RESUMEN
Importance: Thrombotic microangiopathy (TMA) on kidney biopsy is a pattern of endothelial injury commonly seen in malignant hypertension (mHTN), but treatment strategies are not well established. Objective: To evaluate the kidney outcomes of angiotensin receptor-neprilysin inhibitor (ARNI), specifically sacubitril/valsartan, vs angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy for patients with mHTN-associated TMA. Design, Setting, and Participants: This single-center cohort study enrolled consecutive patients in China diagnosed with mHTN-associated TMA through kidney biopsy from January 2008 to June 2023. Follow-up was conducted until the conclusion of the study period. Data were analyzed in September 2023. Exposures: Treatment with sacubitril/valsartan or ACEI/ARBs during hospitalization and after discharge. Main Outcomes and Measures: The primary outcome was a composite of kidney recovery: a 50% decrease in serum creatinine level, decrease in serum creatinine levels to the reference range, or kidney survival free from dialysis for more than 1 month. The secondary and tertiary outcomes were a 15% increase in the estimated glomerular filtration rate (eGFR) relative to baseline and kidney survival free from dialysis, respectively. Propensity score matching (PSM) and Cox proportional hazards regression analysis were used to evaluate the association between sacubitril/valsartan and ACEI/ARB therapy with kidney recovery outcomes. Results: Among the 217 patients (mean [SD] age, 35.9 [8.8] years; 188 men [86.6%]) included in the study, 66 (30.4%) received sacubitril/valsartan and 151 (69.6%) received ACEI/ARBs at baseline. Sacubitril/valsartan treatment was associated with shorter time to the primary outcome compared with ACEI/ARB treatment (20 of 63 [31.7%] vs 38 of 117 [32.5%]; adjusted hazard ratio [aHR], 1.85; 95% CI, 1.05-3.23). Sacubitril/valsartan treatment was independently associated with shorter time to a 15% increase in eGFR (15 of 46 [32.6%] vs 46 of 83 [55.4%]; aHR, 2.13; 95% CI, 1.09-4.17) and kidney survival free from dialysis (11 of 23 [47.8%] vs 16 of 57 [28.1%]; aHR, 2.63; 95% CI, 1.15-5.88) compared with ACEI/ARB treatment. These differences remained significant in the PSM comparison. Conclusions and Relevance: In this cohort study, sacubitril/valsartan treatment was associated with a potential kidney function benefit in patients with mHTN-associated TMA compared with ACEI/ARB treatment. The findings suggested that sacubitril/valsartan could be a superior therapeutic approach for managing this serious condition in terms of kidney recovery.
Asunto(s)
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Compuestos de Bifenilo , Combinación de Medicamentos , Microangiopatías Trombóticas , Valsartán , Humanos , Masculino , Femenino , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Microangiopatías Trombóticas/tratamiento farmacológico , Persona de Mediana Edad , Valsartán/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Aminobutiratos/uso terapéutico , Adulto , Hipertensión Maligna/tratamiento farmacológico , Riñón/efectos de los fármacos , Riñón/fisiopatología , Neprilisina/antagonistas & inhibidores , Estudios de Cohortes , China , Tetrazoles/uso terapéutico , Resultado del Tratamiento , Tasa de Filtración Glomerular/efectos de los fármacosRESUMEN
INTRODUCTION: Heart failure (HF) is a complex syndrome that affects millions of people worldwide and leads to significant morbidity and mortality. Sacubitril/valsartan, a combination drug consisting of a neprilysin inhibitor and an angiotensin receptor blocker (ARB), has shown a greater improvement in the prognosis of HF than ACE inhibitors (ACEI) or ARB. Recent studies have found that ACEI/ARB or sacubitril/valsartan can increase flow-mediated dilation (FMD) and reduce pulse wave velocity (PWV), which are independent predictors of cardiovascular events and HF prognosis. The purpose of this study is to assess and compare the effect of sacubitril/valsartan and ACEI/ARB on FMD and PWV using meta-analysis and further provide a reference for the role of sacubitril/valsartan in the treatment of HF. METHODS AND ANALYSIS: Clinical randomised controlled trials investigating the effect of sacubitril/valsartan and/or ACEI/ARB on FMD and PWV in patients with HF will be searched in the relevant database, including PubMed, Web of Science, Embase, Cochrane Library and China's National Knowledge Infrastructure up to January 2024. The outcomes of interest are changes in endothelial function assessed by FMD and changes in arterial stiffness assessed by PWV. The risk of bias was evaluated using the revised Cochrane risk of bias tool for randomised trials (RoB2.0). Review Manager V.5.3 software is used for meta-analysis data synthesis, sensitivity analysis, meta-regression analysis, subgroup analysis and risk of bias assessment. The reporting bias of studies will be evaluated using the funnel plot, in which symmetry will be assessed by Begg's and Egger's tests. The evidence quality of the included studies will be evaluated by the Grading of Recommendations Assessment, Development, and Evaluation. ETHICS AND DISSEMINATION: This study only analyses research data from the published literature and therefore does not require ethical approval. We will submit the systematic review to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42024538148.
Asunto(s)
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto , Valsartán , Rigidez Vascular , Humanos , Valsartán/uso terapéutico , Aminobutiratos/uso terapéutico , Aminobutiratos/farmacología , Rigidez Vascular/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Tetrazoles/uso terapéutico , Proyectos de Investigación , Análisis de la Onda del PulsoRESUMEN
In a double-blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up-dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D-dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D-dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group (p = 0.046). D-dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up-dosing antihistamines may be more effective for CSU patients with high D-dimer levels compared to up-dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D-dimer levels observed in the antiplatelet group.
Asunto(s)
Urticaria Crónica , Cilostazol , Dipiridamol , Quimioterapia Combinada , Productos de Degradación de Fibrina-Fibrinógeno , Loratadina , Inhibidores de Agregación Plaquetaria , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Urticaria Crónica/tratamiento farmacológico , Cilostazol/administración & dosificación , Cilostazol/uso terapéutico , Dipiridamol/administración & dosificación , Dipiridamol/uso terapéutico , Método Doble Ciego , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Antagonistas de los Receptores Histamínicos/administración & dosificación , Antagonistas de los Receptores Histamínicos/uso terapéutico , Loratadina/administración & dosificación , Loratadina/uso terapéutico , Loratadina/análogos & derivados , Inhibidores de Agregación Plaquetaria/administración & dosificación , Calidad de Vida , Tetrazoles/administración & dosificación , Tetrazoles/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Cenobamate (CNB) is a new antiseizure medication (ASM) to treat drug-resistant, focal-onset seizures. Data on its use in early therapy lines are not yet available, and clinicians frequently consider CNB to be a later ASM drug choice. We investigated the efficacy and safety of CNB as an early adjunctive treatment in drug-resistant, focal-onset seizures. METHODS: The study population were patients with drug-resistant, focal-onset seizures who were initiated with CNB after they did not respond to two or three lifetime ASMs, including all prior and concomitant ASMs. These patients were matched (1:2) by sex, age, and seizure frequency to controls who were initiated with any ASM other than CNB. All participants participated in the Mainz Epilepsy Registry. We evaluated the retention rate after 12 months of CNB and after each new adjunctive ASM in the control group. In addition, seizure freedom and the response rate (reduction of seizure frequency by ≥ 50% from baseline) after 12 months were estimated. RESULTS: We included 231 patients aged 44.4 ± 15.8 years. Of these, 33.3% (n = 77) were on CNB, 19.0% (n = 44) on valproate (VPA), 17.3% (n = 40) on lacosamide (LCS), 16.4% (n = 38) on levetiracetam (LEV), and 13.9% (n = 32) on topiramate (TPM). The highest retention rate after 12 months since the beginning of the early adjunctive therapy was observed on CNB (92.0%), compared with LCS (80.0%), LEV (73.3%), VPA (68.2%), or TPM (62.5%) (p < 0.05). Seizure freedom and response rate were also the best on CNB (19.5% and 71.4%, respectively) compared with other ASMs (8.3% and 52.5%, respectively; p < 0.05). No significant differences in adverse events between CNB and other ASMs were observed. CONCLUSIONS: Our study provides evidence that CNB is an effective ASM with a good safety profile in the early therapy lines of drug-resistant, focal-onset seizures. This data should support medical decision making in the management of patients with refractory epilepsy. CLINICAL TRIAL ID: NCT05267405.
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Anticonvulsivantes , Carbamatos , Clorofenoles , Epilepsia Refractaria , Quimioterapia Combinada , Convulsiones , Humanos , Masculino , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/efectos adversos , Femenino , Adulto , Carbamatos/uso terapéutico , Carbamatos/efectos adversos , Carbamatos/administración & dosificación , Persona de Mediana Edad , Estudios de Cohortes , Epilepsia Refractaria/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Clorofenoles/administración & dosificación , Clorofenoles/efectos adversos , Clorofenoles/uso terapéutico , Resultado del Tratamiento , Tetrazoles/administración & dosificación , Tetrazoles/uso terapéutico , Tetrazoles/efectos adversos , Ácido Valproico/uso terapéutico , Ácido Valproico/administración & dosificación , Ácido Valproico/efectos adversosRESUMEN
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 , Compuestos de Bifenilo , Cardiomiopatía Chagásica , Combinación de Medicamentos , Enalapril , Insuficiencia Cardíaca , Tetrazoles , Valsartán , Humanos , Compuestos de Bifenilo/uso terapéutico , Aminobutiratos/uso terapéutico , Enalapril/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Cardiomiopatía Chagásica/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Tetrazoles/uso terapéutico , Volumen Sistólico/fisiología , Fragmentos de Péptidos/sangre , Enfermedad Crónica , Péptido Natriurético Encefálico/sangre , Masculino , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Femenino , Resultado del TratamientoRESUMEN
Since 2014, sacubitril/valsartan (Entresto®) is widely prescribed for heart failure. Despite neprilysin inhibition's benefits in heart failure, concerns about potential amyloid-beta (Aß) accumulation and Alzheimer's disease (AD) risk have persisted. This narrative review, a decade post-approval, evaluates the risk of amyloid pathology and neurocognitive disorders in long-term sacubitril/valsartan use. Clinical trials, real-world studies, and pharmacovigilance data do not indicate an increased risk of cognitive decline. In patients treated with sacubitril/valsartan blood-based amyloid biomarkers show perturbations, while neuroimaging biomarkers reveal no significant increase in amyloid load. Despite a theoretical risk of amyloid accumulation and AD under treatment with sacubitril/valsartan, current clinical data appears reassuring, and there is no signal indicating an increased risk of cognitive decline, but a perturbation of amyloid blood-based biomarkers, which implies great caution when interpreting biomarkers in this context.
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Enfermedad de Alzheimer , Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Combinación de Medicamentos , Tetrazoles , Valsartán , Humanos , Aminobutiratos/uso terapéutico , Aminobutiratos/efectos adversos , Enfermedad de Alzheimer/tratamiento farmacológico , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Tetrazoles/uso terapéutico , Tetrazoles/efectos adversos , Insuficiencia Cardíaca/inducido químicamente , Péptidos beta-Amiloides/metabolismo , Biomarcadores/sangreRESUMEN
Heart failure with reduced ejection fraction (HFrEF) is a commonly seen clinical entity in the family physician's practice. This clinical review focuses on the pharmacologic management of chronic HFrEF. Special attention is paid to the classification of heart failure and the newest recommendations from the American Heart Association concerning the use of guideline-directed medical therapy. ß blockers, ACE inhibitors, ARBs, mineralocorticoid receptor antagonists are discussed in detail. The new emphasis on sacubitril-valsartan and SGLT2i's as therapies for HFrEF are reviewed, followed by a brief discussion of more advanced therapies and comorbidity management.
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Antagonistas Adrenérgicos beta , Antagonistas de Receptores de Angiotensina , Insuficiencia Cardíaca , Antagonistas de Receptores de Mineralocorticoides , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Enfermedad Crónica , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Aminobutiratos/uso terapéutico , Guías de Práctica Clínica como Asunto , Compuestos de Bifenilo/uso terapéutico , Valsartán , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Combinación de Medicamentos , Tetrazoles/uso terapéuticoRESUMEN
The aim of this network meta-analysis was to compare the efficacy of various commonly used drugs in treating patients with hypertrophic cardiomyopathy (HCM). Randomized controlled trials on drugs for HCM treatment were retrieved from PubMed, Embase, Cochrane Library, and Web of Science (search cutoff: January 10, 2024). Quality assessment was performed using the risk of bias tool, and data analysis used R software. Seventeen studies (1,133 patients with HCM) were included. The network meta-analysis indicated that mavacamten and perhexiline improved peak oxygen consumption compared with placebo. Mavacamten reduced N-terminal pro-B-type natriuretic peptide, left ventricular mass index, left atrial volume index, and septal E/e' ratio. Losartan decreased systolic blood pressure, whereas candesartan, mavacamten, and valsartan reduced maximum wall thickness. Perhexiline had better efficacy in increasing peak oxygen consumption, and candesartan in reducing maximum wall thickness. No drug significantly improved left ventricular ejection fraction compared with placebo. In conclusion, on the basis of current studies, commonly used drugs may effectively improve some of the outcome measures in patients with HCM, whereas the novel drug mavacamten showed significant therapeutic effects in most of the remaining outcome measures except for left ventricular ejection fraction.
Asunto(s)
Compuestos de Bifenilo , Cardiomiopatía Hipertrófica , Metaanálisis en Red , Humanos , Cardiomiopatía Hipertrófica/tratamiento farmacológico , Compuestos de Bifenilo/uso terapéutico , Volumen Sistólico , Consumo de Oxígeno/efectos de los fármacos , Tetrazoles/uso terapéutico , Bencimidazoles/uso terapéutico , Fármacos Cardiovasculares/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Losartán/uso terapéutico , Valsartán/uso terapéutico , Resultado del TratamientoRESUMEN
Sepsis is a life-threatening situation that ultimately affects cardiac function, leading to cardiomyopathy and myocardial injury as a result of uncontrolled response to infection.Till now, there is limited effective treatment to rescue those cases. Thus, novel therapeutic strategies should be identified to achieve better outcomes for septic patients. For the first time, we aimed to evaluate the effect of sacubitril/valsartan (Sac/Val) on sepsis-induced cardiac injury. Wistar male adult albino rats were randomly divided into four groups; Group I received the vehicle; Group II was given the vehicle plus 1 ml saline containing viable Escherichia coli (E. coli) (2.1 × 109 cfu) by intraperitoneal (i.p.) injection on the 1st and 2nd days; Group III received i.p. injection as group II plus oral administration of Sac/Val (30 mg/kg/day) and Nitro- ω-L-arginine (L-NNA) (25 mg/kg/day) for 7 days. Group IV was administered i.p. injection as group II plus oral administration of Sac/Val (30 mg/kg/day) for 7 days. Our data (n = 10) revealed successful induction of sepsis as it showed a significant increase in the measured cardiac enzymes, malondialdehyde (MDA), angiotensin II (Ang II), neprilysin, inflammasome, caspase 1, interleukin (IL)1ß, and caspase 3 with cardiac histopathological changes, but there was a significant decrease in the antioxidants and blood pressure (BP). Co-administration of Sac/Val could obviously improve these changes. Interestingly, L-NNA given group showed a decrease in the cardioprotective effect of Sac/Val. Sac/Val could ameliorate sepsis induced cardiac damage via inhibition of Ang II and neprilysin with anti-inflammatory, anti-oxidant and anti-apoptotic properties.
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Aminobutiratos , Compuestos de Bifenilo , Caspasa 1 , Combinación de Medicamentos , Inflamasomas , Interleucina-1beta , Neprilisina , Sepsis , Tetrazoles , Valsartán , Animales , Masculino , Ratas , Aminobutiratos/farmacología , Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Compuestos de Bifenilo/farmacología , Compuestos de Bifenilo/uso terapéutico , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/etiología , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Caspasa 1/metabolismo , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Miocardio/patología , Miocardio/metabolismo , Neprilisina/antagonistas & inhibidores , Neprilisina/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Receptores de Angiotensina/metabolismo , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Transducción de Señal/efectos de los fármacos , Tetrazoles/farmacología , Tetrazoles/uso terapéutico , Valsartán/farmacología , Valsartán/uso terapéuticoRESUMEN
Background and Objectives: The efficacy and safety of a lower target dose of sacubitril/valsartan (angiotensin receptor neprilysin inhibitor [ARNI]) for treating heart failure with reduced ejection fraction (HFrEF) in Chinese patients with moderate-to-severe chronic kidney disease (CKD) remain unknown. We performed a retrospective study to compare the efficacy of ARNI with that of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) in patients with HFrEF and moderate-to-severe CKD. Methods: This retrospective study included 129 patients. An inverse probability of treatment weighting (IPTW) analysis was performed to compare the baseline characteristics and outcomes between the 2 groups. The incidence of death due to cardiovascular disease, rehospitalization due to heart failure after treatment, and improvement in cardiac function symptoms (New York Heart Association [NYHA]) were assessed after 12 months. Improvements of ejection fraction (EF), N-terminal pro-brain natriuretic peptide (NT-proBNP) level, left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD) were compared. Results: Compared with the ACEI/ARB group, the ARNI group, with 90.77% (59/65) in the lower target dose group, showed a lower rate of death due to cardiovascular disease (6.6% vs 0.9% after IPTW) and a lower incidence of rehospitalization (46.5% vs 30.4% after IPTW). NYHA class, estimated glomerular filtration rate, EF, NT-ProBNP levels, LVEDD, and LVESD improved in the ARNI group. None of the patients withdrew from treatment because of adverse drug reactions. Conclusion: Our study showed that ARNI resulted in a greater improvement in heart failure than ACEIs/ARBs in patients with HFrEF and moderate-to-severe CKD.
Asunto(s)
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca , Neprilisina , Insuficiencia Renal Crónica , Volumen Sistólico , Valsartán , Función Ventricular Izquierda , Humanos , Aminobutiratos/efectos adversos , Aminobutiratos/uso terapéutico , Valsartán/uso terapéutico , Masculino , Femenino , Estudios Retrospectivos , Volumen Sistólico/efectos de los fármacos , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/diagnóstico , Anciano , Persona de Mediana Edad , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/efectos adversos , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacos , Neprilisina/antagonistas & inhibidores , Índice de Severidad de la Enfermedad , Tetrazoles/efectos adversos , Tetrazoles/uso terapéutico , Readmisión del Paciente , Factores de Tiempo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Péptido Natriurético Encefálico/sangre , China/epidemiología , Recuperación de la Función , Fragmentos de Péptidos/sangreRESUMEN
Heart failure (HF) remains a huge medical burden worldwide, with aging representing a major risk factor. Here, we report the effects of sacubitril/valsartan, an approved drug for HF with reduced EF, in an experimental model of aging-related HF with preserved ejection fraction (HFpEF). Eighteen-month-old female Fisher 344 rats were treated for 12 weeks with sacubitril/valsartan (60 mg/kg/day) or with valsartan (30 mg/kg/day). Three-month-old rats were used as control. No differential action of sacubitril/valsartan versus valsartan alone, either positive or negative, was observed. The positive effects of both sacubitril/valsartan and valsartan on cardiac hypertrophy was evidenced by a significant reduction of wall thickness and myocyte cross-sectional area. Contrarily, myocardial fibrosis in aging heart was not reduced by any treatment. Doppler echocardiography and left ventricular catheterization evidenced diastolic dysfunction in untreated and treated old rats. In aging rats, both classical and non-classical renin-angiotensin-aldosterone system (RAAS) were modulated. In particular, with respect to untreated animals, both sacubitril/valsartan and valsartan showed a partial restoration of cardioprotective non-classical RAAS. In conclusion, this study evidenced the favorable effects, by both treatments, on age-related cardiac hypertrophy. The attenuation of cardiomyocyte size and hypertrophic response may be linked to a shift towards cardioprotective RAAS signaling. However, diastolic dysfunction and cardiac fibrosis persisted despite of treatment and were accompanied by myocardial inflammation, endothelial activation, and oxidative stress.
Asunto(s)
Envejecimiento , Aminobutiratos , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca , Ratas Endogámicas F344 , Tetrazoles , Valsartán , Animales , Aminobutiratos/farmacología , Aminobutiratos/uso terapéutico , Compuestos de Bifenilo/farmacología , Valsartán/farmacología , Valsartán/uso terapéutico , Envejecimiento/efectos de los fármacos , Envejecimiento/patología , Femenino , Tetrazoles/farmacología , Tetrazoles/uso terapéutico , Ratas , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Sistema Renina-Angiotensina/efectos de los fármacos , Fibrosis , Estrés Oxidativo/efectos de los fármacos , Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Volumen Sistólico/efectos de los fármacos , Modelos Animales de Enfermedad , Neprilisina/antagonistas & inhibidores , Neprilisina/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patologíaRESUMEN
BACKGROUND: Heart failure with reduced ejection fraction is associated with potentially deleterious imbalance of the cardiac autonomic nervous system. Sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor [ARNI]) reduces cardiovascular mortality and hospitalization for heart failure with reduced ejection fraction. Whether ARNI affects the cardiac autonomic nervous system has not been studied. METHODS AND RESULTS: This investigator-initiated, prospective, single-center cohort study compared heart rate (HR) variability, HR, deceleration capacity, and periodic repolarization dynamics as noninvasive measures of the cardiac autonomic nervous system before and after initiation of ARNI therapy. Patients underwent standardized 12-lead Holter-ECG, echocardiography and laboratory testing before and 3 months after start of therapy. End points were changes in HR variability (SD of normal-to-normal intervals, mean square of differences between consecutive R-R intervals), HR, deceleration capacity, and periodic repolarization dynamics as well as ventricular function and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Of 63 patients with heart failure with reduced ejection fraction enrolled, 48 (76.2%) patients were still on ARNI at follow-up. SD of normal-to-normal intervals increased from 25 to 36 milliseconds (P<0.001), mean square of differences between consecutive R-R intervals increased from 12 to 19 milliseconds (P<0.001), HR decreased from 73±9 bpm to 67±4 bpm, (P<0.001), and deceleration capacity increased from 2.1 to 4.4 milliseconds (P<0.001). A trend for periodic repolarization dynamics reduction was observed (5.6 deg2 versus 4.7 deg2, P=0.09). Autonomic changes were accompanied by increased left ventricular ejection fraction (29±6% versus 40±8%, P<0.001) and reduced NT-proBNP (3548 versus 685 ng/L, P<0.001). Correlation analysis showed a significant relationship between volume-unloading (as evidenced by NT-proBNP reduction) and autonomic improvement. CONCLUSIONS: Three months of ARNI therapy resulted in a significant increase in cardiac parasympathetic tone. The improvement in autonomic properties may be mediated by "volume unloading" and likely contributes to the beneficial effects of ARNI in heart failure with reduced ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04587947.
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Sistema Nervioso Autónomo , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca , Frecuencia Cardíaca , Neprilisina , Volumen Sistólico , Tetrazoles , Valsartán , Función Ventricular Izquierda , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Masculino , Femenino , Valsartán/uso terapéutico , Aminobutiratos/uso terapéutico , Aminobutiratos/farmacología , Sistema Nervioso Autónomo/fisiopatología , Sistema Nervioso Autónomo/efectos de los fármacos , Anciano , Estudios Prospectivos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/farmacología , Volumen Sistólico/efectos de los fármacos , Volumen Sistólico/fisiología , Persona de Mediana Edad , Frecuencia Cardíaca/efectos de los fármacos , Tetrazoles/uso terapéutico , Neprilisina/antagonistas & inhibidores , Función Ventricular Izquierda/efectos de los fármacos , Electrocardiografía Ambulatoria , Fragmentos de Péptidos/sangre , Resultado del Tratamiento , Péptido Natriurético Encefálico/sangre , Corazón/inervación , Corazón/efectos de los fármacosRESUMEN
BACKGROUND Heart failure and end-stage renal disease often coexist, and management of heart failure can be challenging in patients during hemodialysis. Sacubitril-valsartan (SV) is the first drug to receive regulatory approval for use in patients with chronic heart failure with reduced ejection fraction (HFrEF) and New York Heart Association (NYHA) classification II, III, or IV. This study aimed to evaluate the efficacy and safety of SV for use in chronic heart failure patients on maintenance hemodialysis (MHD). MATERIAL AND METHODS From September 2021 to October 2022, 28 patients on MHD with chronic heart failure at the hemodialysis center of Shaanxi Second Provincial People's Hospital were regularly followed. During the 12-week follow-up period, all patients were administered SV at doses of 100-400 mg per day. Biochemical indicators, echocardiographic parameters, life quality scores, and adverse events were evaluated. RESULTS We enrolled 28 patients. Compared with the baseline levels, NYHA class III in these patients treated with SV was significantly decreased from 60.71% to 32.14% (P<0.05), left ventricular ejection fraction (LVEF) was significantly improved from 44.29±8.92% to 53.32±7.88% (P<0.001), the Physical Component Summary (PCS) score was significantly improved from 40.0±6.41 to 56.20±9.86 (P<0.001), and the Mental Component Summary (MCS) score was significantly improved from 39.99±6.14 to 52.59±11.0 (P<0.001). CONCLUSIONS We demonstrated that SV improved NYHA classification and LVEF values of patients on MHD with chronic heart failure and also improved their quality of life.
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Aminobutiratos , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca , Diálisis Renal , Valsartán , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Valsartán/uso terapéutico , Masculino , Femenino , Aminobutiratos/uso terapéutico , Aminobutiratos/farmacología , Aminobutiratos/efectos adversos , Compuestos de Bifenilo/uso terapéutico , Persona de Mediana Edad , Diálisis Renal/métodos , Estudios Retrospectivos , Anciano , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/fisiopatología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/efectos adversos , Resultado del Tratamiento , Calidad de Vida , Volumen Sistólico/efectos de los fármacos , Volumen Sistólico/fisiología , Tetrazoles/uso terapéutico , Tetrazoles/efectos adversos , Tetrazoles/farmacología , Enfermedad CrónicaRESUMEN
Sacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) that has been shown in multiple clinical trials to have clinical benefits and is recommended by major clinical management guidelines as a first-line treatment for heart failure with reduced ejection fraction (HFrEF). The most significant benefit that was observed in clinical trials is its effect in reducing hospital readmissions. However, little evidence supports its effectiveness in practice, especially in Saudi Arabia. A multicenter retrospective cohort study was conducted using the patient medical records at 2 tertiary hospitals in Saudi Arabia. Eligible patients were adults (≥18 years old) with a confirmed diagnosis of HFrEF who were discharged on either sacubitril/valsartan or angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) in addition to the other recommended therapy for HFrEF. The primary endpoint was the all-cause 30-day readmission rate. The secondary endpoints included all-cause readmissions at 60-day, 90-day, and 12 months. Additionally, 30-day, 60-day, and 90-day readmissions due to HF were evaluated. A total of 398 patients were included in our analysis; 199 (50.0%) received sacubitril/valsartan (group 1), and 199 (50.0%) received ACEI/ARB (group 2). Our results showed that all-cause 30-day readmissions in group 1 were significantly lower than in group 2 (7% vs 25.0%, RR 0.28, 95% Cl 0.16-0.49; Pâ <â .001). Additionally, the secondary outcomes showed significantly fewer 60-day, 90-day, and 12-month all-cause readmissions were identified in group 1 compared to group 2 (11% vs 30.7%, RR 0.36, 95% CI 0.23-0.56; Pâ <â .001), (11.6%. vs 32.6%, RR 0.35, 95% CI 0.23-0.55; Pâ <â .001) and (23.6% vs 51.2%, RR 0.46, 95% CI 0.35-0.62; Pâ <â .001), respectively. Furthermore, HF readmissions at 30-day, 60-day, and 90-day in group 1 were significantly lower than in group 2 (Pâ <â .05). Sacubitril/valsartan for the treatment of HFrEF is associated with a significantly lower rate of all-cause readmission as well as HF readmissions compared to ACEI/ARB. These benefits extend up to 12 months post-discharge.
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca , Readmisión del Paciente , Volumen Sistólico , Tetrazoles , Valsartán , Humanos , Aminobutiratos/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Valsartán/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Readmisión del Paciente/estadística & datos numéricos , Masculino , Estudios Retrospectivos , Femenino , Arabia Saudita , Volumen Sistólico/efectos de los fármacos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Persona de Mediana Edad , Anciano , Tetrazoles/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéuticoRESUMEN
BACKGROUND: Although some patients with heart failure (HF) with mildly reduced/preserved ejection fraction have low natriuretic peptide levels, there are no large-scale systematic studies of how common these individuals are or what happens to them. OBJECTIVES: The purpose of this study was to examine the proportion of patients in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction) trial with an N-terminal pro-B-type natriuretic peptide (NT-proBNP) level <125 pg/mL, their clinical characteristics, and outcomes. METHODS: I- PRESERVE enrolled patients with symptomatic HF and a LVEF ≥45% but who did not have NT-proBNP or body mass index inclusion/exclusion criteria. Baseline NT-proBNP was measured after enrollment but not reported to investigators. The primary outcome in this analysis was the composite of cardiovascular death or HF hospitalization. RESULTS: Overall, 808 of 3,480 patients (23.2%) had NT-proBNP <125 pg/mL. Patients with a low NT-proBNP were younger (68.6 years vs 72.6 years; P < 0.001), were less often men (36.1% vs 40.9%; P = 0.015), and had a higher body mass index (48.4% vs 38.7% obese; P < 0.001) than those with a higher NT-proBNP level. Patients with a low NT-proBNP had less atrial fibrillation (8.5% vs 35.1%; P < 0.001), myocardial infarction, diabetes, chronic obstructive pulmonary disease, and anemia but better kidney function. Patients with a lower NT-proBNP level had less marked echocardiographic abnormalities and were less likely to experience cardiovascular death or HF hospitalization; adjusted HR: 0.35 (95% CI: 0.27-0.46; P < 0.001). However, health status was similarly impaired in patients with lower and higher NT-proBNP levels (median Minnesota Living with Heart Failure Questionnaire 43 vs 43; P = 0.95). CONCLUSIONS: Almost one-quarter of patients with HF with mildly reduced/preserved ejection fraction had a low NT-proBNP level. Although these patients have a favorable prognosis, compared to those with a high NT-proBNP level, they have similarly impaired health status which should be a target for treatment. (Irbesartan in Heart Failure With Preserved Systolic Function [I- PRESERVE]; NCT00095238).
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Insuficiencia Cardíaca , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/mortalidad , Masculino , Volumen Sistólico/fisiología , Femenino , Anciano , Fragmentos de Péptidos/sangre , Péptido Natriurético Encefálico/sangre , Persona de Mediana Edad , Tetrazoles/uso terapéutico , Irbesartán/uso terapéutico , Hospitalización/estadística & datos numéricos , Compuestos de Bifenilo , Pronóstico , Biomarcadores/sangre , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéuticoRESUMEN
We assessed the real-world effectiveness of sacubitril/valsartan in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF) with an emphasis on those with older age (≥ 75 years) or with New York Heart Association (NYHA) class IV, for whom greater uncertainty existed regarding clinical outcomes. We conducted a retrospective cohort study based on patient-level linkage of electronic healthcare datasets. Data from all adults with HFrEF in Belgium receiving a prescription for sacubitril/valsartan between 01-November-2016 and 31-December-2018 were collected, with a follow-up of > 6 years. The total study population comprised 5446 patients, older than the PARADIGM-HF trial participants, and with higher NYHA class (all P < 0.0001). NYHA class improved following sacubitril/valsartan initiation (P < 0.0001 baseline vs. reassessment). Most concomitant medications were reduced. Remarkably, the risk of hospitalization for a cardiovascular reason and for HF was reduced by > 26% in the overall cohort, and in subgroups of patients ≥ 75 years, with NYHA class III/IV (all P < 0.0001) or with NYHA class IV (P < 0.05), vs. baseline. All-cause mortality did not increase in real-world patients with NYHA class III/IV. The results support the long-term beneficial effects of sacubitril/valsartan in older patients and in those experiencing the most severe symptoms.
Asunto(s)
Aminobutiratos , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca , Volumen Sistólico , Valsartán , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Bélgica , Compuestos de Bifenilo/uso terapéutico , Pueblo Europeo , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/mortalidad , Hospitalización , Estudios Retrospectivos , Volumen Sistólico/efectos de los fármacos , Tetrazoles/uso terapéutico , Resultado del Tratamiento , Valsartán/uso terapéuticoRESUMEN
BACKGROUND: A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-ß peptides in the brain, some of which are neurotoxic and linked to Alzheimer-type dementia. To address this, we examined the effect of sacubitril/valsartan compared with valsartan on cognitive function in patients with heart failure with preserved ejection fraction in a prespecified substudy of PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). METHODS: In PARAGON-HF, serial assessment of cognitive function was conducted in a subset of patients with the Mini-Mental State Examination (MMSE; score range, 0-30, with lower scores reflecting worse cognitive function). The prespecified primary analysis of this substudy was the change from baseline in MMSE score at 96 weeks. Other post hoc analyses included cognitive decline (fall in MMSE score of ≥3 points), cognitive impairment (MMSE score <24), or the occurrence of dementia-related adverse events. RESULTS: Among 2895 patients included in the MMSE substudy with baseline MMSE score measured, 1453 patients were assigned to sacubitril/valsartan and 1442 to valsartan. Their mean age was 73 years, and the median follow-up was 32 months. The mean±SD MMSE score at randomization was 27.4±3.0 in the sacubitril/valsartan group, with 10% having an MMSE score <24; the corresponding numbers were nearly identical in the valsartan group. The mean change from baseline to 96 weeks in the sacubitril/valsartan group was -0.05 (SE, 0.07); the corresponding change in the valsartan group was -0.04 (0.07). The mean between-treatment difference at week 96 was -0.01 (95% CI, -0.20 to 0.19; P=0.95). Analyses of a ≥3-point decline in MMSE, decrease to a score <24, dementia-related adverse events, and combinations of these showed no difference between sacubitril/valsartan and valsartan. No difference was found in the subgroup of patients tested for apolipoprotein E ε4 allele genotype. CONCLUSIONS: Patients with heart failure with preserved ejection fraction in PARAGON-HF had relatively low baseline MMSE scores. Cognitive change, measured by MMSE, did not differ between treatment with sacubitril/valsartan and treatment with valsartan in patients with heart failure with preserved ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Cognición , Combinación de Medicamentos , Insuficiencia Cardíaca , Volumen Sistólico , Tetrazoles , Valsartán , Humanos , Compuestos de Bifenilo/uso terapéutico , Valsartán/uso terapéutico , Valsartán/efectos adversos , Aminobutiratos/uso terapéutico , Aminobutiratos/efectos adversos , Masculino , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Femenino , Anciano , Cognición/efectos de los fármacos , Volumen Sistólico/efectos de los fármacos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/efectos adversos , Persona de Mediana Edad , Tetrazoles/uso terapéutico , Tetrazoles/efectos adversos , Estudios Prospectivos , Neprilisina/antagonistas & inhibidores , Resultado del Tratamiento , Disfunción Cognitiva/tratamiento farmacológico , Anciano de 80 o más AñosRESUMEN
AIMS: Cardiovascular-kidney-metabolic (CKM) multimorbidity is prevalent among individuals with heart failure (HF), but whether cardiac structure and function, clinical outcomes, and treatment response to sacubitril/valsartan vary in relation to CKM status is unknown. METHODS AND RESULTS: In this PARAGON-HF post-hoc analysis, we evaluated the impact of CKM multimorbidity (atherosclerotic cardiovascular [CV] disease, chronic kidney disease, and type 2 diabetes) on cardiac structure and function, clinical outcomes, and treatment effects of sacubitril/valsartan versus valsartan. The primary outcome was a composite of total HF hospitalizations and CV death. Secondary outcomes included the individual components of the primary outcome and a composite kidney outcome (sustained estimated glomerular filtration rate reduction of ≥50%, end-stage kidney disease, or kidney-related death). At baseline, 35.2% had one CKM condition, 33.3% had two, 15.9% had three, and only 15.6% had HF alone. CKM multimorbidity was associated with higher septal and posterior wall thickness, lower global longitudinal strain, higher E/e', and worse right ventricular function. Total HF hospitalizations or CV death increased with greater CKM multimorbidity, with the highest relative risk observed with three CKM conditions (rate ratio 3.06, 95% confidence interval 2.33-4.03), compared with HF alone. Treatment effects of sacubitril/valsartan were consistent irrespective of the number of CKM conditions for the primary endpoint (pinteraction = 0.75), CV death (pinteraction = 0.82), total HF hospitalizations (pinteraction = 0.67), and the composite kidney endpoint (pinteraction = 0.99). CONCLUSIONS: Cardiovascular-kidney-metabolic multimorbidity was common in PARAGON-HF and associated with adverse changes in cardiac structure and function and with a stepwise increase in risk of clinical outcomes. Treatment effects of sacubitril/valsartan were consistent irrespective of CKM burden. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01920711.
Asunto(s)
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca , Volumen Sistólico , Valsartán , Humanos , Aminobutiratos/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Masculino , Femenino , Volumen Sistólico/fisiología , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Persona de Mediana Edad , Tetrazoles/uso terapéutico , Resultado del Tratamiento , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/tratamiento farmacológico , Tasa de Filtración Glomerular , MultimorbilidadRESUMEN
AIMS: This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m2) patients combined with heart failure based on randomized controlled trials (RCTs) and observational studies. METHODS: The Embase, PubMed and the Cochrane Library were searched for relevant studies from inception to December 2023. Dichotomous variables were described as event counts with the odds ratio (OR) and 95% confidence interval (CI) values. Continuous variables were expressed as mean standard deviation (SD) with 95% CIs. RESULTS: A total of 6 RCTs and 8 observational studies were included, involving 17335 eGFR below 60 ml/min/1.73m2 patients combined with heart failure. In terms of efficacy, we analyzed the incidence of cardiovascular events and found that sacubitril/valsartan significantly reduced the risk of cardiovascular death or heart failure hospitalization in chronic kidney disease (CKD) stages 3-5 patients with heart failure (OR: 0.65, 95%CI: 0.54-0.78). Moreover, sacubitril/valsartan prevented the serum creatinine elevation (OR: 0.81, 95%CI: 0.68-0.95), the eGFR decline (OR: 0.83, 95% CI: 0.73-0.95) and the development of end-stage renal disease in this population (OR:0.73, 95%CI:0.60-0.89). As for safety outcomes, we did not find that the rate of hyperkalemia (OR:1.31, 95%CI:0.79-2.17) and hypotension (OR:1.57, 95%CI:0.94-2.62) were increased in sacubitril/valsartan group among CKD stages 3-5 patients with heart failure. CONCLUSIONS: Our meta-analysis proves that sacubitril/valsartan has a favorable effect on cardiac function without obvious risk of adverse events in abnormal renal function patients combined with heart failure, indicating that sacubitril/valsartan has the potential to become perspective treatment for these patients.