In the present study,we aimed to investigate the clinical potential of sacubitril/valsartan compared with valsartan in patients with newly diagnosed hypertensive acute heart failure(H-AHF).A total of 63 patients were ...In the present study,we aimed to investigate the clinical potential of sacubitril/valsartan compared with valsartan in patients with newly diagnosed hypertensive acute heart failure(H-AHF).A total of 63 patients were retrospectively enrolled from our hospital,with 32 patients assigned to the sacubitril/valsartan group and 31 patients to the valsartan group.Clinical characteristics,laboratory examinations,and echocardiographic data at baseline,during hospitalization,and follow-up were collected to assess.The results demonstrated that patients treated with sacubitril/valsartan achieved better control of systolic and diastolic blood pressures than those treated with valsartan.Sacubitril/valsartan also resulted in more significant reductions in N-terminal pro-brain natriuretic peptide(NT-proBNP),high-sensitivity troponin I(hs-TnI),and creatinine,as well as an increase in estimated glomerular filtration rate(eGFR).Moreover,sacubitril/valsartan significantly improved left ventricular ejection fraction(LVEF),the E/e'ratio[the ratio between the early diastolic filling velocity(E-wave)and early diastolic mitral annular velocity(E')],and reduced left atrial dimension(LAD)and left ventricular mass index(LVMI).Additionally,sacubitril/valsartan might offer potential benefits in managing cardiac arrhythmias such as atrial fibrillation,ventricular or supraventricular premature beats,and left bundle branch block(LBBB).No fatal or nonfatal adverse effects were observed in the sacubitril/valsartan group,although one patient in the valsartan group experienced angioedema.In conclusion,after short-term administration,sacubitril/valsartan proved to be more effective than valsartan in lowering blood pressure,improving cardiac function and remodeling,and enhancing biomarker profiles.Furthermore,it had favorable effects on renal function and cardiac arrhythmias in newly diagnosed H-AHF patients.展开更多
This article presents a case study of a 20-year-old male patient diagnosed with dilated cardiomyopathy(DCM)(NYHA IV).This condition was diagnosed as"heart failure disease"(water overflowing due to yang defic...This article presents a case study of a 20-year-old male patient diagnosed with dilated cardiomyopathy(DCM)(NYHA IV).This condition was diagnosed as"heart failure disease"(water overflowing due to yang deficiency,intermingled phlegm and stasis)in traditional Chinese medicine(TCM).The treatment approach employed a combination of TCM and Western medicine.Western medicine involved the administration of sacubitril valsartan sodium tablets to inhibit ventricular remodeling,in conjunction with diuretics and cardiotonic agents.Initially,TCM utilized a static infusion of Shenfu injection,which was subsequently supplemented with Qiliqiangxin capsules to invigorate qi,warm yang,activate blood circulation,and promote diuresis.After a follow-up period of 3 years,the patient's ejection fraction(EF)improved from 23%to 51%,and the left ventricular end diastolic diameter(LVed)decreased from 68 to 52 mm,accompanied by a significant alleviation of symptoms.These findings indicate that the combined treatment of TCM and Western medicine can synergistically enhance cardiac function and impede the progression of the disease,thereby offering valuable insights for the optimal management of DCM.展开更多
To evaluate the effects of sacubitril/valsartan and ARB on renal function in patients with and without heart failure, we conducted a comprehensive literature search using both Chinese and English databases. These incl...To evaluate the effects of sacubitril/valsartan and ARB on renal function in patients with and without heart failure, we conducted a comprehensive literature search using both Chinese and English databases. These included the Cochrane Library, Wanfang Database, PubMed, CNKI, Embase, and Clinical Trials. The search encompassed studies published from the inception of the databases to March 2024. Randomized controlled studies meeting the inclusion criteria were assessed for bias using the Cochrane risk of bias assessment tool. Data were analyzed using Review Manager 5.4, with relative risk (RR) as the effect indicator. Depending on the heterogeneity of the studies, either a fixed-effects model or a random-effects model was employed to combine effect sizes. Seven studies met the inclusion criteria. Compared with ARB drugs, sacubitril/valsartan showed a reduction in the deterioration of renal function (RR = 0.70, 95% CI: 0.44–1.12, P = 0.14) and acute renal function injury (RR = 0.77, 95% CI: 0.59–1.00, P = 0.05). The risk of end-stage renal disease was also lower (RR = 0.53, 95% CI: 0.30–0.96, P = 0.16). For serum creatinine levels greater than 2.5 mg/dL, the RR was 0.88 (95% CI: 0.68–1.15, P = 0.37). For a reduction in eGFR of more than 25%, the RR was 0.89 (95% CI: 0.57–1.41, P = 0.63). The incidence of serum potassium levels greater than 5.5 mmol/L was not significantly different between the groups (RR = 1.23, 95% CI: 0.86–1.75, P = 0.26), nor was the incidence of serum potassium levels greater than 6.0 mmol/L (RR = 1.06, 95% CI: 0.58–1.93, P = 0.86). However, the incidence of eGFR decreasing by more than 50% was significantly reduced (RR = 0.58, 95% CI: 0.34–0.99, P < 0.05). In conclusion, sacubitril/valsartan demonstrated a protective effect on the kidneys, effectively reducing the risk of renal deterioration and presenting a potential alternative to ARB drugs.展开更多
BACKGROUND Sacubitril/valsartan is a first-in-class angiotensin receptor neprilysin inhibitor(ARNI)which combines an angiotensin receptor blocker(valsartan)with sacubitril,an inhibitor of the enzyme neprilysin.By virt...BACKGROUND Sacubitril/valsartan is a first-in-class angiotensin receptor neprilysin inhibitor(ARNI)which combines an angiotensin receptor blocker(valsartan)with sacubitril,an inhibitor of the enzyme neprilysin.By virtue of combined effect of blocking the action of angiotensin-II and inhibiting the breakdown of natriuretic peptides,ARNIs have beneficial role in heart failure(HF).AIM To evaluate the effect of sacubitril/valsartan on N-terminal pro-B-type natriuretic peptide(NT-pro BNP),inflammatory marker[high-sensitivity C-reactive protein(hs-CRP)],and quality of life when given as add-on to standard therapy in patients with HF.METHODS Sacubitril/valsartan as add-on therapy for improvement in HF study was a randomised controlled trial conducted from July 2023 to November 2024 in a public tertiary care hospital in India.Eligible patients were randomised in 1:1 ratio to either of the 2 study arms:(1)Group A(sacubitril/valsartan+standard treatment);and(2)Group B(standard treatment)for 12 weeks.Primary end point was change in NT-pro BNP levels at 12 weeks from baseline.Secondary endpoints included(1)Change in hs-CRP levels;(2)Change in World Health Organisation Quality of Life Questionnaire(WHOQOL-BREF)score;and(3)Incidence of treatment-related adverse events or worsening HF.Statistical analysis was done using Statistical Package for the Social Sciences trial version 29.0 and P<0.05 was considered significant.RESULTS Out of 124 patients screened,80 were enrolled of which 25 patients in each group were available for per-protocol analysis.At baseline,both the groups were comparable.Sacubitril/valsartan group exhibited a statistically significant greater reduction in NT-pro BNP(-35.91±28.01 vs 24.68±31.86;P<0.0001)and hs-CRP(-2.87±3.22 vs 0.76±1.60;P<0.0001)levels at 12 weeks compared to standard treatment group.There was also a greater improvement in quality of life with sacubitril/valsartan group(overall change in WHOQOL-BREF:13.16±8.73 in sacubitril/valsartan vs-4.12±6.25 in standard treatment arm).No major adverse events were reported in two groups.CONCLUSION Sacubitril/valsartan demonstrated significant improvements in HF biomarkers,inflammation,and quality of life without compromising safety supporting its role as an effective addition to standard HF therapy.Further research is needed to evaluate its long-term benefits on mortality and cardiac remodeling.展开更多
AIM： To assess whether treatment with insulinsensitizing agents （ISAs） in combination with ezetimibe and valsartan have greater effect on hepatic fat content and lipid peroxidation compared to monotherapy in the me...AIM： To assess whether treatment with insulinsensitizing agents （ISAs） in combination with ezetimibe and valsartan have greater effect on hepatic fat content and lipid peroxidation compared to monotherapy in the methionine choline-deficient diet （MCDD） rat model of non-alcoholic fatty liver disease （NAFLD）. METHODS： Rats （n = 6 per group） were treated with different drugs, including MCDD only, MCDD diet with either metformin （200 mg/kg）, rosiglitazone （3 mg/kg）, metformin plus rosiglitazone （M＋R）, ezetimibe （2 mg/ kg）, valsartan （2 mg/kg）, or combination of all drugs for a total of 15 wk. Liver histology, lipids, parameters of oxidative stress and TNF-alpha were measured. RESULTS： Fatty liver （FL） rats demonstrated severe hepatic fatty infiltration （〉 91% fat）, with an increase in hepatic TG （＋1263%, P 〈 0.001）, hepatic cholesterol （＋245%, P 〈 0.03）, hepatic MDA levels （＋225%, P 〈 0.001）, serum TNF-alpha （17.8 ＋ 10 vs 7.8 ＋ 0.0, P 〈 0.001）, but a decrease in hepatic alpha tocopherol （-74%, P 〈 0.001） as compared to the control rats. Combination therapy with all drugs produced a significant decrease in liver steatosis （-54%）, hepatic TG （-64%）, hepatic cholesterol （-31%） and hepatic MDA （-70%）, but increased hepatic alpha tocopherol （＋443%） as compared to FL rats. Combination therapy with ISA alone produced a smaller decrease in liver steatosis （-32% vs -54%, P 〈 0.001） and in hepatic MDA levels （-55% vs -70%, P 〈 0.01）, but a similar decrease in hepatic lipids when compared with the all drugs combination. TNF-alpha levels decreased significantly in all treatment groups except in ISA group. CONCLUSION： Combination therapies have a greater effect on liver fat content as compared to monotherapy. Rosiglitazone appears to improve hepatic steatosis to a greater extent than metformin.展开更多
Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects.A novel and a...Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects.A novel and accurate liquid chromatography tandem mass spectrometry method using electrospray ionization mode has been developed and validated for the simultaneous determination of amlodipine（AMD）,valsartan（VAL） using losartan（LOS） as an internal standard（IS）,and hydrochlorothiazide（HCT） using furosemide（FSD） as an IS.The separation was carried on Aquasil C18（50 mm×2.1 mm,5μm） reversed phase column using acetonitrile and water containing 0.1%formic acid（50：50,v/v） as the mobile phase.The method was validated in terms of linearity,accuracy and precision over the concentration range of 1-1000 ng/mL.The intra and inter-day precision and accuracy,stability and extraction recoveries of all the analytes were in the acceptable range.This method can be successfully applied to the pharmacokinetic study of AMD,VAL and HCT when given as a polypill.展开更多
Valsartan 1, one of the most important agents used in antihypertensive therapy today, was synthesized starting from L-valin methyl ester hydrochloride 2 through four steps in an overall yield of 60%. The key step invo...Valsartan 1, one of the most important agents used in antihypertensive therapy today, was synthesized starting from L-valin methyl ester hydrochloride 2 through four steps in an overall yield of 60%. The key step involves the palladium-catalyzed Suzuki coupling. This method overcomes many of the drawbacks associated with the previously reported syntheses and is more suitable for industrial production.展开更多
A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry...A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry(LC–MS/MS). The analytes and their deuterated analogs were quantitatively extracted from100 μL human plasma by solid phase extraction on Oasis HLB cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18 e(100 mm × 4.6 mm) analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively,under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/m L for AML, 5.00–10,000 ng/m L for VAL and 0.20–200 ng/m L for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean IS-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision(% CV) across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation(test and reference) in 18 healthy Indian males under fasting. The mean log-transformed ratios of C max, AUC0–120 h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.展开更多
AIM:To evaluate efficacy and tolerability of the combination valsartan plus hydrochlorothiazide(160 mg and 25 mg daily,respectively) in young-middle aged males with high-normal blood pressure(BP) or firstdegree arteri...AIM:To evaluate efficacy and tolerability of the combination valsartan plus hydrochlorothiazide(160 mg and 25 mg daily,respectively) in young-middle aged males with high-normal blood pressure(BP) or firstdegree arterial hypertension with evidence of target organ damage.METHODS:Twenty males with high-normal BP or first-degree hypertension associated with left ventricular concentric remodeling and/or increased aortic stiffness were enrolled.BP at rest and during exercise,and echocardiographic parameters of the left ventricle(LV),were evaluated at baseline and after 3 mo of treatment.The effects of treatment on aortic stiffness,metabolic parameters,renal and erectile function were also assessed.RESULTS:BP was significantly reduced by treatment both at rest(P < 0.001) and during exercise(P < 0.001),and 85% of patients achieved BP normalization(< 130/85 mmHg).Doppler echocardiography showed a significant reduction of LV mass(P < 0.005).LV hypertrophy was identified in 70% of subjects at baseline and in 5% after 3 mo of treatment.The ratio of early(E) to late(A) trans-mitral diastolic flow velocity increased,(P < 0.05),the relative wall thickness decreased(P < 0.05) and the left ventricular relaxation time shortened(P < 0.005).The left atrial diameter(P < 0.05) and the aortic diameter(P < 0.05) and stiffness(P < 0.005) also decreased.CONCLUSION:The full-dose combination of valsartan plus hydrochlorothiazide produced optimal BP control with regression of target organ damage,already after 3 mo,without relevant side effects.展开更多
Angiotensin Ⅱ (ANGⅡ) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs).In our study,we observed the effects of valsartan on proliferatio...Angiotensin Ⅱ (ANGⅡ) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs).In our study,we observed the effects of valsartan on proliferation of cultured VSMCs treated with or without ANGⅡ by cell counting and methyl thiazolyl tetrazolium (MTT) assay,and detected the expression of mitofusin 2 (Mfn2),a newly discovered cell proliferation inhibitor and a related cell proliferation signaling pathway pro-tein by Western blotting.ANGⅡ at a concentration of 10-6 mol/L significantly stimulated VSMCs proliferation,down-regulated the expression of Mfn2 and upregulated the expression of Raf and ERK1/2.Valsartan inhibited such effects of ANGⅡ at concentrations of 10-5 and 10-6 mol/L,but not at 10-7 mol/L.Valsartan had no significant effect on the proliferation of untreated VSMCs.These results suggest that valsartan inhibits ANGⅡ-induced proliferation of VSMCs in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway.展开更多
Despite significant therapeutic advances, patients with chronic heart failure （HF） remain at high risk of morbidity and mortality. Sacubitill valsartan （previously known as LCZ696） is a new oral agent approved for...Despite significant therapeutic advances, patients with chronic heart failure （HF） remain at high risk of morbidity and mortality. Sacubitill valsartan （previously known as LCZ696） is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the fast in class angiotensin receptor neprilysin inhibitor （ARNI） since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin Ⅱ receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides （NPs）, bradykinin, endothelin and angiotensin II （Ang-II）. Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-Ⅱ （with opposite biological actions）. So, a combined inhibition of these both systems （Sacubitril / valsartan） may enhance the benefits of NPs effects in HF （natriuresis, diuresis, etc） while Ang-Ⅱ receptor is inhibited （reducing vasoconstriction and aldosterone release）. In a large clinical trial （PARADIGM-HF with 8442 patients）, this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF （compared to enalapril）. This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.展开更多
BACKGROUND Duchenne muscular dystrophy(DMD),which is caused by a mutation/deletion in the dystrophin gene on the X-chromosome,is the most common type of neuromuscular disorder in pediatrics.Skeletal muscle weakness pr...BACKGROUND Duchenne muscular dystrophy(DMD),which is caused by a mutation/deletion in the dystrophin gene on the X-chromosome,is the most common type of neuromuscular disorder in pediatrics.Skeletal muscle weakness progressively develops in DMD patients and usually leads to respiratory failure in the early adolescent years.Cardiac muscle is frequently affected in DMD patients,which leads to a high burden of cardiomyopathy and heart failure.In the era of improved respiratory care,cardiac deaths are becoming the major cause of mortality in DMD patients.CASE SUMMARY We report the case of a 15-year-old boy who presented to the hospital due to recurrent orthopnea for 6 mo and palpitations for 4 mo.He was diagnosed with progressive muscular dystrophy at the age of 3 years and was confined to a wheelchair at 12 years.He was prescribed diuretics and digoxin at the outpatient clinic;however,his symptoms did not resolve.Sacubitril/valsartan was added 1 mo prior to presentation,but he experienced recurrent episodes of palpitations.The electrocardiogram showed atrial tachycardia with a heart rate of 201 bpm,and he was then hospitalized.Hypotension was found following the administration of sacubitril/valsartan tablets;he could not tolerate even a small dose,always developing tachyarrhythmia.His symptoms were relieved after discontinuing sacubitril/valsartan,and his heart rate was controlled by a small dose of metoprolol tartrate and digoxin.Atrial tachycardia spontaneously converted in this patient,and his symptoms attenuated in the following 6 mo,without palpitation episodes.CONCLUSION Blood pressure should be closely monitored in DMD patients with advanced heart failure when taking sacubitril/valsartan.展开更多
The purpose of this study was to develop the immediate release stomach-specific spraydried formulation of valsartan(VAL) using Eudragit?E PO(EPO) as the carrier for enhancing dissolution rate in a gastric environment....The purpose of this study was to develop the immediate release stomach-specific spraydried formulation of valsartan(VAL) using Eudragit?E PO(EPO) as the carrier for enhancing dissolution rate in a gastric environment. Enhanced solubility and dissolution in gastric pH was achieved by formulating the solid dispersion using a spray drying technique. Different combinations of drug–polymer–surfactant were dissolved in 10% ethanol solution and spraydried in order to obtain solid dispersion microparticles. Use of the VAL–EPO solid dispersion microparticles resulted in significant improvement of the dissolution rate of the drug at pH 1.2 and pH 4.0, compared to the free drug powder and the commercial product. A hard gelatin capsule was filled with the VAL–EPO solid dispersion powder prior to the dissolution test.The increased dissolution of VAL from solid dispersion microparticles in gastric pH was attributed to the effect of EPO and most importantly the transformation of crystalline drugs to amorphous solid dispersion powder, which was clearly shown by scanning electron microscopy(SEM), differential scanning calorimetry(DSC), and powder X-ray diffraction(PXRD) studies. Thus, VAL, a potential antihypertensive drug in the form of a solid dispersion microparticulate powder, can be effectively delivered in the immediate release dosage form for stomach-specific drug delivery.展开更多
Amlodipine/valsartan(Aml/Val)single-pill combination(SPC)therapy has been widely used and studied in clinical practice in recent years.This article reviews the Chinese and English literature on the clinical use of Aml...Amlodipine/valsartan(Aml/Val)single-pill combination(SPC)therapy has been widely used and studied in clinical practice in recent years.This article reviews the Chinese and English literature on the clinical use of Aml/Val SPC therapy in Chinese hypertensive patients.According to five studies concerning the efficacy and safety of this treatment,Aml/Val SPC therapy was more efficacious than monotherapy with valsartan,amlodipine,or the nifedipine gastrointestinal therapeutic system.This treatment showed greater blood pressure-lowering effects,a higher blood pressure control rate,and a higher response rate.Aml/Val SPC treatment was well tolerated,with adverse event rates similar to those of monotherapy with valsartan or amlodipine and significantly rarer adverse events compared with the nifedipine gastrointestinal therapeutic system.Aml/Val SPC is a highly efficacious and well-tolerated antihypertensive treatment in Chinese hypertensive patients.展开更多
1 Introduction Sacubitril/valsartan(SV)is a first in class dual action molecule of the neprilysin(NEP)inhibitor prodrug sacubitril(AHU377)and the angiotensin II receptor(Ang-II)type 1 antagonist valsartanJ11 It is the...1 Introduction Sacubitril/valsartan(SV)is a first in class dual action molecule of the neprilysin(NEP)inhibitor prodrug sacubitril(AHU377)and the angiotensin II receptor(Ang-II)type 1 antagonist valsartanJ11 It is the first angiotensin receptor-neprilysin inhibitor(ARNI)whose pharmacodynamic effects are consistent with a simultaneous stimulation of the natriuretic peptides system(via NEP inhibition)and the blockade of the renin-angiotensin-aldosterone system(valsartan effect)that finally results in systemic vasodilation,increased diuresis and natriuresis,reduction of plasmatic volume and diminution of peripheral vascular resistance.展开更多
Summary: The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-relat...Summary: The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.展开更多
基金Key R&D Projects in Shandong Province(Grant No.2017G006029).
文摘In the present study,we aimed to investigate the clinical potential of sacubitril/valsartan compared with valsartan in patients with newly diagnosed hypertensive acute heart failure(H-AHF).A total of 63 patients were retrospectively enrolled from our hospital,with 32 patients assigned to the sacubitril/valsartan group and 31 patients to the valsartan group.Clinical characteristics,laboratory examinations,and echocardiographic data at baseline,during hospitalization,and follow-up were collected to assess.The results demonstrated that patients treated with sacubitril/valsartan achieved better control of systolic and diastolic blood pressures than those treated with valsartan.Sacubitril/valsartan also resulted in more significant reductions in N-terminal pro-brain natriuretic peptide(NT-proBNP),high-sensitivity troponin I(hs-TnI),and creatinine,as well as an increase in estimated glomerular filtration rate(eGFR).Moreover,sacubitril/valsartan significantly improved left ventricular ejection fraction(LVEF),the E/e'ratio[the ratio between the early diastolic filling velocity(E-wave)and early diastolic mitral annular velocity(E')],and reduced left atrial dimension(LAD)and left ventricular mass index(LVMI).Additionally,sacubitril/valsartan might offer potential benefits in managing cardiac arrhythmias such as atrial fibrillation,ventricular or supraventricular premature beats,and left bundle branch block(LBBB).No fatal or nonfatal adverse effects were observed in the sacubitril/valsartan group,although one patient in the valsartan group experienced angioedema.In conclusion,after short-term administration,sacubitril/valsartan proved to be more effective than valsartan in lowering blood pressure,improving cardiac function and remodeling,and enhancing biomarker profiles.Furthermore,it had favorable effects on renal function and cardiac arrhythmias in newly diagnosed H-AHF patients.
文摘This article presents a case study of a 20-year-old male patient diagnosed with dilated cardiomyopathy(DCM)(NYHA IV).This condition was diagnosed as"heart failure disease"(water overflowing due to yang deficiency,intermingled phlegm and stasis)in traditional Chinese medicine(TCM).The treatment approach employed a combination of TCM and Western medicine.Western medicine involved the administration of sacubitril valsartan sodium tablets to inhibit ventricular remodeling,in conjunction with diuretics and cardiotonic agents.Initially,TCM utilized a static infusion of Shenfu injection,which was subsequently supplemented with Qiliqiangxin capsules to invigorate qi,warm yang,activate blood circulation,and promote diuresis.After a follow-up period of 3 years,the patient's ejection fraction(EF)improved from 23%to 51%,and the left ventricular end diastolic diameter(LVed)decreased from 68 to 52 mm,accompanied by a significant alleviation of symptoms.These findings indicate that the combined treatment of TCM and Western medicine can synergistically enhance cardiac function and impede the progression of the disease,thereby offering valuable insights for the optimal management of DCM.
基金Hebei Medical Science Research Project(Grant No.20221849)。
文摘To evaluate the effects of sacubitril/valsartan and ARB on renal function in patients with and without heart failure, we conducted a comprehensive literature search using both Chinese and English databases. These included the Cochrane Library, Wanfang Database, PubMed, CNKI, Embase, and Clinical Trials. The search encompassed studies published from the inception of the databases to March 2024. Randomized controlled studies meeting the inclusion criteria were assessed for bias using the Cochrane risk of bias assessment tool. Data were analyzed using Review Manager 5.4, with relative risk (RR) as the effect indicator. Depending on the heterogeneity of the studies, either a fixed-effects model or a random-effects model was employed to combine effect sizes. Seven studies met the inclusion criteria. Compared with ARB drugs, sacubitril/valsartan showed a reduction in the deterioration of renal function (RR = 0.70, 95% CI: 0.44–1.12, P = 0.14) and acute renal function injury (RR = 0.77, 95% CI: 0.59–1.00, P = 0.05). The risk of end-stage renal disease was also lower (RR = 0.53, 95% CI: 0.30–0.96, P = 0.16). For serum creatinine levels greater than 2.5 mg/dL, the RR was 0.88 (95% CI: 0.68–1.15, P = 0.37). For a reduction in eGFR of more than 25%, the RR was 0.89 (95% CI: 0.57–1.41, P = 0.63). The incidence of serum potassium levels greater than 5.5 mmol/L was not significantly different between the groups (RR = 1.23, 95% CI: 0.86–1.75, P = 0.26), nor was the incidence of serum potassium levels greater than 6.0 mmol/L (RR = 1.06, 95% CI: 0.58–1.93, P = 0.86). However, the incidence of eGFR decreasing by more than 50% was significantly reduced (RR = 0.58, 95% CI: 0.34–0.99, P < 0.05). In conclusion, sacubitril/valsartan demonstrated a protective effect on the kidneys, effectively reducing the risk of renal deterioration and presenting a potential alternative to ARB drugs.
文摘BACKGROUND Sacubitril/valsartan is a first-in-class angiotensin receptor neprilysin inhibitor(ARNI)which combines an angiotensin receptor blocker(valsartan)with sacubitril,an inhibitor of the enzyme neprilysin.By virtue of combined effect of blocking the action of angiotensin-II and inhibiting the breakdown of natriuretic peptides,ARNIs have beneficial role in heart failure(HF).AIM To evaluate the effect of sacubitril/valsartan on N-terminal pro-B-type natriuretic peptide(NT-pro BNP),inflammatory marker[high-sensitivity C-reactive protein(hs-CRP)],and quality of life when given as add-on to standard therapy in patients with HF.METHODS Sacubitril/valsartan as add-on therapy for improvement in HF study was a randomised controlled trial conducted from July 2023 to November 2024 in a public tertiary care hospital in India.Eligible patients were randomised in 1:1 ratio to either of the 2 study arms:(1)Group A(sacubitril/valsartan+standard treatment);and(2)Group B(standard treatment)for 12 weeks.Primary end point was change in NT-pro BNP levels at 12 weeks from baseline.Secondary endpoints included(1)Change in hs-CRP levels;(2)Change in World Health Organisation Quality of Life Questionnaire(WHOQOL-BREF)score;and(3)Incidence of treatment-related adverse events or worsening HF.Statistical analysis was done using Statistical Package for the Social Sciences trial version 29.0 and P<0.05 was considered significant.RESULTS Out of 124 patients screened,80 were enrolled of which 25 patients in each group were available for per-protocol analysis.At baseline,both the groups were comparable.Sacubitril/valsartan group exhibited a statistically significant greater reduction in NT-pro BNP(-35.91±28.01 vs 24.68±31.86;P<0.0001)and hs-CRP(-2.87±3.22 vs 0.76±1.60;P<0.0001)levels at 12 weeks compared to standard treatment group.There was also a greater improvement in quality of life with sacubitril/valsartan group(overall change in WHOQOL-BREF:13.16±8.73 in sacubitril/valsartan vs-4.12±6.25 in standard treatment arm).No major adverse events were reported in two groups.CONCLUSION Sacubitril/valsartan demonstrated significant improvements in HF biomarkers,inflammation,and quality of life without compromising safety supporting its role as an effective addition to standard HF therapy.Further research is needed to evaluate its long-term benefits on mortality and cardiac remodeling.
文摘AIM： To assess whether treatment with insulinsensitizing agents （ISAs） in combination with ezetimibe and valsartan have greater effect on hepatic fat content and lipid peroxidation compared to monotherapy in the methionine choline-deficient diet （MCDD） rat model of non-alcoholic fatty liver disease （NAFLD）. METHODS： Rats （n = 6 per group） were treated with different drugs, including MCDD only, MCDD diet with either metformin （200 mg/kg）, rosiglitazone （3 mg/kg）, metformin plus rosiglitazone （M＋R）, ezetimibe （2 mg/ kg）, valsartan （2 mg/kg）, or combination of all drugs for a total of 15 wk. Liver histology, lipids, parameters of oxidative stress and TNF-alpha were measured. RESULTS： Fatty liver （FL） rats demonstrated severe hepatic fatty infiltration （〉 91% fat）, with an increase in hepatic TG （＋1263%, P 〈 0.001）, hepatic cholesterol （＋245%, P 〈 0.03）, hepatic MDA levels （＋225%, P 〈 0.001）, serum TNF-alpha （17.8 ＋ 10 vs 7.8 ＋ 0.0, P 〈 0.001）, but a decrease in hepatic alpha tocopherol （-74%, P 〈 0.001） as compared to the control rats. Combination therapy with all drugs produced a significant decrease in liver steatosis （-54%）, hepatic TG （-64%）, hepatic cholesterol （-31%） and hepatic MDA （-70%）, but increased hepatic alpha tocopherol （＋443%） as compared to FL rats. Combination therapy with ISA alone produced a smaller decrease in liver steatosis （-32% vs -54%, P 〈 0.001） and in hepatic MDA levels （-55% vs -70%, P 〈 0.01）, but a similar decrease in hepatic lipids when compared with the all drugs combination. TNF-alpha levels decreased significantly in all treatment groups except in ISA group. CONCLUSION： Combination therapies have a greater effect on liver fat content as compared to monotherapy. Rosiglitazone appears to improve hepatic steatosis to a greater extent than metformin.
文摘Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects.A novel and accurate liquid chromatography tandem mass spectrometry method using electrospray ionization mode has been developed and validated for the simultaneous determination of amlodipine（AMD）,valsartan（VAL） using losartan（LOS） as an internal standard（IS）,and hydrochlorothiazide（HCT） using furosemide（FSD） as an IS.The separation was carried on Aquasil C18（50 mm×2.1 mm,5μm） reversed phase column using acetonitrile and water containing 0.1%formic acid（50：50,v/v） as the mobile phase.The method was validated in terms of linearity,accuracy and precision over the concentration range of 1-1000 ng/mL.The intra and inter-day precision and accuracy,stability and extraction recoveries of all the analytes were in the acceptable range.This method can be successfully applied to the pharmacokinetic study of AMD,VAL and HCT when given as a polypill.
基金the National Natural Science Foundation of China (No.20272012)the Special Research Grant for Doctoral Sites in Chinese Universities (No.20010730001).
文摘Valsartan 1, one of the most important agents used in antihypertensive therapy today, was synthesized starting from L-valin methyl ester hydrochloride 2 through four steps in an overall yield of 60%. The key step involves the palladium-catalyzed Suzuki coupling. This method overcomes many of the drawbacks associated with the previously reported syntheses and is more suitable for industrial production.
文摘A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry(LC–MS/MS). The analytes and their deuterated analogs were quantitatively extracted from100 μL human plasma by solid phase extraction on Oasis HLB cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18 e(100 mm × 4.6 mm) analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively,under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/m L for AML, 5.00–10,000 ng/m L for VAL and 0.20–200 ng/m L for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean IS-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision(% CV) across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation(test and reference) in 18 healthy Indian males under fasting. The mean log-transformed ratios of C max, AUC0–120 h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.
文摘AIM:To evaluate efficacy and tolerability of the combination valsartan plus hydrochlorothiazide(160 mg and 25 mg daily,respectively) in young-middle aged males with high-normal blood pressure(BP) or firstdegree arterial hypertension with evidence of target organ damage.METHODS:Twenty males with high-normal BP or first-degree hypertension associated with left ventricular concentric remodeling and/or increased aortic stiffness were enrolled.BP at rest and during exercise,and echocardiographic parameters of the left ventricle(LV),were evaluated at baseline and after 3 mo of treatment.The effects of treatment on aortic stiffness,metabolic parameters,renal and erectile function were also assessed.RESULTS:BP was significantly reduced by treatment both at rest(P < 0.001) and during exercise(P < 0.001),and 85% of patients achieved BP normalization(< 130/85 mmHg).Doppler echocardiography showed a significant reduction of LV mass(P < 0.005).LV hypertrophy was identified in 70% of subjects at baseline and in 5% after 3 mo of treatment.The ratio of early(E) to late(A) trans-mitral diastolic flow velocity increased,(P < 0.05),the relative wall thickness decreased(P < 0.05) and the left ventricular relaxation time shortened(P < 0.005).The left atrial diameter(P < 0.05) and the aortic diameter(P < 0.05) and stiffness(P < 0.005) also decreased.CONCLUSION:The full-dose combination of valsartan plus hydrochlorothiazide produced optimal BP control with regression of target organ damage,already after 3 mo,without relevant side effects.
基金supported by grants from the National Natural Science Foundation of China (No. 30872714 and No.30971244)
文摘Angiotensin Ⅱ (ANGⅡ) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs).In our study,we observed the effects of valsartan on proliferation of cultured VSMCs treated with or without ANGⅡ by cell counting and methyl thiazolyl tetrazolium (MTT) assay,and detected the expression of mitofusin 2 (Mfn2),a newly discovered cell proliferation inhibitor and a related cell proliferation signaling pathway pro-tein by Western blotting.ANGⅡ at a concentration of 10-6 mol/L significantly stimulated VSMCs proliferation,down-regulated the expression of Mfn2 and upregulated the expression of Raf and ERK1/2.Valsartan inhibited such effects of ANGⅡ at concentrations of 10-5 and 10-6 mol/L,but not at 10-7 mol/L.Valsartan had no significant effect on the proliferation of untreated VSMCs.These results suggest that valsartan inhibits ANGⅡ-induced proliferation of VSMCs in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway.
文摘Despite significant therapeutic advances, patients with chronic heart failure （HF） remain at high risk of morbidity and mortality. Sacubitill valsartan （previously known as LCZ696） is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the fast in class angiotensin receptor neprilysin inhibitor （ARNI） since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin Ⅱ receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides （NPs）, bradykinin, endothelin and angiotensin II （Ang-II）. Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-Ⅱ （with opposite biological actions）. So, a combined inhibition of these both systems （Sacubitril / valsartan） may enhance the benefits of NPs effects in HF （natriuresis, diuresis, etc） while Ang-Ⅱ receptor is inhibited （reducing vasoconstriction and aldosterone release）. In a large clinical trial （PARADIGM-HF with 8442 patients）, this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF （compared to enalapril）. This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.
基金Natural Science Foundation of Zhejiang Province,No.LQ16H020004
文摘BACKGROUND Duchenne muscular dystrophy(DMD),which is caused by a mutation/deletion in the dystrophin gene on the X-chromosome,is the most common type of neuromuscular disorder in pediatrics.Skeletal muscle weakness progressively develops in DMD patients and usually leads to respiratory failure in the early adolescent years.Cardiac muscle is frequently affected in DMD patients,which leads to a high burden of cardiomyopathy and heart failure.In the era of improved respiratory care,cardiac deaths are becoming the major cause of mortality in DMD patients.CASE SUMMARY We report the case of a 15-year-old boy who presented to the hospital due to recurrent orthopnea for 6 mo and palpitations for 4 mo.He was diagnosed with progressive muscular dystrophy at the age of 3 years and was confined to a wheelchair at 12 years.He was prescribed diuretics and digoxin at the outpatient clinic;however,his symptoms did not resolve.Sacubitril/valsartan was added 1 mo prior to presentation,but he experienced recurrent episodes of palpitations.The electrocardiogram showed atrial tachycardia with a heart rate of 201 bpm,and he was then hospitalized.Hypotension was found following the administration of sacubitril/valsartan tablets;he could not tolerate even a small dose,always developing tachyarrhythmia.His symptoms were relieved after discontinuing sacubitril/valsartan,and his heart rate was controlled by a small dose of metoprolol tartrate and digoxin.Atrial tachycardia spontaneously converted in this patient,and his symptoms attenuated in the following 6 mo,without palpitation episodes.CONCLUSION Blood pressure should be closely monitored in DMD patients with advanced heart failure when taking sacubitril/valsartan.
文摘The purpose of this study was to develop the immediate release stomach-specific spraydried formulation of valsartan(VAL) using Eudragit?E PO(EPO) as the carrier for enhancing dissolution rate in a gastric environment. Enhanced solubility and dissolution in gastric pH was achieved by formulating the solid dispersion using a spray drying technique. Different combinations of drug–polymer–surfactant were dissolved in 10% ethanol solution and spraydried in order to obtain solid dispersion microparticles. Use of the VAL–EPO solid dispersion microparticles resulted in significant improvement of the dissolution rate of the drug at pH 1.2 and pH 4.0, compared to the free drug powder and the commercial product. A hard gelatin capsule was filled with the VAL–EPO solid dispersion powder prior to the dissolution test.The increased dissolution of VAL from solid dispersion microparticles in gastric pH was attributed to the effect of EPO and most importantly the transformation of crystalline drugs to amorphous solid dispersion powder, which was clearly shown by scanning electron microscopy(SEM), differential scanning calorimetry(DSC), and powder X-ray diffraction(PXRD) studies. Thus, VAL, a potential antihypertensive drug in the form of a solid dispersion microparticulate powder, can be effectively delivered in the immediate release dosage form for stomach-specific drug delivery.
文摘Amlodipine/valsartan(Aml/Val)single-pill combination(SPC)therapy has been widely used and studied in clinical practice in recent years.This article reviews the Chinese and English literature on the clinical use of Aml/Val SPC therapy in Chinese hypertensive patients.According to five studies concerning the efficacy and safety of this treatment,Aml/Val SPC therapy was more efficacious than monotherapy with valsartan,amlodipine,or the nifedipine gastrointestinal therapeutic system.This treatment showed greater blood pressure-lowering effects,a higher blood pressure control rate,and a higher response rate.Aml/Val SPC treatment was well tolerated,with adverse event rates similar to those of monotherapy with valsartan or amlodipine and significantly rarer adverse events compared with the nifedipine gastrointestinal therapeutic system.Aml/Val SPC is a highly efficacious and well-tolerated antihypertensive treatment in Chinese hypertensive patients.
文摘1 Introduction Sacubitril/valsartan(SV)is a first in class dual action molecule of the neprilysin(NEP)inhibitor prodrug sacubitril(AHU377)and the angiotensin II receptor(Ang-II)type 1 antagonist valsartanJ11 It is the first angiotensin receptor-neprilysin inhibitor(ARNI)whose pharmacodynamic effects are consistent with a simultaneous stimulation of the natriuretic peptides system(via NEP inhibition)and the blockade of the renin-angiotensin-aldosterone system(valsartan effect)that finally results in systemic vasodilation,increased diuresis and natriuresis,reduction of plasmatic volume and diminution of peripheral vascular resistance.
文摘Summary: The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.
