Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 148
Filtrar
1.
Int Heart J ; 61(1): 1-6, 2020 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-31875616

RESUMEN

Chronic heart failure (CHF) seriously affects the quality of patients' lives. Sacrubitril/valsartan is a combination angiotensin receptor-neprilysin inhibitor, a new therapeutic drugs to treat CHF.This study aims to observe the impact of sacrubitril/valsartan on clinical treatment and high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-brain natriuretic peptide (NT-ProBNP) serum levels, the improvement of the left atrial diameter (LAD) and left ventricular end diastolic dimension (LVEDD), and the left ventricular ejection fraction (LVEF) in patients with CHF.120 patients were randomly divided into a sacrubitil/valsartan group and a valsantan group, with 60 cases in each. Patients in the sacrubitil/valsartan group were administered sacrubitril/valsartan; while in the valsantan group, they were administered valsartan. The clinical effects, adverse reactions, and rehospitalization were observed eight weeks later, and hs-cTnT and NT-ProBNP serum levels and LAD, LVEDD, and LVEF were assayed.There were 53 cases of positive effect in the sacrubitil/valsartan group and 42 in the valsartan group (P < 0.05). Eight participants demonstrated adverse reactions in the sacrubitil/valsartan group, while 17 in the control group (P < 0.05). Hs-cTnT and NT-ProBNP serum levels, the measurements of LAD, LVEDD, and LVEF in the sacrubitil/valsartan group before the treatments were (24.47 ± 7.54) pg/mL, (10,356.94 ± 5,447.68) pg/mL, (49.41 ± 5.22) mm, (68.06 ± 6.20) mm and (31.12 ±6.65) %; in the valsartan group were (29.752 ± 10.03) pg/mL, (9,518.17 ± 5,905.17) pg/mL, (49.65 ± 4.91) mm, (67.06 ± 3.97) mm, and (30.41 ± 6.11) % (P > 0.05), while in the sacrubitil/valsartan group, the values decreased after the treatments to (17.92 ± 4.74) pg/mL, (3,881.59 ± 2,087.79) pg/mL, (42.18 ± 4.87) mm, (60.35 ± 7.12) mm and (45.35 ± 4.49) %; in the valsartan group to (25.81 ± 7.36) pg/mL, (6,278.35 ± 2,643.11) pg/mL, (46.53 ± 4.80) mm, (64.51 ± 4.34) mm, and (36.47 ± 5.21) % (P < 0.05). There were significant differences within the same group, before and after treatments (P < 0.05).Sacrubitril/valsartan treatment of patients with CHF improves their symptoms and is deserving of clinical application. This is also evident from significantly improved levels of serum hs-cTnT and NT-ProBNP and the left ventricular function.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Troponina T/sangre , Valsartán/uso terapéutico , Función Ventricular Izquierda/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Biomarcadores/sangre , Enfermedad Crónica , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Valsartán/farmacología
2.
Emergencias (Sant Vicenç dels Horts) ; 31(6): 407-412, dic. 2019. tab, graf
Artículo en Español | IBECS | ID: ibc-185139

RESUMEN

Objetivo. Identificar el patrón de práctica clínica habitual respecto al tratamiento crónico con sacubitrilo-valsartán (SV) durante los episodios de insuficiencia cardiaca aguda (ICA), sus determinantes y su efecto sobre la evolución. Método. Estudio exploratorio de pacientes con ICA incluidos en el Registro EAHFE-6 en tratamiento crónico con SV. Se recogieron características basales, del episodio y del tratamiento con SV, y se identificaron factores relacionados con la interrupción de SV y su asociación con eventos adversos 180 días postevento índice (mortalidad por cualquier causa) y postalta (reconsulta a urgencias u hospitalización por ICA, muerte o evento combinado). Resultados. Se incluyeron 50 pacientes (mediana desde inicio de SV: 81 días; RIC: 43-284) y SV se interrumpió en 19 casos (38%; 5 en urgencias, 14 en hospitalización). Se identificó un motivo de retirada en 16 casos (4 por insuficiencia renal; y 3 por hipotensión arterial, hiperpotasemia, debilidad/mareo y empeoramiento de ICA, respectivamente). La retirada de SV se asoció con edad avanzada, no estar en tratamiento con betabloqueantes e hiperpotasemia. No hubo diferencias significativas entre grupos en eventos adversos a los 180 días postevento índice o postalta. Conclusión. En los pacientes en tratamiento crónico con SV que presentan ICA, este es suspendido en más de un tercio de casos, si bien ello no se asocia con cambios evolutivos


Objectives. To describe the pattern of care usually given to patients with acute heart failure (AHF) who are taking sacubitril/valsartan (SV) and to explore the effects of care characteristics on clinical outcomes. Methods. Exploratory study of AHF cases in patients taking SV who were included in the register for the Epidemiology of Acute Heart Failure in Emergency Departments during the sixth period of data collection (EAHFE-6). We extracted baseline and episode variables and information related to SV treatment. We also analyzed associations between the discontinuation of SV therapy and adverse events within 180 days (all-cause mortality) and after discharge (emergency revisits, admission for AHF, death from any cause, or a composite event). Results. Fifty patients on SV were included. The median time on SV therapy was 81 days (interquartile range, 43-284 days). SV was discontinued in 19 cases (38%; 5 in the emergency department and 14 on the ward). Sixteen records specified the reason for discontinuing SV: renal insufficiency, 4 cases; arterial hypotension, 3; weakness/dizziness, 3; and exacerbated AHF, 3. SV discontinuation was associated with older age, absence of treatment with a betablocker, and hyperkalemia. The EAHFE-6 cases did not reveal significant differences related to SV discontinuation with respect to the rates of adverse events within 180 days or on discharge after the index event. Conclusions. Long-term SV therapy is discontinued in over a third of patients who present with exacerbated AHF even though no association with clinical outcomes could be identified


Asunto(s)
Humanos , Masculino , Femenino , Anciano , Insuficiencia Cardíaca/tratamiento farmacológico , Servicios Médicos de Urgencia , Hospitalización , Valsartán/uso terapéutico , Antihipertensivos/uso terapéutico , Conocimientos, Actitudes y Práctica en Salud , Antagonistas Adrenérgicos beta/uso terapéutico , Hiperpotasemia/tratamiento farmacológico
3.
Buenos Aires; CONETEC; nov. 2019.
No convencional en Español | BRISA/RedTESA | ID: biblio-1048404

RESUMEN

INTRODUCCIÓN: La insuficiencia cardíaca es la primera causa de hospitalización en mayores de 65 años y da cuenta de aproximadamente el 5% de todas las hospitalizaciones. Se estima una prevalencia del 1% de la población en América Latina que se incrementa a partir de los 65 años, y genera una alta tasa de internaciones. Es la tercera causa de muerte en los países desarrollados después de la cardiopatía isquémica y la enfermedad cerebro vascular. Algunos estudios señalan una supervivencia a los 5 años del 50%. A pesar de un progreso considerable en el desarrollo de una terapia médica eficaz, los pacientes con insuficiencia cardíaca (IC) siguen teniendo un alto riesgo de hospitalización recurrente. Entre los mayores de 65 años, aproximadamente 1 de cada 4 pacientes se reingresa dentro de los 30 días de la hospitalización y casi la mitad se reingresa dentro de los 6 meses. Los altos costos asociados con la atención hospitalaria amenazan con duplicar el gasto en atención de la salud en insuficiencia cardíaca para 2030. Esta carga financiera anticipada, junto con la preocupación de que muchas readmisiones tempranas pueden prevenirse al mejorar la calidad de la atención hospitalaria y las transiciones de atención, ha centrado la atención en las tasas de reingreso por insuficiencia cardíaca como una medida de la calidad de la atención. DESCRIPCIÓN DE LA TECNOLOGÍA: Sacubitrilo/valsartan es una combinación de un inhibidor de la neprilisina y un bloqueante del receptor de angiotensina II que se administra por vía oral. El objetivo del presente informe es evaluar la eficacia, seguridad, cambios en la calidad de vida y aspectos económicos de sacubitrilo/valsartán para pacientes con insuficiencia cardíaca crónica con fracción de eyección reducida. OBJETIVO: El objetivo del presente informe es evaluar la eficacia, seguridad, cambios en la calidad de vida y aspectos económicos de sacubitrilo/valsartán para pacientes con insuficiencia cardíaca crónica con fracción de eyección reducida. MÉTODOS: Se buscó en Pubmed con la siguiente estrategia de búsqueda:((LCZ 696 [Supplementary Concept] OR LCZ696[tiab] OR LCZ 696[tiab] OR Entresto[tiab]) OR (Sacubritil[tiab] AND (Valsartan[MeSH] OR Valsartan[tiab] OR Diovan[tiab] OR Kalpress[tiab] OR Tareg[tiab] OR Nisis[tiab] OR Provas[tiab] OR Vals[tiab] OR CGP 48933[tiab] OR 48933,CGP[tiab] OR Miten[tiab])) AND (Heart Failure[MeSH] OR Cardiac Failure[tiab] OR HeartFailure[tiab] OR Heart Decompens*[tiab] OR Congestive Heart[tiab]) AND (Systematic Review[sb] OR Systematic Review[tiab] OR Meta-Analysis[pt] OR Meta-Analys*[tiab] OR "Cochrane Database Syst Rev"[ta] OR Metaanalysis[tiab] OR Metanalysis[tiab] OR Sysrev Methods[sb] OR (MEDLINE[tiab] AND Cochrane[tiab]) OR Guideline[pt] OR Practice Guideline[pt] OR Guide-line*[ti] OR Guide Line*[tiab] OR Consensus[tiab] OR Recommendation*[ti] OR Randomized Controlled Trial[pt] OR Random*[ti] OR Controlled Trial*[tiab] OR Control Trial*[tiab] OR Technology Assessment, Biomedical[Mesh] OR Tech-nology Assessment[tiab] OR Technology Appraisal[tiab] OR HTA[tiab] OR Overview[ti] OR (Review[ti] AND Litera-ture[ti])). Se buscó en Embase Lilacs, BRISA ­Redetsa-, CRD, Cochrane, agencias nacionales de evaluación de tecnologías sanitarias; y buscadores genéricos de internet con la siguiente estrategia de búsqueda "sacubitril and heart failure" o "neprilysin and heart failure". Se utilizaron como criterios de inclusión textos en inglés o español a los que se pueda tener acceso al texto completo, publicados entre 2000 y 2019. La búsqueda se limitó a pacientes adultos mayores de 18 años con insuficiencia cardíaca. Se excluyeron textos en otro idioma, sin acceso a texto completo, que no fueran pertinentes de acuerdo con el título y el resumen, y que no aplicaran para el objetivo del presente análisis. Se priorizó la inclusión de revisiones sistemáticas y meta-análisis, ensayos clínicos controlados y aleatorizados, registros de seguridad de pacientes, evaluaciones de tecnologías sanitarias y guías de práctica clínica. RESULTADOS: Se incorporaron un total de 32 estudios en el informe. En el estudio PARADIGM-HF, de 2014, financiado por el patrocinante, doble ciego, se aleatorizaron 8442 pacientes con insuficiencia cardíaca clase funcional II, III, IV y una fracción de eyección de 35% o menor a sacubitrilo/valsartan a una dosis de 200 mg dos veces al día o enalapril (10 mg dos veces al día) sumado a la terapia habitual recomendada para esta patología. La muerte por causas cardiovasculares u hospitalización por insuficiencia cardíaca ocurrieron en el 21,8% de los pacientes en el grupo sacubitrilo/valsartán y en el 26,5% de los pacientes en el grupo de enalapril (hazard ratio 0,80; intervalo de confianza [IC] del 95%, 0,73 a 0,87; p <0,001). La diferencia a favor de sacubitrilo/valsartán se observó al principio del ensayo y en cada análisis intermedio. De todas estas muerte el 13,3% en el grupo sacubitrilo/valsartán y el 16,5% en el grupo enalapril se debieron a causas cardiovasculares (hazard ratio 0,80; IC del 95%, 0,71 a 0,89; P <0,001). De los pacientes que recibieron sacubitrilo/valsartán, 537 (12,8%) fueron hospitalizados por insuficiencia cardíaca, en comparación con 658 pacientes (15,6%) que recibieron enalapril (hazard ratio 0,79; IC del 95%, 0,71 a 0,89; p <0.001). El número de pacientes que necesitarían ser tratados para prevenir un evento primario y una muerte por causas cardiovasculares son de 21 y 32, respectivamente. Sacubitrilo/valsartán fue más efectivo para reducir el riesgo de muerte por causas cardiovasculares u hospitalización por insuficiencia cardíaca, el riesgo de muerte por cualquier causa y en la reducción de los síntomas y las limitaciones físicas de la insuficiencia cardíaca. CONCLUSIÓN: Sacubitrilo/valsartán fue marcadamente superior a enalapril en la reducción del riesgo de muerte y de hospitalización por insuficiencia cardiaca en pacientes con insuficiencia cardíaca clase funcional II-IV y fracción de eyección del ventrículo izquierdo menor a 35%. No hubieron diferencias estadísticamente significativas entre el grupo sacubitrilo/valsartán y los pacientes en el grupo enalapril con respecto a la disminución de la función renal (definida por el protocolo) como así tampoco en suspensión del tratamiento debido a presencia de evento adverso (tos, hiperkalemia, disfunción renal, angioedema o hipotensión). A los 8 meses, el grupo sacubitrilo/valsartán presentó mejor puntuación en la escala de calidad de vida (KCCQ) y de síntomas (EQ-5D VAS) aunque los resultados probablemente no impacten en la calidad de vida (RR=1.03). El estudio PARADIGM-HF se interrumpió anticipadamente por beneficio tras una mediana de seguimiento de 27 meses. La interrupción anticipada del ensayo se ha juzgado justificada al mostrar los datos una clara reducción del riesgo de hospitalización y muerte. Pero cuando los ensayos se suspenden por beneficio antes de lo previsto, tienden a representar una selección de resultados extremos. Los países de altos ingresos en general brindan cobertura, habitualmente ante la falta de respuesta con dosis máximas toleradas de enalapril o BRA. Sin embargo, los países de Latinoamérica no brindan cobertura (con excepción de Brasil). El impacto presupuestario estimado de la incorporación de esta tecnología en Argentina es muy elevado. Existe incertidumbre en el beneficio en los pacientes mayores de 75 años, quienes podrían no beneficiarse del uso de esta tecnología. En los estudios de vida real, solo el 25% de los pacientes cumplen con los criterios y toleran las dosis establecidas en el protocolo.


Asunto(s)
Humanos , Valsartán/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Antihipertensivos/uso terapéutico , Volumen Sistólico , Evaluación de la Tecnología Biomédica , Análisis Costo-Eficiencia
4.
J Coll Physicians Surg Pak ; 29(10): 1009-1011, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31564281

RESUMEN

The aim of this study was to compare curative effects of valsartan alone or combined with alpha-lipoic acid (ALA) on inflammatory cytokine indices including hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and renal function indices including urinary albumin excretion rate (UAER), ß2-microglobulin (ß2-MG) and cystatin C (Cys C) of patients with early-stage diabetic kidney disease (DKD). One hundred and two patients with early-stage DKD were randomly divided into group A and group B, with 51 patients in each group. Group A was administered with valsartan alone, while group B was administered with valsartan combined with ALA. Research showed that 14 days after treatment, group B had significantly lowered hs-CRP, TNF-α, UAER, ß2-MG and Cys C when compared with group A (all p<0.001). Compared to valsartan alone, valsartan combined with ALA can reduce level of inflammatory cytokines in serum and improve renal function.


Asunto(s)
Antihipertensivos/uso terapéutico , Citocinas/sangre , Citocinas/efectos de los fármacos , Nefropatías Diabéticas/tratamiento farmacológico , Ácido Tióctico/uso terapéutico , Valsartán/uso terapéutico , Anciano , Anciano de 80 o más Años , China , Quimioterapia Combinada , Femenino , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad
5.
Med Arch ; 73(3): 157-162, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31391706

RESUMEN

Introduction: Hypertension is significantly contributing to global mortality and morbidity and has been identified as the most important modifiable risk factor for early development of cardiovascular diseases (CVD). Aim: The aim of this study was to investigate the efficacy of different combinations of antihypertensive therapy on blood pressure, arterial stiffness and peripheral resistance in patients with essential hypertension using the brachial oscillometric ambulatory blood pressure monitor. Methods: This study was designed as an observational, prospective, multi centric study conducted in eight primary care centers of the Health Center of Canton Sarajevo during the period of six months. The study included 655 participants, both genders, aged between 30 and 75, who were diagnosed with hypertension according to the ESC/ESH guidelines. Participants were divided into six treatment groups based on the hypertensive drug therapy they were using; lisinopril, losartan or valsartan alone or in combination with hydrochlorothiazide (A, B and C group respectively) or combination of lisinopril, losartan or valsartan with/without hydrochlorothiazide together with amlodipine (D, E and F respectively). The participants were monitored at baseline, after 3 and 6 months (1st and 2nd follow-up). Brachial oscillometric ambulatory blood pressure monitor was used for measuring systolic (SBP), diastolic (DBP), pulse pressure (PP), pulse wave velocity (PWV) and peripheral resistance (PR). Results: SBP, DPB, PP, and PWV significantly decreased from baseline to 2nd follow-up in all treatment groups. The mean reductions in SBP were from -11.7 (95%CI; 9.3- 14.1) to -23.2 (95%CI; 18.3-28.1) mmHg and DBP reductions varied from -5.5 (95%CI; 3.9- 7.1) to -13.4 (95%CI; 7.7-19.1) mmHg. PWV decreased in all treatment groups (from -3.3% to -8.2%). Treatment regiment was not associated with significant differences in SBP, DBP, PP or PWV reductions or their values measured at 2nd follow-up. Peripheral resistance significantly decreased only in group C (p=0.011), group D (p=0.009) and group F (p=0.027). Conclusion: These data suggest that lisinopril/lisinopril + hydrochlorothiazide, losartan/losartan + hydrochlorothiazide and valsartan/valsartan + hydrochlorothiazide alone or in combination with amlodipine are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension.


Asunto(s)
Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos , Rigidez Vascular/efectos de los fármacos , Anciano , Amlodipino/farmacología , Amlodipino/uso terapéutico , Antihipertensivos/uso terapéutico , Arterias , Diástole/efectos de los fármacos , Combinación de Medicamentos , Hipertensión Esencial/tratamiento farmacológico , Femenino , Humanos , Hidroclorotiazida/farmacología , Hidroclorotiazida/uso terapéutico , Lisinopril/farmacología , Lisinopril/uso terapéutico , Losartán/farmacología , Losartán/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de la Onda del Pulso , Sístole/efectos de los fármacos , Valsartán/farmacología , Valsartán/uso terapéutico
6.
Ther Adv Cardiovasc Dis ; 13: 1753944719868134, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31401939

RESUMEN

Since the launch of the first orally available angiotensin II (AngII) type 1 receptor (AT1R) blocker (ARB) losartan (Cozaar) in the late 1990s, the class of ARBs (or 'sartans', short for Angiotensin-RecepTor-ANtagonistS) quickly expanded to include candesartan, eprosartan, irbesartan, valsartan, telmisartan, and olmesartan. All ARBs have high affinity for the AT1 receptor, expressed in various tissues, including smooth muscle cells, heart, kidney, and brain. Since activation of AT1R, the target of these drugs, leads, among other effects, to vascular smooth muscle cell growth, proliferation and contraction, activation of fibroblasts, cardiac hypertrophy, aldosterone secretion from the adrenal cortex, thirst-fluid intake (hypervolemia), etc., the ARBs are nowadays one of the most useful cardiovascular drug classes used in clinical practice. However, significant differences in their pharmacological and clinical properties exist that may favor use of particular agents over others within the class, and, in fact, two of these drugs, candesartan and valsartan, continuously appear to distinguish themselves from the rest of the 'pack' in recent clinical trials. The reason(s) for the potential superiority of these two agents within the ARB class are currently unclear but under intense investigation. The present short review gives an overview of the clinical properties of the ARBs currently approved by the United States Food and Drug Administration, with a particular focus on candesartan and valsartan and the areas where these two drugs seem to have a therapeutic edge. In the second part of our review, we outline recent data from our laboratory (mainly) on the molecular effects of the ARB drugs on aldosterone production and on circulating aldosterone levels, which may underlie (at least in part) the apparent clinical superiority of candesartan (and valsartan) over most other ARBs currently in clinical use.


Asunto(s)
Aldosterona/sangre , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Bencimidazoles/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Sistema Renina-Angiotensina/efectos de los fármacos , Tetrazoles/uso terapéutico , Valsartán/uso terapéutico , Animales , Biomarcadores/sangre , Regulación hacia Abajo , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Recuperación de la Función , Resultado del Tratamiento
7.
Brasília; CONITEC; ago. 2019. ilus, tab.
No convencional en Portugués | BRISA/RedTESA | ID: biblio-1024619

RESUMEN

CONTEXTO: O objetivo do presente relatório é analisar as evidências científicas sobre a eficácia, segurança e custo-efetividade do medicamento sacubitril/valsartana para o tratamento de pacientes adultos com ICFEr. TECNOLOGIA: Sacubitril/Valsartana. PERGUNTA: O uso de sacubitril/valsartana é eficaz e seguro para o tratamento de pacientes adultos com ICFEr, quando comparado a outros ativos ou ao placebo? EVIDÊNCIAS CIENTÍFICAS: Foram incluídos pela nova seleção um Ensaio Clínico Randomizado (ECR) fase III, uma Revisão Sistemática (RS) com meta-análise em rede, uma meta-análise e dois estudos de coorte, em sua maioria com boa qualidade metodológica, que avaliaram os resultados de sacubitril/valsartana para o tratamento de pacientes com ICFEr. O ECR PARADIGM-HF avaliou a eficácia e segurança do sacubitril/valsartana versus enalapril em 8.442 pacientes com ICFEr, demonstrando resultados positivos, com significância estatística, para os desfechos morte por todas as causas/causas cardiovasculares, hospitalização por insuficiência cardíaca e mudanças no escore KCCQ. Contudo, esse resultado não se manteve para os pacientes maiores de 75 anos, com classe funcional NYHA III-IV, fração de ejeção ventricular esquerda (FEVE) > 35% e virgens de tratamento com Inibidores da Enzima Conversora da Angiotensina (IECA). Em relação à segurança, demonstrou não haver diferenças significantes quando comparado ao enalapril. A meta-análise de Komajda e colaboradores (2018) avaliou o tratamento da ICFEr com todos os grupos de medicamentos recomendados pelas diretrizes, demonstrando redução do risco de morte com significância estatística e superioridade das associações em relação ao placebo. O estudo de Vecchis & Ariano (2017) avaliou 44 pacientes tratados com sacubitril/valsartana e 88 pacientes controles (em uso de IECA ou Bloqueadores dos Receptores de Angiotensina II (BRA)), para desfechos de segurança e eficácia. Os resultados de eficácia foram melhores no grupo sacubitril/valsartana quando comparados ao grupo controle, enquanto os desfechos de segurança mostraram perfis comparáveis nos dois grupos. A meta-análise de Li e colaboradores (2017) avaliou a segurança de ensaios clínicos com sacubitril/valsartana versus IECA/BRA/placebo para o tratamento de pacientes com IC e hipertensão e, para todos os eventos adversos avaliados, os resultados demonstraram não haver diferença estatisticamente significante entre os grupos. Já a coorte de Vecchis e colaboradores (2018) avaliou o impacto do uso de sacubitril/valsartana na função cognitiva de 102 pacientes com IC (51 tratados com sacubitril/valsartana e 51 tratados com outras terapias farmacológicas) e demonstrou não haver diferenças estatisticamente significativas entre os grupos. AVALIAÇÃO ECONÔMICA: A razão de custo-efetividade incremental (RCEI) do tratamento com sacubitril/valsartana versus enalapril foi de R$ 25.832,89 por ano de vida ajustado por qualidade (AVAQ) e de R$ 22.769,82 por ano de vida ganho (AVG). O cenário alternativo, comparando losartana ao sacubitril/valsartana, resultou em uma RCEI de R$ 24.649,49 por AVAQ e de R$ 21.222,76 por AVG. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Estima-se um custo adicional com medicamentos de aproximadamente R$ 64 milhões para o ano de 2019 e impacto de R$ 701 milhões em 5 anos, em um cenário de incorporação do sacubitril/valsartana. EXPERIÊNCIA INTERNACIONAL: O NICE (Reino Unido), CADTH (Canadá), PBAC (Austrália), HAS (França) e SMC (Escócia) recomendaram o uso do sacubitril/valsartana para pacientes com ICFEr sintomática. O IQWiG (Alemanha) apenas constatou uma indicação de benefício adicional do sacubitril/valsartana em comparação ao enalapril, assim como a AEMPS (Espanha), que considerou o mesmo como uma opção de tratamento para um grupo específico de pacientes. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram detectadas quatro potenciais tecnologias para o tratamento de pacientes adultos com insuficiência cardíaca crônica sintomática (NYHA classe IIIV) com fração de ejeção reduzida, em estudos clínicos de fase 3 ou 4. CONSIDERAÇÕES: As evidências elencadas no presente relatório, em sua maioria de boa qualidade, indicam que o uso de sacubitril/valsartana, em esquema triplo de tratamento, é eficaz e potencialmente seguro para pacientes com IC classe NYHA II sintomáticos, com fração de ejeção ventricular esquerda menor ou igual a 35%, refratários ao tratamento com IECA e/ou BRA e com idade igual ou inferior a 75 anos. Tais evidências, somadas ao custo elevado do tratamento com essa tecnologia, indicam que seria necessário o estabelecimento de critérios de elegibilidade para o uso de sacubitril/valsartana. RECOMENDAÇÃO PRELIMINAR: Considerou-se que o medicamento não apresenta benefícios clínicos condizentes com o preço proposto para o medicamento no Brasil. Assim, a CONITEC, em sua 72ª reunião em 07 de novembro de 2018, recomendou a não incorporação no SUS de sacubitril/valsartana para tratamento de pacientes adultos com insuficiência cardíaca crônica sintomática NYHA II-IV com fração de ejeção reduzida. CONSULTA PÚBLICA: A Consulta Pública (CP) nº 70 foi realizada entre os dias 28/11/2018 e 17/12/2018. Foram recebidas 2.187 contribuições, sendo 231 pelo formulário para contribuições técnico-científicas (161 contrárias e 20 neutras) e 1.956 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema (1.797 contrárias e 159 a favor). Após apreciação das contribuições encaminhadas pela CP, principalmente as novas condições propostas pelo demandante para a incorporação de sacubitril/valsartana, com redução de preço e restrição de indicação ao tratamento, o plenário da CONITEC entendeu que houve argumentação suficiente para alterar a recomendação inicial e incorporar sacubitril/valsartana ao SUS. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 77ª reunião ordinária, no dia 09 de maio de 2019, deliberaram, por maioria simples, por recomendar a incorporação do sacubitril/valsartana para o tratamento de insuficiência cardíaca crônica em pacientes com classe funcional NYHA II e BNP > 150 (ou NT-ProBNP > 600), com fração de ejeção reduzida (FEVE ≤ 35%), idade menor ou igual a 75 anos e refratários ao melhor tratamento disponível, conforme estabelecido em Protocolo Clínico e Diretrizes Terapêuticas. DECISÃO: Incorporar o sacubutril/valsartanapara o tratamento de insuficiência cardíaca crônica em pacientes com classe funcional NYHA II e BNP > 150 (ou NT-ProBNP > 600), com fração de ejeção reduzida (FEVE < ou = 35%), idade menor ou igual a 75 anos e refratários ao melhor tratamento disponível, no âmbito do Sistema Único de Saúde - SUS. Dada pela Portaria nº 40, publicada no Diário Oficial da União nº 153, seção 1, página 186 e 187, em 9 de agosto de 2019.


Asunto(s)
Humanos , Valsartán/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Evaluación de la Tecnología Biomédica , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio/economía
9.
World J Pediatr Congenit Heart Surg ; 10(3): 292-295, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31084317

RESUMEN

BACKGROUND: Heart failure (HF) is the leading cause of hospitalizations and death in patients with adult congenital heart disease (ACHD). Sacubitril/valsartan is a new agent in the treatment of HF, but its effects have not been assessed in ACHD. METHODS: We retrospectively studied all 15 patients with ACHD at our center who were prescribed sacubitril/valsartan between June 2017 and June 2018. We assessed baseline characteristics and clinical and laboratory changes after initiation of sacubitril/valsartan. Adverse events, including renal function, medication intolerance, and worsening HF were documented. RESULTS: The median age was 53.2 (27.6-83.6) years, with a median follow-up duration of 69 (8-419) days. At baseline, all patients had refractory HF despite guideline-directed medical therapy, with ten (67%) patients as New York Heart Association (NYHA) class II, and five (33%) patients NYHA class III. The medication was discontinued in one (7%) patient secondary to worsening kidney function. No patients reported clinical deterioration; four NYHA class III patients with complex CHD, pulmonary hypertension, and cyanosis reported significant improvement to NYHA class II. Baseline creatinine was 1.1 (0.9-1.7) and two weeks after starting sacubitril/valsartan it was 1.3 (0.8-2.5, P = .22). CONCLUSIONS: Sacubitril/valsartan seems to be well tolerated in patients with ACHD who present with refractory HF symptoms. Patients with complex CHD associated with cyanosis and pulmonary hypertension could benefit the most, but larger studies are needed to assess the safety as well as the effectiveness of sacubitril/valsartan in this patient population.


Asunto(s)
Aminobutiratos/uso terapéutico , Cardiopatías Congénitas/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Volumen Sistólico/fisiología , Tetrazoles/uso terapéutico , Valsartán/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/complicaciones , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Persona de Mediana Edad , Neprilisina , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
10.
Can J Physiol Pharmacol ; 97(8): 708-720, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30970225

RESUMEN

This study examined the effect of the aromatase inhibitor letrozole (0.5 mg/kg) alone or in combination with the angiotensin-receptor blocker valsartan (30 mg/kg) against streptozocin-induced diabetic nephropathy (DN) in hypogonadal (HG) rats for 12 weeks. First, we tested the HG effect on hormone levels, inflammatory cytokines, and oxidative stress in nondiabetic (ND) and diabetic (D) rats. HG was induced with the luteinizing hormone-releasing hormone antagonist cetrorelix (0.71 mg/kg). Diabetes enhanced hormonal hypogonadism and increased inflammation and oxidative stress. Next, experiments examined the effect of early letrozole and valsartan intervention on DN in HG rats. HG-ND and HG-D rats were treated with letrozole alone or in combination with valsartan. HG-D rats developed proteinuria and had increased blood urea nitrogen and creatinine, and histopathological evidence of renal injury, including glomerular hypertrophy and mesangial expansion. Valsartan alone or in combination with letrozole reduced proteinuria, improved renal functions, and reduced diabetes-induced renal angiotensin II. Both agents ameliorated nuclear factor kappa light chain enhancer of activated B cells, interleukin 1ß, interleukin 6, and tumor necrosis factor alpha levels. The combination decreased superoxide dismutase, malondialdehyde, and glutathione peroxidase levels, and prevented glomerular hypertrophy. In HG-D rats, valsartan reduced renal collagen IV and transforming growth factor-beta 1, especially when the testosterone level was corrected by letrozole. Thus, normalizing testosterone and inhibiting renal angiotensin II have a renoprotective effect against DN in HG male rats.


Asunto(s)
Angiotensinas/antagonistas & inhibidores , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Hipogonadismo/complicaciones , Angiotensina II/sangre , Animales , Colágeno Tipo IV/sangre , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Estradiol/sangre , Hormona Folículo Estimulante/sangre , Hemoglobina A Glucada/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Letrozol/farmacología , Letrozol/uso terapéutico , Hormona Luteinizante/sangre , Masculino , FN-kappa B/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Transducción de Señal/efectos de los fármacos , Testosterona/sangre , Factor de Crecimiento Transformador beta1/sangre , Valsartán/farmacología , Valsartán/uso terapéutico
11.
Int J Mol Sci ; 20(8)2019 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-31013989

RESUMEN

The incidence of aging-related disorders may be decreased through strategies influencing the expression of longevity genes. Although numerous approaches have been suggested, no effective, safe, and easily applicable approach is yet available. Efficacy of low-dose fluvastatin and valsartan, separately or in combination, on the expression of the longevity genes in middle-aged males, was assessed. Stored blood samples from 130 apparently healthy middle-aged males treated with fluvastatin (10 mg daily), valsartan (20 mg daily), fluvastatin-valsartan combination (10 and 20 mg, respectively), and placebo (control) were analyzed. They were taken before and after 30 days of treatment and, additionally, five months after treatment discontinuation. The expression of the following longevity genes was assessed: SIRT1, PRKAA, KLOTHO, NFE2L2, mTOR, and NF-κB. Treatment with fluvastatin and valsartan in combination significantly increased the expression of SIRT1 (1.8-fold; p < 0.0001), PRKAA (1.5-fold; p = 0.262) and KLOTHO (1.7-fold; p < 0.0001), but not NFE2L2, mTOR and NF-κB. Both fluvastatin and valsartan alone significantly, but to a lesser extent, increased the expression of SIRT1, and did not influence the expression of other genes. Five months after treatment discontinuation, genes expression decreased to the basal levels. In addition, analysis with previously obtained results revealed significant correlation between SIRT1 and both increased telomerase activity and improved arterial wall characteristics. We showed that low-dose fluvastatin and valsartan, separately and in combination, substantially increase expression of SIRT1, PRKAA, and KLOTHO genes, which may be attributed to their so far unreported pleiotropic beneficial effects. This approach could be used for prevention of ageing (and longevity genes)-related disorders.


Asunto(s)
Fluvastatina/farmacología , Expresión Génica/efectos de los fármacos , Longevidad/genética , Enfermedades Neurodegenerativas/prevención & control , Valsartán/farmacología , Proteínas Quinasas Activadas por AMP/genética , Adulto , Envejecimiento/genética , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Fluvastatina/uso terapéutico , Glucuronidasa/genética , Humanos , Masculino , Persona de Mediana Edad , Efecto Placebo , Sirtuina 1/genética , Telomerasa/metabolismo , Valsartán/uso terapéutico
12.
Rev. Soc. Cardiol. Estado de Säo Paulo ; 29(2): 133-136, abr.-jun. 2019.
Artículo en Portugués | LILACS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1009419

RESUMEN

As doenças cardiovasculares, principalmente as decorrentes de casos de acidente vascular cerebral e infarto agudo do miocárdio, têm importante impacto na mortalidade global e nas internações hospitalares em todo o mundo. A despeito do vasto conhecimento dos diversos fatores de risco implicados na gênese da doença cardiovascular, o número de eventos ainda se mantém elevado e a instituição de medidas de prevenção primária e secundária são essenciais e complementares. Nos últimos anos, importantes avanços no campo do tratamento farmacológico de aterosclerose e insuficiência cardíaca, predominantemente em decorrência de cardiopatia isquêmica, foram publicados e seus principais resultados são destacados no presente artigo


Cardiovascular diseases, particularly those arising from cases of stroke and acute myocardial infarction, have a significant impact on global mortality and hospital admissions around the world. Despite the vast knowledge of the various risk factors involved in the genesis of cardiovascular disease, the number of events remains high and institution of primary and secondary prevention measures is essential and complementary. In recent years, important advances in the field of pharmacological treatment of atherosclerosis and heart failure, particularly those arising from ischemic heart disease, have been published. The main results are highlighted in this article


Asunto(s)
Humanos , Masculino , Femenino , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Prevención Secundaria/métodos , Terapéutica/métodos , Factores de Riesgo , Diabetes Mellitus , Aterosclerosis , Canagliflozina/uso terapéutico , Rivaroxabán/uso terapéutico , Valsartán/uso terapéutico , Insuficiencia Cardíaca , Antiinflamatorios/uso terapéutico , Actividad Motora
13.
J Am Med Inform Assoc ; 26(5): 429-437, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30869798

RESUMEN

OBJECTIVE: Participants enrolled into randomized controlled trials (RCTs) often do not reflect real-world populations. Previous research in how best to transport RCT results to target populations has focused on weighting RCT data to look like the target data. Simulation work, however, has suggested that an outcome model approach may be preferable. Here, we describe such an approach using source data from the 2 × 2 factorial NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial, which evaluated the impact of valsartan and nateglinide on cardiovascular outcomes and new-onset diabetes in a prediabetic population. MATERIALS AND METHODS: Our target data consisted of people with prediabetes serviced at the Duke University Health System. We used random survival forests to develop separate outcome models for each of the 4 treatments, estimating the 5-year risk difference for progression to diabetes, and estimated the treatment effect in our local patient populations, as well as subpopulations, and compared the results with the traditional weighting approach. RESULTS: Our models suggested that the treatment effect for valsartan in our patient population was the same as in the trial, whereas for nateglinide treatment effect was stronger than observed in the original trial. Our effect estimates were more efficient than the weighting approach and we effectively estimated subgroup differences. CONCLUSIONS: The described method represents a straightforward approach to efficiently transporting an RCT result to any target population.


Asunto(s)
Antihipertensivos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Aprendizaje Automático , Nateglinida/uso terapéutico , Estado Prediabético/tratamiento farmacológico , Valsartán/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2 , Progresión de la Enfermedad , Registros Electrónicos de Salud , Medicina Basada en la Evidencia , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Investigación en Medicina Traslacional
14.
Minerva Cardioangiol ; 67(3): 214-222, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30895762

RESUMEN

INTRODUCTION: The efficacy and safety of sacubitril/valsartan used as an antihypertensive agent has not yet been completely assessed. Thus, to investigate them in elderly hypertensive patients, a meta-analysis has been performed. EVIDENCE ACQUISITION: The meta-analysis incorporated only randomized controlled trials (RCTs) in which sacubitril/valsartan was compared with a reference drug. The mean reductions in systolic blood pressure (msSBP) and diastolic blood pressure (msDBP) in the sitting position as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events were taken as safety outcomes. EVIDENCE SYNTHESIS: Five RCTs were included for a total of 1513 patients for analysis. In all studies, the comparator drug was an angiotensin receptor blocker (ARB) - valsartan in two cases and olmesartan in the remaining three cases. Compared with ARBs, there was a significant reduction in msSBP (weight mean difference [WMD] -5.41 mmHg, 95% CI: -7.0 to -3.8; P<0.01), msDBP (WMD=-1.22 mmHg, 95% CI: -2.15 to -0.3; P<0.01), maSBP (WMD=-4.58 mmHg, 95% CI: -5.62 to -3.54; P<0.01) and maDBP (WMD=-2.17 mmHg, 95% CI: - 2.78 to -1.56; P<0.01) in elderly hypertensive patients at 12 weeks. CONCLUSIONS: Sacubitril/valsartan may reduce arterial pressure more efficaciously than ARBs in elderly hypertensive patients.


Asunto(s)
Aminobutiratos/uso terapéutico , Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Tetrazoles/uso terapéutico , Valsartán/uso terapéutico , Anciano , Anciano de 80 o más Años , Aminobutiratos/efectos adversos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antihipertensivos/efectos adversos , Combinación de Medicamentos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Tetrazoles/efectos adversos , Valsartán/efectos adversos
15.
Medicine (Baltimore) ; 98(6): e14428, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30732201

RESUMEN

RATIONALE: Angiotensin receptor blocker (ARB) can increase serum creatinine or potassium levels in patients with renal insufficiency, renal artery stenosis, heart failure or hypovolemia, but hardly cause severe kidney injury in patients without any risk factors. A case of severe acute interstitial nephritis (AIN) induced by valsartan was reported here. PATIENT CONCERNS: A 62-year-old female with nausea for 1 month and acute deterioration of kidney function for 2 weeks was admitted. She had a history of hypertension for 5 months and had taken valsartan 40 mg daily for 4 months. Although the valsartan had been stopped for 2 weeks, the serum creatinine continuously increased after admission. Kidney biopsy demonstrated the eosinophils infiltration in interstitium. DIAGNOSES: AIN induced by valsartan. INTERVENTIONS: The patient was treated with glucocorticoid. OUTCOMES: The serum creatinine decreased gradually and got back to normal level 5 months later. Then therapy of glucocorticoid was stopped. Renal artery stenosis was excluded by computed tomography angiography (CTA). LESSONS: Although valsartan-induced allergy has been reported previously, AIN was firstly recognized as a severe complication of this drug. We suggest when there is a ARB-associated continuous deterioration of kidney function for patients without renal insufficiency, renal artery stenosis, heart failure or hypovolemia, AIN should be thought of and therapy with glucocorticoid should be considered if necessary.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Nefritis Intersticial/inducido químicamente , Valsartán/efectos adversos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Creatinina/sangre , Femenino , Glucocorticoides/uso terapéutico , Humanos , Hipertensión/tratamiento farmacológico , Persona de Mediana Edad , Nefritis Intersticial/tratamiento farmacológico , Valsartán/uso terapéutico
16.
Herz ; 44(7): 651-658, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29520644

RESUMEN

INTRODUCTION: In heart failure with reduced left ventricular ejection fraction (HFREF) patients, the dosage of sacubitril/valsartan is modulated according to a gradual increase regimen. Nevertheless, if patients exhibit tolerability problems, a provisional reduction of the dose of sacubitril/valsartan or even its interruption are recommended. MATERIAL AND METHODS: This study provides estimates of respective proportions of patients receiving minimum or intermediate doses of sacubitril/valsartan. In addition, a comparison was made to detect possible differences regarding all-cause mortality and heart failure hospitalization in patients treated with the recommended optimum dose compared to those receiving submaximum maintenance doses of sacubitril/valsartan. RESULTS: Patients treated with sacubitril/valsartan in addition to beta-blocker and mineralocorticoid receptor blocker were 68. Among them, 20 patients (29.4%), were identified as having clinical features that were contraindications to the administration of sacubitril/valsartan at full dose. The subsequent decision was to maintain an intermediate dose in 11 patients and to reduce the dose to the minimum level allowed, i.e., 24 mg/26 mg twice daily in nine patients. After a median follow-up of 5.25 months, no differences were found concerning the risk of all-cause death by comparing patients treated with reduced versus those subjected to target doses of sacubitril/valsartan (odds ratio [OR] = 1.666; 95% confidence interval [CI] = 0.256-10.823; p = 0.6266). Patients taking reduced doses had a similar risk of heart failure hospitalizations when compared to patients treated with the target dose (OR = 0.789; 95% CI: 0.077-8.0808; p = 1.00). CONCLUSION: During a median follow-up of 5.25 months, in the group of patients who had proven to be intolerant to the maximum dose of sacubitril/valsartan, use of reduced doses of the drug did not result in increased all-cause mortality or heart failure hospitalization compared to patients treated with sacubitril/valsartan at the target dose.


Asunto(s)
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Insuficiencia Cardíaca , Tetrazoles , Valsartán , Disfunción Ventricular Izquierda , Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Hospitalización , Humanos , Estudios Retrospectivos , Volumen Sistólico , Tetrazoles/uso terapéutico , Resultado del Tratamiento , Valsartán/uso terapéutico , Disfunción Ventricular Izquierda/tratamiento farmacológico
17.
Herz ; 44(5): 425-432, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29350254

RESUMEN

BACKGROUND: The combination drug sacubitril/valsartan was reported to be superior to enalapril in reducing all-cause death, cardiovascular mortality, and heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction (HFREF) with NYHA class II-IV. METHODS: Our retrospective cohort study aimed to assess the effects of sacubitril/valsartan in addition to a beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients with NYHA class II-III HF vs. conventional therapy (ACE inhibitor or angiotensin II receptor blocker added to a beta-blocker plus an MRA) administered to a control group of HFREF patients with comparable clinical features. In both groups, treatment was supplemented by a loop diuretic, usually furosemide, at variable doses. The primary outcomes were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia, and worsening renal function. RESULTS: Mortality at 6 months was 6.8% in patients taking sacubitril/valsartan vs. 34% in those on conventional therapy (odds ratio [OR] = 0.14; 95% CI: 0.04-0.49). Moreover, there was a 4.5% rate of HF hospitalizations in the sacubitril/valsartan group vs. 59% in the control group (OR = 0.03; 95% CI: 0.01-0.14). Safety outcomes were comparable in the two groups, although hypotension (systolic blood pressure < 100 mm Hg) was found in 15.9% of patients in the sacubitril/valsartan group vs. 5.7% in the control group (OR = 3.14; 95% CI: 0.94-10.55). CONCLUSION: Sacubitril/valsartan offered strong protection against all-cause death and HF hospitalizations at 6 months without any significant side effects. To validate this efficacious molecule, further postmarketing observational studies, focusing mainly on hypotension and angioedema are warranted.


Asunto(s)
Aminobutiratos , Antihipertensivos , Insuficiencia Cardíaca , Neprilisina , Tetrazoles , Valsartán , Aminobutiratos/uso terapéutico , Antihipertensivos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Masculino , Neprilisina/uso terapéutico , Estudios Retrospectivos , Volumen Sistólico , Tetrazoles/uso terapéutico , Resultado del Tratamiento , Valsartán/uso terapéutico
18.
Herz ; 44(6): 534-540, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29450561

RESUMEN

BACKGROUND: Sacubitril, a neprilysin inhibitor in the combination molecule sacubitril/valsartan, slows down degradation of endogenous natriuretic peptides, thereby enhancing their beneficial cardiovascular effects. However, sacubitril might also promote neuronal dysfunction and cognitive impairment in patients with chronic heart failure (CHF) treated with sacubitril/valsartan, due to possible neprilysin inhibition at the level of Central Nervous System. METHODS: A retrospective cohort study was undertaken to detect the effects exerted by sacubitril/valsartan on cognitive function in CHF patients. The patients' clinical data were examined for information provided in the Mini-Mental State Examination (MMSE), which was routinely administered during clinical visits at two centers from 15 March to 31 October 2017. Patients in the sacubitril/valsartan group had a clinical history of at least 3 months of continuous sacubitril/valsartan administration. The control group comprised CHF patients on conventional therapy not taking sacubitril/valsartan. In the between-group comparison, patients were matched for mean age, educational level, sex, NYHA class, and comorbidities. In the present retrospective study only patients in NYHA class II-III were enrolled. RESULTS: The mean MMSE score was 22.72 ± 2.68 (mean ± standard deviation [SD]) in the sacubitril/valsartan group (n = 51 patients) vs. 21.96 ± 2.73 (mean ± SD) in the control group (n = 51; p = 0.1572, independent samples t-test). Thus, a similar mild-to-moderate impairment in cognitive performance was found in the comparison between the two groups. CONCLUSION: In our study, we did not find any evidence of the alleged harmful influence of sacubitril/valsartan on cognitive function. Patients taking sacubitril/valsartan for at least 3 months had similar mean MMSE scores to control subjects.


Asunto(s)
Aminobutiratos , Bloqueadores del Receptor Tipo 1 de Angiotensina II , Antagonistas de Receptores de Angiotensina , Cognición , Insuficiencia Cardíaca , Tetrazoles , Valsartán , Aminobutiratos/efectos adversos , Aminobutiratos/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Cognición/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/psicología , Humanos , Estudios Retrospectivos , Volumen Sistólico , Tetrazoles/efectos adversos , Tetrazoles/uso terapéutico , Valsartán/uso terapéutico
19.
Clin Exp Hypertens ; 41(1): 62-69, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-29595329

RESUMEN

BACKGROUND: Sacubitril (SAC), a neprilysin inhibitor prevent degradation of neprilysin and activate cGMP signaling pathways leading to rise in blood volume concurrent to blood pressure by means of vasoactive peptides, adrenomedullin, and bradykinin. OBJECTIVE: The aim of this study was to evaluate the anti-ischemic effects of SAC through inhibiting neprilysin in isoproterenol (ISO) induced myocardial infarction (MI) in Wistar albino rats. ISO (85 mg/kg) was injected subcutaneously at the end of 14 days pre-treatment with SAC and valsartan (VAL). RESULT: Biochemical investigation revealed that SAC along with VAL significantly prevented the antioxidant enzymes (SOD, Catalase, GR, GPx, GST, and GSH) degradation and malondialdehyde (MDA) induced by ISO intoxication in Wistar rats. Along with this, cardiac biomarkers (LDH, CK-MB, ALT, AST, and ALP) were also significantly ameliorated by SACand VAL in ISO-treated rats. Concurrently, decreased infarction area (IA)and marked reduction in myofibril damage by SACand VAL further supported its protective benefits in MI. CONCLUSION: Taken together, the results suggest that inhibition of enzyme neprilysin alleviated the ISO induces myocardial damage mediated by its strong antioxidant potential.


Asunto(s)
Aminobutiratos/farmacología , Antihipertensivos/farmacología , Infarto del Miocardio/enzimología , Infarto del Miocardio/prevención & control , Miocardio/enzimología , Neprilisina/antagonistas & inhibidores , Tetrazoles/farmacología , Valsartán/farmacología , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Aminobutiratos/uso terapéutico , Animales , Antihipertensivos/uso terapéutico , Antioxidantes/farmacología , Aspartato Aminotransferasas/metabolismo , Catalasa/metabolismo , Forma MB de la Creatina-Quinasa/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Isoproterenol , Lactato Deshidrogenasas/metabolismo , Masculino , Malondialdehído/metabolismo , Infarto del Miocardio/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Tetrazoles/uso terapéutico , Valsartán/uso terapéutico
20.
Clin Exp Hypertens ; 41(3): 244-254, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-29781736

RESUMEN

This study aimed to compare the real-world effectiveness of valsartan and non renin-angiotensin system (non-RAS) agent monotherapy on the incidence of new on-set diabetes (NOD) in Chinese hypertensive patients. It was based on an electronic Health Recording System database from Minhang District of Shanghai. Hypertensive patients aged ≥18 years continuously taking either valsartan or non-RAS agent monotherapy for >12 months were included. Hazard ratios (HR) of NOD events were estimated using propensity score matching method and multivariate regression. Of 29295 patients, there were 2107 in valsartan group, 21397 in CCB group, 4094 in ß-blockers group and 1697 in diuretics group. Two-year follow-up revealed NOD rates of 11.09 and 14.22 per 100 persons per year in valsartan and non-RAS inhibitor groups (HR = 0.77, 95% confidence interval 0.65-0.93, P = 0.006), respectively. Among non-RAS agents, CCB group had the highest incidence of NOD (21.72 per 100 persons per year). Comparisons between CCB sub-groups revealed the highest NOD incidence for nifedipine, followed by amlodipine and felodipine. NOD incidences in ß-blockers and diuretics groups (11.70 and 10.50 per 100 persons per year, respectively) were not significantly different from valsartan group. Compared with non-RAS inhibitors, particularly CCBs, valsartan could significantly reduce the incidence of NOD.


Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Valsartán/uso terapéutico , Adolescente , Antagonistas Adrenérgicos beta/uso terapéutico , Adulto , Anciano , Amlodipino/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , China , Angiopatías Diabéticas/tratamiento farmacológico , Diuréticos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA