Assuntos
Benzazepinas , Ivabradina , Ivabradina/uso terapêutico , Ivabradina/farmacologia , Humanos , Benzazepinas/uso terapêutico , Benzazepinas/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Antiarrítmicos/uso terapêutico , Antiarrítmicos/farmacologia , Taquicardia Ventricular/tratamento farmacológicoRESUMO
RESUMEN Introducción y objetivos : La insuficiencia cardíaca (IC) es una preocupación creciente de salud pública. Si bien los betabloqueantes (BB) son la base del tratamiento, lograr reducciones objetivo de frecuencia cardíaca puede ser difícil debido a los efectos secundarios y la tolerancia limitada. La ivabradina, un inhibidor único de la corriente If, ofrece un enfoque complementario para controlar la frecuencia cardíaca sin afectar la contractilidad. El objetivo de este estudio fue evaluar la eficacia de agregar ivabradina a la terapia BB en pacientes con IC. Métodos: Se realizó un estudio observacional retrospectivo en un hospital privado en San José, Costa Rica se analizaron 7 casos de pacientes tratados con BB a los cuales posteriormente se les adicionó ivabradina. Se recopilaron datos demo- gráficos, las características clínicas, la frecuencia cardíaca previa y posterior a la ivabradina, la clase funcional NYHA y los valores de laboratorio seleccionados. Resultados: La ivabradina redujo significativamente la frecuencia cardíaca en reposo en un promedio de 26,87 latidos por minuto. El 42,86% alcanzó la dosis meta de su BB inicial después de agregar ivabradina. La clase funcional NYHA se mantuvo estable o mejoró en todos los casos. Conclusiones: Estos resultados sugieren que agregar ivabradina a la terapia BB puede ser una estrategia eficaz para optimizar el control de la frecuencia cardíaca en pacientes con IC. Este enfoque puede mejorar la tolerabilidad de BB, lo que lleva a un mayor manejo de la dosis meta y posiblemente mejores resultados clínicos.
ABSTRACT Introduction and objectives: Heart failure (HF) is a growing public health concern. While beta-blockers (BBs) are the cornerstone of treatment, achieving target heart rate reductions can be difficult due to side effects and limited tolerance. Ivabradine, a unique inhibitor of the If current, offers a complementary approach to controlling heart rate without affecting contractility. This study aimed to evaluate the effectiveness of adding ivabradine to BB therapy in patients with HF. Methods : A retrospective observational study was conducted at a private hospital in San José, Costa Rica. Seven cases of patients treated with BBs who were subsequently added to ivabradine were analyzed. Demographic data, clinical characteristics, heart rate before and after ivabradine, NYHA functional class, and selected laboratory values were collected. Results : Ivabradine significantly reduced resting heart rate by an average of 26.87 beats per minute. Forty-two-point eight-six percent (42.86%) achieved the target dose of their initial BB after adding ivabradine. NYHA functional class remained stable or improved in all cases. Conclusions: These results suggest that adding ivabradine to BB therapy may be an effective strategy to optimize heart rate control in patients with HF. This approach may improve BB tolerability, leading to greater target dose management and possibly better clinical outcomes.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Ivabradina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Costa RicaRESUMO
BACKGROUND/INTRODUCTION: Heart failure patients with reduced ejection fraction are at high risk for ventricular arrhythmias and sudden cardiac death. Ivabradine, a specific inhibitor of the If current in the sinoatrial node, provides heart rate reduction in sinus rhythm and angina control in chronic coronary syndromes. OBJECTIVE: The effect of ivabradine on ventricular arrhythmias in heart failure patients with reduced ejection fraction patients has not been fully elucidated. The aim of this study was to investigate the effect of ivabradine use on life-threatening arrhythmias and long-term mortality in heart failure patients with reduced ejection fraction patients. METHODS: In this retrospective study, 1,639 patients with heart failure patients with reduced ejection fraction were included. Patients were divided into two groups: ivabradine users and nonusers. Patients presenting with ventricular tachycardia, the presence of ventricular extrasystole, and ventricular tachycardia in 24-h rhythm monitoring, appropriate implantable cardioverter-defibrillator shocks, and long-term mortality outcomes were evaluated according to ivabradine use. RESULTS: After adjustment for all possible variables, admission with ventricular tachycardia was three times higher in ivabradine nonusers (95% confidence interval 1.5-10.2). The presence of premature ventricular contractions and ventricular tachycardias in 24-h rhythm Holter monitoring was notably higher in ivabradine nonusers. According to the adjusted model for all variables, 4.1 times more appropriate implantable cardioverter-defibrillator shocks were observed in the ivabradine nonusers than the users (95%CI 1.8-9.6). Long-term mortality did not differ between these groups after adjustment for all covariates. CONCLUSION: The use of ivabradine reduced the appropriate implantable cardioverter-defibrillator discharge in heart failure patients with reduced ejection fraction patients. Ivabradine has potential in the treatment of ventricular arrhythmias in heart failure patients with reduced ejection fraction patients.
Assuntos
Insuficiência Cardíaca , Taquicardia Ventricular , Disfunção Ventricular Esquerda , Humanos , Ivabradina/uso terapêutico , Ivabradina/farmacologia , Volume Sistólico/fisiologia , Estudos Retrospectivos , Arritmias Cardíacas/tratamento farmacológico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Taquicardia Ventricular/tratamento farmacológicoRESUMO
INTRODUCTION: Classic coronary artery bypass grafting (CABG) surgery involves diastolic cardiac arrest under cardiopulmonary bypass, while off-pump CABG (OPCABG) has become widespread in recent years. METHODS: 174 patients who underwent OPCABG were included in the study. Patients were divided into two groups. Group I (n=90) received ivabradine and Group M (n=84) received metoprolol before surgery until postoperative day 10. Intraoperative arrhythmias and hypotension were recorded. Postoperative atrial fibrillation (AF) and arrhythmia, mortality and morbidity rates were assessed based on the 30-day postoperative follow-up. RESULTS: There were no significant differences in the intraoperative amount of inotropic support and red blood cell transfusion between groups (P=0.87 and P=0.31). However, the rates of intraoperative arrhythmias and hypotension were not significantly higher in Group M (P=0.317 and P=0.47). Ventricular tachycardia/ventricular fibrillation (VT/VF) was observed in 2 patients in both groups. Postoperative AF occurred in 7 patients (7.7%) in Group I and in 10 patients (11.9%) in Group M. Although there was a trend towards a higher prevalence of AF in Group M patients, this did not reach statistical significance. In addition, mortality and morbidity rates were comparable between groups.
Assuntos
Fibrilação Atrial , Hipotensão , Humanos , Fibrilação Atrial/etiologia , Metoprolol , Ivabradina , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Complicações Pós-Operatórias/epidemiologiaAssuntos
Humanos , Isquemia Miocárdica/tratamento farmacológico , Doença das Coronárias/mortalidade , Doença das Coronárias/prevenção & controle , Doença das Coronárias/terapia , Metabolismo dos Lipídeos , Infarto do Miocárdio/tratamento farmacológico , Trimetazidina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Ivabradina/efeitos adversos , LDL-Colesterol/metabolismo , Anticoagulantes/administração & dosagem , Nitratos/efeitos adversosRESUMO
Resumen La taquicardia ectópica de la unión en su variante congénita es una taquiarritmia pediátrica poco frecuente, que por su naturaleza incesante y su refractariedad a los agentes farmacológicos tradicio nales lleva asociada una alta morbimortalidad. Se presentan los casos clínicos de dos pacientes pediátricos con diagnóstico de taquicardia ectópica de la unión congénita, que mostraron respuesta inadecuada a las alternativas de tratamiento habituales y que, en consecuencia, desarrollaron miocardiopatía dilatada y disfunción ventricular secundaria a la taquicardia sostenida. En ambos se utilizó ivabradina como alternativa farmacológica innovadora pare el control de ésta con excelente respuesta clínica.
Abstract The congenial form of junctional ectopic tachycardia is a rare variant of pediatric tachyarrhythmia that due to its incessant nature and its refractoriness to the traditionally used antiarrhythmic agents has a high morbimortality The clinical cases of two patients with a diagnosis of congenital junctional ectopic tachycardia with inadequate response to the regular pharmacological options, who developed dilated cardiomyopathy and ventricular dysfunc tion secondary to sustained tachycardia, are presented. In both ivrabadine, a new innovative option was used with excellent clinical response.
Assuntos
Humanos , Criança , Taquicardia Ectópica de Junção/tratamento farmacológico , Eletrocardiografia , Ivabradina/uso terapêutico , Antiarrítmicos/uso terapêuticoRESUMO
The congenial form of junctional ectopic tachycardia is a rare variant of pediatric tachyarrhythmia that due to its incessant nature and its refractoriness to the traditionally used antiarrhythmic agents has a high morbimortality The clinical cases of two patients with a diagnosis of congenital junctional ectopic tachycardia with inadequate response to the regular pharmacological options, who developed dilated cardiomyopathy and ventricular dysfunction secondary to sustained tachycardia, are presented. In both ivrabadine, a new innovative option was used with excellent clinical response.
La taquicardia ectópica de la unión en su variante congénita es una taquiarritmia pediátrica poco frecuente, que por su naturaleza incesante y su refractariedad a los agentes farmacológicos tradicionales lleva asociada una alta morbimortalidad. Se presentan los casos clínicos de dos pacientes pediátricos con diagnóstico de taquicardia ectópica de la unión congénita, que mostraron respuesta inadecuada a las alternativas de tratamiento habituales y que, en consecuencia, desarrollaron miocardiopatía dilatada y disfunción ventricular secundaria a la taquicardia sostenida. En ambos se utilizó ivabradina como alternativa farmacológica innovadora pare el control de ésta con excelente respuesta clínica.
Assuntos
Taquicardia Ectópica de Junção , Antiarrítmicos/uso terapêutico , Criança , Eletrocardiografia , Humanos , Ivabradina/uso terapêutico , Taquicardia Ectópica de Junção/tratamento farmacológicoRESUMO
The absence of afferent nerves for heart rate (HR) regulation leaves the transplanted heart under the influence of its internal and hormonal control. The HR of heart transplantation (HTx) recipients varies from to 90-110 bpm, indicating a lack of vagal parasympathetic tone. We hypothesized that the reduction in mean HR using an If-channel antagonist (ivabradine) could be effective and safe in HTx recipients. The primary objective of this open-label randomized clinical trial was to compare the mean HR at 3, 6, 12, 18, 24, 30, and 36 months after randomization between an ivabradine plus conventional treatment group (IG) and conventional treatment alone group (CG). The secondary objectives were reduction in mortality, graft dysfunction, and ventricular mass. All patients were randomized between 1 and 12 months after HTx. Ivabradine started at randomization. Of the 35 patients, 54.28% were in the CG and 45.72% in the IG. There were no significant between-group differences in demographics. Over time, the HR differences between the groups became significant (P < .01). There were no significant between-group differences in mortality, graft dysfunction, and ventricular mass. We conclude that ivabradine could effectively and consistently reduce the HR in HTx recipients.
Assuntos
Benzazepinas , Transplante de Coração , Benzazepinas/uso terapêutico , Coração , Frequência Cardíaca , Humanos , Ivabradina/uso terapêutico , Resultado do TratamentoRESUMO
The prevalence of heart failure with preserved ejection fraction (HFpEF) is about 30-75% of the patients living with heart failure. A hallmark symptom of these patients is exercise intolerance. Ivabradine can, eventually, increase exercise capacity by heart rate control. However, clinical trials show conflicting results about the effects of ivabradine on exercise capacity, an important prognostic variable. The aim of this study was to investigate the effects of ivabradine on exercise capacity in individuals with HFpEF. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and supplemented by guidance from the Cochrane Collaboration Handbook for Systematic Reviews of Interventions. For the meta-analysis, a forest plot was used to graphically present the effect sizes and the 95% CIs. Four randomized controlled trials were included. Ivabradine did not change exercise capacity expressed by peak VO2 and 6MWT (MD = 0.8; 95% CI - 2.5 to 4.3; P = 0.62) (Fig. 4a). In our secondary analysis, the ivabradine group showed a significant resting HR reduction when compared with placebo (MD = - 13.2; 95% CI - 16.6 to -9.8; P < 0.00001) and ivabradine showed increased values of E/e' ratio compared with placebo (MD = 0.8; 95% CI 0.0 to 1.6; P = 0.04). Current available evidence suggests that there is no effect of ivabradine on exercise capacity in patients with HFpEF. Also, questions about negative effects on E/e' values and adverse events associated with ivabradine treatment need to be considered in future studies.
Assuntos
Insuficiência Cardíaca , Tolerância ao Exercício , Insuficiência Cardíaca/tratamento farmacológico , Frequência Cardíaca , Humanos , Ivabradina , Volume SistólicoRESUMO
INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de ivabradina en pacientes con falla cardiaca (FC) crónica y con fracción de eyección (FE) ventricular izquierda reducida (FC-FEr) que persisten sintomáticos a pesar del tratamiento con la terapia médica óptima (TMO) que incluye el uso de la dosis máxima tolerada (DMT) de beta-bloqueadores (BB) teniendo en cuenta el rol potencial de la frecuencia cardiaca como modificador de efecto. En ese sentido, de ahora en adelante, para efectos del presente dictamen, se hará referencia a la falla cardíaca crónica como FC, y a la fracción de eyección ventricular izquierda como FE. La falla cardíaca (FC) con fracción de eyección (FE) reducida (FC-FEr) se define como la presencia de signos y síntomas de FC crónica, con una FE ventricular izquierda ≤ 40 %. La clasificación sintomática de los pacientes con FC considera a las escalas de la clase funcional (CF) de la New York Heart Association, que va desde la I (sin síntomas durante el ejercicio común) hasta el IV (síntomas al reposo). El tratamiento de los pacientes con FC-FEr se realiza con la terapia médica óptima (TMO), la cual incluye el uso de la dosis máxima tolerada (DMT) de inhibidores de la enzima convertidora de angiotensina, antagonistas de receptores de angiotensina II, de betabloqueadores (BB), y de antagonistas de mineralocorticoides. El Petitorio Farmacológico de EsSalud cuenta con la TMO para el tratamiento de los pacientes con FC-FEr. Así, el Instituto de Evaluación de Tecnología Sanitaria - IETSI recibió una solicitud de evaluación de ivabradina, en el contexto de la elaboración de la Guía de Práctica Clínica de Diagnóstico y Tratamiento de Falla Cardíaca. Los expertos del grupo elaborador de dicha guía propusieron se evalué ivabradina bajo la hipótesis que ofrecería un beneficio adicional al uso de la DMT de BB, para el control de la frecuencia cardíaca en los pacientes con FC-FEr sintomáticos a pesar del uso de TMO. METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva y jerárquica de la literatura con respecto a la eficacia y seguridad de ivabradina en pacientes con FC-FEr, sintomática a pesar del tratamiento con la TMO, que incluye el uso de la DMT de BB, con un enfoque especial sobre el potencial rol de modificador del efecto de la frecuencia cardiaca. La búsqueda se inició revisando la información sobre el uso del medicamento de acuerdo con entidades reguladoras como FDA, EMA, y DIGEMID en el Perú. Se realizó tanto una búsqueda sistemática en las principales bases de datos, tales como MEDLINE vía PubMed, Cochrane Library y LILACS. Así mismo, se realizó una búsqueda manual en las páginas web de grupos dedicados a la investigación y educación en salud que elaboran guías de práctica clínica: National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), Scottish Medicines Consortium (SMC), Haute Authorité de Santé (HAS), Institute for Quality and Efficiency in Healthcare (IQWiG) y el Ministerio de Salud del Perú y (MINSA). Además, se realizó una búsqueda de las guías de las principales sociedades o instituciones especializadas en cardiología, tales como el Instituto Nacional del Corazón (INCOR) del Perú, la American Heart Association (AHA), la American College of Cardiology (ACC), la European Society of Cardiology (ESC), la Sociedad Española de Cardiología (SEC). Por último, se buscaron ensayos clínicos en desarrollo o que no hayan sido publicados aún en la página web www.clinicaltrials.gov que ayuden a responder la pregunta PICO, con el fin de disminuir el sesgo de publicación. RESULTADOS: De acuerdo con la pregunta PICO, se llevó a cabo una búsqueda de evidencia científica relacionada al uso de ivabradina en pacientes con FC-FEr, sintomáticos a pesar del tratamiento con la TMO, la cual incluye la DMT de BB, con enfoque especial sobre el potencial rol de modificador de efecto de la frecuencia cardiaca. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (GPC, ETS, RS, MA y ECA fase III). CONCLUSIONES: El presente dictamen evaluó la evidencia científica disponible a la actualidad en relación a la eficacia y seguridad del uso de la terapia médica óptima (TMO) con ivabradina comparado con la TMO con placebo en pacientes adultos con falla cardíaca con fracción de eyección reducida (FC-FEr) que permanecen sintomáticos a pesar del tratamiento con la TMO que incluye el uso de la dosis máxima tolerada (DMT) de betabloqueadores (BB), con un especial enfoque sobre el potencial rol de la frecuencia cardíaca como modificador del efecto. La evidencia principal que responde a la pregunta PICO establecida en el presente dictamen proviene de los ensayos clínicos aleatorizados (ECA) de fase III BEAUTIFUL y SHIFT, los cuales son estudios de doble ciego, controlados con placebo, y financiados por la compañía farmacéutica que produce ivabradina, Servier, que evaluaron la eficacia y seguridad de ivabradina comparada con placebo para los pacientes con FC-FEr que se encontraban sintomáticos a pesar de la TMO. Dichos ECA fueron incluidos en el meta-análisis (MA) llevado a cabo por Hartmann et al., 2018, cuyos resultados se usaron para derivar las conclusiones del presente dictamen. El análisis combinado de los ECA SHIFT y BEAUTIFUL, llevado a cabo por el MA de Hartmann et al., 2018, mostró que el uso de la TMO e ivabradina, en comparación con el uso de la TMO y placebo, no presentaron diferencias estadísticamente significativas respecto a la mortalidad por cualquier causa, mortalidad cardiovascular y hospitalizaciones por FC; ni en los principales desenlaces de seguridad, tales como eventos adversos (EA) serios totales, la descontinuación del tratamiento y los EA serios cardíacos, respiratorios, neurológicos y renales, entre los grupos de tratamiento, en una población representativa de la población de la PICO. Sobre el potencial rol de la frecuencia cardíaca como modificador de los desenlaces de interés del presente dictamen se tiene que la evidencia que sustenta las restricciones de uso de ivabradina en pacientes con FC-FEr con frecuencias cardíacas por encima de 70, 75, o 77 LPM provienen únicamente de análisis por subgrupos de los ECA SHIFT y BEAUTIFUL, lo cual introduce un potencial riesgo de sesgo de selección en dichos resultados. Siendo que, no se cuenta a la fecha con evidencia empírica adicional que justifique valorar los resultados de manera separada sólo para aquellos pacientes con una frecuencia cardíaca mayor de 70 LPM, o 77 latidos por minuto (LPM). En relación a las recomendaciones de las guías de práctica clínica (GPC) y evaluación de tecnologías sanitarias (ETS) incluidas en el presente dictamen, sobre el uso de ivabradina en la población de la pregunta PICO, se tiene que todas usaron la evidencia proveniente del ECA SHIFT mientras que unas pocas también usaron la evidencia proveniente del ECA BEAUTIFUL, y que fueron elaborados en contextos diferentes al nuestro. Además, dichas GPC y ETS fueron elaboradas antes de la publicación del MA de Hartmann et al., 2018, el cual mostró que ivabradina presentaría una eficacia y seguridad similar al placebo en la población de la pregunta PICO. En consecuencia, se dificulta la extrapolación de dichas recomendaciones para la población de interés del presente dictamen. En consecuencia, actualmente se desconoce si la frecuencia cardíaca ejerce un potencial rol de modificador del efecto sobre los desenlaces planteados en la pregunta PICO para la población de interés del presente dictamen. Y la mejor evidencia disponible a la fecha, surgida del MA de Hartmann et al., 2018, indica que ivabradina no ofrecería un beneficio adicional frente al placebo en los desenlaces clínicos de interés planteados en la pregunta PICO, para la población de interés del presente dictamen preliminar. Por lo tanto, no existen argumentos técnicos para recomendar el uso ivabradina en EsSalud.
Assuntos
Humanos , Arritmias Cardíacas/tratamento farmacológico , Volume Sistólico , Ivabradina/uso terapêutico , Eficácia , Análise Custo-BenefícioRESUMO
BACKGROUND: Pharmacological treatment improves survival in patients with heart failure with reduced ejection fraction. The use of sacubutril/valsartan and ivabradine has been recently approved and incorporated in the latest guidelines. AIM: To identify candidates eligible for these therapies among patients treated in a heart failure clinic, considering the inclusion criteria for the PARADIGM-HF and SHIFT trials. MATERIAL AND METHODS: Cross-sectional study on 158 patients aged 62 ± 11 years (67% male) with heart failure and reduced ejection fraction, with at least three months of follow-up and without decompensation. The percentage of patients complying for the inclusion criteria for the PARADIGM-HF y SHIFT trials was determined. RESULTS: In 37%, the etiology of heart failure was ischemic, 49% were in functional class I, their ejection fraction was 33 ± 11% and their median Pro-brain natriuretic peptide was 800 pg/mL. Ninety five percent were treated with vasodilators, 97% with beta-blockers and 82% with aldosterone antagonists. Using PARADIGM-HF and SHIFT criteria, 11 patients (7%) were eligible for sacubitril / valsartan and 21 patients (13.3%) for ivabradine. Among the main causes of non-eligibility for sacubitril / valsartan were being functional class I (48.7%) and not achieving a stable dose of enalapril ≥ 20 mg / day or losartan ≥ 100 mg / day (24.7%). In the case of ivabradine, apart from those in functional class I, the absence of sinus rhythm and a heart rate < 70 / min when receiving a maximal tolerated dose of beta-blockers, were present in 22%. CONCLUSIONS: A low percentage of our patients were eligible for these therapies. Among the causes that explain these results were clinical stability, a high percentage of patients in functional class I and being in a disease modifying treatment.
Assuntos
Aminobutiratos/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Fármacos Cardiovasculares/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Ivabradina/administração & dosagem , Tetrazóis/administração & dosagem , Idoso , Compostos de Bifenilo , Estudos Transversais , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , ValsartanaRESUMO
Neste artigo analisamos criticamente artigos que foram importantes para modificar nossa prática clínica. Na insuficiência cardíaca, doença com características de malignidade, é sempre importante adotarmos condutas que melhorem essa história natural. O primeiro artigo é um Registro europeu, o BIOSTAT-CHF, que documentou dois pontos importantes da prática clínica. O primeiro é que, apesar das evidências científicas, os médicos continuam não prescrevendo os medicamentos de comprovada eficácia como deveriam e o segundo é que quando os prescrevem indicam doses baixas e que essas doses baixas não melhoram a evolução dos pacientes. O segundo e terceiro artigos analisados documentaram que é possível melhorar a evolução dos indivíduos com IC, reduzindo a frequência cardíaca quando elevada, apesar do tratamento prescrito e que um bloqueio neuro-hormonal mais completo reduz a mortalidade. Prescrever, numa doença com essa potencial gravidade, a ivabradina e o sacubitril/valsartana melhora substancialmente a qualidade de vida e reduz a descompensação e a mortalidade nas pessoas com IC. O quarto artigo documentou que a suspensão do tratamento quando ocorre reversão do remodelamento cardíaco leva a agravamento do quadro clínico em cerca de metade dos pacientes e sua reintrodução promove melhora novamente, mas não de todos que pioraram. Os artigos indicam caminhos para um tratamento mais eficaz da IC
In this article we critically analyze articles that have been important in modifying our clinical practice. In heart failure, a disease with characteristics of malignancy, it is always important to adopt conducts that improve this natural history. The first article is a European Registry, the BIOSTAT-CHF, that documents two important points in clinical practice. The first is that, despite scientific evidence, physicians continue to not prescribe drugs proven to be effective, as they should, and the second point is that, when they do prescribe them, they prescribe low doses that do not improve the patients' evolution. The second and third papers analyzed state that it is possible to improve the evolution of individuals with HF by reducing the heart rate when elevated, despite the prescribed treatment, and that a more complete neuro-hormonal block reduces mortality. In a disease with this potential severity, prescribing ivabradine and sacubitril/valsartan substantially improves the quality of life and reduces decompensation and mortality in people with HF. The fourth paper reports that discontinuation of treatment when reversion of cardiac remodelling occurs could lead to the worsening of the clinical situation in around 50% of patients and that its reintroduction promotes improvement again, but not for all worsening patients. These papers showed us ways to treat heart failure more effectively
Assuntos
Humanos , Masculino , Feminino , Prática Clínica Baseada em Evidências/métodos , Insuficiência Cardíaca/terapia , Remodelação do Consumo , Ivabradina/uso terapêutico , Frequência CardíacaRESUMO
INTRODUCTION: Heart failure with reduced ejection fraction (HFrEF) is associated with a worse outcome. Heart rate (HR) is related to outcome in HFrEF. Ivabradine selectively inhibits If (funny) channels in a concentration-dependent manner reducing HR. AREAS COVERED: The effects of ivabradine in HF were reviewed. The SHIFT trial results indicated that ivabradine improves chronic HFrEF outcomes, whereas published data suggest that amiodarone, digoxin, or verapamil may not be safe or the safety is controversial in HFrEF patients. In the CONSTATHE-DHF study, ivabradine reduced HR and improved left ventricular (LV) ejection fraction, LV diastolic functions, and right ventricle function in acute decompensated HF (ADHF). In chagasic patients, ivabradine reduced HR and a trend toward reduction in all-cause death was observed with ivabradine (p = 0.07). In children with HFrEF, ivabradine increased NYHA functional class. The most common side effects with ivabradine are bradycardia, atrial fibrillation, and phosphenes. Ivabradine was approved for HFrEF treatment by the EMA and FDA and seems to be cost-effective in HFrEF treatment. Ivabradine is indicated for HFrEF by the ESC HF Guidelines (IIa) and by the 2016 ACC/AHA/HFSA Guidelines (IIa-B-R). EXPERT OPINION: Published evidences demonstrate that ivabradine improves the outcome of chronic HFrEF and it seems to have a promising role in ADHF.
Assuntos
Fármacos Cardiovasculares/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Ivabradina/administração & dosagem , Animais , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/farmacologia , Relação Dose-Resposta a Droga , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Ivabradina/efeitos adversos , Ivabradina/farmacologia , Guias de Prática Clínica como Assunto , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Background: Pharmacological treatment improves survival in patients with heart failure with reduced ejection fraction. The use of sacubutril/valsartan and ivabradine has been recently approved and incorporated in the latest guidelines. Aim: To identify candidates eligible for these therapies among patients treated in a heart failure clinic, considering the inclusion criteria for the PARADIGM-HF and SHIFT trials. Material and Methods: Cross-sectional study on 158 patients aged 62 ± 11 years (67% male) with heart failure and reduced ejection fraction, with at least three months of follow-up and without decompensation. The percentage of patients complying for the inclusion criteria for the PARADIGM-HF y SHIFT trials was determined. Results: In 37%, the etiology of heart failure was ischemic, 49% were in functional class I, their ejection fraction was 33 ± 11% and their median Pro-brain natriuretic peptide was 800 pg/mL. Ninety five percent were treated with vasodilators, 97% with beta-blockers and 82% with aldosterone antagonists. Using PARADIGM-HF and SHIFT criteria, 11 patients (7%) were eligible for sacubitril / valsartan and 21 patients (13.3%) for ivabradine. Among the main causes of non-eligibility for sacubitril / valsartan were being functional class I (48.7%) and not achieving a stable dose of enalapril ≥ 20 mg / day or losartan ≥ 100 mg / day (24.7%). In the case of ivabradine, apart from those in functional class I, the absence of sinus rhythm and a heart rate < 70 / min when receiving a maximal tolerated dose of beta-blockers, were present in 22%. Conclusions: A low percentage of our patients were eligible for these therapies. Among the causes that explain these results were clinical stability, a high percentage of patients in functional class I and being in a disease modifying treatment.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Tetrazóis/administração & dosagem , Fármacos Cardiovasculares/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Ivabradina/administração & dosagem , Aminobutiratos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Estudos Transversais , Seleção de Pacientes , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Insuficiência Cardíaca/fisiopatologiaRESUMO
BACKGROUND: Heart rate (HR) reduction with ivabradine has been proved to reduce hospitalization and death from heart failure (HF). We sought to investigate whether pyridostigmine would effectively reduce HR in patients with chronic HF as compared with ivabradine. METHODS: Twenty-one patients with HF who were in sinus rhythm with a resting HR over 70 bpm, despite optimal medical treatment, were included in a randomized, double-blind study comparing pyridostigmine versus ivabradine. The initial dose of ivabradine was 5 mg twice daily to reach a target HR between 50 and 60 bpm and could be titrated to a maximum of 7.5 mg twice daily. Pyridostigmine was used in a fixed dose of 30 mg 3 times daily. RESULTS: The baseline HR for ivabradine and pyridostigmine groups was 89.1 (13.5) and 80.1 (7.2) bpm, respectively (P = .083). After 6 months of treatment, HR was significantly reduced to 64.8 (8.3) bpm in the ivabradine group (P = .0014) and 63.6 (5.9) bpm in the pyridostigmine group (P = .0001). The N-terminal pro-B-type natriuretic peptide was reduced in the ivabradine group (median: 1308.4 [interquartile range: 731-1896] vs 755.8 [134.5-1014] pg/mL; P = .027) and in the pyridostigmine group (132.8 [89.9-829] vs 100.7 [38-360] pg/mL; P = .002). Inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor were reduced in both groups. Exercise capacity was improved in both groups, with increments in volume of oxygen utilization (VËO2; ivabradine: 13.1 vs 15.6, P = .048; pyridostigmine: 13.3 vs 16.7, P = .032). Heart rate recovery in the first minute postexercise was improved with pyridostigmine (11.8 [3.9] vs 18 [6.5]; P = .046), but not with ivabradine (13.3 [6.9] vs 14.1 [8.2]; P = .70). No differences in either group were observed in the myocardial scintigraphy with 123-iodine-metaiodobenzylguanidine. CONCLUSION: Both drugs significantly reduced HR, with improvements in exercise capacity and in neurohormonal and inflammatory profiles.
Assuntos
Fármacos Cardiovasculares/farmacologia , Inibidores da Colinesterase/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Ivabradina/farmacologia , Brometo de Piridostigmina/farmacologia , Adulto , Idoso , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Cardiomiopatia Chagásica , Ivabradina , Doença de Chagas , Coração , Insuficiência Cardíaca , HumanosRESUMO
Background Ivabradine is currently indicated to lower heart rate in Heart Failure with Reduced Ejection Fraction (HFrEF) patients. However its effect apart from beta-blockers is not clear. Aim of the review To study the additional effect of ivabradine, apart from the effect of beta-blockers, on cardiovascular death, all-cause mortality, hospitalization due to HF and heart rate in HFrEF population. Method Electronic searches were conducted up to June 2016 to include randomized controlled trials where ivabradine was compared to a control group. Relative risks RRs and their 95% confidence intervals (CI 95%) were pooled and the random and fixed effect were used to summarize the results according to heterogeneity levels. Heterogeneity among studies was measured by the I-squared statistic Results Of 1790 studies, seven met the inclusion criteria for the systematic review and meta-analysis. The population consisted of 17,747 patients. Risk of bias was generally high for beta-blocker doses lower than recommended. Interventions lasted 1.5-22.9 months and pooled relative risks RR (95%) for all-cause mortality, cardiovascular death and hospitalization for HF were 0.98 (0.90-1.06); 0.99 (0.91-1.08); and 0.87 (0.68-1.12) respectively. Heart rate (CI 95%) decreased by 8.7 (6.37-11.03) beats per minute with ivabradine compared to the control group. Subgroup analysis by beta-blocker dose showed that for patients on recommended treatment (at least 50% of the beta-blocker target dose), heart rate (CI 95%) decreased by 4.70 (3.67-5.73), whereas for patients not on recommended treatment or with unreported dose, heart rate decreased by 8.60 (8.13-9.08). Conclusion Ivabradine significantly reduced heart rate and its additional effect on heart rate appears to be inversely correlated with the dose of beta-blocker. It showed no significant effect for all-cause mortality, cardiovascular death and hospitalization due to HF. Unreported beta-blocker doses and beta-blocker doses lower than recommended limited the conclusions.
Assuntos
Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Ivabradina/uso terapêutico , Volume Sistólico , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Cardiotônicos/efeitos adversos , Insuficiência Cardíaca/mortalidade , Humanos , Ivabradina/efeitos adversos , Resultado do TratamentoRESUMO
Abstract Introduction and objectives: Heart rate (HR) elevation in patients (p) with heart failure with reduced ejection fraction (HFrEF) is related to increased mortality and hospitalization for HF; its reduction improves the filling of the left ventricle, increases the myocardial oxygen supply and reduces its consumption, all of which is beneficial in p with impaired left ventricular systolic function. Use of ivabradine (IBRA) in p with HFrEF, in sinus rhythm (SR) and HR > 70 beats per minute (bpm), reduces hospitalizations for HF and mortality for HF. The management of p with advanced HF in PIC ensures a morbidity and mortality reduction with the highest levels of evidence. The first retrospective analysis in a PIC at a private hospital in CA, during 3 years of all case p with HFrEF who received treatments (tx) recommended by International Guidelines and maintained HR > 70 bpm at rest in SR, with the purpose of reducing it. The use of baseline clinical data, natriuretic peptides (NP) and LVEF at rest, compared with same variables in follow up, in a region where these PICs are borning. Methods: 26 p with HFrEF for 3 years of PIC. General data, tx, baseline clinical condition, BP, pulse, NYHA, quality of life (QoL), NP, LVEF by Doppler Echocardiography were registered, and IBRA tx response was compared baseline and end. 18 p completed data; 8 incomplete (baseline or follow-up data). Results: Ambulatory p, with HFrEF (<35%) and SR HR > 70 bpm; age 78 years, 17 men. Tx average time with IBRA 11 months, 53.5% more than 1 year. Baseline medications, 93% ACEIs or ARAs II; 85% beta-blockers and 74% MRA, maximum tolerated doses. No patient used IBRA prior baseline. 20% CRT. Variables behavior assessed: HR (baseline 89 bpm vs 62 bpm after IBRA 2 months); BP (baseline systolic 100 mmHg vs 123 mmHg end; baseline diastolic 55 mmHg vs 65 mmHg end); LVEF (baseline 29% vs 35% end); BNP baseline 7,550 pg/ml vs 1,935 pg/ml end. 5 p improved NYHA III to NYHA I, 5 p improved NYHA III to NYHA II, 3 had deterioration NYHA III; rest remained unchanged. 77% p no dose adjustment required (HR below 70 bpm). 6 p began with 2.5 mg every 12 hours and increased to 5 mg every 12 hours after 15 days. By KCCQ-12 increase 42 to 59 points. 1 discontinuation case of IBRA due to bradycardia (HR < 50 bpm). 2 p hospitalized, one pneumonia and one HF decompensation. 3 dead: 1 myocardial infarction, 2 HF progression. Conclusions: 26 p studied, registered and treated with IBRA in the PIC at private hospital in CA, most of them registered metric improvements identified as prognosis factors (HR, BP, LVEF, NP, NYHA and QoL). This assessment, registration and follow up of p with HFrEF with use of IBRA in a PIC, is the first one carried out in CA. Results reflect the usual clinical practice in a PIC, with cardiologists and nurses trained to support and follow-up p, and evidence the importance of PIC when using and prescribing drugs like IBRA, in a region where these PICs are rare.
Resumen Introducción y objetivos: La elevación de la frecuencia cardíaca (FC) en pacientes (p) con insuficiencia cardíaca (IC) con fracción de eyección reducida (ICFE) se relaciona con un aumento de la mortalidad y la hospitalización por IC; su reducción mejora el llenado del ventrículo izquierdo, aumenta el suministro de oxígeno al miocardio y reduce su consumo, todo lo cual es beneficioso en p con deterioro de la función sistólica del ventrículo izquierdo. El uso de ivabradina (IBRA) en p con ICFE, en ritmo sinusal (SR) y FC> 70 latidos por minuto (lpm), reduce las hospitalizaciones por insuficiencia cardíaca y la mortalidad por insuficiencia cardíaca. El manejo de p con FC avanzada en PIC asegura una reducción de la morbilidad y la mortalidad con los mayores niveles de evidencia. El primer análisis retrospectivo en un PIC en un hospital privado en centroamérica, durante 3 años de todos los casos p con ICFE que recibieron tratamientos (tx) recomendados por Interna tional Guidelines y mantuvieron FC> 70 lpm en reposo en SR, con el objetivo de reducirlo. El uso de datos clínicos basales, péptidos natriuréticos (NP) y FEVI en reposo, en comparación con las mismas variables en el seguimiento, en una región donde estos PIC están naciendo. Métodos: 26 p con ICFE durante 3 años de PIC. Se registraron datos generales, tx, estado clínico basal, presión arterial, pulso, NYHA, calidad de vida (QoL), NP, FEVI por ecocardiografía Doppler, y se comparó la respuesta de IBRA tx al inicio y al final. 18 p datos completados; 8 incompleto (datos iniciales o de seguimiento). Resultados: p ambulatorios, con ICFE (<35%) y SR FC> 70 lpm; 78 años de edad, 17 hombres. Tiempo promedio de Tx con IBRA 11 meses, 53.5% más de 1 año. Medicamentos de referencia, 93% IECA o IRA II; 85% de betabloqueantes y 74% de MRA, dosis máximas toleradas. Ningún paciente usó IBRA antes de la línea base. 20% de CRT. Comportamiento de las variables evaluado: FC (basal 89 lpm frente a 62 lpm después de IBRA 2 meses); BP (sistólica basal de 100 mmHg frente a 123 mmHg de extremo, línea diastólica basal de 55 mmHg frente a 65 mmHg de extremo); FEVI (línea de base 29% frente a 35% de final); BNP línea de base 7.550 pg / ml vs 1.935 pg / ml final. 5 p mejoró NYHA III a NYHA I, 5 p mejoró NYHA III a NYHA II, 3 sufrió deterioro NYHA III; el resto se mantuvo sin cambios. 77% p no se requiere ajuste de dosis (FC por debajo de 70 lpm). 6 p comenzó con 2.5 mg cada 12 horas y aumentó a 5 mg cada 12 horas después de 15 días. Por KCCQ-12 aumenta de 42 a 59 puntos. 1 caso de discontinuación de IBRA debido a bradicardia (FC <50 lpm). 2 p hospitalizados, una neumonía y una descompensación de FC. 3 muertos: 1 infarto de miocardio, progresión de 2 FC. Conclusiones: 26 p estudiados, registrados y tratados con IBRA en el PIC en un hospital privado en CA, la mayoría de ellas registraron mejorías métricas identificadas como factores pronósticos (FC, BP, FEVI, NP, NYHA y QoL). Esta evalua ción, registro y seguimiento de p con ICFE con uso de IBRA en un PIC, es la primera llevada a cabo en CA. Los resultados reflejan la práctica clínica habitual en un CFP, con cardiólogos y enfermeras capacitados para apoyar y dar seguimiento p, y evidencian la importancia del CFP al usar y prescribir fármacos como el IBRA, en una región donde estos PIC son raros.