Low dosis of alteplase, for ischemic stroke after Enchanted and its determinants, a single center experience / Dosis reducida de alteplase en el accidente cerebrovascular isquémico después del estudio Enchanted y sus determinantes, una experiencia de un solo centro

Abstract Background: Low-dose alteplase (LrtPA) has been shown not to be inferior to the standard-dose (SrtPA) with respect to death/disability. Objective: We aim to evaluate the percentage of patients treated with LrtPA at our center after the ENCHANTED trial and the factors associated with the use of this dosage. Methods: Prospective study in consecutive patients with an acute stroke admitted between June 2016 and November 2018. Results: 160 patients were treated with intravenous thrombolysis, 50% female; mean age 65.4±18.5 years. Of these, 48 patients (30%) received LrtPA. In univariate analysis, LrtPA was associated with patient's age (p=0.000), previous modified Rankin scale scores (mRS) (p<0.000), hypertension (p=0.076), diabetes mellitus (p=0.021), hypercholesterolemia (p=0.19), smoking (p=0.06), atrial fibrillation (p=0.10), history of coronary artery disease (p=0.06), previous treatment with antiplatelet agents (p<0.000), admission International Normalized Ratio-INR (p=0.18), platelet count (p=0.045), leukoaraiosis on neuroimaging (p<0.003), contraindications for thrombolytic treatment (p=0.000) and endovascular treatment (p=0.027). Previous relevant bleedings were determinants for treatment with LrtPA. Final diagnosis on discharge of stroke mimic was significant (p=0.02) for treatment with SrtPA. In multivariate analysis, mRS (OR: 2.21; 95%CI 1.37‒14.19), previous antiplatelet therapy (OR: 11.41; 95%CI 3.98‒32.70), contraindications for thrombolysis (OR: 56.10; 95%CI 8.81‒357.80), leukoaraiosis (OR: 4.41; 95%CI 1.37‒14.10) and diagnosis of SM (OR: 0.22; 95%CI 0.10‒0.40) remained independently associated. Conclusions: Following the ENCHANTED trial, LrtPA was restricted to 30% of our patients. The criteria that clinicians apply are based mostly on clinical variables that may increase the risk of brain or systemic hemorrhage or exclude the patient from treatment with lytic drugs.

RESUMEN Introducción: Dosis reducidas de trombolitico (LrtPA) podrían no ser inferiores en muerte/discapacidad. Objetivo: Evaluar el porcentaje de pacientes tratados con LrtPA en nuestro centro después del ensayo ENCHANTED, y los factores asociados con el uso de esta dosis. Métodos: Estudio prospectivo de pacientes consecutivos con infarto cerebral ingresados ​entre junio de 2016 y noviembre de 2018. Resultados: 160 pacientes fueron tratados con trombólisis intravenosa, 50% mujeres; edad media 65,4±18,5 años. 48 casos (30%) recibieron LrtPA. En el análisis univariado, LrtPA se asoció con la edad del paciente (p=0,000), escala de Rankin modificadas (mRS) (p<0,000), hipertensión arterial (p=0,076), diabetes mellitus (p=0,021), hipercolesterolemia (p=0,19), tabaquismo (p=0,06), fibrilación auricular (p=0,10), antecedentes de enfermedad coronaria (p=0,06), tratamiento previo con antiplaquetarios (p<0,000), International Normalized Ratio-INR (p=0,18), recuento de plaquetario (p=0,045), leucoaraiosis en neuroimagen (p<0,003), contraindicaciones para el tratamiento trombolítico (p=0,000) y tratamiento endovascular (p=0,027). Las hemorragias previas relevantes fueron determinantes para el tratamiento con LrtPA. El diagnóstico al alta de imitador de accidente cerebrovascular fue significativo (p=0,02) para el tratamiento con dosis estándar. El análisis multivariado demostró que mRS (OR: 2,21; IC95% 1,37‒14,19), tratamiento antiplaquetario previo (OR: 11,41; IC95% 3,98‒32,7), contraindicaciones para trombólisis (OR: 56,1; IC95% 8,81‒357,8), leucoaraiosis (OR: 4,41; IC95% 1,37‒14,1) y un diagnóstico de imitador de accidente cerebrovascular (OR: 0,22; IC95% 0,1‒0,40) fueron asociados con la dosis recibida. Conclusiones: LrtPA está restringido al 30% de nuestros pacientes. Los criterios para tomar esta decisión se basan en variables que podrían aumentar el riesgo de hemorragia cerebral/sistémica o excluir al paciente del tratamiento con fármacos líticos.

Thrombolysis in acute pulmonary embolism

SUMMARY OBJECTIVES Acute pulmonary embolism (APE) is an important cause of cardiovascular mortality, due mainly to hemodynamic instability. In these cases, the recommendation is to perform some reperfusion procedure, with systemic thrombolysis being the main therapy used. However, national data evaluating the efficacy and safety of thrombolysis are scarce. METHODS Retrospective analysis of a case series. We included 13 patients diagnosed with high-risk APE and 4 patients with intermediate-high risk from a single-center, who were treated with alteplase 100mg. RESULTS The mean age of the patients was 55 years, most of them female (76.4%). Among the risk factors for VTE were immobilization (41.17%), contraceptive use (35.29%), cancer (17.63%), and previous history of DVT (11.76%). The most frequent clinical manifestations of APE were dyspnea (88.23%), hypoxia (82.35%), hypotension (82.35%), and tachycardia (64.70%). 82.35% of the patients had echocardiographic signs of right ventricular dysfunction, and 52.94% had increased troponin and BNP. Severe bleeding associated with thrombolysis occurred in 17.54% of cases. No patient died due to bleeding. There were 8 deaths from right ventricular failure (47%), 6 in the cases of patients presenting as high-risk APE (35.3%), and 2 in the cases of intermediate-high risk (11.8%). CONCLUSION Thrombolysis in patients with high-risk APE or intermediate-high risk had a severe bleeding rate of 17.6%. However, the high mortality of this population (47%) due to right ventricular failure justifies the use of this therapeutic modality.

RESUMO OBJETIVOS A embolia pulmonar aguda (EAP) é uma causa importante de mortalidade cardiovascular ao causar instabilidade hemodinâmica. Nesses casos, a recomendação é a realização de algum procedimento de reperfusão, sendo a trombólise sistêmica a principal terapia utilizada. No entanto, dados nacionais avaliando a eficácia e a segurança da trombólise são escassos. MÉTODO Análise retrospectiva de uma série de casos. Foram incluídos 13 pacientes com o diagnóstico de EAP de alto risco e quatro pacientes de risco intermediário-alto, de um único centro, e que foram tratados com alteplase 100 mg. RESULTADOS A média de idade dos pacientes foi 55 anos, sendo a maioria do gênero feminino (76,4%). Dos fatores de risco para TEV, estavam presentes a imobilização (41,17%), o uso de anticonceptivos (35,29%), câncer (17,63%) e história prévia de TVP (11,76%). As manifestações clínicas mais frequentes da EAP foram dispneia (88,23%), hipóxia (82,35%), hipotensão (82,35%) e taquicardia (64,70%); 82,35% dos pacientes apresentaram sinais ecocardiográficos de disfunção ventricular direita e 52,94% apresentaram aumento da troponina e BNP. Sangramento grave associado à trombólise ocorreu em 17,54% dos casos. Nenhum paciente faleceu em decorrência de sangramento. Houve oito mortes por insuficiência ventricular direita (47%): seis nos casos de paciente que se apresentaram como EAP de alto risco (35,3%) e duas nos casos de risco intermediário-alto (11,8%). CONCLUSÃO A trombólise nos pacientes com EAP de alto risco ou risco intermediário-alto apresentou uma taxa de sangramento grave de 17,6%. No entanto, a alta mortalidade dessa população (47%) por insuficiência ventricular direita justifica o uso desta modalidade terapêutica.

Validação de um escore para predição de eventos hemorrágicos em síndromes coronarianas agudas / Validation of a score for predicting bleeding events during acute coronary syndromes / Validación de un escore para predicción de eventos hemorrágicos en síndromes coronarios agudos

FUNDAMENTO: Sangramento é uma complicação grave em pacientes tratados para síndromes coronarianas agudas (SCA) com antitrombóticos e terapias invasivas. Consequentemente, o benefício dessas terapias deve ser analisado contra os potenciais riscos de complicações hemorrágicas. Desta forma, a determinação de um escore para estimar o risco individual de sangramento pode representar uma importante ferramenta na tomada de decisões clínicas. OBJETIVO: Criar e validar um escore de risco de sangramento para pacientes com SCA. MÉTODOS: Foram utilizados preditores independentes de sangramento relatados pelo Registro GRACE. Variáveis com odds ratio (OR) > 2,5 nesse Registro somaram 3 pontos (histórico anterior de sangramento), OR=1,5-2,4 somaram 2 pontos (clearance de creatinina< 30 ml/min, sexo feminino) e aquelas com OR < 1,5 somaram 1 ponto (clearance entre 30 e 60 ml/min, a cada 10 anos de idade > 30, infra ou supra-desnivelamento do segmento ST, doença arterial periférica e fumo). O escore foi validado em uma coorte de 383 indivíduos com SCA. Sangramento hospitalar foi definido como queda de hematócrito > 10 por cento, transfusão de sangue > 2 unidades, sangramento intracerebral ou sangramento fatal. RESULTADOS: A incidência de eventos hemorrágicos foi de 3,1 por cento e a estatística-C do escore foi 0,66 (IC95 por cento = 0,52-0,80), indicando capacidade preditiva para esses eventos. Aqueles com escore > 7 apresentaram 6 por cento de incidência de sangramento, comparados com 1,9 por cento se o escore era < 7 (RR=3,2; IC95 por cento=1,04-9,9; p=0,03). Houve uma interação entre um escore > 7 e um maior risco imposto pelo tratamento com Clopidogrel (p=0,02), bloqueadores IIb/IIIa (p=0,06) e revascularização cirúrgica (p < 0,001). CONCLUSÃO: O escore discrimina o risco de sangramento e é potencialmente útil na tomada de decisão clínica em SCA.

BACKGROUND: Bleeding is a major complication in patients treated for acute coronary syndromes (ACS) with antithrombotic and invasive therapies. Consequently, the benefit of such therapies should be balanced against the potential risk of hemorrhagic complications. Therefore, a score to estimate individual risk of bleeding might represent an important tool in clinical decision-making. OBJECTIVE: This study aims to create and validate a bleeding risk score for patients with ACS. METHODS: Independent predictors of bleeding reported by the GRACE Registry were utilized. Variables with odds ratio (OR) > 2.5 in that Registry added 3 points (previous history of bleeding), OR = 1.5-2.4 added 2 points (creatinine clearance < 30 ml/min, female gender) and those with OR < 1.5 added 1 point (clearance between 30 and 60 ml/min, each 10 years of age>30, ST-deviation, peripheral artery disease and smoking). The score was validated in a cohort of 383 individuals with ACS. In-hospital bleeding was defined as hematocrit fall > 10 percent, blood transfusion > 2 units, intracerebral bleeding or fatal bleeding. RESULTS: The incidence of bleeding events was 3.1 percent and the score's C-statistics was 0.66 (95 percent CI = 0.52-0.80), indicating a predictive ability towards these events. Those with a score > 7 had 6 percent incidence of bleeding, compared with 1.9 percent if the score was < 7 (RR = 3.2; 95 percentCI = 1.04-9.9; p = 0.03). There was an interaction between a score > 7 and greater risk imposed by treatment with Clopidogrel (p = 0.02), IIb/IIIa blockers (p = 0.06) and surgical revascularization (p < 0.001). CONCLUSION: The score discriminates bleeding risk and is potentially useful in clinical decision-making during ACS.

FUNDAMENTO: Sangrado es una complicación grave en pacientes tratados por síndromes coronarios agudos (SCA) con antitrombóticos y terapias invasivas. Consecuentemente, el beneficio de esas terapias debe ser analizado contra los potenciales riesgos de complicaciones hemorrágicas. De esta forma, la determinación de un escore para estimar el riesgo individual de sangrado puede representar una importante herramienta en la toma de decisiones clínicas. OBJETIVO: Crear y validar un escore de riesgo de sangrado para pacientes con SCA. MÉTODOS: Fueron utilizados predictores independientes de sangrado relatados por el Registro GRACE. Variables con odds ratio (OR) > 2,5 en ese Registro sumaron 3 puntos (histórico anterior de sangrado), OR=1,5-2,4 sumaron 2 puntos (clearance de creatinina < 30 ml/min, sexo femenino) y aquellas con OR < 1,5 sumaron 1 punto (clearance = 30-60 ml/min, a cada 10 años de edad > 30, infra o supra-desnivel del segmento ST, enfermedad arterial periférica y tabaco). El escore fue validado en una cohorte de 383 individuos con SCA. Sangrado intrahospitalario fue definido como caída de hematocrito > 10 por ciento, transfusión de sangre > 2 unidades, sangrado intracerebral o sangrado fatal. RESULTADOS: La incidencia de eventos hemorrágicos fue de 3,1 por ciento y la estadística-C del escore fue 0,66 (IC95 por ciento = 0,52-0,80), indicando capacidad predictiva para esos eventos. Aquellos con escore > 7 presentaron 6 por ciento de incidencia de sangrado, comparados con 1,9 por ciento si el escore era < 7 (RR=3,2; IC95 por ciento=1,04-9,9; P=0,03). Hubo una interacción entre un escore > 7 y un mayor riesgo impuesto por el tratamiento con Clopidogrel (P=0,02), bloqueadores IIb/IIIa (P=0,06) y revascularización quirúrgica (P<0,001). CONCLUSIÓN: El escore discrimina el riesgo de sangrado y es potencialmente útil en la toma de decisión clínica en SCA.

Utilidad de la terapia trombolítica con estreptokinasa a dosis baja en infarto agudo del miocardio / Usefulness of thrombolytic therapy with low doses of streptokinase in acute myocardial infarction

Background: The optimal dose of Streptokinase in the treatment of acute myocardial infarction is not well established. Apparently, the thrombolytic efficacy would not increase with doses over 750.000 units. Aim: To compare the effectiveness and safety of treatment with low doses of Streptokinase, ranging from 500.000 to 750.000 units, in patients with ST elevation acute myocardial infarction. Patients and methods: From September 1993 to September 1998, the GEMI register of patients with acute myocardial infarction, was carried out in 37 hospitals, incorporating 4,938 patients. Of these, 1,631 patients received streptokinase. According to the administered dose of Streptokinase, patients were divided in two groups: 1,465 patients who received 1.5 millions U in 60 minutes (classical therapy group), and 166 patients with ischemic chest discomfort and either ST-segment elevation or left bundle-branch block on the electrocardiogram, who received 500.000 to 750.000 U streptokinase administered in no more than 30 minutes, with heparin, within 0 to 6 hours of symptom onset. Successful reperfusion, mortality, complications, and hospital outcome was evaluated in both groups. Results: The low dose group of patients had a better reperfusion criteria profile. No differences between groups were observed in patient evolution, mortality, maximum Killip classification, post myocardial infarction heart failure, ischemic complications, arrhythmias or mechanical complications. Conclusions: These results suggest that streptokinase in low doses is at least as effective as classical therapy, in the treatment of ST elevation acute myocardial infarction.