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Esta es una revisión sobre el papel de los péptidos natriuréticos y los intentos de utilizarlos como diana terapéutica a medida que se iba comprendiendo mejor su papel en la fisiopatología de la insuficiencia cardíaca con función sistólica deprimida. Se hace un recuento de su participación en sucesivos estudios fallidos y se explican los motivos de sus fracasos, hasta lograr el éxito deseado con la combinación del sacubitrilo/valsartan, lo que produjo un cambio de paradigma en el manejo de la insuficiencia cardíaca.
This review is conducted on the role of natriuretic peptides and the attempts to use them as a treatment as their role in the pathophysiology of heart failure with depressed systolic function was better understood. A recount of their participation in successive failed studies is provided, explaining the reasons for their failures, until achieving the desired success with the combination of sacubitril/valsartan. This produced a paradigm shift in the management of heart failure.
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Objective:To study the effects of sacubitril valsartan sodium on vascular sclerosis and ventricular remodeling in patients with ischemic cardiomyopathical coronary heart disease.Methods:A prospective research method was adopted. One hundred and eighty-six patients with coronary heart disease who were treated in Hangzhou Ninth People′s Hospital from January to December 2021 were selected and divided into control group and observation group by random digits table method, with 93 cases in each group. The control group adopted routine treatment method of aspirin + metoprolol + nitroglycerin + captopril according to the guideline, while the observation group was additionally treated with sacubitril valsartan sodium on the basis of the control group. The clinical efficacy, vascular endothelial function and hardness, cardiac function, ventricular remodeling and adverse reactions were compared between the two groups.Results:The total effective rate of treatment in observation group was significantly higher than that in control group: 96.77%(90/93) vs. 87.10%(81/93), and there was statistical difference ( P<0.05). After treatment, the brachial artery flow-mediated dilation in observation group was significantly higher than that in control group: (14.46 ± 2.80)% vs. (13.09 ± 2.74)%, the level of endothelin-1 was significantly lower than that in control group: (73.32 ± 9.63) ng/L vs. (77.47 ± 10.35) ng/L, and there were statistical differences ( P<0.05). After treatment, the left ventricular ejection fraction (LVEF) in observation group was significantly higher than that in control group: (50.87 ± 3.52)% vs. (49.72 ± 3.71)%, the left ventricular end-systolic diameter, left ventricular end-diastolic diameter and ventricular remodeling indicators of interventricular septal thickness and left ventricular mass index were significantly lower than those in control group: (38.26 ± 5.18) mm vs. (40.05 ± 5.20) mm, (50.49 ± 4.33) mm vs. (52.08 ± 4.25) mm, (8.95 ± 0.39) mm vs. (9.08 ± 0.41) mm, (118.49 ± 9.58) g/m 2 vs. (121.58 ± 9.62) g/m 2, and there were statistical differences ( P<0.05). There were no statistical differences in the levels of total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol after treatment between the two groups ( P>0.05). There were no statistical differences in the incidences of adverse reactions between the two groups ( P>0.05). Conclusions:Sacubitril valsartan sodium has a good clinical efficacy in the treatment of coronary heart disease, and it can improve cardiac function and vascular sclerosis and reverse ventricular remodeling. In addition, it has no significant adverse reactions and is conducive to disease recovery.
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OBJECTIVE To analyze the research status and development trends of the use of sacubitril/valsartan. METHODS Related literature about the use of sacubitril/valsartan were retrieved from CNKI and the core database of Web of Science. CiteSpace 5.8.R3 software was used to analyze authors， countries/areas， institutions and keywords. RESULTS & CONCLUSIONS Totally 1 193 Chinese literature and 1 060 English literature were included. The number of literature increased， with numerous literature covering the United States （429）， the United Kingdom （185） and China （184）. ZHANG Jing （5） and Solomon S D （118） published the highest number of Chinese and English articles. The authors of Chinese literature had less cooperation while the authors of English literature were in close contact. Dept. of Cardiology in the First Affiliated Hospital of Zhengzhou University （9）， Dept. of Cardiology in the Affiliated Hospital of Xuzhou Medical University （9） and Novartis AG （134） had the highest quantity of publications of Chinese and English literature. The institutions of Chinese literature had a small number of overall publications and less cooperation while the institutions of English literature were closely connected. The clinical efficacy of sacubitril/valsartan for heart failure， hypertension and their complications were research hotspots in Chinese and English literature. Chinese scholars and research teams need to strengthen cooperation and communication in the future， as well as conduct research from the perspectives of sacubitril/valsartan in the treatment of heart failure， hypertension and related complication， the improvement of oxidative stress， and the evaluation of the efficacy of combination therapy with dapagliflozin.
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【Objective】 To observe the clinical effect of combination therapy of sacubitril valsartan and dapagliflozin in heart failure with reduced ejection fraction (HFrEF) and non-diabetes patients. 【Methods】 This study involved 96 patients with HFrEF and non-diabetes. The patients were randomly divided into control group (50 cases) and observation group (46 cases). On the basis of routine treatment, the control group was treated with sacubitril valsartan, while the observation group was treated with sacubitril valsartan and dapagliflozin. After 1-month and 6-month treatment, we monitored blood pressure, N-terminal pro brain natriuretic peptide (NT-proBNP), high sensitivity troponin T (cTnT), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDd), left atrial diameter (LAD), left ventricular posterior wall thickness (LVPW), Minnesota soda heart failure life quality score (MLHFQ), the incidence of rehospitalization and death, and major adverse cardiovascular events (MACE) in the two groups. 【Results】 After 6 months, systolic blood pressure, cTnT, NT-proBNP, LVEDd, LVPW, and LAD of the observation group were significantly decreased compared with the control group (P0.05). 【Conclusion】 The combination treatment of sacubitril valsartan and dapagliflozin on HFrEF and non-diabetes patients can significantly improve cardiac function, inhibit myocardial remodeling, reduce the incidence of MACE, and improve the prognosis.
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Objective:To observe the effects of sacubitril/valsartan (LCZ696) on viral replication and cardiomyocyte apoptosis in mice with coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC) and to analyze the underlying mechanisms.Methods:Forty BALB/c mice were randomly divided into four groups with 10 in each group: Sham, Sham+ LCZ696, VMC, and VMC+ LCZ696 groups. VMC model was established by intraperitoneal injection of 0.1 ml of CVB3 with a concentration of 10 6 TCID 50/ml into BALB/c mice, while the sham intervention was an equal volume of saline. The day of virus injection was defined as day 0. LCZ696 was administered by gavage at a dose of 60 mg/kg every day for seven consecutive days starting from day 1. Mouse survival rates were calculated. Echocardiography was used to evaluate the cardiac function of mice. The level of creatine kinase-MB (CK-MB) was detected by ELISA. Western blot was used to detect the levels of inflammatory cytokines (IL-6, TNF-α), apoptosis-related proteins (caspase-3, cleaved-caspase-3, Bax, Bcl-2), CVB3 surface protein (VP-1) and p-AKT/AKT in the hearts of mice. CVB3 mRNA in mouse hearts was measured by PCR. Inflammatory cell infiltration and cell apoptosis in mouse hearts were observed by HE staining and TUNEL staining, respectively. Results:Compared with the Sham group, the mice in the VMC group had a decreased survival rate and impaired cardiac function ( P<0.05). The levels of CK-MB, IL-6, TNF-α, cleaved-caspase-3/caspase-3, Bax/Bcl-2, VP-1, and CVB3 mRNA in the hearts of VMC mice increased significantly ( P<0.05), accompanied by increased expression of AKT, decreased phosphorylation of AKT ( P<0.05) and increased cell apoptosis. LCZ696 reversed the above changes. It could increase the survival rate, improve the cardiac function ( P<0.05), decrease cardiac inflammation, cell apoptosis and viral replication ( P<0.05), and increase the phosphorylation of AKT ( P<0.05). LCZ696 had no significant effects on the survival rate, cardiac function, myocardial injury, cardiac inflammation, cell apoptosis, viral replication or the expression of PI3K/AKT signaling pathway-related proteins in normal mice. Conclusions:LCZ696 could significantly inhibit cardiomyocyte apoptosis and reduce CVB3 replication in the hearts of VMC mice by regulating the PI3K/AKT pathway, thereby improving mouse cardiac function and survival rate.
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Objective:To observe the clinical efficacy of angiotensin-receptor neprilysin inhibitors (ARNI) in the treatment of maintenance hemodialysis (MHD) with heart failure.Methods:The clinical data of heart failure patients who accepted MHD in Central China Fuwai Hospital were retrospectively collected. All patients accepted regular treatments of heart failure, and then the treatment group was treated with ARNI, while the control group was treated with valsartan. The treatment course was 6 months. The cardiac parameters: left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), pulmonary artery pressure, right ventricular end-diastolic dimension (RVED), right atrial end-diastolic dimension (RAED), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), and serum potassium were collected and compared between the two groups. Multivariate ordered logistic regression analysis was adopted to analyze the influencing factors of treatment effect.Results:A total of 60 MHD patients with heart failure were enrolled with age of (53.92±11.88) years old, 37 males (61.7%), dialysis age of (27.83±12.92) months, and blood pressure of (154.22±15.27) mmHg/(85.43±12.31) mmHg. (1) There was no significant difference of the clinical data and cardiac parameters between the treatment group ( n=30) and the control group ( n=30) before treatment (all P>0.05); (2) After treatment of 6 months, the total effective rate [28/30(93.3%)] in the treatment group was significantly higher than that in the control group [20/30(66.7%)] and the rehospitalization rate [2/30(6.7%)] in the treatment group was significantly lower than that in the control group [10/30(33.3%)] (both P<0.05); (3) After treatment of 6 months, LVEF, LVEDD, LVESD, pulmonary artery pressure, RVED, RAED, NT-pro BNP, and blood pressure were all improved significantly compared with the baseline in both groups (all P<0.05) and there was no significant difference of serum potassium and body weight before and after treatment in the two groups (all P>0.05); (4) After treatment of 6 months, LVEF in the treatment group was higher than that in the control group and LVEDD, LVESD, pulmonary artery pressure, NT-pro BNP, and blood pressure in the treatment group were lower than those in the control group (all P<0.05). There was no significant difference of RVED, RAED, serum potassium and body weight between the two groups after treatment (all P>0.05); (5)The difference values before and after treatment of LVEF, LVEDD, LVESD, NT-pro BNP, body weight, systolic blood pressure, and diastolic blood pressure were different between the two groups (all P<0.05); (6)Therapy method ( β=-1.863, 95% CI -2.948-0.777, P=0.001) and residual urine ( β=-1.686, 95% CI -3.079- -0.293, P=0.018) were independent influencing factors of treatment effect (the treatment effect of ARNI was better than that of valsartan; the treatment effect of patients with normal urine volume was better than that of patients with oliguria and anuria). Conclusions:ARNI can effectively improve cardiac function in MHD patients with heart failure, inhibit ventricular remodeling, and improve disease prognosis.
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Objective:To investigate the serum levels of soluble growth stimulation expression gene 2 protein (sST2) and inflammatory factors in patients with acute left ventricular ejection fraction reduction heart failure (HFrEF) treated with sacubitril/valsartan.Methods:Ninety six patients with acute HFrEF admitted in The Affiliated Hospital of Qingdao University from March 2020 to March 2021 were enrolled. The patients were treated with sacubitril/valsartan,the dose was gradually increased from 50 mg b.i.d to the target dose of 200 mg b.i.d according to hemodynamics. After 12 weeks, the target dose was achieved in 72 cases (compliance group), and did not achieved in 24 cases (non-compliance group). The serum levels of sST2, IL-1β, IL-6, TNF-αand IL-10 were measured and compared between the two groups. The changes in left atrial anteroposterial diameter (LA), left ventricular end-diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) values were assessed with echocardiography. The adverse reactions, readmission rate and all-cause death within 3 months after discharge were compared between the two groups.Results:A total of 96 patients with acute HFrEF completed the follow-up, including 72 patients (75.0%) in the compliance group and 24 (25.0%) in the non-compliance group; aged 50-75 (66.1±6.7) years old, and 68 (70.8%) males. After treatment, the serum levels of sST2, IL-1β, IL-6 and TNF-α were decreased, and the IL-10 level was increased in both groups ( P<0.05); while the improvement of serum indicators in the compliance group was more marked ( P<0.05). Echocardiography showed that the LA, LVDd, and LVEF were significantly increased after treatment ( P<0.05) in compliance group, while there was no significant changes before and after treatment in the non-compliance group. SST2, inflammatory factors and echocardiographic measurements of patients in the standard group had statistical significance before and after treatment ( P<0.05), and the difference showed a downward trend. No deterioration of renal function and angioedema were observed in both groups, and there was no significant difference in hyperkalemia (two in compliance group and one in non-compliance group), symptom hypotension (each in two groups) between the two groups (χ 2=0.12, 0.68; P>0.05). In the non-compliance group, 10 patients (41.7%) were readmitted due to heart failure, and 6 patients (25.0%) died; while there were no readmitted cases or fatal cases in compliance group (χ 2=33.49, 19.20; P<0.05). Conclusion:Early application of sacubitril and valsartan sodium in patients with acute HFrEF after hemodynamic stabilization can significantly improve left ventricular remodeling, for those with earlier escalation to the target dose, it is more beneficial. The changes of serum sST2 and inflammatory factor level after treatment may predict the efficacy of sacubitril/valsartan therapy.
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Objective:To study the effect of sacubitril valsartan sodium tablets on serum tenascin-C (TN-C) level and myocardial remodeling in patients of chronic left heart failure (CHF) complicated with renal failure.Methods:A total of 84 patients with chronic left heart failure complicated with renal failure admitted to Qinhuangdao Jungong Hospital from October 2020 to October 2021 were included and divided into the observation group (treated with sacubitril valsartan sodium tablets) and the control group (treated with valsartan), with 42 cases in each group according to the random number table method. The clinical efficacy of the two groups was compared after 3 months of treatment. The TN-C level and cardiac function index left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), troponin T (cTnT) and other index before the treatment and after 3 months of treatment were compared between the two groups.Results:After 3 months of treatment, the total effective rate between the two groups had no significant difference ( P>0.05). After 3 months of treatment, the TN-C level in the observation group was lower than that in the control group: (32.42 ± 4.22) μg/L vs. (37.32 ± 4.86) μg/L; and the LVEF in the observation group was higher than that in the control group: (41.21 ± 5.39)% vs. (37.76 ± 5.45)%, the differences were statistically significant ( P<0.05). The LVEDD and cTnT in the two groups had no significant differences ( P>0.05). After 3 months of treatment, neuroendocrine factors norepinephrine, aldosterone, angiotensin Ⅱlevels in the in the observation group were lower than those in the control group: (1 668.60 ± 251.19) pmol/L vs. (2 005.86 ± 280.91) pmol/L, (246.97 ± 13.99) ng/L vs. (275.41 ± 19.38) ng/L, (99.68 ± 8.57) ng/L vs. (112.20 ± 9.52) ng/L, the differences were statistically significant ( P<0.05). Conclusions:Sacubitril valsartan sodium tablets have a good effect in the treatment of CHF complicated with renal failure, which can improve the cardiac function and inhibit the over-activation of neuroendocrine hormones.
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Objective:To observe the clinical efficacy of sacubitril-valsartan combined with Haikun Shenxi in the treatment of chronic left heart failure with renal insufficiency.Methods:A total of 80 patients with chronic left heart failure and renal insufficiency who were admitted to Dalian Municipal Central Hospital from October 2019 to October 2020 were selected as the research objects. They were divided into two groups by random digits table method, 40 cases in each group. The control group was treated with sacubitril-valsartan. The observation group was based on the control group plus Haikun Shenxi Capsule, and N-terminal pro-brain natriuretic peptide (NT-proBNP), heart function indexes, kidney function indexes, blood gas indexes and quality of life in two groups were compared.Results:NT-proBNP, serum creatinine and blood urea nitrogen in the observation group were significantly lower than those in the control group after treatment: (1 034.27 ± 87.33) μg/L vs. (1 421.46 ± 105.54) μg/L, (240.53 ± 45.26) μmol/L vs. (284.52 ± 52.47) μmol/L, (12.05 ± 1.87) mmol/L vs. (15.79 ± 1.87) mmol/L, the difference was statistically significant ( t = 17.88, 4.01 and 8.62; P<0.01); left ventricular end-diastolic dimension (LVEDD) after treatment in the observation group was significantly lower than that in the control group: (46.12 ± 1.05) mm vs. (48.81 ± 1.74) mm, left ventricular ejection fraction (LVEF) and cardiac index (CI) were significantly higher than those in the control group: (49.95 ± 2.17)% vs. (45.24 ± 3.22)%, (2.98 ± 0.55) L/(min·m 2) vs. (2.45 ± 0.73) L/(min·m 2), the difference was statistically significant ( t = 7.67, 8.38 and 3.66; P<0.01); the blood gas index arterial partial pressure of carbon dioxide (PaCO 2) in the observation group after treatment was significantly lower than that in the control group: (46.34 ± 3.52) mmHg (1 mmHg = 0.133 kPa) vs. (51.63 ± 4.25) mmHg, arterial partial pressure of oxygen (PaO 2), oxygen saturation of haemoglobin (SO 2), pH, HCO 3-, base excess (BE) were significantly higher than the control group: (69.35 ± 5.12) mmHg vs. (62.45 ± 4.86) mmHg, (90.46 ± 4.02)% vs. (85.36 ± 4.32)%, 7.32 ± 0.12 vs. 7.22 ± 0.15, (23.1 ± 2.0) mmol/L vs. (21.5 ± 1.9) mmol/L, (-1.57 ± 0.67) mmol/L vs. (-2.15 ± 0.85) mmol/ L, the differences were statistically significant ( t = 6.06, 6.18, 5.47, 3.33, 3.67 and 3.39; P<0.01); the quality of life scores PD, ED, OD and TS in the observation group after treatment were lower than those in the control group: (17.80 ± 3.11) scores vs. (22.35 ± 2.72) scores, (12.28 ± 2.10) scores vs. (15.74 ± 1.73) scores, (18.27 ± 1.69) scores vs. (25.54 ± 2.33) scores, (46.68 ± 3.15) scores vs. (62.17 ± 3.63) scores, the differences was statistically significant ( t = 6.97, 8.05, 15.30 and 20.38; P<0.01). Conclusions:The sacubitril-valsartan combined with Haikun Shenxi in the treatment of chronic left heart failure with renal insufficiency has a significant clinical effect. It could effectively improve the patient's heart and kidney function and blood gas indicators, and further improve the patient's quality of life.
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Objective:To investigate the effects of Sacubitril/Valsartan on the recurrence of atrial fibrillation(AF), cardiac structure and function after catheter ablation(CA)of persistent AF.Methods:A total of 180 patients with persistent AF were randomly divided into the treatment group(n=90)and the control group(n=90)before undergoing CA.The control group was given routine perioperative medication according to the guidelines for AF management, and the treatment group was additionally given Sacubitril/Valsartan.Blood pressure, N-terminal pro-B-type natriuretic peptide(NT-proBNP), P-wave dispersion, left atrial dimension, left atrial volume index, mitral regurgitation area, left ventricular end-systolic volume index, end-diastolic volume index and left ventricular ejection fraction(LVEF)were measured at 3, 6 and 12 months after the procedure.Results:Blood pressure was lower in the treatment group than in the control group( P<0.05), but no hypotension or related symptoms occurred.The sinus rhythm maintenance rate was higher in the treatment group than in the control group at 3, 6 and 12 months during the follow-up(80.0%, 72.2%, 78.9% vs.70.0%, 75.6%, 68.9%, χ2=4.866, 6.667 and 4.091, P=0.027, 0.010 and 0.043, respectively). At 6 and 12 months during the follow-up, NT-proBNP, P-wave dispersion, left atrial diameter, left atrial volume index, mitral regurgitation area, left ventricular end-systolic volume index and end-diastolic volume index were lower(all P<0.05)and LVEF was higher( P<0.05)in the treatment group than in the control group. Conclusions:In patients with persistent AF after CA, Sacubitril/Valsartan has favorable effects in maintaining sinus rhythm, reversing cardiac remodeling and improving cardiac function.
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OBJECTIVE：To investigate the effec ts of angiotensin receptor neprilysin inhibitor （ARNI）sacubitril valsartan sodium（SVS）on the short-term prognosis of patients with acute anterior myocardial infarction （AAMI）complicated with acute cardiac insufficiency. METHODS ：A total of 80 patients with AAMI and Killip grade Ⅱ-Ⅳ of cardiac function ，who met the inclusion criteria ，were randomly divided into ARNI group and control group ，with 40 patients in each group. Both groups were given the same basic standardized drug treatment ，vital signs support treatment and percutaneous coronary intervention treatment at the same time. On this basis ，ARNI group was given SVS tablet orally ，with initial dose of 25 mg each time ，twice a day ； thereafter，gradually adjust the dose to 200 mg each time ，twice a day. Control group was given Enalapril maleate tablets orally ， with an initial dose of 5 mg each time ，twice a day ；thereafter，gradually adjust the dose to 10 mg each time ，twice a day. Both groups took medicine for a long time ，and were followed up after 1，3 and 6 months of medication to the clinic. The levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， soluble growth stimulation expressed gene 2 protein （sST2） and echocardiography indexes were compared between 2 groups before and after medication. The 6-minute walking test （6MWT）and the incidence of cardiogenic readmission events were recorded in 2 groups after medication. RESULTS ：Compared with before treatment，the indexes of the two groups were significantly improved at 1，3 and 6 months after treatment （P＜0.05）. Compared with control group ，the levels of NT-proBNP and sST 2 in ARNI group decreased significantly （P＜0.05），the levels of left ventricular ejection fraction and 6MWT increased significantly（P＜0.05），and the left ventricular end systolic diameter and left ventricular end diastolic diameter decreased significantly，after 3 and 6 months of treatm ent（P＜0.05）. However ，there was no significant difference in the velocity ratio of peak E to peak A ，pulmonary artery pressure ，right ventricular end diastolic diameter and the incidence of cardiogenic readmission events between 2 groups（P＞0.05）. CONCLUSIONS ：For patients with AAMI complicated with acute cardiac insufficiency ， compared with enalapril ，SVS can significantly improve the cardiac function （especially the left ventricular systolic function ）， reduce the inflammatory reaction of cardiomyocytes ，protect cardiomyocytes ，so as to improve the short-term prognosis of patients.
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OBJECTIVE：To study the efficacy and safety of sacubitril valsartan sodium tablets combined with Bailing capsules in the treatment of chronic left heart failure with renal insufficiency ，and to provide reference for clinical drug use. METHODS ： Totally 96 patients with chronic left heart failure with renal insufficiency who sought medical care in our hospital from Nov. 2018 to Nov. 2019 were divided into group A ，B and C according to table of random numbers ，with 32 cases in each group. Group A received conventional heart failure treatment and and Bailing capsules （2 g each time ，3 times a day ）；group B received conventional heart failure treatment and Sacubitril valsartan sodium tablets （50 mg each time ，twice a day ）；group C was given with heart failure treatment and Sacubitril valsartan sodium tablets （50 mg each time ，twice a day ）and Bailing capsules （2 g each time，3 times a day ）. 3 groups received consecutive 6 months of treatment. Clinical response rates of 3 groups were compared. Left heart function indexes [left ventricular end systolic diameter （LVESD），left ventricular end-diastolic diameter （LVEDD），left ventricular ejection fraction （LVEF）] and serological indexes [interleukin 1（IL-1），IL-6，N terminal brain natriuretic peptide precursor，glomerular filtration rate （GFR）] were detected before and after treatment. The occurrence of ADR were observed and recorded. RESULTS ：During this study ，a total of 6 patients fell off ，and eventually 90 patients completed the study ，including 29 cases in group A ，30 cases in group B and 31 cases in group C. Before treatment ，there was no statistical significance in left heart function indexes or serological indexes among 3 groups（P＞ 0.05）. After 6 months of treatment ，clinical response rate of group C was significantly higher than those of group A and B 163.com （P＜0.05）. Compared with before treatment ， LVEDD， LVESD and serological indexes of 3 groups were decreased significantly after treatment （P＜0.05），while LVEF and GFR were increased significantly （P＜0.05）；the changes of above indexes （except for IL- 1 level in serum ） in group C were significantly better than group A and B ，the changes of above indexes in group B （except for GFR ）were significantly better than group A （P＜0.05）. No significant ADR were observed in 3 groups. CONCLUSIONS ：Sacubitril valsartan sodium tablets combined with Bailing capsules can significantly decrease the level of serum inflammation factors ，and improve cardiac and renal function in patients with chronic left heart failure with renal insufficiency ，with good safety.
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Sacubitril valsartan sodium (LCZ696) is an ionic cocrystal drug. The purpose of this study was to explore the cocrystal features of LC696 by establishing a variety of characterization methods, and thus provide basic research data for effective quality control. The cocrystal characteristics of LCZ696 and its tablets were identified by applying analytical means including powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), Raman spectra (RM), differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy (ssNMR). The crystalline water and hygroscopicity of LCZ696 were analyzed by thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), hygroscopicity test and Karl Fischer reaction method. The results show that PXRD, FTIR, DSC and ssNMR can effectively distinguish the features of LCZ696 cocrystal, sacubitril monomer, valsartan monomer, and sacubitril-valsartan (1∶1) mixture. RM can be used as a supplementary approach. Combined with the analysis by TGA, DVS, hygroscopicity test and Karl Fischer reaction method results, LCZ696 contains 2.5 crystalline water molecules and is very hygroscopic; we recommend that LCZ696 be stored in an environment with a relative humidity below 60%. By characterizing the crystal features we can establish quality control measure and evaluate the stability of the drug tablets. This study provides data in support for the establishment of the LCZ696 quality standard.
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Resumen Introducción y objetivos: La Insuficiencia Cardíaca (IC) es un síndrome frecuente en la población adulta. Sacubitril / Valsartán (S/V) es un tratamiento novedoso para esta patología. El presente estudio pretende analizar el efecto de este medicamento sobre las variables clínicas, de laboratorio y ecocardiográficas en pacientes con IC con FEVIr. Metodología: Se realizó un estudio observacional retrospectivo de los expedientes de los pacientes del PIC que tuvieran prescrito S/V. De estos, se recopilaron datos basales y de seguimiento de los principales parámetros de relevancia pronóstica, para estos pacientes. Luego se cuantificaron los cambios generados en el tiempo una vez establecido el tratamiento y se hicieron análisis estadísticos para validar si los cambios fueron significativos. Resultados: De la totalidad de pacientes del PIC, 27 cumplieron los criterios de inclusión, con una edad promedio de 70 años y en donde 37.0% se encontraron en la dosis meta después de un seguimiento promedio de 16.4 meses. A través del estudio fue posible encontrar una diferencia estadísticamente significativa para el cambio en la FEVI para 17 pacientes (p=0.016). En los pacientes en los que se pudo recopilar la información se observó que el NT-proBNP mejoró en un 68.75%, por su parte la caminata de 6 minutos mejoró en un 77.8%. Además, solamente 7.4% de los pacientes empeoraron en su escala funcional NYHA, 7.4% fallecieron y 3.7% sufrieron hospitalización durante el estudio. Conclusiones: Basados en los parámetros estudiados y a través de los cambios generados durante el tiempo de seguimiento, fue posible definir una mejoría en los pacientes tras el uso de S/V, asociado también a una baja mortalidad e incidencia de hospitalizaciones.
Abstract Effect of Sacubitril / Valsartan on the clinical, laboratory and echocardiographic variables used for the control of heart failure with reduced left ventricular ejection fraction (LVEFr) in active patients of the Heart Failure Program (HFP) of the Hospital Clínica Bíblica Introduction and objectives: Heart failure (HF) is a common syndrome in the adult population. Sacubitril /Valsartan (S/V) is a novel treatment for this pathology. This study aims to analyze the effect of this medication on clinical, laboratory and echocardiographic variables in patients with HF and left ventricular eyección fracción reduced (LVEFr). Methodology: A retrospective observational study was conducted on patients records who are enrolled in the Heart Failure Program (HFP) and have been prescribed with S/V. For these patients, baseline and follow-up data was collected for relevant parameters. Changes over time were then quantified once the treatment with S/V was initiated, and a statistical analysis was conducted to validate whether the changes were significant. Results: Of all HFP patients, 27 met the inclusion criteria, with an average age of 70 years and where 37.0% of them were at the target dose after an average follow- up of 16.4 months. Through the study it was possible to find a statistically significant difference in a change for the ejection fraction in 17 patients (p.0.016). In patients with available clinical data, it was observed that NT-proBNP improved by 68.75%, meanwhile the 6-minute walk improved by 77.8%. In addition, only 7.4% of patients worsened their NYHA functional scale, 3.7% were hospitalized and 7.4% died during the time. Conclusions: Based on the studied parameters and throughout all the clinical changes during the follow-up time, it was possible to establish an improvement in patients after the S/V therapy, which is also associated with a low hospitalization incidence and a low mortality rate.
Subject(s)
Humans , Aged , Aged, 80 and over , Valsartan/therapeutic use , Heart Failure/drug therapy , AgedABSTRACT
Resumo Fundamento O tratamento com sacubitril-valsartana teve seu benefício prognóstico confirmado no ensaio PARADIGM-HF. No entanto, dados sobre alterações no teste de esforço cardiopulmonar (TECP) com o uso de sacubitril-valsartana são escassos. Objetivo O objetivo deste estudo foi comparar os parâmetros do TECP antes e depois do tratamento com sacubitril-valsartana. Métodos Avaliação prospectiva de pacientes com insuficiência cardíaca (IC) crônica e fração de ejeção do ventrículo esquerdo ≤40%, mesmo sob terapia padrão otimizada, que iniciaram tratamento com sacubitril-valsartana, sem expectativa de tratamentos adicionais para a IC. Os dados do TECP foram coletados na semana anterior e 6 meses depois do tratamento com sacubitril-valsartana. Diferenças estatísticas com valor p <0,05 foram consideradas significativas. Resultados De 42 pacientes, 35 (83,3%) completaram o seguimento de 6 meses, uma vez que 2 (4,8%) morreram e 5 (11,9%) interromperam o tratamento devido a eventos adversos. A média de idade foi de 58,6±11,1 anos. A classe NYHA (classificação da New York Heart Association) melhorou em 26 (74,3%) pacientes. O consumo máximo de oxigênio (VO2max) (14,4 vs. 18,3 ml/kg/min, p<0,001), a inclinação VE/VCO2 (36,7 vs. 31,1, p<0,001) e a duração do exercício (487,8 vs. 640,3 s, p<0,001) também melhoraram com o uso de sacubitril-valsartana. O benefício foi mantido mesmo com a dose de 24/26 mg (13,5 vs. 19,2 ml/kg/min, p=0,018) de sacubitril-valsartana, desde que esta tenha sido a maior dose tolerada. Conclusões O tratamento com sacubitril-valsartana está associado a uma melhora acentuada do VO2max, da inclinação VE/VCO2 e da duração do exercício no TECP. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)
Abstract Background Sacubitril/valsartan had its prognosis benefit confirmed in the PARADIGM-HF trial. However, data on cardiopulmonary exercise testing (CPET) changes with sacubitril-valsartan therapy are scarce. Objective This study aimed to compare CPET parameters before and after sacubitril-valsartan therapy. Methods Prospective evaluation of chronic heart failure (HF) patients with left ventricular ejection fraction ≤40% despite optimized standard of care therapy, who started sacubitril-valsartan therapy, expecting no additional HF treatment. CPET data were gathered in the week before and 6 months after sacubitril-valsartan therapy. Statistical differences with a p-value <0.05 were considered significant. Results Out of 42 patients, 35 (83.3%) completed the 6-month follow-up, since 2 (4.8%) patients died and 5 (11.9%) discontinued treatment for adverse events. Mean age was 58.6±11.1 years. New York Heart Association class improved in 26 (74.3%) patients. Maximal oxygen uptake (VO2max) (14.4 vs. 18.3 ml/kg/min, p<0.001), VE/VCO2slope (36.7 vs. 31.1, p<0.001), and exercise duration (487.8 vs. 640.3 sec, p<0.001) also improved with sacubitril-valsartan. Benefit was maintained even with the 24/26 mg dose (13.5 vs. 19.2 ml/kg/min, p=0.018) of sacubitril-valsartan, as long as this was the highest tolerated dose. Conclusions Sacubitril-valsartan therapy is associated with marked CPET improvement in VO2max, VE/VCO2slope, and exercise duration. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)
Subject(s)
Humans , Middle Aged , Aged , Ventricular Function, Left , Heart Failure/drug therapy , Oxygen , Stroke Volume , Tetrazoles , Prospective Studies , Treatment Outcome , Drug Combinations , Angiotensin Receptor Antagonists , AminobutyratesABSTRACT
Sacubitril/Valsartan (SAC/VAL) is a combination drug used for the treatment of heart failure. In the present work,novel and rapid, sensitive, specific, and robust ultra high-performance liquid chromatography method was developedand validated for the simultaneous estimation of SAC/VAL in presence of their seven related impurities anddegradation products. The chromatographic separation was achieved on Accucore XL C8, (100 × 4.6) mm; 3 μmreverse phase column maintained at 30°C. The peaks were eluted using tetrahydrofuran (THF) and 0.1% perchloricacid in water (8:92, %v/v) as a mobile phase A and THF:water:acetonitrile (5:15:80, %v/v/v) as mobile phase B in agradient mode. The flow rate was set at 0.6 ml/minute and the analytes were monitored in the range of 200–400 nmusing a Photo Diode Array (PDA) detector for 21 minutes run time. The method was validated as per ICH Q2 (R1)guideline and all the validation parameters were found within the acceptance criteria. The forced degradation studyfor SAC/VAL showed that the drugs were prone to acidic, alkaline, and neutral hydrolytic as well as oxidative stressconditions. All the degradation products were separated from each other, SAC/VAL and their impurities showing thestability indicating power of the method. The newly developed method can be used for estimation of assay and relatedsubstances from bulk or their finished products with good efficiency.
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Resumen Objetivo: describir las características y el comportamiento clínico de pacientes tratados con sacubitril/valsartán en una clínica de falla cardiaca de un hospital de alta complejidad. Métodos: se analizaron en retrospectiva 56 pacientes en manejo con sacubitril/valsartán, entre enero de 2017 y mayo de 2018. A los tres meses de inicio del tratamiento, 87% de los pacientes fueron evaluados. Se determinaron cambios en clase funcional, fracción de eyección ventricular izquierda (FEVI) y presión arterial sistólica y diastólica. Se registraron reingresos hospitalarios por falla cardiaca, mortalidad cardiovascular y eventos adversos asociados a la medicación. Resultados: la edad promedio fue 71,3 años; 51,7% correspondían al sexo masculino, 73% tenía etiología isquémica, 35% clase funcional NYHA II y 60% NYHA III antes de iniciar el tratamiento con sacubitril/valsartán. Al finalizar el seguimiento, 57% mejoró su clase funcional y 81,7% se encontraba en clase funcional NYHA II (IC95%, -0,52 a-0,18; p=0,0002). Hubo mejoría significativa en los valores de FEVI respecto a los basales (IC95%, 4,27 a 11,86; p=0,0002). Se observó una disminución significativa de la presión arterial tanto sistólica como diastólica (p<0,01). Un paciente presentó muerte súbita (2%) y uno hospitalización por falla cardiaca (2%). Ningún paciente descontinuó la terapia por efectos adversos. Conclusión: sacubitril/valsartán es una terapia útil en pacientes con falla cardiaca sintomática y FEVI reducida. La población evaluada tenía un perfil demográfico y clínico semejante al del ensayo clínico PARADIGM-HF, lo cual sugiere que los desenlaces clínicos son similares en la población colombiana.
Abstract Objective: The aim of this study is to describe the characteristics and clinical behaviour of patients treated with sacubitril/valsartan in a heart failure clinic of a high complexity hospital. Methods: A retrospective analysis was performed on a total of 56 patients on treatment with sacubitril/valsartan, between January 2017 and May 2018. At three months from the start of the treatment, 87% of the patients were evaluated. Changes were observed in functional class, left ventricular ejection fraction (LVEF), and systolic and diastolic arterial pressure. A record was made of hospital re-admissions due to heart failure, cardiovascular mortality, and adverse events associated with the medication. Results: The mean age of the patients was 71.3 years, of which 51.7% were male. An ischaemic origin was found in 73%. NYHA II and NYHA III functional class was observed 35% and 60%, respectively, before starting the treatment with sacubitril/valsartan. At the end of follow-up, 57% improved their functional class, and 81.7% were found to be in NYHA II functional class (95% CI; -0.52 to -0.18:=0.0002). There was a significant improvement in the LVEF values compared to baseline (95% CI; 4.27 to 11.86; P=0.0002). A significant decrease was observed in both systolic and diastolic blood pressure (P<0.01). There was sudden death in one (2%) patient and one (2%) patient admitted due to heart failure. None of the patients stopped the therapy due to secondary effects. Conclusion: Sacubitril/valsartan is a useful therapy in patients with symptomatic heart failure and a decreased LVEF. The population evaluated had a demographic and similar clinical signs and symptoms to the PARADIGM-HF clinical trial, which suggests that the clinical outcomes are similar in the Colombian population.
Subject(s)
Humans , Male , Aged , Valsartan , Heart Failure , Signs and Symptoms , Blood Pressure , Ventricular Dysfunction, LeftABSTRACT
OBJECTIVE：To analyze the situation of inpatients with heart failure taking sacubitril-valsartan. METHODS ：The data of heart failture inpatients using sacubitril-valsartan in our hospital were collected during Oct. 2019 to Mar. 2020，including basic information of patients such as gender ，age，inpatient department ，length of stay ；the application of sacubitril-valsartan ， including indications ，contraindications，usage and dosage ，course of medication ；conversion with angiotensin converting enzyme inhibitor（ACEI）/angiotensin Ⅱ receptor antagonist （ARB）and adverse drug reactions ，were summarized. RESULTS ：A total of 252 cases were collected ，including 172 males（68.25％）and 80 females（31.75％）. The average age of the patients was （67.02± 14.23）years old ，and 85 cases were 75 years or older （33.73％）. Average hospitalization time was （12.03±8.19）d，the average left ventricular ejection fraction （LVEF）before medication was （38.69±10.45）％，the average blood potassium was （4.16±0.65） mmol/L，and the average estimated value of glomerular filtration （eGFR）was（69.14±32.01）mL/（min·1.73 m2）. The main distri- bution departments were cardiology department （59.14％），followed by nephrology department （8.73％），respiration department （7.14％），cardiac surgery department （5.95％），geriatrics department （5.56％），emergency medicine department （3.57％）and neurology department （3.17％）. All patients had indications ，but 25 cases（9.92％）had contraindications ，6 cases（2.38％）had blood potassium ＞5.4 mmol/L，19 cases（7.54％）had eGFR ＜15 mL/（min·1.73 m2）. The usage and dosage was 50 mg/bid （45.24％）；39 cases（15.47％）were given medicine once a day ，which was unreasonable. Average treatment course was （7.80± 5.86）d. 7 patients（2.78％）converted to ACEI ，and 3 patients（42.86％）had a conversion interval less than 36 h；20 patients （7.93％） were converted to ARB ，and there was no obvious inappropriate conversion. Hypotension occurred in 14 patients （5.56％）. Blood pressure returned to the normal range in 2 patients after drug withdrawal and 12 patients after dose reduction. No patient had adverse reactions such as involuntary muscle tremor and arrhythmia. CONCLUSIONS ： All the inpatients wit h heart failure in our hospital have indications and good safety. Only a few patients have blood pressure intolerance. However ，there were problems such as low dosage ，inappropriate frequency of administration ，drug use against contraindications，and inappropriate timing of drug conversion. Clinical pharmacists can carry out the knowledge propaganda of rational drug use ，strengthen the pharmaceutical care of patients ，timely detect the situation of irrational drug use and monitor adverse drug reactions ，and actively intervene to ensure the rationality and safety of patients ’medication.
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OBJECTIVE：To systematically evaluate the efficacy and saf ety of sacubitril-valsartan in the treatment of heart failure without reduced ejection fraction （non-HFrEF）patients，and to provide evidence-based reference for its clinical treatment. METHODS：Retrieved from Cochrane Library ，PubMed，Embase，CNKI，VIP and Wanfang data ，during the inception to Feb. 29th，2020，randomized controlled trials （RCTs）about sacubitril-valsartan （trial group ）versus routine medicine as renin- angio- tensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists （control group ） in the treatment of non-HFrEF were collected. After literature screening and data extraction ，the quality of included literatures were evaluated with Cochrane bias risk evaluation tool 5.3.0. Meta-analysis was conducted with Stata 14.0 software，and the publication bias analysis and sensitivity analysis were performed. RESULTS ：Totally 6 RCTs were included ，involving 5 502 patients. Results of Meta-analysis showed that the HF re-hospitalization rate [RR ＝0.84，95％CI（0.77，0.91），P＜0.001] and the serum creatinine elevation rate [RR ＝0.78，95％ CI（0.67，0.91），P＝0.001] in trial group were significantly lower than control group. NYHA classification improvement rate [RR ＝ 1.25，95％CI（1.10，1.43），P＝0.001] and the hypotension rate [RR ＝1.43，95％CI（1.24，1.65），P＜0.001] were significantly higher than control group. There was no statistical significance in the cardiovascular mortality [RR ＝0.94，95％CI（0.79，1.12）， P＝0.481]，all-cause mortality [RR ＝0.95，95％CI（0.83，1.08），P＝0.417]，the levels of NT-proBNP [WMD ＝－301.16，95％CI （－602.77，0.44），P＝0.050] and LVEF [WMD ＝1.49，95％CI（－1.33，4.32），P＝0.300] after treatment ，and the hyperkalaemia rate [RR ＝0.88，95％CI（0.77，1.01），P＝0.070] between 2 groups. The results of publication bias analysis and sensitivity analysis showed there was a high possibility of publication bias ，and the results of several indexes were not stable. CONCLUSIONS ： Sacubitril-valsartan may effectively reduce HF re-hospitalization rate and the risk of elevated serum creatinine in non-HFrEFpatients，improve the heart function but the risk of hypotension is high. The results should be interpreted carefully.