Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.334
Filtrar
1.
High Blood Press Cardiovasc Prev ; 28(2): 167-175, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33599965

RESUMO

INTRODUCTION: Sacubitril/valsartan (S-V) has been shown to reduce clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). This benefit has been mostly attributed to an improvement in systolic function. AIM: This study aimed to evaluate longitudinal changes in several echocardiographic parameters of diastolic function in a cohort of patients with HFrEF receiving S-V. METHODS: Echocardiographic parameters of consecutive patients receiving S-V, such as diastolic dysfunction (DD) grade and other individual diastolic and systolic function parameters, were prospectively collected at baseline and at 6-month follow-up. New York Heart Association (NYHA) functional class was also recorded. RESULTS: 65 patients (73.9% males; 61.5 ± 13 years) with HFrEF in NYHA class II-IV were evaluated. There was a significant reduction in DD grade after treatment with maximal tolerated doses (p < 0.001). Patients with advanced DD showed the most significant improvements: 75% and 60% of patients with initial grade 3 and 2, respectively, had better grade after 6 months of S-V. Moreover, there was a reduction in E/e' ratio (p = 0.004), left atrial longitudinal strain (p = 0.002), and an improvement of left ventricle ejection fraction (p < 0.001) and NYHA functional class (p = 0.001). Among those subjects who improved their functional class, a higher percentage improved their DD grade (39.3%, p = 0.025) in comparison with those not improving their NYHA class (25%, p = 0.434). CONCLUSIONS: In addition to an improvement in systolic function parameters, patients with HFrEF receiving S-V improved their diastolic function. This echocardiographic improvement is particularly relevant in those patients with better NYHA class at 6-month follow-up.


Assuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Tetrazóis/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Diástole , Combinação de Medicamentos , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteases/efeitos adversos , Recuperação de Função Fisiológica , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
2.
Expert Rev Clin Pharmacol ; 14(2): 161-172, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33470139

RESUMO

Introduction: Despite the introduction of numerous new antiseizure medications (ASMs) still about one-third of epilepsies remain drug-resistant. Therefore, new compounds with advanced efficacy are urgently needed. Cenobamate (CNB) is a new ASM that has been recently introduced in the United States for the treatment of adults with focal-onset seizures. The approval in Europe is under way.Areas covered: This review covers the pharmacological profile of CNB, the proof-of-concept trial, the two double-blind, placebo-controlled phase 2 trials investigating adjunct CNB in adults with focal-onset seizures, one open-label safety trial, and a variety of published abstract material that provided additional post hoc data.Expert opinion: In two placebo-controlled randomized multicenter phase 2 trials adjunct CNB showed unusually high efficacy with rates of seizure-free people with epilepsy (PWE) partially beyond 20%. However, during the clinical program cases of drug-related reactions with eosinophilia and systemic symptoms (DRESS syndrome) occurred. Therefore, an open-label safety study was performed in more than 1300 PWE with particularly slower titration schedules which did not add more cases with similar reactions. Taking into consideration the promising efficacy and the safety experience from the open-label trial, CNB applied according to the meanwhile recommended titration strategy, might offer a new prospect.


Assuntos
Anticonvulsivantes/administração & dosagem , Carbamatos/administração & dosagem , Clorofenóis/administração & dosagem , Epilepsias Parciais/tratamento farmacológico , Tetrazóis/administração & dosagem , Adulto , Animais , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacologia , Carbamatos/efeitos adversos , Carbamatos/farmacologia , Clorofenóis/efeitos adversos , Clorofenóis/farmacologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Comprimidos , Tetrazóis/efeitos adversos , Tetrazóis/farmacologia
4.
Neurologia ; 35(9): 628-632, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32896463

RESUMO

INTRODUCTION: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2. MATERIAL AND METHODS: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin gene-related peptide in the context of the COVID-19 pandemic. RESULTS: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence. CONCLUSIONS: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias.


Assuntos
Analgésicos/efeitos adversos , Infecções por Coronavirus/complicações , Cefaleia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Pneumonia Viral/complicações , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Antivirais/farmacologia , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Betacoronavirus , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/efeitos adversos , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Carbamazepina/efeitos adversos , Carbamazepina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Suscetibilidade a Doenças/induzido quimicamente , Interações Medicamentosas , Indução Enzimática/efeitos dos fármacos , Cefaleia/complicações , Cefaleia/prevenção & controle , Humanos , Ibuprofeno/efeitos adversos , Ibuprofeno/farmacologia , Ibuprofeno/uso terapêutico , Lisinopril/efeitos adversos , Lisinopril/uso terapêutico , Neuralgia/complicações , Pandemias , Peptidil Dipeptidase A/biossíntese , Peptidil Dipeptidase A/genética , Receptores Virais/biossíntese , Receptores Virais/genética , Fatores de Risco , Tetrazóis/efeitos adversos , Tetrazóis/uso terapêutico
5.
Cardiovasc Drugs Ther ; 34(5): 707-722, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32519065

RESUMO

An abundance of new data regarding the use of the novel drug compound sacubitril/valsartan in chronic heart failure (CHF) patients is published every year since the initial publication of the PARADIGM-HF study in 2014. This review summarises the most recent evidence (2019 and onwards) of sacubitril/valsartan in CHF patients as well as provides a critical appraisal of these data. New data are grouped in categories such as real-world data, randomised controlled trials, surrogate end-points, cost-effectiveness, use of sacubitril/valsartan as an anti-hypertensive treatment, effect on diuretic dosing and implementation of this novel compound in other populations. This review of recent literature identified important messages such as early initiation during index hospitalisation or immediately post-discharge, barriers against implementation of this novel treatment modality, analytical issues regarding measuring natriuretic peptides in patients under treatment and extrapolated use of sacubitril/valsartan in other than PARADIGM-HF populations. This update may serve as a very helpful evidence-based resource for practising clinicians, future research planning and health-related policy makers.


Assuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Tetrazóis/uso terapêutico , Aminobutiratos/efeitos adversos , Aminobutiratos/economia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/economia , Análise Custo-Benefício , Combinação de Medicamentos , Custos de Medicamentos , Medicina Baseada em Evidências , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/fisiopatologia , Humanos , Neprilisina/antagonistas & inibidores , Segurança do Paciente , Inibidores de Proteases/efeitos adversos , Inibidores de Proteases/economia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Tetrazóis/efeitos adversos , Tetrazóis/economia , Resultado do Tratamento
7.
Drugs Today (Barc) ; 56(4): 233-240, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32309819

RESUMO

Focal-onset or partial seizures are localized to a specific brain area or areas of the cerebral hemisphere. Cenobamate (CNB, Xcopri, YKP-3089; SK Life Science) is a recent U.S. Food and Drug Administration (FDA)-approved drug for the treatment of focal-onset seizures in the adult population. CNB has demonstrated broad-spectrum efficacy in alternative preclinical models of epilepsy. The molecule exerts an antiseizure effect due to its dual mechanism of action: besides inhibiting the voltage-gated persistent component of the sodium currents, CNB is additionally an allosteric GABA(A) channel modulator in a non-benzodiazepine fashion. The superior clinical effect of this molecule over placebo in reducing seizure frequency may be observed after 2 weeks following a starting oral dose of 50 mg/day. The drug can be titrated up to a maximum daily maintenance dose of 400 mg/day. CNB has mild to moderate side effects. During initial development, a critical drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome was noticed in 3 patients. However, the DRESS effect was not observed in the large C021 safety study involving 1,347 patients, suggesting a maximum potential risk of no more than 0.3%. The present monograph describes the background, preclinical and clinical pharmacology, indication and safety of CNB for the treatment of partial/focal seizures.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamatos/uso terapêutico , Clorofenóis/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Convulsões/tratamento farmacológico , Tetrazóis/uso terapêutico , Adulto , Anticonvulsivantes/efeitos adversos , Carbamatos/efeitos adversos , Clorofenóis/efeitos adversos , Humanos , Tetrazóis/efeitos adversos
8.
Rev Cardiovasc Med ; 21(1): 113-118, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32259909

RESUMO

Patients with heart failure (HF) are prone to combine with renal insufficiency. Recently, LCZ696 has been used in the treatment of HF, but whether LCZ696 is better than angiotensin converting enzyme inhibitors/angiotensin receptor antagonists (ACEI/ARB) in renal protection for HF patients has not been investigated. Therefore, we conducted a meta-analysis focusing on LCZ696 and its role in preservation of renal function in HF patients. Embase, PubMed, the Cochrane Library and ClinicalTrials.gov databases were electronically searched for available randomized controlled trials (RCTs). HF patients taking LCZ696 or ACEI/ARB were assessed for renal adverse events. The last search date was Sep 20, 2019. A total of 14959 patients from 6 trials were included in this meta-analysis. As compared to ACEI/ARB, LCZ696 significantly reduced the risk of renal function deterioration (odds ratio 0.77, 95% confidence interval 0.61-0.97, P = 0.02). In summary, LCZ696 may have superior renal protection in HF patients compared with ACEI/ARB.


Assuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Rim/efeitos dos fármacos , Inibidores de Proteases/uso terapêutico , Tetrazóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Combinação de Medicamentos , Medicina Baseada em Evidências , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Tetrazóis/efeitos adversos , Resultado do Tratamento
9.
Circ Heart Fail ; 13(4): e006645, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32248695

RESUMO

BACKGROUND: In PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-pro BNP in Patients Stabilized From an Acute Heart Failure Episode), the in-hospital initiation of sacubitril/valsartan in patients hospitalized for acute decompensated heart failure (ADHF) was well-tolerated and led to improved outcomes. We aim to determine the representativeness of the PIONEER-HF trial among patients hospitalized for ADHF using real-world data. METHODS: The study population was derived from all patients discharged alive for ADHF in the Get With The Guidelines-HF registry from 2006 to 2018 with HF with reduced ejection fraction (HFrEF; all HFrEF with ADHF). We then determined the proportion of patients meeting PIONEER-HF eligibility criteria (PIONEER-HF eligible) and those meeting a set of limited eligibility criteria (actionable cohort). Rates of HF readmissions and all-cause mortality were then compared between the all HFrEF with ADHF, PIONEER-HF eligible, and actionable cohorts using linked Medicare claims data. RESULTS: A total of 99 767 patients with HFrEF in Get With The Guidelines-HF were hospitalized for ADHF. PIONEER-HF inclusion criteria were met by 71 633 (71.8%) patients, and both inclusion and exclusion criteria were met by 20 704 (20.8%) patients. Further, 68 739 (68.9%) patients met the criteria for the actionable cohort. Among the Centers for Medicare and Medicaid-linked patients, the HF rehospitalization rate at 1 year was 35.1% (95% CI, 34.5-35.8) for all HFrEF with ADHF patients, 32.6% (95% CI, 31.3-33.9) for the PIONEER-HF eligible cohort, and 33.1% (95% CI, 32.3-33.9) for the actionable cohort. The 1-year all-cause mortality was 36.7% (95% CI, 36.1-7.4) for all HFrEF with ADHF patients, 31.6% (95% CI, 30.3-32.9) for the PIONEER-HF eligible cohort, and 32.2% (95% CI, 31.4-33.0) for the actionable cohort. CONCLUSIONS: Patient characteristics and clinical outcomes for patients eligible for PIONEER-HF only modestly differ when compared with those encountered in routine practice, suggesting that the in-hospital initiation of sacubitril/valsartan should be routinely considered for patients with HFrEF hospitalized for ADHF.


Assuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Admissão do Paciente , Inibidores de Proteases/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Tetrazóis/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Biomarcadores/sangue , Tomada de Decisão Clínica , Combinação de Medicamentos , Definição da Elegibilidade , Medicina Baseada em Evidências , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Neprilisina/antagonistas & inibidores , Seleção de Pacientes , Fragmentos de Peptídeos/sangue , Inibidores de Proteases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Sistema de Registros , Fatores de Risco , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
10.
Rev. esp. geriatr. gerontol. (Ed. impr.) ; 55(2): 65-69, mar.-abr. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-199849

RESUMO

BACKGROUND: HF elderly patients are underrepresented in Sacubitril/Valsartan HF trials, and the effect of S/V in real-life patients with advanced age is unknown. The aim of this study was to evaluate the use and safety of S/V in a real-word cohort of elderly patients. METHODS: We performed a prospective registry of patients who started S/V in clinical practice. We compared baseline characteristics, adverse events during follow-up and causes of S/V withdrawal according to age. RESULTS: A total of 427 patients started treatment with S/V: 222 (52.0%)<70 years old, 140 (32.8%) between 70 and 79 and 65 (15.2%)≥80. During a mean follow-up of 7.0+/-0.1months S/V was well tolerated, with no age-related differences in adverse events (26.8%, 25.9%, 23.1% respectively; p = 0.83). Symptomatic hypotension tended to be more frequent in the elderly (19.8%, 25.6%, 33.3% respectively; p = 0.17). The withdrawal of S/V was more frequent in younger patients (14.4%, 10.0%, 4.6% respectively; p = 0.05) and related to poor prognosis (HR 13.51, 95% CI 3.22-56.13, p < 0.001). CONCLUSIONS: Sacubitril/Valsartan is useful and safe in elderly people with HF-rEF in real-life clinical practice, and withdrawal is associated to poor prognosis. The doses achieved are lower in elderly people


ANTECEDENTES: Los pacientes ancianos con IC están sub-representados en los ensayos de IC sacubitril/valsartán (S/V), y se desconoce el efecto del S/V en pacientes de la vida real con edad avanzada. El objetivo de este estudio fue evaluar el uso y la seguridad del S/V en una cohorte de pacientes ancianos. MÉTODOS: Se realizó un registro prospectivo de los pacientes que iniciaron el S/V en la práctica clínica. Se compararon las características iniciales, los eventos adversos durante el seguimiento y las causas de la abstinencia del S/V según la edad. RESULTADOS: Un total de 427 pacientes iniciaron el tratamiento con S/V: 222 (52,0%)<70 años, 140 (32,8%) entre 70-79 años y 65 (15,2%)≥80 años. Durante un seguimiento medio de 7,0+/-0,1 meses, el S/V fue bien tolerado, sin diferencias en los eventos adversos relacionados con la edad (26,8, 25,9 y 23,1%, respectivamente; p = 0,83). La hipotensión sintomática tendió a ser más frecuente en los ancianos (19,8, 25,6 y 33,3%, respectivamente; p = 0,17). El retiro del S/V fue más frecuente en pacientes más jóvenes (14,4, 10,0 y 4,6%, respectivamente; p = 0,05) y se relacionó con un pronóstico precario (CRI: 13,51; IC del 95%: 3,22-56,13; p < 0,001). CONCLUSIONES: El sacubitril/valsartán es útil y seguro en personas de edad avanzada con HF-rEF en la práctica clínica de la vida real, y la abstinencia se asocia con un pronóstico deficiente. Las dosis alcanzadas son más bajas en las personas mayores


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Aminobutiratos/administração & dosagem , Tetrazóis/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Aminobutiratos/efeitos adversos , Tetrazóis/efeitos adversos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Estimativa de Kaplan-Meier , Prognóstico
13.
PLoS One ; 15(2): e0228926, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32053711

RESUMO

Unveiling the mechanism of action of a drug is key to understand the benefits and adverse reactions of a medication in an organism. However, in complex diseases such as heart diseases there is not a unique mechanism of action but a wide range of different responses depending on the patient. Exploring this collection of mechanisms is one of the clues for a future personalized medicine. The Therapeutic Performance Mapping System (TPMS) is a Systems Biology approach that generates multiple models of the mechanism of action of a drug. Each molecular mechanism generated could be associated to particular individuals, here defined as prototype-patients, hence the generation of models using TPMS technology may be used for detecting adverse effects to specific patients. TPMS operates by (1) modelling the responses in humans with an accurate description of a protein network and (2) applying a Multilayer Perceptron-like and sampling strategy to find all plausible solutions. In the present study, TPMS is applied to explore the diversity of mechanisms of action of the drug combination sacubitril/valsartan. We use TPMS to generate a wide range of models explaining the relationship between sacubitril/valsartan and heart failure (the indication), as well as evaluating their association with macular degeneration (a potential adverse effect). Among the models generated, we identify a set of mechanisms of action associated to a better response in terms of heart failure treatment, which could also be associated to macular degeneration development. Finally, a set of 30 potential biomarkers are proposed to identify mechanisms (or prototype-patients) more prone of suffering macular degeneration when presenting good heart failure response. All prototype-patients models generated are completely theoretical and therefore they do not necessarily involve clinical effects in real patients. Data and accession to software are available at http://sbi.upf.edu/data/tpms/.


Assuntos
Aminobutiratos/farmacologia , Biologia de Sistemas/métodos , Tetrazóis/farmacologia , Valsartana/farmacologia , Aminobutiratos/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Biomarcadores , Simulação por Computador , Combinação de Medicamentos , Coração/efeitos dos fármacos , Insuficiência Cardíaca/diagnóstico , Humanos , Neprilisina/farmacologia , Software , Volume Sistólico/fisiologia , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos , Função Ventricular Esquerda/fisiologia
14.
Vasc Health Risk Manag ; 16: 41-51, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021227

RESUMO

This review aims to elucidate the optimal dosing of angiotensin receptor-neprilysin inhibitor (ARNI) therapy in the heart failure (HF) treatment paradigm through examination of the trial population characteristics and the mortality benefit observed in the Prospective Comparison of ARNI with angiotensin-converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF; NCT01035255) trial. Considerations regarding the initiation and titration of sacubitril/valsartan, a first-in-class ARNI, will also be addressed. The approval of sacubitril/valsartan heralded the first novel pharmacological class in over a decade for the treatment of heart failure with reduced ejection fraction (HFrEF). The PARADIGM-HF trial showed that treatment with valsartan/valsartan reduced the risk of first occurrence of either cardiovascular death or HF-related hospitalization (composite primary endpoint) by 20% compared with enalapril in patients with HFrEF. The incremental benefits of treatment with valsartan/valsartan over enalapril demonstrated in the PARADIGM-HF trial led to strong recommendations for its use over ACEIs or angiotensin receptor blockers to further reduce morbidity and mortality in the 2016 and 2017 American College of Cardiology/American Heart Association/Heart Failure Society of America updates to the guidelines for the management of HF. Although the optimal timing for the initiation of valsartan/valsartan has yet to be determined, its early use is likely to have a positive impact on patient outcomes.


Assuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Tetrazóis/uso terapêutico , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/efeitos adversos , Fatores de Risco , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
15.
J Cardiovasc Med (Hagerstown) ; 21(3): 223-230, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31990748

RESUMO

AIMS: Myocardial work is a new transthoracic echocardiogram (TTE) parameter that enhances the information provided through left ventricular (LV) global longitudinal strain (GLS). Nothing is known about the impact of sacubitril/valsartan (LCZ696) therapy on myocardial work parameters. The aim of this study was to evaluate the effects of LCZ696 on LV myocardial work in heart failure patients. METHODS: Prospective evaluation of chronic heart failure patients with LV ejection fraction of 40% or less despite optimized standard of care therapy, in which LCZ696 therapy was started and no other heart failure treatment was expected to change. TTE study was performed before and 6 months after LCZ696 therapy. A semiautomated analysis of LV GLS was made and myocardial work estimated using custom software of the GE Vivid E95 ultrasound system. RESULTS: Of the 42 patients, 35 (83.3%) completed the 6 months, follow-up, since 2 (4.8%) patients died and 5 (11.9%) discontinued treatment due to adverse events. Mean age was 58.6 ±â€Š11.1 years. TTE data showed a significant reduction in LV dimensions and atrial volumes, as well as an improvement in LV ejection fraction (29.3 vs. 35.2%, P = 0.001) and GLS (-7.0 vs. -8.9%, P = 0.001). Myocardial work had a significant increase in global constructive work (720.2 vs. 900.6 mmHg%, P = 0.016) and global work efficiency (78.6 vs. 86.6%, P = 0.027), with a nonsignificant decrease in global wasted work (150.2 vs. 136.8 mmHg%, P = 0.441) at 6 months. CONCLUSION: LCZ696 therapy was associated with signs of reverse remodelling by usual TTE parameters and LV myocardial work at 6 months, including an increase in global constructive work and work efficiency.


Assuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Ecocardiografia , Insuficiência Cardíaca/tratamento farmacológico , Contração Miocárdica/efeitos dos fármacos , Inibidores de Proteases/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Tetrazóis/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Combinação de Medicamentos , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Neprilisina/antagonistas & inibidores , Valor Preditivo dos Testes , Estudos Prospectivos , Inibidores de Proteases/efeitos adversos , Recuperação de Função Fisiológica , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Remodelação Ventricular/efeitos dos fármacos
19.
J Cardiovasc Med (Hagerstown) ; 21(1): 6-12, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31789711

RESUMO

BACKGROUND: The PARADIGM-HF trial showed that sacubitril-valsartan - an angiotensin receptor-neprilysin inhibitor (ARNI) - is more effective than enalapril for some patients with heart failure. However, the eligibility of the PARADIGM-HF study to a real-world heart failure population was not well established. METHODS: We made secondary analysis of patients (n = 4872) with heart failure prospectively enrolled in the Swedish Heart Failure Registry from Sahlgrenska University Hospital/Östra Hospital, Sweden during 2005-2016. The eligibility of the PARADIGM-HF trial in the real world was studied based on patients whether they were either fully or partially compatible with the PARADIGM-HF population. Patients were judged to be fully eligible for the PARADIGM-HF trial if they completely met the inclusion and exclusion criteria, and partially eligible if they did not stay on target dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), despite their having been treated with ACEI/ARB for at least 6 months. RESULTS: Among patients who had heart failure with reduced left ventricular ejection fraction (≤40%) (HFrEF) (n = 2165), 653 (30%) and 958 (44%) patients were fully and partially compatible with PARADIGM-HF criteria, respectively. In both fully and partially eligible groups, patients were more male. Despite those fully eligible patients being younger (77.6 ±â€Š12.7 vs. 84.0 ±â€Š13.7 years) than noneligible patients, they were much older than in the PARADIGM-HF trial. Moreover, those fully eligible patients had lower all-cause mortality compared with both partially and noneligible patients. However, both fully and partially eligible patients had higher all-cause mortality than that in the PARADIGM-HF trial. CONCLUSION: In a real-world outpatient clinical setting, around 1/3-1/2 of HFrEF were eligible for treatment of Sac/Val except that they are older, sicker, and carry higher risk for all-cause mortality than the PARADIGM-HF trial population.


Assuntos
Assistência Ambulatorial , Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Ensaios Clínicos como Assunto , Definição da Elegibilidade , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Tetrazóis/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Tomada de Decisão Clínica , Comorbidade , Combinação de Medicamentos , Feminino , Nível de Saúde , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Neprilisina/antagonistas & inibidores , Seleção de Pacientes , Inibidores de Proteases/efeitos adversos , Recuperação de Função Fisiológica , Sistema de Registros , Medição de Risco , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Suécia , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
20.
Circulation ; 141(5): 338-351, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31736337

RESUMO

BACKGROUND: Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction, the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women compared with men. METHODS: In a prespecified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), which compared sacubitril-valsartan and valsartan in patients with heart failure with preserved ejection fraction. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. RESULTS: Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older and had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI, 0.59-0.90) in women and 1.03 (95% CI, 0.84-1.25) in men (P interaction = 0.017). The benefit from sacubitril-valsartan was attributable to reduction in heart failure hospitalization. The improvement in New York Heart Association class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in Kansas City Cardiomyopathy Questionnaire clinical summary score was less in women than in men. The difference in adverse events between sacubitril-valsartan and valsartan was similar in women and men. CONCLUSIONS: As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. Whereas the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.


Assuntos
Aminobutiratos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Fatores Sexuais , Tetrazóis/farmacologia , Valsartana/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Aminobutiratos/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Combinação de Medicamentos , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico/efeitos dos fármacos , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...