Publication: Evaluación a largo plazo de la torasemida y de la furosemida en el tratamiento de la insuficiencia cardíaca congestiva secundaria a enfermedad mitral degenerativa crónica en perros
Authors
Miralles Plaza, Iván
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Escuela Internacional de Doctorado
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Fernández del Palacio, María Josefa
Publisher
Universidad de Murcia
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DOI
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info:eu-repo/semantics/doctoralThesis
Description
Abstract
La enfermedad mitral degenerativa crónica (EMDC) es la principal causa de insuficiencia cardíaca congestiva (ICC) en perros. Los diuréticos de asa, tales como la furosemida y la torasemida, son pilares fundamentales del tratamiento de estos pacientes en estadio C según las recomendaciones del Consenso ACVIM (2019). Los estudios sobre la torasemida, recientemente aprobada para su administración en perros, han demostrado su seguridad y eficacia a corto plazo. Sin embargo, en conocimiento de los investigadores, estos aspectos no han sido evaluados a largo plazo en perros.
Hipótesis: La torasemida no es inferior a la furosemida en el control de los signos clínicos a largo plazo cuando se emplea como diurético de primera elección en este contexto.
Objetivos: El objetivo primario fue determinar la seguridad y eficacia de la torasemida en perros con ICC crónica secundaria a EMDC a largo plazo, en relación con la furosemida. Secundariamente, se evaluaron los efectos de ambos diuréticos sobre los parámetros clínicos, ecocardiográficos y biomarcadores cardíacos circulantes relacionados con daño miocárdico, activación neurohormonal, remodelado y fibrosis miocárdica, inflamación y estrés oxidativo en perros con EMDC en estadio C.
Materiales y métodos: Se incluyeron prospectivamente 20 perros diagnosticados de EMDC en estadio C estables y 11 perros sanos de edades y pesos similares como grupo control. Los perros con EMDC se distribuyeron aleatoriamente en dos grupos de tratamiento diurético (Grupo TOR, torasemida 0.18 mg/kg/día; Grupo FUR, furosemida 3.57 mg/kg/día); los cuales recibieron también benazepril, espironolactona y pimobendan. Tras la obtención de la historia clínica, a todos se les realizaron: examen físico, análisis laboratoriales (incluyendo biomarcadores cardíacos), presión arterial, ECG, radiografías torácicas y ecocardiografía en el momento de la inclusión en el estudio. Los seguimientos se realizaron a los 10, 30, 90, 180, 270 y 360 días de la inclusión.
Resultados: Un total de 13/20 perros completaron el estudio (6 Grupo FUR, 7 Grupo TOR). La poliuria en el Grupo TOR fue el efecto adverso más frecuente atribuible al fármaco, que se corrigió reduciendo la dosis. Las recaídas fueron más frecuentes en el Grupo FUR (6 perros, 9 recaídas) que en el Grupo TOR (3 perros, 3 recaídas). El tiempo medio de supervivencia fue de 230 días para el Grupo TOR y 138 días para el Grupo FUR, aunque sin significancia estadística (p = 0.1). El ratio AI:Ao y el volumen diastólico del ventrículo izquierdo disminuyeron en ambos grupos al Día 30, manteniéndose inferiores en el Grupo TOR que en el Grupo FUR, aunque sin diferencia estadísticamente significativa entre grupos. Las velocidades de la onda E del flujo transmitral se redujeron en el Grupo TOR significativamente a partir del Día 90, al contrario que en el Grupo FUR, que se mantuvieron más elevadas a lo largo del estudio. La onda E’ se redujo significativamente el Día 30 en el Grupo TOR (p = 0.006), siendo significativamente más baja en el Día 360 que en el Grupo FUR (p = 0.046). La HP estuvo presente en el 30% de los perros agravándose en el Grupo FUR hacia el Día 180, mientras que en el Grupo TOR se mantuvo estable en todas las visitas. La cTnI, la CRP y el WBC se redujeron en ambos grupos al Día 30, aunque solo hubo diferencia estadísticamente significativa para la CRP del Grupo FUR (p = 0.019). En el Grupo TOR, el WBC fue significativamente inferior al Día 360 respecto al Día 0 (p = 0.03). El PICP y ratio PICP/PIIINP fueron estadísticamente inferiores al Día 270 en el grupo TOR (p = 0.04), permaneciendo inferiores en todas las visitas del estudio respecto al grupo FUR.
Conclusión: Este estudio muestra que la administración de torasemida a dosis mínima efectiva es segura y eficaz como diurético de primera elección en perros con EMDC en estadio C a largo plazo en base a una disminución del número de recaídas en el Grupo TOR, así como a un mayor tiempo de supervivencia
Chronic degenerative mitral valve disease (CDMVD) is the most common cause of congestive heart failure (CHF) in dogs. Loop diuretics such as furosemide and torasemide are the cornerstones in the treatment of these patients in stage C, according to the ACVIM Consensus (2019) guidelines. Studies on torasemide, recently approved for use in dogs, have demonstrated its safety and efficacy in the short term. However, to the best of our knowledge, these aspects have not been evaluated in the long term in dogs. Hypothesis: Torasemide is not inferior to furosemide in the long-term control of clinical signs when used as a first-line diuretic in this context. Objectives: The primary objective was to determine the long-term safety and efficacy of torasemide in dogs with chronic CHF secondary to CDMVD, in comparison to furosemide. Secondarily, the study aimed to evaluate the effects of both diuretics on clinical parameters, echocardiographic findings, and circulating cardiac biomarkers related to myocardial injury, neurohormonal activation, myocardial remodeling and fibrosis, inflammation, and oxidative stress in dogs with CDMVD in stage C. Materials and Methods: A total of 20 dogs diagnosed with stable stage C CDMVD and 11 healthy dogs of similar age and weight were prospectively included as a control group. Dogs with CDMVD were randomly assigned in two diuretic treatment groups (Group TOR, torasemide 0.18 mg/kg/day; Group FUR, furosemide 3.57 mg/kg/day); both groups also received benazepril, spironolactone, and pimobendan. Following the clinical history, all dogs underwent physical examination, laboratory analysis (including cardiac biomarkers), blood pressure measurement, ECG, thoracic radiographs, and echocardiography at the time of study inclusion. Follow-up visits occurred at Days 10, 30, 90, 180, 270, and 360 after inclusion. Results: A total of 13/20 dogs completed the study (6 in Group FUR, 7 in Group TOR). Polyuria in Group TOR was the most frequent adverse effect attributed to the drug, which resolved after dose reduction. Relapses were more frequent in Group FUR (6 dogs, 9 relapses) than in Group TOR (3 dogs, 3 relapses). The mean survival time was 230 days for Group TOR and 138 days for Group FUR, although without statistical significance (p = 0.1). The AI:Ao ratio and left ventricular diastolic volume decreased in both groups by Day 30, remaining lower in Group TOR than in Group FUR, without statistically significant differences between groups. The peak velocities of the E wave of the transmitral flow were significantly reduced in Group TOR from Day 90 onwards, in contrast to Group FUR, where they remained higher throughout the study. The E' wave diminished significantly on Day 30 in Group TOR (p = 0.006), being significantly lower on Day 360 compared to Group FUR (p = 0.046). Pulmonary hypertension (PH) was present in 30% of the dogs, worsening in Group FUR by Day 180, while in Group TOR PH remained stable and lower at all visits. Biomarkers cTnI, CRP and WBC were reduced in both groups by Day 30, with a statistically significant difference only for CRP in Group FUR (p = 0.019). In Group TOR, WBC diminished significantly on Day 360 compared to Day 0 (p = 0.03). PICP and the PICP/PIIINP ratio were statistically lower at Day 270 in Group TOR (p = 0.04), remaining lower at all study visits compared to Group FUR. Conclusion: This study shows that the administration of torasemide at the minimum effective dose is safe and effective as a first-line diuretic in dogs with stage C CDMVD over the long term, based on a reduction in the number of relapses in Group TOR as well as a longer survival time.
Chronic degenerative mitral valve disease (CDMVD) is the most common cause of congestive heart failure (CHF) in dogs. Loop diuretics such as furosemide and torasemide are the cornerstones in the treatment of these patients in stage C, according to the ACVIM Consensus (2019) guidelines. Studies on torasemide, recently approved for use in dogs, have demonstrated its safety and efficacy in the short term. However, to the best of our knowledge, these aspects have not been evaluated in the long term in dogs. Hypothesis: Torasemide is not inferior to furosemide in the long-term control of clinical signs when used as a first-line diuretic in this context. Objectives: The primary objective was to determine the long-term safety and efficacy of torasemide in dogs with chronic CHF secondary to CDMVD, in comparison to furosemide. Secondarily, the study aimed to evaluate the effects of both diuretics on clinical parameters, echocardiographic findings, and circulating cardiac biomarkers related to myocardial injury, neurohormonal activation, myocardial remodeling and fibrosis, inflammation, and oxidative stress in dogs with CDMVD in stage C. Materials and Methods: A total of 20 dogs diagnosed with stable stage C CDMVD and 11 healthy dogs of similar age and weight were prospectively included as a control group. Dogs with CDMVD were randomly assigned in two diuretic treatment groups (Group TOR, torasemide 0.18 mg/kg/day; Group FUR, furosemide 3.57 mg/kg/day); both groups also received benazepril, spironolactone, and pimobendan. Following the clinical history, all dogs underwent physical examination, laboratory analysis (including cardiac biomarkers), blood pressure measurement, ECG, thoracic radiographs, and echocardiography at the time of study inclusion. Follow-up visits occurred at Days 10, 30, 90, 180, 270, and 360 after inclusion. Results: A total of 13/20 dogs completed the study (6 in Group FUR, 7 in Group TOR). Polyuria in Group TOR was the most frequent adverse effect attributed to the drug, which resolved after dose reduction. Relapses were more frequent in Group FUR (6 dogs, 9 relapses) than in Group TOR (3 dogs, 3 relapses). The mean survival time was 230 days for Group TOR and 138 days for Group FUR, although without statistical significance (p = 0.1). The AI:Ao ratio and left ventricular diastolic volume decreased in both groups by Day 30, remaining lower in Group TOR than in Group FUR, without statistically significant differences between groups. The peak velocities of the E wave of the transmitral flow were significantly reduced in Group TOR from Day 90 onwards, in contrast to Group FUR, where they remained higher throughout the study. The E' wave diminished significantly on Day 30 in Group TOR (p = 0.006), being significantly lower on Day 360 compared to Group FUR (p = 0.046). Pulmonary hypertension (PH) was present in 30% of the dogs, worsening in Group FUR by Day 180, while in Group TOR PH remained stable and lower at all visits. Biomarkers cTnI, CRP and WBC were reduced in both groups by Day 30, with a statistically significant difference only for CRP in Group FUR (p = 0.019). In Group TOR, WBC diminished significantly on Day 360 compared to Day 0 (p = 0.03). PICP and the PICP/PIIINP ratio were statistically lower at Day 270 in Group TOR (p = 0.04), remaining lower at all study visits compared to Group FUR. Conclusion: This study shows that the administration of torasemide at the minimum effective dose is safe and effective as a first-line diuretic in dogs with stage C CDMVD over the long term, based on a reduction in the number of relapses in Group TOR as well as a longer survival time.
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