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Chronic Chagas cardiomyopathy (CCC) has unique pathogenic and clinical features with worse prognosis than other causes of heart failure (HF), despite the fact that patients with CCC are often younger and have fewer comorbidities. Patients with CCC were not adequately represented in any of the landmark HF studies that support current treatment guidelines. PARACHUTE-HF (Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation) is an active-controlled, randomized, phase IV trial designed to evaluate the effect of sacubitril/valsartan 200 mg twice daily vs enalapril 10 mg twice daily added to standard of care treatment for HF. The study aims to enroll approximately 900 patients with CCC and reduced ejection fraction at around 100 sites in Latin America. The primary outcome is a hierarchical composite of time from randomization to cardiovascular death, first HF hospitalization, or relative change from baseline to week 12 in NT-proBNP levels. PARACHUTE-HF will provide new data on the treatment of this high-risk population. (Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With CCC [PARACHUTE-HF]; NCT04023227).
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Cardiomiopatia Chagásica , Combinação de Medicamentos , Enalapril , Insuficiência Cardíaca , Tetrazóis , Valsartana , Humanos , Compostos de Bifenilo/uso terapêutico , Aminobutiratos/uso terapêutico , Enalapril/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Cardiomiopatia Chagásica/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Tetrazóis/uso terapêutico , Volume Sistólico/fisiologia , Fragmentos de Peptídeos/sangue , Doença Crônica , Peptídeo Natriurético Encefálico/sangue , Masculino , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Feminino , Resultado do TratamentoRESUMO
INTRODUCTION: The evidence supporting pharmacological heart failure treatment relies on randomized clinical trials with stringent inclusion and exclusion criteria. OBJECTIVES: Assess the eligibility of outpatients with chronic heart failure for the trials DAPA-HF, EMPEROR-reduced, and PARADIGM-HF, while exploring potential differences among study populations. METHODS: By reviewing medical records, we determined the eligibility rate for each study and evaluated the incidence of heart failure hospitalizations and all-cause mortality during this period. RESULTS: A total of 446 patients were included in the cohort. Approximately 75% would be ineligible for the trials, mainly because of their comorbidities. Ineligible patients had a higher all-cause mortality, but a similar incidence of hospitalization. CONCLUSION: Approximately 1 in 4 patients from a heart failure clinic in Medellin, Colombia would meet the eligibility criteria for the DAPA-HF, EMPEROR-reduced, and PARADIGM-HF trials. These findings highlight the need to complement randomized clinical trials with real-world data.
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Cardiologia , Insuficiência Cardíaca , Humanos , Valsartana/uso terapêutico , Volume Sistólico , Tetrazóis/efeitos adversos , Estudos Retrospectivos , Colômbia/epidemiologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Combinação de Medicamentos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapiaRESUMO
BACKGROUND: To characterize the use of sacubitril/valsartan in a group of patients with heart failure in Colombia. RESEARCH DESIGN AND METHODS: Follow-up study of patients with heart failure who started sacubitril/valsartan and were affiliated with the Colombian health system between 2019 and 2021. Sociodemographic, clinical, and pharmacological variables and adherence and persistence of use were identified. RESULTS: A total of 514 patients were identified, with a mean age of 65.7 years, 73.7% of whom started sacubitril/valsartan at low doses, and only 12.5% reached the maximum dose. Adherence was 78.2% and persistence was 56.8% at 1 year of follow-up. The increase in systolic blood pressure (odds ratio (OR): 1.01; 95% CI: 1.00-1.03) and the use of ß-blockers (OR: 2.63; 95% CI: 1.42-4.85) were correlated with a greater persistence, while receiving furosemide (OR: 0.59; 95% CI: 0.39-0.89) and not having received renin - angiotensin - aldosterone system inhibitors in the 3 months before starting sacubitril/valsartan (OR: 0.48; 95% CI: 0.31-0.76) were associated with lower persistence. CONCLUSIONS: The persistence of treatment 1 year after starting sacubitril/valsartan was not high, and a small proportion of patients reached the target dose of the drug. Nontitration of the drug dose was common.
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Insuficiência Cardíaca , Tetrazóis , Humanos , Idoso , Seguimentos , Tetrazóis/uso terapêutico , Volume Sistólico/fisiologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Resultado do Tratamento , Valsartana/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Aminobutiratos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Combinação de MedicamentosRESUMO
Heart failure (HF) is a significant event for public health. It has a prevalence between 1-2%, mortality rate between 7-17%, and hospitalization between 32-44%. This implies a risk to health and quality of life, but also great financial efforts for health systems. Sacubitril/valsartan is a medication recognized for its efficacy, and this consensus seeks to synthesize the available information regarding its use for the benefit of patients. This document consists of a description of the epidemiology of HF, pharmacology of the drug, clinical trials, use of the drug in cases with reduced ejection fraction, mildly reduced ejection fraction and preserved ejection fraction, available literature on HF guidelines, recommendations and conclusions.
La insuficiencia cardiaca (IC) es un evento significativo para la salud pública. Tiene una prevalencia entre el 1 y 2%, tasa de mortalidad entre el 7 y 17% y de hospitalización entre el 32 y 44%. Esto implica un riesgo a la salud y calidad de vida, pero también grandes esfuerzos financieros para los sistemas de salud. El sacubitrilo/valsartán es un medicamento reconocido por su eficacia, y este consenso busca sintetizar la información disponible respecto a su uso en búsqueda del beneficio de los pacientes. El presente documento se compone de una descripción de la epidemiología de la IC, farmacología del medicamento, estudios clínicos sobre este, uso del medicamento en casos con fracción de eyección reducida, fracción de eyección ligeramente reducida y fracción de eyección preservada, literatura disponible en guías de IC, recomendaciones y conclusiones.
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Cardiologia , Insuficiência Cardíaca , Hipertensão , Disfunção Ventricular Esquerda , Humanos , Estados Unidos , Qualidade de Vida , Consenso , Tetrazóis/efeitos adversos , Volume Sistólico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Valsartana/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão/tratamento farmacológicoRESUMO
Esta es una revisión sobre el papel de los péptidos natriuréticos y los intentos de utilizarlos como diana terapéutica a medida que se iba comprendiendo mejor su papel en la fisiopatología de la insuficiencia cardíaca con función sistólica deprimida. Se hace un recuento de su participación en sucesivos estudios fallidos y se explican los motivos de sus fracasos, hasta lograr el éxito deseado con la combinación del sacubitrilo/valsartan, lo que produjo un cambio de paradigma en el manejo de la insuficiencia cardíaca.
This review is conducted on the role of natriuretic peptides and the attempts to use them as a treatment as their role in the pathophysiology of heart failure with depressed systolic function was better understood. A recount of their participation in successive failed studies is provided, explaining the reasons for their failures, until achieving the desired success with the combination of sacubitril/valsartan. This produced a paradigm shift in the management of heart failure.
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One of the most relevant and differentiating aspects provided by the 2021 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure is the retraction of the historical stepped and vertical pharmacological treatment scheme for heart failure with reduced ejection fraction (HFrEF). Subsequently, it was replaced by an updated algorithm that places four therapeutic families in the same initial horizontal step with an equally high degree of recommendation (class I). In this context, these four pillars, which have demonstrated a significant reduction in mortality and hospitalizations in patients with HFrEF, include (1) angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB)/angiotensin II receptor-neprilysin inhibitors (ARNi), (2) beta blockers, (3) mineralocorticoid receptor antagonists (MRA) and (4) sodium-glucose cotransporter 2 inhibitors (SGLT2is) as the main novelty. This manuscript reviews the current therapeutic algorithm with a special focus on the therapeutic value of adding an MRA (still underused in both clinical trials and real world), changing an ACEi/ARB for an ARNi and incorporating an SGLT2i in patients with HFrEF. This article is part of the Emerging concepts in heart failure management and treatment Special Issue: https://www.drugsincontext.com/special_issues/emerging-concepts-in-heart-failure-management-and-treatment.
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AIM: The win ratio can incorporate different types of outcomes and enhance statistical power, making it a useful method for analysing composite outcomes in cardiovascular trials. The application of this approach to the PARADISE-MI trial provides an additional perspective into understanding the effects of sacubitril/valsartan in patients with acute myocardial infarction. METHODS AND RESULTS: We conducted a post-hoc analysis of the PARADISE-MI trial, which randomly assigned patients with acute myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril/valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to guideline-recommended therapy. The principal composite outcome was analysed in the hierarchical order of death due to cardiovascular causes, first hospitalization for heart failure, and first outpatient episode of symptomatic heart failure. We included events confirmed by the clinical events classification (CEC) committee as well as events identified by investigators that did not meet study definitions. Results were analysed by the unmatched win-ratio method. A win ratio that exceeds 1.00 reflects a better outcome. A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril/valsartan and 2831 to receive ramipril. The hierarchical analysis of the principal composite outcome demonstrated a larger number of wins (1 265 767 [15.7%]) than losses (1 079 502 [13.4%]) in the sacubitril/valsartan group (win ratio of 1.17, 95% confidence interval [CI] 1.03-1.33; p = 0.015). Sensitivity analyses using alternative definitions of the composite outcome showed results similar to those of the principal analysis, except for analysis restricted to events that met CEC definitions (win ratio of 1.11, 95% CI 0.96-1.30; p = 0.16). CONCLUSION: In this post-hoc analysis of the PARADISE-MI trial using the win ratio and including investigator-identified events not having CEC confirmation, sacubitril/valsartan was superior to ramipril among high-risk survivors of acute myocardial infarction.
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Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Ramipril/uso terapêutico , Ramipril/farmacologia , Volume Sistólico , Antagonistas de Receptores de Angiotensina , Neprilisina , Tetrazóis/uso terapêutico , Função Ventricular Esquerda , Aminobutiratos/uso terapêutico , Valsartana/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Combinação de Medicamentos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/complicaçõesRESUMO
Chagas cardiomyopathy is the most prevalent non-ischaemic cardiomyopathy in Latin America, with high morbidity and mortality even today. Treatment of these patients is based on the use of medications for heart failure. This study evaluated a case series of patients with Chagas heart disease who used sacubitril/valsartan at a referral hospital for this disease in Brazil. After 6 months, there was a symptomatic improvement in these individuals assessed by the New York Heart Association (NYHA) functional class, with a 44.3% reduction in the absolute number of patients classified as III-IV in the period (P = 0.035), but without changes in the parameters on the echocardiogram for reverse ventricular remodelling. There was a high mortality rate and number of hospitalizations. These results emphasize the importance of studying the use of sacubitril/valsartan in Chagas heart disease to better describe its effectiveness considering the particularities of these individuals.
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Insuficiência Cardíaca , Tetrazóis , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Combinação de Medicamentos , Ecocardiografia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Volume Sistólico , Tetrazóis/uso terapêutico , Resultado do Tratamento , ValsartanaRESUMO
BACKGROUND: Cancer therapy-related cardiac dysfunction (CTRCD) is a critical problem with an impact on both oncological and cardiovascular prognosis, especially when it prevents patients from receiving cancer treatment. Standard therapy for heart failure (HF) is recommended for CTRCD, but there is no well-established evidence on how sacubitril/valsartan may help cancer patients with cardiotoxicity. OBJECTIVES: The aim of this trial was to study the effectiveness of sacubitril-valsartan in patients with CTRCD treated in cardio-oncology units. METHODS: We enrolled 635 patients with breast cancer and followed them with echocardiography and NT- proBNP. Patients who developed left ventricular dysfunction and heart failure were treated with angiotensin-converting enzyme inhibitors (ACEI) (enalapril) or angiotensin receptor blockers (ARB) (valsartan), aldosterone antagonists (eplerenone), digitalis and diuretics (furosemide), as needed. When patients remained symptomatic and met the PARADIGM-HF inclusion criteria, sacubitril/valsartan was started instead of enalapril or valsartan. We analyzed clinical, laboratory and echocardiographic variables to determine the beneficial effects of sacubitril/valsartan on left ventricular remodeling (improvement of left ventricular ejection fraction (LVEF), left ventricle internal diameter in diastole), diastolic dysfunction (E/e' ratio), reduction in NT-proBNP levels, New York Heart Association (NHYA) class and improvement in the 6-min walk test. Also, we analyzed serum creatinine and potassium levels to determine treatmentsafety in this population. Median follow-up was 20 months. RESULTS: Twenty-eight patients developed cardiotoxicity and were treated with sacubitril/valsartan. The sacubitril/valsartan dose was 100 mg (sacubitril 49 mg/valsartan 51 mg) in 12 patients (42.85%) and 200 mg (sacubitril 97 mg/valsartan 103 mg) in 16 patients (57.15%). No deaths were reported, and one patient underwent heart transplantation. Baseline median NT-proBNP was 997.5 pg/ml (IQR 663.8 - 2380.8), which decreased to a median of 416.5 pg/ml (IQR 192.0-798.2) on follow-up with p < 0.001. Baseline NYHA functional class was III (78.6%) or IV (21.4%), and it improved to I (57.1%) or II (42.9%) on follow-up. LVEF increased with treatment from 26.7 ± 5.4% to 32.3 ± 5.5% (p < 0.001). There were also significant improvements in left ventricle internal diameter in diastole (LVIDD), diastolic function, 6-min walk test, and mitral valve regurgitation. There were no differences between basal and follow-up levels of serum creatinine or potassium. CONCLUSION: Sacubitril/valsartan might be a promising treatment option in patients with refractory CTRCD.
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Resumen Introducción y objetivos: La Insuficiencia Cardíaca (IC) es un síndrome frecuente en la población adulta. Sacubitril / Valsartán (S/V) es un tratamiento novedoso para esta patología. El presente estudio pretende analizar el efecto de este medicamento sobre las variables clínicas, de laboratorio y ecocardiográficas en pacientes con IC con FEVIr. Metodología: Se realizó un estudio observacional retrospectivo de los expedientes de los pacientes del PIC que tuvieran prescrito S/V. De estos, se recopilaron datos basales y de seguimiento de los principales parámetros de relevancia pronóstica, para estos pacientes. Luego se cuantificaron los cambios generados en el tiempo una vez establecido el tratamiento y se hicieron análisis estadísticos para validar si los cambios fueron significativos. Resultados: De la totalidad de pacientes del PIC, 27 cumplieron los criterios de inclusión, con una edad promedio de 70 años y en donde 37.0% se encontraron en la dosis meta después de un seguimiento promedio de 16.4 meses. A través del estudio fue posible encontrar una diferencia estadísticamente significativa para el cambio en la FEVI para 17 pacientes (p=0.016). En los pacientes en los que se pudo recopilar la información se observó que el NT-proBNP mejoró en un 68.75%, por su parte la caminata de 6 minutos mejoró en un 77.8%. Además, solamente 7.4% de los pacientes empeoraron en su escala funcional NYHA, 7.4% fallecieron y 3.7% sufrieron hospitalización durante el estudio. Conclusiones: Basados en los parámetros estudiados y a través de los cambios generados durante el tiempo de seguimiento, fue posible definir una mejoría en los pacientes tras el uso de S/V, asociado también a una baja mortalidad e incidencia de hospitalizaciones.
Abstract Effect of Sacubitril / Valsartan on the clinical, laboratory and echocardiographic variables used for the control of heart failure with reduced left ventricular ejection fraction (LVEFr) in active patients of the Heart Failure Program (HFP) of the Hospital Clínica Bíblica Introduction and objectives: Heart failure (HF) is a common syndrome in the adult population. Sacubitril /Valsartan (S/V) is a novel treatment for this pathology. This study aims to analyze the effect of this medication on clinical, laboratory and echocardiographic variables in patients with HF and left ventricular eyección fracción reduced (LVEFr). Methodology: A retrospective observational study was conducted on patients records who are enrolled in the Heart Failure Program (HFP) and have been prescribed with S/V. For these patients, baseline and follow-up data was collected for relevant parameters. Changes over time were then quantified once the treatment with S/V was initiated, and a statistical analysis was conducted to validate whether the changes were significant. Results: Of all HFP patients, 27 met the inclusion criteria, with an average age of 70 years and where 37.0% of them were at the target dose after an average follow- up of 16.4 months. Through the study it was possible to find a statistically significant difference in a change for the ejection fraction in 17 patients (p.0.016). In patients with available clinical data, it was observed that NT-proBNP improved by 68.75%, meanwhile the 6-minute walk improved by 77.8%. In addition, only 7.4% of patients worsened their NYHA functional scale, 3.7% were hospitalized and 7.4% died during the time. Conclusions: Based on the studied parameters and throughout all the clinical changes during the follow-up time, it was possible to establish an improvement in patients after the S/V therapy, which is also associated with a low hospitalization incidence and a low mortality rate.
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Humanos , Idoso , Idoso de 80 Anos ou mais , Valsartana/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , IdosoRESUMO
Resumo Fundamento O tratamento com sacubitril-valsartana teve seu benefício prognóstico confirmado no ensaio PARADIGM-HF. No entanto, dados sobre alterações no teste de esforço cardiopulmonar (TECP) com o uso de sacubitril-valsartana são escassos. Objetivo O objetivo deste estudo foi comparar os parâmetros do TECP antes e depois do tratamento com sacubitril-valsartana. Métodos Avaliação prospectiva de pacientes com insuficiência cardíaca (IC) crônica e fração de ejeção do ventrículo esquerdo ≤40%, mesmo sob terapia padrão otimizada, que iniciaram tratamento com sacubitril-valsartana, sem expectativa de tratamentos adicionais para a IC. Os dados do TECP foram coletados na semana anterior e 6 meses depois do tratamento com sacubitril-valsartana. Diferenças estatísticas com valor p <0,05 foram consideradas significativas. Resultados De 42 pacientes, 35 (83,3%) completaram o seguimento de 6 meses, uma vez que 2 (4,8%) morreram e 5 (11,9%) interromperam o tratamento devido a eventos adversos. A média de idade foi de 58,6±11,1 anos. A classe NYHA (classificação da New York Heart Association) melhorou em 26 (74,3%) pacientes. O consumo máximo de oxigênio (VO2max) (14,4 vs. 18,3 ml/kg/min, p<0,001), a inclinação VE/VCO2 (36,7 vs. 31,1, p<0,001) e a duração do exercício (487,8 vs. 640,3 s, p<0,001) também melhoraram com o uso de sacubitril-valsartana. O benefício foi mantido mesmo com a dose de 24/26 mg (13,5 vs. 19,2 ml/kg/min, p=0,018) de sacubitril-valsartana, desde que esta tenha sido a maior dose tolerada. Conclusões O tratamento com sacubitril-valsartana está associado a uma melhora acentuada do VO2max, da inclinação VE/VCO2 e da duração do exercício no TECP. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)
Abstract Background Sacubitril/valsartan had its prognosis benefit confirmed in the PARADIGM-HF trial. However, data on cardiopulmonary exercise testing (CPET) changes with sacubitril-valsartan therapy are scarce. Objective This study aimed to compare CPET parameters before and after sacubitril-valsartan therapy. Methods Prospective evaluation of chronic heart failure (HF) patients with left ventricular ejection fraction ≤40% despite optimized standard of care therapy, who started sacubitril-valsartan therapy, expecting no additional HF treatment. CPET data were gathered in the week before and 6 months after sacubitril-valsartan therapy. Statistical differences with a p-value <0.05 were considered significant. Results Out of 42 patients, 35 (83.3%) completed the 6-month follow-up, since 2 (4.8%) patients died and 5 (11.9%) discontinued treatment for adverse events. Mean age was 58.6±11.1 years. New York Heart Association class improved in 26 (74.3%) patients. Maximal oxygen uptake (VO2max) (14.4 vs. 18.3 ml/kg/min, p<0.001), VE/VCO2slope (36.7 vs. 31.1, p<0.001), and exercise duration (487.8 vs. 640.3 sec, p<0.001) also improved with sacubitril-valsartan. Benefit was maintained even with the 24/26 mg dose (13.5 vs. 19.2 ml/kg/min, p=0.018) of sacubitril-valsartan, as long as this was the highest tolerated dose. Conclusions Sacubitril-valsartan therapy is associated with marked CPET improvement in VO2max, VE/VCO2slope, and exercise duration. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)
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Humanos , Pessoa de Meia-Idade , Idoso , Função Ventricular Esquerda , Insuficiência Cardíaca/tratamento farmacológico , Oxigênio , Volume Sistólico , Tetrazóis , Estudos Prospectivos , Resultado do Tratamento , Combinação de Medicamentos , Antagonistas de Receptores de Angiotensina , AminobutiratosRESUMO
OBJECTIVES: The purpose of this study was to investigate the effect of sacubitril/valsartan therapy on sudden cardiac death (SCD) according to the use of and eligibility for an implantable cardioverter-defibrillator (ICD), stratified by heart failure cause. BACKGROUND: SCD still accounts for a significant proportion of overall mortality in heart failure with reduced ejection fraction (HFrEF). METHODS: Patients enrolled in the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial (n = 8,399) were evaluated to assess patterns of ICD implantation and eligibility according to clinical guidelines. The impact of ICD (adjusted for propensity of ICD implantation) and sacubitril/valsartan therapy on SCD was evaluated by using cause-specific Cox models and competing risk analysis. RESULTS: At baseline, of the 7,145 patients (85%) eligible for ICD implantation, only 1,243 (15%) had an ICD. Use of ICD varied by region with the highest rates in North America (56%) and lowest in Asia-Pacific (1.7%). In a propensity score-adjusted analysis, use of an ICD was associated with a 56% lower risk of SCD in ICD-eligible patients, in both patients with ischemic (p < 0.001) and nonischemic cardiomyopathy (p = 0.02). Sacubitril/valsartan reduced SCD risk in patients with an ICD (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.25 to 0.99) and in those who were eligible for but did not receive an ICD (HR: 0.81; 95% CI: 0.67 to 0.98). This effect was particularly evident in nonischemic cardiomyopathy (p < 0.05), although interaction with the cause of HF was not significant (p = 0.11 in subjects using an ICD and p = 0.25 in eligible nonusers). CONCLUSIONS: Use of an ICD was associated with lower rates of SCD, regardless of HF cause but was underused in most regions of the world in the PARADIGM-HF study. Sacubitril/valsartan reduced SCD risk regardless of use of an ICD or eligibility, particularly in ICD users and nonischemic cardiomyopathy.
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Aminobutiratos , Compostos de Bifenilo , Morte Súbita Cardíaca , Desfibriladores Implantáveis , Insuficiência Cardíaca , Valsartana , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo/uso terapêutico , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , América do Norte , Estudos Prospectivos , Volume Sistólico , Tetrazóis , Valsartana/uso terapêuticoRESUMO
The use of sacubitril/valsartan significantly reduces death or hospitalization in patients with ejection fraction < 40%. There is no study evaluating this drug effects in non-compaction cardiomyopathy (NCCM) individuals. The aim of this article is to report a case of a patient with NCCM initially refractory to gold standard treatment and afterwards treated with sacubitril/valsartan and its improvements. This is a case report of a 48-year-old woman, presenting with NCCM heart failure, who had received standard guideline-directed medical therapy for 18 months without any improvement in clinical and echocardiographic parameters. After that period, sacubitril/valsartan was initiated. After 18 months of refractory usage of guideline-directed medical therapy, sacubitril/valsartan was started, and significant change in functional class (III to I) and important ventricular remodelling were achieved with an improvement of 29% in the ejection fraction, reduction of 7 mm in ventricular diastolic diameter, and mild to none mitral valve functional regurgitation. In this case report, sacubitril/valsartan use was associated with improvement of echocardiographic and clinical parameters in a patient with NCCM.
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Antagonistas de Receptores de Angiotensina , Cardiomiopatias , Aminobutiratos , Compostos de Bifenilo , Combinação de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Volume Sistólico , ValsartanaRESUMO
Resumen Objetivo: describir las características y el comportamiento clínico de pacientes tratados con sacubitril/valsartán en una clínica de falla cardiaca de un hospital de alta complejidad. Métodos: se analizaron en retrospectiva 56 pacientes en manejo con sacubitril/valsartán, entre enero de 2017 y mayo de 2018. A los tres meses de inicio del tratamiento, 87% de los pacientes fueron evaluados. Se determinaron cambios en clase funcional, fracción de eyección ventricular izquierda (FEVI) y presión arterial sistólica y diastólica. Se registraron reingresos hospitalarios por falla cardiaca, mortalidad cardiovascular y eventos adversos asociados a la medicación. Resultados: la edad promedio fue 71,3 años; 51,7% correspondían al sexo masculino, 73% tenía etiología isquémica, 35% clase funcional NYHA II y 60% NYHA III antes de iniciar el tratamiento con sacubitril/valsartán. Al finalizar el seguimiento, 57% mejoró su clase funcional y 81,7% se encontraba en clase funcional NYHA II (IC95%, -0,52 a-0,18; p=0,0002). Hubo mejoría significativa en los valores de FEVI respecto a los basales (IC95%, 4,27 a 11,86; p=0,0002). Se observó una disminución significativa de la presión arterial tanto sistólica como diastólica (p<0,01). Un paciente presentó muerte súbita (2%) y uno hospitalización por falla cardiaca (2%). Ningún paciente descontinuó la terapia por efectos adversos. Conclusión: sacubitril/valsartán es una terapia útil en pacientes con falla cardiaca sintomática y FEVI reducida. La población evaluada tenía un perfil demográfico y clínico semejante al del ensayo clínico PARADIGM-HF, lo cual sugiere que los desenlaces clínicos son similares en la población colombiana.
Abstract Objective: The aim of this study is to describe the characteristics and clinical behaviour of patients treated with sacubitril/valsartan in a heart failure clinic of a high complexity hospital. Methods: A retrospective analysis was performed on a total of 56 patients on treatment with sacubitril/valsartan, between January 2017 and May 2018. At three months from the start of the treatment, 87% of the patients were evaluated. Changes were observed in functional class, left ventricular ejection fraction (LVEF), and systolic and diastolic arterial pressure. A record was made of hospital re-admissions due to heart failure, cardiovascular mortality, and adverse events associated with the medication. Results: The mean age of the patients was 71.3 years, of which 51.7% were male. An ischaemic origin was found in 73%. NYHA II and NYHA III functional class was observed 35% and 60%, respectively, before starting the treatment with sacubitril/valsartan. At the end of follow-up, 57% improved their functional class, and 81.7% were found to be in NYHA II functional class (95% CI; -0.52 to -0.18:=0.0002). There was a significant improvement in the LVEF values compared to baseline (95% CI; 4.27 to 11.86; P=0.0002). A significant decrease was observed in both systolic and diastolic blood pressure (P<0.01). There was sudden death in one (2%) patient and one (2%) patient admitted due to heart failure. None of the patients stopped the therapy due to secondary effects. Conclusion: Sacubitril/valsartan is a useful therapy in patients with symptomatic heart failure and a decreased LVEF. The population evaluated had a demographic and similar clinical signs and symptoms to the PARADIGM-HF clinical trial, which suggests that the clinical outcomes are similar in the Colombian population.
Assuntos
Humanos , Masculino , Idoso , Valsartana , Insuficiência Cardíaca , Sinais e Sintomas , Pressão Sanguínea , Disfunção Ventricular EsquerdaRESUMO
Arterial hypertension is the most prevalent chronic disease in the adult population of developed countries and it constitutes a significant risk factor in the development of cardiovascular disease, contributing to the emergence of many comorbidities, among which heart failure excels, a clinical syndrome that nowadays represents a major health problem with uncountable hospitalizations and the indolent course of which progressively worsens until quality of life decreases and lastly death occurs prematurely. In the light of this growing menace, each day more efforts are invested in the field of cardiovascular pharmacology, searching for new therapeutic options that allow us to modulate the physiological systems that appear among these pathologies. Therefore, in the later years, the study of natriuretic peptides has become so relevant, which mediate beneficial effects at the cardiovascular level such as diuresis, natriuresis, and decreasing cardiac remodeling; their metabolism is mediated by neprilysin, a metalloproteinase, widely expressed in the human and capable of catalyzing many substrates. The modulation of these functions has been studied by decades, giving room to Sacubitril, the first neprilysin inhibitor, which in conjunction with an angiotensin receptor blocker has provided a high efficacy and tolerability among patients with heart failure, for whom it has already been approved and recommended. Nonetheless, in the matter of arterial hypertension, significant findings have arisen that demonstrate the potential role that it will play among the pharmacological alternatives in the upcoming years.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Hipertensão/tratamento farmacológico , Neprilisina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Humanos , Neprilisina/farmacologiaRESUMO
Resumen: El Congreso de la American Heart Association 2018 tuvo lugar en la ciudad de Chicago, Illinois, del 10 al 12 de noviembre. Contó con múltiples novedades, se presentaron tres nuevas guías de recomendaciones (abordaje de las bradicardias y trastornos de conducción, actividad física, y tal vez la más esperada, la nueva guía de tratamiento de las dislipemias). Al revisar las recomendaciones de 2013, los expertos norteamericanos introdujeron varios cambios, el más importante de los cuales quizá sea disminuir la trascendencia que se le da al cálculo del riesgo a diez años para volver a enfocarse en la meta de las lipoproteínas de baja densidad (LDL), bajo la premisa de que cuanto más bajo, mejor. Realizaremos un breve resumen de algunos de los principales trabajos científicos presentados durante este evento que, sin duda, tendrán una influencia importante en el futuro próximo de la cardiología mundial. - Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial - REDUCE-IT. - Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease - VITAL. - Angiotensin Receptor-Neprilysin Inhibition in Patients Hospitalized With Acute Decompensated Heart Failure: Primary Results of the PIONEER - HF Randomized Controlled Trial. - Pre-hospital Resuscitation Intra-arrest Cooling Effectiveness Survival Study - the PRINCESS Trial.
Summary: The American Heart Association 2018 Congress was held in the city of Chicago, Illinois, from November 10 to 12. There were many news, three new recommendations guidelines were presented (approach to bradycardia and driving disorders, physical activity, and perhaps the most anticipated, the new treatment guide for dyslipidemia). In reviewing the 2013 recommendations, US experts introduced several changes, the most important of which may be to reduce the significance of the 10-year risk calculation to refocus on the LDL goal, under the premise of that the lower, the better. We will make a brief summary of some of the main scientific papers presented during this event that will undoubtedly have an important influence in the near future of global cardiology. - Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial - REDUCE-IT. - Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease - VITAL. - Angiotensin Receptor-Neprilysin Inhibition in Patients Hospitalized With Acute Decompensated Heart Failure: Primary Results of the PIONEER-HF Randomized Controlled Trial. - Pre-hospital Resuscitation Intra-arrest Cooling Effectiveness Survival Study - the PRINCESS Trial.
Resumo: O Congresso da American Heart Association 2018 foi realizado na cidade de Chicago, Illinois, de 10 a 12 de novembro. Havia muitos novos recursos, três novos guias de recomendações foram apresentados (abordagem para bradicardia e transtornos de direção, atividade física e talvez o mais aguardado, o novo guia de tratamento para dislipidemia). Ao rever as recomendações de 2013, os especialistas norte-americanos introduziram várias mudanças, a mais importante das quais pode ser reduzir a significância do cálculo do risco de 10 anos para reorientar a meta de LDL, sob a premissa de que quanto menor, melhor. Faremos um breve resumo de alguns dos principais trabalhos científicos apresentados durante este evento que, sem dúvida, terão uma influência importante no futuro próximo da cardiologia global. - Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial - REDUCE-IT. - Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease - VITAL. - Angiotensin Receptor-Neprilysin Inhibition in Patients Hospitalized With Acute Decompensated Heart Failure: Primary Results of the PIONEER - HF Randomized Controlled Trial. - Pre-hospital Resuscitation Intra-arrest Cooling Effectiveness Survival Study - the PRINCESS Trial.
RESUMO
Resumen La insuficiencia cardiaca es una de las principales enfermedades a nivel cardiaco debido a su mayor riesgo de mortalidad y de hospitalizaciones por descompensaciones agudas o por presencia de novo de falla cardiaca, por eso en los últimos años se desarrollaron a partir de estudios clínicos randomizados, medicamentos que mejoraran estos eventos, a partir del estudio PARADIGM-HF. Con el surgimiento de sacubitril/valsartan se evaluó su efecto en diferentes escenarios, así el enfoque de este artículo se basa en la revisión de artículos con el objetivo de analizar la importancia de los efectos be neficiosos del sacubitril/valsartan en comparación con enalapril en diferentes análisis y subestudios basado en el estudio PARADIGM-HF, en los cuales se evaluó el impacto del sacubitril/valsartan en diabetes mellitus tipo 2, en la función renal, hipertensión arterial, a nivel de mortalidad y seguridad, a nivel de edad, de hiperkalemia e hiperkalemia severa, en los factores asociados con la falta de cumplimiento durante el período de ejecución antes de la aleatorización y la influen cia en el beneficio estimado de sacubitril/valsartan en el ensayo PARADIGM-HF, eficacia de sacubitril/valsartan con dosis metas bajas, tolerabilidad y seguridad en el inicio de sacubitril/valsartan en insuficiencia cardiaca, efectos de sacubitril/ valsartan asociado a antagonistas de receptores de mineralocorticoides en la reducción de hiperkalemia, implicaciones en el pronóstico de los pacientes con insuficiencia cardiaca con fracción de eyección reducida con los cambios de pépti dos natriuréticos, eficacia y seguridad de sacubitril/valsartan en distintos rangos de edades, efecto del fármaco sobre la terapia de fondo utilizada en insuficiencia cardiaca y eficacia e influencia de sacubitril/valsartan en la fracción de eyección y desenlace primario.
Abstract Descriptores: sacubitril/valsartan, enalapril, insuficiencia cardiaca, péptidos natriureticos Heart failure is one of the main diseases at the cardiac level due to its higher risk of mortality and hospitalizations due to acute decompensation or de novo heart failure, which is why in recent years they were developed from randomized clinical trials. medicines that will improve these events, from there and from the PARADIGM-HF study. From the emergence of sacubitril / valsartan its effect was evaluated in different scenarios, hence the focus of this article was based on the review of articles and with the aim of analyzing the importance of the beneficial effects of sacubitril / valsartan compared to enalapril in different analyzes and substudies from the PARADIGM-HF study, which will evaluate the impact of sacubitril / valsartan in type 2 diabetes mellitus, in renal function, arterial hypertension, in terms of mortality and safety, in terms of age, hyperkalemia and severe hyperkalemia, in the factors associated with non-compliance during the execution period before randomization and the influence on the estimated benefit of sacubitril / valsartan in the PARADIGM-HF trial, efficacy of sacubitril / valsartan with low target doses , tolerability and safety at the onset of sacubitril / valsartan in heart failure, effects of sacubitril / valsartan associated with antag of mineralocorticoid receptors in the reduction of hyperkalemia, implications in the prognosis of patients with heart failure with reduced ejection fraction with changes in natriuretic peptides, efficacy and safety of sacubitril / valsartan in different age ranges, effect of the drug on the background therapy used in heart failure and the efficacy and influence of sacubitril / valsartan on the ejection fraction and primary outcome.
Assuntos
Humanos , Enalapril/uso terapêutico , Fármacos Cardiovasculares , Neprilisina , Costa Rica , Peptídeos Natriuréticos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Valsartana/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológicoRESUMO
BACKGROUND: Sacubitril/valsartan (SAC/VAL) is approved by the U.S. Food and Drug Administration for heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: This study investigated the effects of SAC/VAL on acute myocardial infarction (MI) and cardiac remodeling in a translational rabbit model of MI. METHODS: New Zealand White rabbits were sedated and underwent conscious MI (45-min ischemia) by balloon inflation (previously implanted surgically) followed by 72 h (acute protocol) or 10 weeks (chronic protocols) of reperfusion. "Infarct-sparing" protocol: SAC/VAL, VAL, or placebo were randomly allocated and administered at reperfusion. "HFrEF-treatment" protocol: rabbits were randomized, and treatment commenced after echocardiography-confirmed left ventricular ejection fraction (LVEF) ≤40%. "HFrEF-prevention" protocol: treatment started at reperfusion and continued daily throughout the study. RESULTS: Compared with placebo, SAC/VAL and VAL significantly reduced infarct size (TTC staining) and plasma troponin levels; however, only SAC/VAL preserved LVEF at 72 h post-MI. In the HFrEF-treatment protocol, LVEF improvement was observed with SAC/VAL compared with both placebo and VAL starting 2 weeks post-treatment, a benefit that persisted throughout study duration. In the HFrEF-prevention protocol, SAC/VAL and VAL attenuated the decline in LVEF post-MI, although SAC/VAL offered better functional protection. The functional improvement observed in both treatment protocols was paralleled by significant reduction in left ventricular (LV) scar size (Picrosirius red staining) in the SAC/VAL groups. CONCLUSIONS: Reperfusion therapy with SAC/VAL or VAL offers robust acute infarct-sparing benefits; however, SAC/VAL treatment offered superior short-term and long-term benefits in preventing MI-induced LV dysfunction compared with VAL. SAC/VAL also significantly attenuated LV scar size following MI compared with placebo, whereas VAL did not reach statistical significance in scar reduction.