Real-world setting comparison of bridging therapy versus direct mechanical thrombectomy for acute ischemic stroke: A meta-analysis.

BACKGROUND AND PURPOSE: Intravenous Thrombolysis (IVT) prior to Mechanical Thrombectomy (MT) for Acute Ischaemic Stroke (AIS) due to Large-Vessel Occlusion (LVO) remains controversial. Therefore, the authors performed a meta-analysis of the available real-world evidence focusing on the efficacy and safety of Bridging Therapy (BT) compared with direct MT in patients with AIS due to LVO. METHODS: Four databases were searched until 01 February 2023. Retrospective and prospective studies from nationwide or health organization registry databases that compared the clinical outcomes of BT and direct MT were included. Odds Ratios (ORs) and 95 % Confidence Intervals (CIs) for efficacy and safety outcomes were pooled using a random-effects model. RESULTS: Of the 12 studies, 86,695 patients were included. In patients with AIS due to LVO, BT group was associated with higher odds of achieving excellent functional outcome (modified Rankin Scale score 0-1) at 90 days (OR = 1.48, 95 % CI 1.25-1.75), favorable discharge disposition (to the home with or without services) (OR = 1.33, 95 % CI 1.29-1.38), and decreased mortality at 90 days (OR = 0.62, 95 % CI 0.56-0.70), as compared with the direct MT group. In addition, the risk of symptomatic intracranial hemorrhage did not increase significantly in the BT group. CONCLUSION: The present meta-analysis indicates that BT was associated with favorable outcomes in patients with AIS due to LVO. These findings support the current practice in a real-world setting and strengthen their validity. For patients eligible for both IVT and MT, BT remains the standard treatment until more data are available.

Real-world setting comparison of bridging therapy versus direct mechanical thrombectomy for acute ischemic stroke: A meta-analysis

Abstract Background and purpose Intravenous Thrombolysis (IVT) prior to Mechanical Thrombectomy (MT) for Acute Ischaemic Stroke (AIS) due to Large-Vessel Occlusion (LVO) remains controversial. Therefore, the authors performed a meta-analysis of the available real-world evidence focusing on the efficacy and safety of Bridging Therapy (BT) compared with direct MT in patients with AIS due to LVO. Methods Four databases were searched until 01 February 2023. Retrospective and prospective studies from nationwide or health organization registry databases that compared the clinical outcomes of BT and direct MT were included. Odds Ratios (ORs) and 95 % Confidence Intervals (CIs) for efficacy and safety outcomes were pooled using a random-effects model. Results Of the 12 studies, 86,695 patients were included. In patients with AIS due to LVO, BT group was associated with higher odds of achieving excellent functional outcome (modified Rankin Scale score 0-1) at 90 days (OR = 1.48, 95 % CI 1.25-1.75), favorable discharge disposition (to the home with or without services) (OR = 1.33, 95 % CI 1.29-1.38), and decreased mortality at 90 days (OR = 0.62, 95 % CI 0.56-0.70), as compared with the direct MT group. In addition, the risk of symptomatic intracranial hemorrhage did not increase significantly in the BT group. Conclusion The present meta-analysis indicates that BT was associated with favorable outcomes in patients with AIS due to LVO. These findings support the current practice in a real-world setting and strengthen their validity. For patients eligible for both IVT and MT, BT remains the standard treatment until more data are available.

[Neurological perspective in the choice of direct oral anticoagulants for prevention of stroke in atrial fibrillation]. / Perspectiva neurológica en la elección del anticoagulante oral directo para la prevención del accidente cerebrovascular en fibrilación auricular.

Non-valvular atrial fibrillation (AF) is the most prevalent arrhythmia with high embolic potential, and one of the main and growing causes of stroke. The main objective of anticoagulation in patients with AF is prevention of stroke. Until recently, anticoagulation with vitamin K antagonists (VKAs) was the only available option. Direct oral anticoagulants (DOACs), such as the direct thrombin inhibitor dabigatran, or the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have a more favorable effectiveness/safety profile compared to VKAs. There are no studies comparing the efficacy of DOACs with each other. The choice of a DOAC arose from patient carachterictis, physician preferences, cost, and accessibility. Between 1-2% of patients correctly treated with a DOAC experience a stroke each year. The possibility of having a reversal agent should be taken into account when choosing a DOAC, especially due to the residual risk of stroke occurrences even under DOACs. Currently, in our country only dabigatran has a reversing agent available, making it the only DOAC that does not contraindicate the use of intravenous thrombolysis. This should be taken into account when choosing the DOAC for the prevention of thromboembolic events in patients with AF.

La fibrilación auricular no valvular (FA) es la arritmia con potencial embolígeno más prevalente y una de las principales y crecientes causas de accidente cerebrovascular isquémico (ACVi). El principal objetivo del uso de la anticoagulación en pacientes con FA es la prevención del ACVi. Hasta hace poco tiempo, la anticoagulación con antagonistas de la vitamina K (AVKs) era la única opción disponible. Los anticoagulantes orales directos (DOACs) como el inhibidor directo de la trombina, dabigatrán, o los inhibidores directos del factor Xa, rivaroxabán, apixabán y edoxabán, tienen un perfil de efectividad/seguridad más favorable en comparación con los AVKs. No existen estudios que comparen la efectividad de los DOACs entre sí. La elección del DOAC depende de múltiples factores específicos del paciente, preferencias del médico, costos y accesibilidad. Entre 1-2% de los pacientes correctamente tratados con un DOAC intercurre con un ACVi cada año. La posibilidad de contar con un agente reversor debería ser tenida en cuenta al momento de la elección del DOAC, especialmente por el riesgo residual de ocurrencia de ACVi. En la actualidad, en nuestro país solo el dabigatrán cuenta con un agente reversor disponible y lo convierte en el único DOAC que no contraindica el uso de trombolisis intravenosa con rtPA. Esta situación debería ser considerada en el momento de la elección del DOAC para la prevención de eventos tromboembólicos en pacientes con FA.

Eficacia de tenecteplase comparada con alteplase para tratamiento de ictus isquémico agudo. Una revisión narrativa

Introducción: La trombólisis intravenosa con Alteplase (ALT) se recomienda como tratamiento estándar siendo el único agente trombolítico aprobado por la FDA, en infarto cerebral. La Tenecteplase (TNK), un activador tisular del plasminógeno modificado, surge como agente antitrombótico alternativo. Esta revisión narrativa evalúa la evidencia actual y aborda los problemas prácticos sobre la eficacia y seguridad de tenecteplase en comparación con alteplase. Metodología: Se realizó una búsqueda sistemática y analítica de la literatura, y se proporcionó una síntesis cualitativa de metaanálisis y ensayos clínicos concluidos, que compararon la efectividad y seguridad de la tenecteplase con alteplase en el AIS, utilizando artículos indexados en MEDLINE, Cochrane Library y Scopus. Resultados: Los ensayos clínicos aleatorizados en su mayoría coinciden al encontrar que TNK es al menos tan o más efectiva que la ALT para mejoría neurológica después del AIS; mientras los metaanálisis coinciden en que los pacientes que recibieron TNK presentaron una mayor recanalización exitosa, pero difieren en cuanto a los hallazgos de mejoría neurológica temprana, resultado funcional a los 90 días y mortalidad a los 90 días. Conclusión: La tenecteplase es al menos tan eficaz como la Alteplase con respecto a la mejoría neurológica después del tratamiento del accidente cerebrovascular isquémico agudo.

Introduction: Intravenous thrombolysis with alteplase (ALT) is recommended as standard treatment, being the only thrombolytic agent approved by the FDA. Tenecteplase (TNK), a modified tissue plasminogen activator, is emerging as an alternative antithrombotic agent. This narrative review assesses the current evidence and addresses practical issues regarding the efficacy and safety of tenecteplase compared to alteplase. Methodology: A systematic and analytical search of the literature was performed, providing a qualitative synthesis of meta-analyses and completed clinical trials comparing the effectiveness and safety of tenecteplase with alteplase in AIS, using articles indexed in MEDLINE, the Cochrane Library, and Scopus. Results: Randomized clinical trials mostly agree in finding TNK to be at least as or more effective than ALT for neurological improvement after AIS; while the meta-analyses agree that patients who received TNK had more successful recanalization, they differ in terms of the findings of early neurological improvement, functional outcome at 90 days, and mortality at 90 days. Conclusion: Tenecteplase is at least as effective as alteplase with regard to neurological improvement after treatment of acute ischemic stroke.

Nuevos paradigmas: 12 años de trombólisis sistémica. Unidad ACV, Hospital de Clínicas / New paradigms: 12 years of systemic thrombolysis. Stroke Unit, Clinicas Hospital / Novos paradigmas: 12 anos de trombólise sistêmica. Unidade AVC, Hospital de Clínicas

Introducción: el ACV constituye un problema de salud y la trombólisis sistémica una estrategia de reperfusión con alto nivel de evidencia para su tratamiento. Los reportes nacionales sobre su utilización son escasos. Objetivos: comunicar y analizar los resultados de esta terapia en el Hospital de Clínicas. Establecer predictores de buena evolución, hemorragia intracraneana y mortalidad. Métodos: estudio observacional analítico de los pacientes trombolizados en el Hospital de Clínicas (2010-2021). Resultados: se realizó trombólisis sistémica a 268 pacientes. La mediana del NIHSS al ingreso fue 12 puntos. Un 42% fueron infartos totales de la circulación anterior. La cardioembolia constituyó la etiopatogenia más frecuente. El 59,3% de los pacientes fueron externalizados con independencia funcional y 55,2% con déficit neurológico mínimo. Las tasas de hemorragia intracraneana sintomática y mortalidad fueron 7,1% y 18,7% respectivamente. El 57% de los pacientes se trataron con tiempo puerta aguja ≤60 minutos. El porcentaje de trombólisis en el total de ACV fue 18,9%. La edad, NIHSS al ingreso e internación en unidad de ACV se comportaron como variables importantes para predecir buena evolución, hemorragia intracraneana y muerte. Discusión y conclusiones: se comunicó la mayor casuística nacional sobre el tema. Los parámetros de efectividad y seguridad del tratamiento fueron comparables a los reportados internacionalmente. Se destacaron los buenos tiempos puerta aguja y tasa trombólisis sobre ACV totales como indicadores satisfactorios de calidad asistencial. La internación en unidad de ACV se comportó como un factor predictor de independencia funcional y protector frente a mortalidad hospitalaria.

Introduction: Strokes are a health problem and systemic thrombolysis constitutes a reperfusion strategy backed up by significant evidence on its positive therapeutic impact. National reports on its use are scarce. Objectives: To report and analyze results obtained with this therapeutic approach at the Clinicas Hospital. To establish predictive factors for a good evolution, intracranial hemorrhage and mortality. Method: Observational, analytical study of thrombolysed patients at Clinicas Hospital (2010-2021). Results: Systemic thrombolysis was performed in 268 patients. Average NIHSS score was 12 points when admitted to hospital.42 % of cases were total anterior circulation infarct (TACI). Cardioembolic ischaemmic stroke was the most frequent etiopahogenesis. 59.3% of patients were discharged with functional independence and 55.2% had minimal neurologic deficit. Symptomatic intracranial hemorrhage and mortality rates were 7.1% and 18.7% respectively. 57% of patients were assisted within ≤60 minutes they showed up at the ER. Thrombolysis percentage in total number of strokes was 18.9%. Age, NIHSS score upon arrival to hospital and admission to the stroke unit were significant variables to predict a good evolution, intracranial hemorrhage and death. Discussion and conclusions: The large number of cases in the country was reported. Effectiveness and safety parameters for this treatment were comparable to those reported internationally. The good door-to-needle time and thrombolysis rate versus total number of strokes stood out as satisfactory indicators of healthcare quality. Admission to the stroke unit behaved as a predictive factor of functional independence and it protected patients from hospital mortality.

Introdução: o AVC é um problema de saúde sendo a trombólise sistêmica uma estratégia de reperfusão com alto nível de evidência para seu tratamento. Os dados nacionais sobre seu uso são escassos. Objetivos: comunicar e analisar os resultados desta terapia no Hospital de Clínicas. Estabelecer preditores de boa evolução, hemorragia intracraniana e mortalidade. Métodos: estudo observacional analítico de pacientes trombolisados no Hospital de Clínicas (2010-2021). Resultados: a trombólise sistêmica foi realizada em 268 pacientes. A mediana do índice NIHSS na admissão foi de 12 pontos. 42% eram infartos totais da circulação anterior. A cardioembolia foi a etiopatogenia mais frequente. 59,3% dos pacientes tiveram alta da unidade com independência funcional e 55,2% com déficit neurológico mínimo. As taxas de hemorragia intracraniana sintomática e mortalidade foram de 7,1% e 18,7%, respectivamente. 57% dos pacientes foram tratados com tempo porta-agulha ≤60 minutos. A porcentagem de trombólise no AVC total foi de 18,9%. Idade, NIHSS na admissão e internação na unidade de AVC se comportaram como variáveis importantes para prever boa evolução, hemorragia intracraniana e óbito. Discussão e conclusões: este trabajo inclui a maior casuística nacional sobre o tema. Os parâmetros de eficácia e segurança do tratamento foram comparáveis aos descritos na bibliografia internacional. Foram destacados como indicadores satisfatórios da qualidade do atendimento os bons tempos porta-agulha e taxa de trombólise em relação ao AVC total. A internação em unidade de AVC comportou-se como preditor de independência funcional e protetor contra a mortalidade hospitalar.

Temporal Trends of Intravenous Thrombolysis Utilization in Acute Ischemic Stroke in a Prospective Cohort From 1998 to 2019: Modeling Based on Joinpoint Regression.

Introduction: The frequency of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) is lower than it should be in several regions of the world. It is unclear what interventions can produce significant improvements in IVT utilization. We aimed to investigate the temporal trends in IVT in AIS and identify changes in time that could be associated with specific interventions. Methods: We included patients with AIS who were admitted from January 1998 to December 2019 in our institution. To analyze trends in utilization and time points in which they changed, we performed a Joinpoint regression analysis. Interventions were assigned to a specific category according to the Behavior Change Wheel framework intervention function criteria. Results: A total of 3,361 patients with AIS were admitted, among which 538 (16%) received IVT. There were 245 (45.5%) women, and the mean age and median National Institutes of Health Stroke Scale (NIHSS) scores were 68.5 (17.2) years and 8 (interquartile range, 4-15), respectively. Thrombolysis use significantly increased by an average annual 7.6% (95% CI, 5.1-10.2), with one Joinpoint in 2007. The annual percent changes were.45% from 1998 to 2007 and 9.57% from 2007 to 2019, concurring with the stroke code organization, the definition of door-to-needle times as an institutional performance measure quality indicator, and the extension of the therapeutic window. Conclusions: The IVT rates consistently increased due to a continuous process of protocol changes and multiple interventions. The implementation of a complex multidisciplinary intervention such as the stroke code, as well as the definition of a hospital quality control metric, were associated with a significant change in this trend.

Eficacia y seguridad del tenecteplase en el tratamiento del ACV isquémico agudo / Safety and efficacy of tenecteplase in acute ischemia stroke a narrative review

RESUMEN El alteplase es el único fibrinolítico actualmente autorizado en Colombia para el tratamiento del ACV isquémico agudo. El tenecteplase constituye una nueva alternativa de tratamiento en esta enfermedad al ofrecer mejor perfil farmacológico, mayor eficacia con mejores desenlaces mayores, porcentajes de recanalización, y con seguridad similar a la del alteplase. La posibilidad de desabastecimiento temporal de alteplase con disponibilidad de tenecteplase en Colombia abre la posibilidad de su uso en ACV isquémico agudo.

SUMMARY Alteplase is the only one fibrinolytic currently authorized in Colombia for the treatment of acute ischemic stroke. Tenecteplase constitutes a new treatment alternative in this disease by offering a better pharmacological profile, greater efficacy with better outcomes: like higher recanalization percentages and with similar safety profile. The possibility of a temporary shortage of alteplase with availability of tenecteplase in Colombia opens the possibility of its use in acute ischemic stroke.

The safety and efficacy of tPA intravenous thrombolysis for treating acute ischemic stroke patients with a history of cerebral hemorrhage

Alteplase (tPA) intravenous thrombolysis is an effective treatment for acute ischemic stroke (AIS) when administered within 4.5 h of initial stroke symptoms. Here, its safety and efficacy were evaluated among AIS patients with a previous history of cerebral hemorrhage. Patients who arrived at the hospital within 4.5 h of initial stroke symptoms and who were treated with tPA intravenous thrombolysis or conventional therapies were analyzed. The 90-day modified Rankin scale (90-d mRS) was used alongside mortality and incidence of symptomatic intracerebral hemorrhage (SICH) rates to evaluate the curative effect of these therapies. Among 1,694 AIS patients, 805 patients were treated with intravenous thrombolysis, including patients with (n=793) or without (n=12) a history of cerebral hemorrhage, and the rate of incidence of SICH significantly differed between them (8.3 vs 4.3%, P=0.039). No significant difference was found in 90-d mRS measurements (41.7 vs 43.6%, P=0.530) and 90-d mortality rates (8.3 vs 6.5%, P=0.946). A total of 76 AIS patients with a history of cerebral hemorrhage received tPA thrombolytic therapy (n=12) or conventional therapy (n=64), and a significant difference was noted in the 90-d mRS scores between the two groups (41.7 vs 23.4%, P=0.029), while no significant difference was found in SICH measurements (8.3 vs 4.6%, P=0.610) and 90-d mortality rates (8.3 vs 9.4%, P=0.227). A history of cerebral hemorrhage is not an absolute contraindication for thrombolytic therapy; tPA intravenous thrombolysis does not increase SICH measurements and mortality rates in patients with a history of cerebral hemorrhage, and they may benefit from thrombolytic therapy.

Clinical Outcomes of Patients with Acute Basilar Artery Occlusion in Brazil: An Observational Study.

BACKGROUND: Intravenous thrombolysis (IVT) and endovascular therapy (EVT) were proven safe and effective for anterior circulation proximal occlusions. However, the most appropriate recanalization strategy in patients with acute basilar artery occlusion (BAO) is still controversial. This study aimed to assess outcomes of patients with BAO at an academic stroke center in Brazil. METHODS: This is a retrospective analysis of consecutive patients with BAO from a prospective stroke registry at Ribeirão Preto Medical School. Primary outcomes were mortality and favorable outcome (modified Rankin score [mRS] ≤3) at 90 days. After univariate analyses, multivariate logistic regressions were used to identify independent predictors of primary outcomes. RESULTS: Between August 2004 and December 2015, 63 (65% male) patients with BAO and median National Institutes of Health Stroke Scale (NIHSS) score of 31 (interquartile range: 19-36) were identified. Twenty-nine (46%) patients received no acute recanalization therapy, 15 (24%) received IVT, and 19 (30%) received EVT (68% treated with stent retrievers). Twenty-four (83%) patients treated conservatively died, and only 2 (7%) achieved an mRS less than or equal to 3. Among patients treated with acute recanalization therapies, 15 (44%) died, and 9 (26.5%) had a favorable outcome. On multivariate analysis, baseline systolic blood pressure (odds ratio [OR] = .97; 95% confidence interval [CI]: .95-0.99; P = .023), posterior circulation Alberta Stroke Program Early CT score (OR = .62; 95% CI: .41-0.94; P = .026), and successful recanalization (OR = .18; 95% CI: .04-0.71; P = .015) were independent predictors of lower mortality. Baseline NIHSS (OR = 1.40; 95% CI: 1.08-1.82; P = .012), prior use of statins (OR = .003; 95% CI: .001-0.28; P = .012), and successful recanalization (OR = .05; 95% CI: .001-0.27; P = .009) were independent predictors of favorable outcome. There was no significant difference between the IVT group and the EVT group on primary outcomes. CONCLUSIONS: BAO is associated with high morbidity and mortality in Brazil. Access to acute recanalization therapies may decrease mortality in those patients.

International Survey on the Management of Wake-Up Stroke.

BACKGROUND: Patients who wake up having experienced a stroke while asleep represent around 20% of acute stroke admissions. According to international guidelines for the management of acute stroke, patients presenting with wake-up stroke are not currently eligible to receive revascularization treatments. In this study, we aimed to assess the opinions of stroke experts about the management of patients with wake-up stroke by using an international multicenter electronic survey. METHOD: This study consisted of 8 questions on wake-up stroke treatment. RESULTS: Two hundred invitations to participate in the survey were sent by e-mail. Fifty-nine participants started the survey, 4 dropped out before completing it, and 55 completed the full questionnaire. We had 55 participants from 22 countries. CONCLUSIONS: In this study, most stroke experts recommended a recanalization treatment for wake-up stroke. However, there was considerable disagreement among experts regarding the best brain imaging method and the best recanalization treatment. The results of ongoing randomized trials on wake-up stroke are urgently needed.