RESUMO
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 , Compostos de Bifenilo , Cognição , Combinação de Medicamentos , Insuficiência Cardíaca , Volume Sistólico , Tetrazóis , Valsartana , Humanos , Compostos de Bifenilo/uso terapêutico , Valsartana/uso terapêutico , Valsartana/efeitos adversos , Aminobutiratos/uso terapêutico , Aminobutiratos/efeitos adversos , Masculino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Feminino , Idoso , Cognição/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/efeitos adversos , Pessoa de Meia-Idade , Tetrazóis/uso terapêutico , Tetrazóis/efeitos adversos , Estudos Prospectivos , Neprilisina/antagonistas & inibidores , Resultado do Tratamento , Disfunção Cognitiva/tratamento farmacológico , Idoso de 80 Anos ou maisRESUMO
Effects of angiotensin receptor/neprilysin inhibitors (ARNI) on ventricular remodeling in patients with heart failure, especially heart failure with reduced ejection fraction (HFrEF), are better than those of angiotensin-converting enzyme inhibitors (ACEI). Acute myocardial infarction (AMI) complicated by mitral regurgitation exacerbates ventricular remodeling and increases the risk of heart failure. There is limited evidence on the effects of early administration of ARNI in patients with AMI complicated by mitral regurgitation. The aim of this trial was to examine the effectiveness and the safety of early administration of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation. This was a randomized, single-blind, parallel-group, controlled trial. From June 2021 to June 2022, we enrolled 142 consecutive patients with AMI complicated by moderate-to-severe mitral regurgitation and followed them for 12 months. The patients received standard treatment for AMI and were randomly assigned to receive ARNI or benazepril. The primary efficacy end points were the differences in mitral regurgitant jet area (MRJA), mitral regurgitant volume (MRV), concentration of n-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume and end-systolic volume (LVEDV and LVESV) between groups and within groups at baseline, 1, 3, 6, and 12 months. Secondary end points included the rates of heart failure hospitalization, all-cause mortality, refractory angina, malignant arrhythmias, recurrent myocardial infarction, and stroke. Safety end points included the rates of hyperkalemia, renal dysfunction, hypotension, angioedema, and cough. The ARNI group had significantly lower NT-proBNP levels than the benazepril group at 1 month and later (P < 0.001). MRJA and MRV significantly improved in the ARNI group compared with the benazepril group at 12 months (MRJA: - 3.21 ± 2.18 cm2 vs. - 1.83 ± 2.81 cm2, P < 0.05; MRV: - 27.22 ± 15.22 mL vs. - 13.67 ± 21.02 mL, P < 0.001). The ARNI group also showed significant reductions in LVEDV and LVESV (P < 0.05) and improvement in LVEF (P < 0.05). Secondary end point analysis showed a significantly higher rate of heart failure hospitalization in the benazepril group compared with the ARNI group (HR = 2.03, 95% CI 1.12-3.68, P = 0.021). Safety end point analysis showed a higher rate of hypotension in the ARNI group (P < 0.05). Early use of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation can significantly reduce mitral regurgitation, improve ventricular remodeling, and decrease heart failure hospitalization. Nevertheless, caution is needed to avoid hypotension. Chinese Clinical Trial Registry (ChiCTR2100054255) registered on December 11, 2021.
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Aminobutiratos , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência da Valva Mitral , Infarto do Miocárdio , Intervenção Coronária Percutânea , Valsartana , Humanos , Valsartana/administração & dosagem , Valsartana/efeitos adversos , Masculino , Feminino , Aminobutiratos/administração & dosagem , Aminobutiratos/efeitos adversos , Aminobutiratos/uso terapêutico , Insuficiência da Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/cirurgia , Pessoa de Meia-Idade , Resultado do Tratamento , Infarto do Miocárdio/complicações , Método Simples-Cego , Idoso , Intervenção Coronária Percutânea/métodos , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/uso terapêutico , Volume Sistólico/fisiologia , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologia , Função Ventricular Esquerda/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Índice de Gravidade de Doença , Fatores de TempoRESUMO
INTRODUCTION: Angiotensin receptor blockers are widely used antihypertensive drugs in South Korea. In 2021, the Korea Ministry of Food and Drug Safety acknowledged the need for national compensation for a drug-induced liver injury (DILI) after azilsartan use. However, little is known regarding the association between angiotensin receptor blockers and DILI. OBJECTIVE: We conducted a retrospective cohort study in incident users of angiotensin receptor blockers from a common data model database (1 January, 2017-31 December, 2021) to compare the risk of DILI among specific angiotensin receptor blockers against valsartan. METHODS: Patients were assigned to treatment groups at cohort entry based on prescribed angiotensin receptor blockers. Drug-induced liver injury was operationally defined using the International DILI Expert Working Group criteria. Cox regression analyses were conducted to derive hazard ratios and the inverse probability of treatment weighting method was applied. All analyses were performed using R. RESULTS: In total, 229,881 angiotensin receptor blocker users from 20 university hospitals were included. Crude DILI incidence ranged from 15.6 to 82.8 per 1000 person-years in treatment groups, most were cholestatic and of mild severity. Overall, the risk of DILI was significantly lower in olmesartan users than in valsartan users (hazard ratio: 0.73 [95% confidence interval 0.55-0.96]). In monotherapy patients, the risk was significantly higher in azilsartan users than in valsartan users (hazard ratio: 6.55 [95% confidence interval 5.28-8.12]). CONCLUSIONS: We found a significantly higher risk of suspected DILI in patients receiving azilsartan monotherapy compared with valsartan monotherapy. Our findings emphasize the utility of real-world evidence in advancing our understanding of adverse drug reactions in clinical practice.
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Antagonistas de Receptores de Angiotensina , Doença Hepática Induzida por Substâncias e Drogas , Registros Eletrônicos de Saúde , Humanos , República da Coreia/epidemiologia , Estudos Retrospectivos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Masculino , Feminino , Antagonistas de Receptores de Angiotensina/efeitos adversos , Pessoa de Meia-Idade , Registros Eletrônicos de Saúde/estatística & dados numéricos , Idoso , Estudos de Coortes , Anti-Hipertensivos/efeitos adversos , Incidência , Adulto , Valsartana/efeitos adversos , Fatores de Risco , Benzimidazóis/efeitos adversosRESUMO
PURPOSE: This study was to investigate the association between the use of Sodium-glucose Cotransporter-2 inhibitors (SGLT2i) or angiotensin receptor-neprilysin inhibitor (ARNI; ie, Sacubitril + valsartan, Product name ENTRESTO) and the risk of atherosclerotic cardiovascular disease (ASCVD) in patients with coexisting diabetes and heart failure. Specifically, the study compared outcomes between patients using SGLT2i or valsartan + sacubitril and those not using these medications. METHODS: This study utilized data from the National Health Insurance Research Database (NHIRD) from 2017 to 2018. The case group consisted of 8691 patients with coexisting diabetes and heart failure who did not use SGLT2i or Entresto, while the control group consisted of 8691 patients with coexisting diabetes and heart failure who used SGLT2i or Entresto. The primary outcome was ASCVD, including a composite of cardiovascular death and hospitalization for worsening heart failure. Secondary outcomes included all-cause death, cause of cardiovascular death, and recurrence of heart failure, non-fatal myocardial infarction, non-fatal stroke (including ischemic stroke and hemorrhagic stroke) and new renal replacement therapy. RESULTS: The study found that the use of SGLT2 inhibitors or ARNI was associated with a lower risk of ASCVD in patients with coexisting diabetes and heart failure. CONCLUSION: The study suggests that the use of SGLT2 inhibitors, alone or in combination with Entresto, may be effective in reducing the risk of ASCVD and its associated adverse outcomes in patients with diabetes and heart failure. This finding has important implications for the management of these conditions.
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Aminobutiratos , Aterosclerose , Compostos de Bifenilo , Doenças Cardiovasculares , Diabetes Mellitus , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Neprilisina , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Valsartana/efeitos adversos , Receptores de Angiotensina , Glucose , SódioRESUMO
BACKGROUND: Hypotension is a potential adverse effect of sacubitril/valsartan, but there are limited data regarding the predictors and implications of treatment-related hypotension in heart failure (HF) with mildly reduced and preserved ejection fraction. OBJECTIVES: We investigated predictors of treatment-associated hypotension, clinical outcomes after hypotension, and the relationship between left ventricular ejection fraction (LVEF) and incidence of hypotension in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) trial. METHODS: PARAGON-HF randomized patients with chronic HF (≥45%) to sacubitril/valsartan or valsartan. Following randomization, hypotension was defined as investigator-reported hypotension with a systolic blood pressure <100 mm Hg. Predictors of hypotension were assessed using multivariable Cox models. Associations between hypotension and clinical outcomes were evaluated in time-updated Cox models. The relationship among treatment, LVEF, and incident rates of hypotension and clinical outcomes was estimated using Poisson regression models. RESULTS: Of 4,796 patients in PARAGON-HF, 637 (13%) experienced hypotension, more frequently in the sacubitril/valsartan arm (P < 0.001). Following documented hypotension, patients had higher risk of cardiovascular death and total HF hospitalizations (adjusted RR: 1.63; 95% CI: 1.27-2.09; P < 0.001) and all-cause death (adjusted HR: 1.62; 95% CI: 1.28-2.05; P < 0.001). LVEF modified the association between sacubitril/valsartan and risk of hypotension (Pinteraction = 0.019) such that patients with LVEF ≥60% experienced substantially higher treatment-related risks of hypotension. CONCLUSIONS: In PARAGON-HF, a higher LVEF was associated with an increased risk of hypotension in patients treated with sacubitril/valsartan compared with valsartan. Because these subjects are also less likely to derive clinical benefit from sacubitril/valsartan, our data reinforce that the benefit/risk ratio favors the use of sacubitril/valsartan in patients with LVEF below normal, but not at higher LVEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca , Hipotensão , Volume Sistólico , Valsartana , Humanos , Valsartana/efeitos adversos , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia , Hipotensão/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Aminobutiratos/efeitos adversos , Masculino , Feminino , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/administração & dosagem , Pessoa de Meia-Idade , Tetrazóis/efeitos adversos , Estudos ProspectivosRESUMO
INTRODUCTION: The current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction to improve prognosis and health status. However, evidence on the optimal sequencing of approved drugs is scarce, highlighting the importance of individualised treatment plans. Registry data indicate that only a portion of these patients can tolerate all four recommended classes, underscoring the need to establish the favoured sequence when using these drugs. Additionally, the choice between long-acting and short-acting loop diuretics in the present era remains uncertain. This is particularly relevant given the frequent use of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor, both of which potentiate natriuretic effects. METHODS AND ANALYSIS: In a prospective, randomised, open-label, blinded endpoint method, LAQUA-HF (Long-acting vs short-acting diuretics and neurohormonal Agents on patients' QUAlity-of-life in Heart Failure patients) will be a 2×2 factorial design, with a total of 240 patients randomised to sacubitril/valsartan versus dapagliflozin and torsemide versus furosemide in a 1:1 ratio. Most enrolment sites have participated in an ongoing observational registry for consecutive patients hospitalised for heart failure involved dedicated study coordinators, and used the same framework to enrol patients. The primary endpoint is the change in patients' health status over 6 months, defined by the Kansas City Cardiomyopathy Questionnaire. Additionally, clinical benefit at 6 months defined as a hierarchical composite endpoint will be assessed by the win ratio as the secondary endpoint. ETHICS AND DISSEMINATION: The medical ethics committee Keio University in Japan has approved this trial. All participants provide written informed consent prior to study entry. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses. TRIAL REGISTRATION NUMBER: UMIN000045229.
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Antagonistas de Receptores de Angiotensina , Insuficiência Cardíaca , Humanos , Estudos Prospectivos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Volume Sistólico , Insuficiência Cardíaca/tratamento farmacológico , Valsartana/efeitos adversos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Combinação de Medicamentos , Aminobutiratos/efeitos adversos , Medidas de Resultados Relatados pelo Paciente , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.
Assuntos
Anti-Hipertensivos , Medicamentos de Ervas Chinesas , Hipertensão , Humanos , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , China , Método Duplo-Cego , Tetrazóis/efeitos adversos , Valsartana/efeitos adversosRESUMO
BACKGROUND: This study aimed to evaluate the effect of sacubitril valsartan (SV) on heart failure (HF) hospitalization and cardiovascular mortality in patients on hemodialysis with HF with preserved ejection fraction (EF; HFpEF). METHODS: This single-center, prospective study enrolled 155 stable hemodialysis patients with EF > 40% who were followed up for 12 months. Fifty-nine patients were treated with SV; the others were matched for EF (57.89 ± 9.35 vs. 58.00 ± 11.82, P = 0.9) at a ratio of 1:1 and included as controls. The target dosage of SV was 200 mg/day. RESULTS: Twenty-three (23/155; 14.84%) had HF with mid-range EF (HFmrEF), while 132 (85.16%) had HFpEF. After SV treatment, the peak early diastolic transmitral flow velocity/peak early diastolic mitral annular tissue velocity(E/e') improved from 17.19 ± 8.74 to 12.80 ± 5.52 (P = 0.006), the left ventricular (LV) end-diastolic diameter decreased from 53.14 ± 7.67 mm to 51.56 ± 7.44 mm (P = 0.03), and the LV mass index decreased from 165.7 ± 44.6 g/m2 to 154.8 ± 24.0 g/m2 (P = 0.02). LVEF (P = 0.08) and LV global longitudinal strain (P = 0.7) did not change significantly. The composite outcome of first and recurrent HF hospitalization or cardiovascular death showed no difference between group. However, the Acute Dialysis Quality Initiative Workgroup (ADQI) HF class improved in 39 and 15 patients and worsened in 1 and 11 patients in the SV and control groups, respectively (P < 0.001). Age, diabetes mellitus, and pulmonary arterial pressure were independent risk factors for HF hospitalization and cardiovascular mortality in patients with HFpEF. CONCLUSIONS: SV improved LV hypertrophy, diastolic function, and the ADQI class for HF; however, it failed to reduce the composite endpoints of HF hospitalization and cardiovascular disease-related mortality over 12 months of follow-up in patients on maintenance hemodialysis with EF of > 40%.
Assuntos
Aminobutiratos , Compostos de Bifenilo , Doenças Cardiovasculares , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Estudos Prospectivos , Volume Sistólico , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Diálise Renal/efeitos adversos , Função Ventricular EsquerdaRESUMO
BACKGROUND: Heart failure (HF) remains a major public health problem with a high mortality and morbidity worldwide. Currently, there is no optimal revascularisation strategy for patients with ischaemic cardiomyopathy despite suggestions that coronary artery bypass graft (CABG) may be superior to medical therapy in improving survival. However, CABG may be associated with substantial risk in HF subjects. We therefore aimed to evaluate the safety and efficacy of the early initiation of sacubitril/valsartan in haemodynamically stabilised patients with HF with reduced ejection fraction (HFrEF) after early CABG. METHODS: This was an open-label study in which ~80 patients after CABG were randomised either to the early or late initiation of the sacubitril-valsartan. The study included patients >40 years with left ventricular ejection fraction <45% and New York Heart Association (NYHA) class II-IV at the early stage after CABG. Patients underwent intervention, the starting dose of sacubitril/valsartan (24/26 mg or 49/51 mg two times per day). The follow-up took place every 4 weeks except the first visit, which took place in 2 weeks after initiation. The primary endpoint assessed the key safety outcomes, the secondary endpoints were: the quality of life measured, the N-terminal pro-B-type natriuretic peptide (NT-proBNP) changes and 6 min walk test (6MWT). RESULTS: In total, 83 patients were screened and 77 patients were enrolled. The majority of patients (84.4%) were in the NYHA class III at randomisation. The number of patients who discontinued the study was low in both groups (2.5%, 5.2%), and renal function, hyperkalaemia and symptomatic hypotension rarely seen in both groups did not differ significantly. The improvement in quality of life and distance at the 6MWT in both groups was significant (p<0.001). The NT-proBNP concentration decreased in both groups, the significant reduction was in the early group (p<0.001) versus the postdischarge group. CONCLUSIONS: The early initiation of sacubitril/valsartan in patients after CABG with HFrEF is safe and effective. Adverse events and permanent discontinuation were low. The NT-proBNP concentration reduced significantly with the early in-hospital initiation.
Assuntos
Aminobutiratos , Compostos de Bifenilo , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico , Qualidade de Vida , Assistência ao Convalescente , Tetrazóis/efeitos adversos , Função Ventricular Esquerda , Alta do Paciente , Valsartana/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Combinação de MedicamentosRESUMO
Background: The objective of this study was to evaluate the effect of a high-fat meal on the pharmacokinetics and safety of 80/5 mg valsartan/amlodipine tablets in healthy subjects. Subjects and Methods: These results were derived from a bioequivalence trial where subjects were randomly assigned to take valsartan/amlodipine 80/5mg under fed conditions or after a high-fat meal contained 978.6 kilocalories (54.6% from fat). The blood samples were collected and plasma concentrations of valsartan/amlodipine were measured using high-performance liquid chromatography-mass spectrometry. The non-compartmental module of Phoenix WinNonlin Version 8.2 was used to calculate pharmacokinetic parameters. The BE module of WinNonLin was used to analyze the statistics of the maximum plasma concentration (Cmax), the area under the concentration-time curve from zero to the last quantifiable time point (AUC0-t), and the area under the concentration-time curve from zero to infinity(AUC0-∞) in plasma. 88 healthy subjects were enrolled and divided into in a fasted group and a fed group. Results: The Cmax, AUC0-t, and AUC0-∞ of valsartan in plasma under fed conditions were 51%, 56%, and 57% lower, respectively, than those under fasted conditions, and the 90% confidence interval (90% CI) were outside the 80.00-125.00% range. All the pharmacokinetic parameters for amlodipine under fed conditions were similar to those observed under fasted conditions, and the 90% CIs were within the 80.00-125.00% range. The incidence of treatment emergent adverse events (TEAE) was similar between the fasted group and the fed group, while adverse drug reaction (ADR) was more frequent in the fasted group which may be related to the higher blood concentrations of valsartan, but all were mild. Conclusion: The result indicated that the high-fat meal had a significant effect on the pharmacokinetics of valsartan, but no effect on amlodipine. All treatments were safe and well tolerated in healthy subjects under fed and fasted conditions.
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Anlodipino , Jejum , Humanos , Valsartana/efeitos adversos , Voluntários Saudáveis , Equivalência Terapêutica , Área Sob a Curva , Comprimidos , Estudos Cross-OverRESUMO
AIMS: Angiotensin receptor neprilysin inhibitor (ARNI) therapy is a cornerstone in the treatment of heart failure with reduced ejection fraction (HFrEF), with significant improvement in mortality as well as morbidity and quality of life. However, maximal ARNI doses often result in hypotension. Recent studies with 'real world' experience suggest that lower doses of ARNI are as effective as higher doses.In order to evaluate the symptomatic effect of low-dose ARNI in HFrEF patients, we analyzed physical activity data obtained via home monitoring of patients with cardiac implantable electronic devices (CIEDs). METHODS: We retrospectively analyzed physical activity data obtained from HFrEF patients with CIED-active home monitoring during the years 2021-2022. Patients with ARNI therapy were further divided into subgroups according to the administered dose. Low-dose ARNI included doses of up to 24/26âmg sacubitril/valsartan daily. Intermediate dose and high dose included doses of 72/78-120/130âmg/day, and 144/156-194/206âmg/day, respectively. RESULTS: A total of 122 patients had home monitoring-compatible CIEDs and HFrEF during the study period. Sixty-four of these patients were treated with ARNI. Administration of low-dose ARNI resulted in a 20% increase in daily activity when compared with patients without ARNI treatment ( P â=â0.038). Change in physical activity of patients in the intermediate-dose and high-dose groups was not significant. Younger patients, patients with cardiac resynchronization therapy, and patients without diabetes mellitus were more physically active. CONCLUSION: Low-dose ARNI had a beneficial effect on physical activity in HFrEF patients. MH via CIED provided real-life objective data for patients' follow-up.
Assuntos
Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina , Volume Sistólico , Tetrazóis/efeitos adversos , Qualidade de Vida , Estudos Retrospectivos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Valsartana/efeitos adversos , Combinação de Medicamentos , Receptores de AngiotensinaRESUMO
BACKGROUND: Sacubitril/valsartan, a new pharmacological class of angiotensin receptor neprilysin inhibitor, is beneficial to heart failure through blocking the degradation of natriuretic peptides and inhibiting renin-angiotensin-aldosterone system (RAAS) activation which also relate to the pathophysiologic mechanisms of chronic kidney disease (CKD). However, its effects on CKD remain unclear. To assess the efficacy and safety of sacubitril/valsartan for patients with CKD, we performed this meta-analysis. METHODS: The Embase, PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) that compared sacubitril/valsartan with ACEI/ARBs in patients with CKD whose estimated glomerular filtration rate (eGFR) was below 60 mL/min/1.73 m2. We adopted the Cochrane Collaboration tool for assessing the risk of bias. The effect size was estimated using the odds ratio (OR) with 95% confidence interval (CI). RESULTS: Six trials with a total of 6217 patients with CKD were included. In terms of cardiovascular events, sacubitril/valsartan attenuated the risk of cardiovascular death or heart failure hospitalization (OR: 0.68, 95% CI 0.61-0.76, P < 0.00001, I2 = 43%). With respect to renal function, sacubitril/valsartan prevented the incidence of serum creatinine (Scr) elevation among patients with CKD (OR: 0.79, 95% CI 0.67-0.95, P = 0.01, I2 = 0%). Subgroup analysis about eGFR demonstrated that with long follow-up, sacubitril/valsartan significantly decreased the number of patients with more than 50% reduction in eGFR compared with ACEI/ARBs (OR: 0.52, 95% CI 0.32-0.84, P = 0.008, I2 = 9%). In patients with CKD, the incidence of end-stage renal disease (ESRD) was reduced with sacubitril/valsartan treatment, despite no statistically significant difference between the two groups (OR: 0.59, 95% CI 0.29-1.20, P = 0.14, I2 = 0%). As for the safety, we found that sacubitril/valsartan was associated with the occurrence of hypotension (OR: 1.71, 95% CI 1.15-2.56, P = 0.008, I2 = 51%). However, there was no trend towards increasing the risk of hyperkalemia in patients who received sacubitril/valsartan (OR: 1.09, 95% CI 0.75-1.60, P = 0.64, I2 = 64%). CONCLUSION: This meta-analysis indicated that sacubitril/valsartan improved renal function and conferred effective cardiovascular benefits in patients with CKD, without serious safety issues being observed. Thus, sacubitril/valsartan may be a promising option for patients with CKD. Certainly, further large-scale randomized controlled trials are needed to confirm these conclusions. SYSTEMATIC REVIEW REGISTRATION: [ https://inplasy.com/inplasy-2022-4-0045/ ], identifier [INPLASY202240045].
Assuntos
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Insuficiência Renal Crônica , Valsartana , Humanos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Volume Sistólico/fisiologia , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos , Valsartana/uso terapêutico , Aminobutiratos/efeitos adversos , Aminobutiratos/uso terapêutico , Compostos de Bifenilo/efeitos adversos , Compostos de Bifenilo/uso terapêuticoRESUMO
BACKGROUND: Heart failure is a major cause of morbidity and mortality among older adults. Sacubitril-Valsartan (Sac/Val) has been shown to improve patients' outcomes; however, its safety profile among older adults has not been adequately examined. We therefore aimed to examine its safety profile among this population. METHODS: We conducted a retrospective pharmacovigilance study utilizing the FDA's database of safety reports (FAERS). We employed disproportionality analysis comparing Sac/Val to angiotensin receptor blockers (ARBs). We aim to evaluate the reporting of pre-defined adverse events associated with Sac/Val (hypotension, acute kidney injury (AKI), hyperkalemia and angioedema) in two age groups: adults (< 75 years) and older adults (≥ 75). For each subgroup, we calculated reporting odds ratio (ROR) and compared them by calculating P for interaction. RESULTS: The FAERS database encompassed 18,432 unique reports of Sac/Val. Of them, 12,630 (68.5%) subjects were adults (< 75 years), and 5802 (31.5%) were older adults (≥ 75 years), with a median age (IQR) of 68 (59-77). When compared to ARBs, Sac/Val was associated with higher reporting of hypotension, lower reporting of acute kidney injury (AKI) and hyperkalemia, and similar reporting of angioedema. Notably, we did not observe a significant interaction between the age subgroups and the risk estimates (AKI: Pinteraction = 0.72, hyperkalemia: Pinteraction = 0.94, hypotension: Pinteraction = 0.31, and angioedema: Pinteraction = 0.61). CONCLUSIONS: In this postmarking study, none of the prespecified adverse events was reported more frequently in older adults. These findings provide reassurance for safety use of Sac/Val in older adults.
Assuntos
Injúria Renal Aguda , Angioedema , Insuficiência Cardíaca , Hiperpotassemia , Hipotensão , Humanos , Idoso , Estudos Retrospectivos , Tetrazóis/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Farmacovigilância , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/diagnóstico , Hiperpotassemia/epidemiologia , Inibidores da Enzima Conversora de Angiotensina , Valsartana/efeitos adversos , Aminobutiratos/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/induzido quimicamente , Combinação de Medicamentos , Hipotensão/induzido quimicamente , Hipotensão/diagnóstico , Hipotensão/epidemiologia , Angioedema/induzido quimicamente , Angioedema/diagnóstico , Angioedema/epidemiologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Volume SistólicoRESUMO
Backgrounds: Our study aimed to identify and predict patients with heart failure (HF) taking novel-dose Sacubitril/Valsartan (S/V) at risk for all-cause readmission, as well as investigate the possible role of left ventricular reverse remodeling (LVRR). Methods and results: There were 464 patients recruited from December 2017 to September 2021 in our hospital with a median follow-up of 660 days (range, 17-1494). Competing risk analysis with Gray's Test showed statistically significant differences in all-cause readmission (p-value< .001) across the three different dose groups. Models 1 and 2 were developed based on the results of univariable competing risk analysis, least absolute shrinkage and selection operator approach, backward stepwise regression, and multivariable competing risk analysis. The internal verification (data-splitting method) indicated that Model 1 had better discrimination, calibration, and clinical utility. The corresponding nomogram showed that patients aged 75 years and above, or taking the lowest-dose S/V (≤50â mg twice a day), or diagnosed with ventricular tachycardia, or valvular heart disease, or chronic obstructive pulmonary disease, or diabetes mellitus were at the highest risk of all-cause readmission. In the causal mediation analysis, LVRR was considered as a critical mediator that negatively affected the difference of novel-dose S/V in readmission. Conclusions: A significant association was detected between novel-dose S/V and all-cause readmission in HF patients, in part negatively mediated by LVRR. The web-based nomogram could provide individual prediction of all-cause readmission in HF patients receiving novel-dose S/V. The effects of different novel-dose S/V are still needed to be explored further in the future.
Assuntos
Insuficiência Cardíaca , Readmissão do Paciente , Humanos , Análise de Mediação , Tetrazóis/efeitos adversos , Volume Sistólico , Resultado do Tratamento , Antagonistas de Receptores de Angiotensina/efeitos adversos , Valsartana/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Combinação de Medicamentos , Função Ventricular EsquerdaRESUMO
Heart failure (HF) is a significant event for public health. It has a prevalence between 1-2%, mortality rate between 7-17%, and hospitalization between 32-44%. This implies a risk to health and quality of life, but also great financial efforts for health systems. Sacubitril/valsartan is a medication recognized for its efficacy, and this consensus seeks to synthesize the available information regarding its use for the benefit of patients. This document consists of a description of the epidemiology of HF, pharmacology of the drug, clinical trials, use of the drug in cases with reduced ejection fraction, mildly reduced ejection fraction and preserved ejection fraction, available literature on HF guidelines, recommendations and conclusions.
La insuficiencia cardiaca (IC) es un evento significativo para la salud pública. Tiene una prevalencia entre el 1 y 2%, tasa de mortalidad entre el 7 y 17% y de hospitalización entre el 32 y 44%. Esto implica un riesgo a la salud y calidad de vida, pero también grandes esfuerzos financieros para los sistemas de salud. El sacubitrilo/valsartán es un medicamento reconocido por su eficacia, y este consenso busca sintetizar la información disponible respecto a su uso en búsqueda del beneficio de los pacientes. El presente documento se compone de una descripción de la epidemiología de la IC, farmacología del medicamento, estudios clínicos sobre este, uso del medicamento en casos con fracción de eyección reducida, fracción de eyección ligeramente reducida y fracción de eyección preservada, literatura disponible en guías de IC, recomendaciones y conclusiones.
Assuntos
Cardiologia , Insuficiência Cardíaca , Hipertensão , Disfunção Ventricular Esquerda , Humanos , Estados Unidos , Qualidade de Vida , Consenso , Tetrazóis/efeitos adversos , Volume Sistólico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Valsartana/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão/tratamento farmacológicoRESUMO
BACKGROUND: Heart failure (HF) management has markedly improved, but a clinically meaningful improvement in functional capacity and quality of life is perhaps more important for patients than living longer. OBJECTIVE: This study aimed to review the improvement in quality of life with sacubitril/valsartan in patients with HF and reduced/preserved ejection fraction (EF) from prospective clinical trials. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) and prospective cohort studies published from inception to July 2021. A total of 6 clinical trials and 16854 patients with HF were included. The primary outcome was the change from baseline in KCCQ clinical summary score. The secondary outcomes were scores in other domains of KCCQ, the occurrence of serious adverse events (AEs), and overall mortality. P-values <0.05 were considered statistically significant. RESULTS: Treatment of sacubitril/valsartan showed significantly higher KCCQ-CSS compared to the control (WMD=0.975, 95% CI: 0.885, 1.064, p<0.001; I2=94.8%, pheterogeneity<0.001). A significant decrease in the mortality rate was observed in the sacubitril/valsartan group compared to the control group (RR=0.895, 95%CI:0.831, 0.965, p=0.004; I2=43.6%, pheterogeneity=0.150). Nevertheless, no significant reduction in the occurrence of serious AEs was found among HF patients treated with sacubitril/valsartan compared to the control group (RR=0.950, 95%CI: 0.879, 1.027, p<0.001; I2=68.1%, pheterogeneity=0.024). CONCLUSIONS: Our study demonstrated that sacubitril/valsartan might significantly improve the HRQL compared to other treatments according to the results in KCCQ-CSS and some subdomains in the KCCQ index during the follow-up in patients with HF.
FUNDAMENTO: O manejo da insuficiência cardíaca (IC) tem melhorado acentuadamente, mas uma melhora clinicamente significativa na capacidade funcional e na qualidade de vida talvez seja mais importante para os pacientes do que viver mais. OBJETIVO: Este estudo teve como objetivo revisar a melhora na qualidade de vida com sacubitril/valsartan em pacientes com IC e fração de ejeção (FE) reduzida/preservada a partir de ensaios clínicos prospectivos. MÉTODOS: PubMed, Embase e Cochrane Library foram pesquisados em busca de ensaios clínicos randomizados (ECRs) e estudos de coorte prospectivos publicados desde o início até julho de 2021. Um total de 6 ensaios clínicos e 16.854 pacientes com IC foram incluídos. O desfecho primário foi a alteração da linha de base na pontuação do resumo clínico do KCCQ. Os desfechos secundários foram pontuações em outros domínios do KCCQ, ocorrência de eventos adversos graves (EAs) e mortalidade geral. Valores de p < 0,05 foram considerados estatisticamente significativos. RESULTADOS: O tratamento de sacubitril/valsartan mostrou KCCQ-CSS significativamente maior em comparação com o controle (DMP=0,975, IC 95%:0,885, 1,064, p<0,001; I2=94,8%, pheterogeneidade<0,001). Uma diminuição significativa na taxa de mortalidade foi observada no grupo sacubitril/valsartan em comparação com o grupo controle (RR=0,895, IC 95%: 0,831, 0,965, p=0,004; I2=43,6%, pheterogeneidade=0,150). No entanto, nenhuma redução significativa na ocorrência de EAs graves foi encontrada entre pacientes com IC tratados com sacubitril/valsartan em comparação com o grupo controle (RR=0,950, IC 95%: 0,879, 1,027, p<0,001; I2=68,1%, pheterogeneidade= 0,024). CONCLUSÕES: Nosso estudo demonstrou que o sacubitril/valsartan pode melhorar significativamente a QVRS em comparação com outros tratamentos de acordo com os resultados do KCCQ-CSS e alguns subdomínios do índice KCCQ durante o acompanhamento em pacientes com IC.
Assuntos
Insuficiência Cardíaca , Tetrazóis , Humanos , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Qualidade de Vida , Volume Sistólico , Tetrazóis/uso terapêutico , Valsartana/efeitos adversos , Ensaios Clínicos como AssuntoRESUMO
INTRODUCTION: Hypertension is a significant risk factor in heart failure for worldwide patients. More than half of hypertensive patients suffer from heart failure. Recently, sacubitril/valsartan (sac/val) has been approved as an antihypertensive agent in China and Japan. Additionally, it is not approved for treating hypertension in Europe or the USA. AIM: To accumulate more real-world experiences to investigate the effectiveness and optimize clinical medication of sac/val in hypertensive patients with heart failure. METHODS: We retrospectively enrolled adult patients diagnosed with hypertension (HTN) and heart failure (HF) and newly treated with sac/val. The baseline characteristics and clinical outcomes were retrospectively extracted from electronic medical records (EMR) in three centers. The efficacy and safety of sac/val were first analyzed in all enrolled patients. Stratified analyses were conducted in patients with different ages (≥ 65, < 65), maximum tolerated doses (≥ 200 mg/days, < 200 mg/days), and renal functions (e-GFR ≥ 60 ml/min/1.73 m2, < 60 ml/min/1.73 m2). RESULTS: Overall, 794 patients diagnosed with both HF and HTN were included in our study. During follow-up, significant reductions were found in blood pressure (BP) (SBP 12.8 ± 21.2 mmHg, P < 0.001, DBP 7.1 ± 16.5 mmHg, P < 0.001), and cardiac biomarkers (cardiac troponin 1.78 ± 19.1 ng/mL, P < 0.001, NT-proBNP 1403 ± 6937 pg/mL, P < 0.001) from baseline. In stratification analyses, the lower dosage group earned a higher BP control rate (83.4% vs. 75.6%, P = 0.025) and an overall improvement rate of cardiac indicators (61.3% vs. 48.0%, P = 0.002). The younger patients' group had significantly less cumulative hazard of recurrent cerebral-cardiovascular events than the elder group (log-rank P value < 0.001). Patients with renal dysfunction were observed with more AE incidences. CONCLUSIONS: Sac/val could reduce BP and improve cardiac structural and functional parameters in hypertensive patients with HF, even with less than target doses. However, more attention should be paid to older patients and renal dysfunction patients when using sac/val because of additional risks in adverse events.
Assuntos
Insuficiência Cardíaca , Hipertensão , Nefropatias , Adulto , Humanos , Estudos Retrospectivos , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Aminobutiratos/efeitos adversos , Combinação de Medicamentos , Nefropatias/diagnóstico , Nefropatias/tratamento farmacológico , Rim , Volume Sistólico , Antagonistas de Receptores de Angiotensina/uso terapêuticoRESUMO
BACKGROUND: Lower systolic blood pressure (SBP) is known to be associated with poor prognosis in heart failure (HF). We evaluated the efficacy and safety of sacubitril/valsartan according to baseline SBP tertiles in Japanese patients from the PARALLEL-HF study.MethodsâandâResults: In all, 223 patients were stratified into tertiles according to baseline SBP (≤114 mmHg: n=75; >114 and ≤130 mmHg: n=76; and >130 mmHg: n=72). Patients with lower SBP (≤114 mmHg) had the highest median N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations at baseline (P=0.0184). No significant difference was observed between sacubitril/valsartan and enalapril for the composite outcome of cardiovascular death and HF hospitalization across SBP tertiles (P-interaction=0.2682). Although the P-interaction value was not significant (0.2106), a greater reduction in NT-proBNP with sacubitril/valsartan compared with enalapril was observed in patients with SBP >130 mmHg (P=0.0076). The incidence of hypotension-related events and reduction or discontinuation of treatment due to hypotension-related events was higher in the lower SBP subgroup, and these events were more frequent in the sacubitril/valsartan than enalapril group. CONCLUSIONS: The efficacy of sacubitril/valsartan compared with enalapril was consistent across baseline SBP tertiles in Japanese patients from the PARALLEL-HF study. Hypotension-related events were more common in patients treated with sacubitril/valsartan with lower SBP.
Assuntos
Insuficiência Cardíaca , Hipotensão , Humanos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Pressão Sanguínea , Combinação de Medicamentos , Enalapril/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Hipotensão/induzido quimicamente , Japão , Volume Sistólico/fisiologia , Tetrazóis/efeitos adversos , Valsartana/efeitos adversosRESUMO
Drug combination therapy is the most common pharmacological strategy for hypertension management. No pharmacogenetic biomarkers for guiding hypertension pharmacotherapy are available to date. The study population were 64 volunteers from seven bioequivalence trials investigating formulations with valsartan, olmesartan and/or hydrochlorothiazide. Every volunteer was genotyped for 10 genetic variants in different transporters' genes. Additionally, valsartan-treated volunteers were genotyped for 29 genetic variants in genes encoding for different metabolizing enzymes. Variability in pharmacokinetic parameters such as maximum concentration (Cmax) and time to reach it (tmax), the incidence of adverse drug reactions (ADRs) and blood pressure measurements were analyzed as a function of pharmacogenetic and demographic parameters. Individuals with the ABCB1 rs1045642 T/T genotype were associated with a higher valsartan tmax compared to those with T/G and G/G genotypes (p < 0.001, ß = 0.821, R2 = 0.459) and with a tendency toward a higher postural dizziness incidence (11.8% vs. 0%, p = 0.070). A higher hydrochlorothiazide dose/weight (DW)-corrected area under the curve (AUC∞/DW) was observed in SLC22A1 rs34059508 G/A volunteers compared to G/G volunteers (p = 0.050, ß = 1047.35, R2 = 0.051), and a tendency toward a higher postural dizziness incidence (50% vs. 1.6%, p = 0.063). Sex impacted valsartan and hydrochlorothiazide pharmacokinetics, showing a lower exposure in women, whereas no significant differences were found for olmesartan pharmacokinetics.
Assuntos
Hidroclorotiazida , Hipertensão , Humanos , Feminino , Valsartana/efeitos adversos , Hidroclorotiazida/efeitos adversos , Tontura/induzido quimicamente , Tontura/tratamento farmacológico , Tetrazóis/efeitos adversos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Hipertensão/induzido quimicamente , Variação Genética , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacocinéticaRESUMO
BACKGROUND: Sacubitril/valsartan (LCZ696) is a widely used drug for hypertension in Asia, popular for its efficacy and safety. However, there has been no comprehensive literature review comparing it with olmesartan. This meta-analysis compared the antihypertensive and adverse effects of sacubitril/valsartan and olmesartan. METHODS: We conducted a comprehensive search of Pubmed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov databases to identify eligible randomized controlled trials (RCTs). The data were then analyzed and processed using Revman 5.4 and Stata SE14 software. RESULTS: Six RCTs with 4,127 patients were identified, showing that LCZ696 had better blood pressure control than olmesartan; mean sitting systolic and diastolic blood pressure, sitting pulse pressure, 24-hour ambulatory systolic blood pressure, and 24-hour ambulatory diastolic blood pressure were significantly decreased with LCZ696 compared with olmesartan. No significant difference between LCZ696 and olmesartan was observed in the occurrence of the majority of adverse events, with a decreased probability of headache in patients with sacubitril/valsartan compared with olmesartan. The subgroup analysis showed treatment with 400 mg/d LCZ696 was better than olmesartan in reducing serious adverse events. CONCLUSIONS: Sacubitril/valsartan was better than olmesartan in controlling blood pressure in patients with hypertension, with relatively higher safety.