at non-PSCs. Of 1,223 cerebral ischemia cases, rate of tPA utilization was 43% at PSCs, 27% at pre-PSCs, and 28% at non-PSCs. Mean ED arrival to thrombolysis was 71(±32.7) at PSC, 98(±37.6) at pre-PSC, and 95(±45.0) at non-PSCs. PSCs had improved time to imaging (p = 0.014), percent tPA use (p < 0.001), and time to treatment (p = 0.003).Conclusions: Stroke care at hospitals prior to PSC certification is equivalent to care at non-PSCs.Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT00059332.

The Use of tPA Alone for Fibrinolysis is based on a Misunderstanding that has Cost Many Lives

The Use of tPA Alone for Fibrinolysis is based on a Misunderstanding that has Cost Many Lives