Evaluation of an AT1R Antagonist Valsartan in a Mouse Model Exhibiting Typical Signs of Human-like Heart Failure
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Sacubitril
The combination of an angiotensin receptor blocker (valsartan) and neprilysin inhibitor (sacubitril) reduces cardiovascular mortality more than an angiotensin-converting enzyme (ACE) inhibitor (enalapril [Vasotec]) alone, with an acceptable safety and tolerability profile. The choice of dosage is concerning, however, because the study compared a fairly high dose of valsartan with a moderate dose of enalapril.
Sacubitril
Sacubitril, Valsartan
Tolerability
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Objective To compare the therapeutic effect and safety of valsartan with that of enalapril on patients with essential hypertension.Methods The patients were randomized to two groups:Valsartan group(n=51),Enalapril group(n=49).The effective rate was observed at 4th and 8th week.Results The blood pressure(BP) decreased significantly in both 2 groups after 2,4 and 8 weeks,and BP decreased smoothly and continuously during the entire treatment period.The effective rate for decreased DBP treatment were 88.2% and 92.2% respectively in Valsartan group after 4 and 8 weeks,and that of Enalapril group were 81.6% and 87.8% respectively.There was no significant difference between 2 groups(P0.05).Conclusion Valsartan is a safe,effective,tolerable antihypertensive drug.
Essential hypertension
Therapeutic effect
Antihypertensive drug
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Objective To compare the effects of Valsartan on blood ressure(BP)of patients with mild to moderate essential hypertension(EH).Method 64 patients with EH were randomly divided into 2 groups:Valsartan group(Enalapril 10 mg bid n=32).Treatment lasted for 8 weeks.Result Valsartan and Enalapril significantly reduce BP compared with that bdfore treatment(P 0.05),effective rate and magnitude of decreasing BP were no significantly different between two groups(effective rate of Valsartan group was 78.1％vs 70.0％in Enalapril group(P0.05).Conclusion Valsartan and enalapril have effect for decreasing the BP in EH patients.
Essential hypertension
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Objective To evaluate the effect of valsartan and enalapril on the proinflammatory cytokine levels in patients with congestive heart failure(CHF). Methods 82 patients receiving conventional therapy were randomly divided into the valsartan plus enalapril group(52 patients, valsartan 40~80mg/d and enalapril 10mg/d) and control group(30 patients), the proinflammatory cytokine levels were detected before and 8 weeks after therapy in two groups. Results The clinical symptoms of patients in valsartan plus enalapril group were improved markedly(P0.05) and the levels of TNF-α,IL-6,IL-2 were significantly lower than those in control group(P0.01). Conclusions Combining valsartan with enalapril decreased the levels of proinflammatory cytokine and improved cardiac function in patients with CHF.
Proinflammatory cytokine
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Objective To investigate the method and efficacy of enalapril combined with valsartan treatment for chronic congestive heart failure.Methods 70 selected hospital treated patients with chronic congestive heart failure were randomly and voluntarily divided into two groups,30 cases for control group using only enalapril treatment,40 cases for experimental group using enalapril combined with valsatan treatment.After 1 to 2 months follow-up,they were compared the clinical efficacy and echocardiographic changes.Results Compared between the two groups,total effective rate of experimental group patients was 95.0％,higher than that in control one (76.7％) (P＜ 0.05).The echocardiographic indicators in experimental group were significantly better than those of the control group (P＜ 0.05).Conclusion Application of valsartan combined with enalapril treatment for chronic congestive heart failure can improve the echocardiography indicators and clinical efficacy.
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Valsartan; Enalapril; Chronic congestive heart failure
Clinical efficacy
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Objective To evaluate the effects of enalapril and(or) valsartan on the regulation of extracellular matrix degradation and the improvement of myocardial remodeling in patients with chronic heart failure (CHF).Methods Totally 90 CHF patients were equally randomized into 3 groups:enalapril group (10mg/d of enalapril for 8 weeks),valsartan group (80mg/d of valsartan for 8 weeks),and combined group (10mg/d of enalapril and 80mg/d of valsartan,for 8 weeks).The serum MMP-9 levels and echocardiographic indicators including left ventricular end-systolic volume (LVESV),left ventricular end-diastolic volume (LVEDV),and left ventricular ejection fraction (LVEF) were measured before and after treatment.Results Serum MMP-9 level and echocardiographic parameters were significantly different among three groups (P0.05).In addition,serum MMP-9 level was negatively correlated with LVEF (r=-0.355,P=0.001) and positively correlated with LVEDV (r=0.346,P=0.001).In each group,serum MMP-9 level,LVESV,and LVEDV significantly decreased and LVEF significantly increased after treatment (P0.05).Also,serum MMP-9 level,LVESV,and LVEDV in combined group were significantly lower than those in enalapril group and valsartan group;on the contrary,LVEF in combined group was significantly higher than those in enalapril group and valsartan group (P0.05).However,no such difference was noted between enalapril group and valsartan group (P0.05).Conclusion Enalapril combined with valsartan is remarkably superior than enalapril or valsartan alone in treating patients with CHF.The combined therapy can effectively reduce the MMP-9 level,adjust the levels of MMPs,and thus improve myocardial remodeling.
Ventricular remodeling
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▼ Sacubitril valsartan (Entresto—Novartis) is a new oral drug licensed for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. 1 It is described as an angiotensin receptor neprilysin inhibitor and contains the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan. 1-3 Here, we review the evidence for sacubitril valsartan and consider its place in the management of heart failure.
Sacubitril
Sacubitril, Valsartan
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To compare persistence with valsartan and enalapril in daily practice.The PHARMO Record Linkage System includes various data registries including drug dispensing and hospitalizations for > or =2 million subjects in the Netherlands. Patients newly treated with valsartan or enalapril in the period of 1999-2002 were selected. Persistence was calculated by summing up the number of days of continuous treatment. Patients who remained on therapy with valsartan or enalapril for 12 or 24 months were defined as persistent at 1 or 2 years, respectively.3364 patients received valsartan and 9103 patients received enalapril. About 62% of patients treated with valsartan and 55% of patients treated with enalapril remained on therapy at 12 months after the initial dispensing, while 48% of patients treated with valsartan and 43% of patients treated with enalapril were persistent at 24 months. Patients treated with valsartan were about 20% more likely to stay on treatment than patients treated with enalapril (1 year RR(adj): 1.23, 95% CI: 1.16-1.32; 2 years RR(adj): 1.16, 95% CI: 1.11-1.23).Real-life persistence is higher with valsartan than with enalapril. The results of this and other studies on persistence in daily practice should be taken into account when deciding upon drug treatment for hypertension.
Persistence (discontinuity)
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This study compares efficacy and safety of valsartan with enalapril in hypertensive children aged 6-17 years. This was a 12-week, randomized, double-blind, parallel-group, active-controlled study. After a single-blind placebo run-in period (4-28 days), patients with mean sitting systolic blood pressure (BP) (MSSBP) at least 95th percentile for age, gender, and height were randomized to receive half the assigned dose for first week, and force-titrated to full dose for 11 weeks (≥18 to <35 kg - valsartan: 80 mg, enalapril: 10 mg; ≥35 to <80 kg - valsartan: 160 mg, enalapril: 20 mg; ≥80 to ≤160 kg - valsartan: 320 mg, enalapril: 40 mg). The primary efficacy variable was changed from baseline in MSSBP to show noninferiority of valsartan to enalapril. Other efficacy variables were changed from baseline in MSDBP, SBP control rate, and 24-h ambulatory BP parameters. Of 300 randomized patients, 281 (94%) completed the study. At week 12, MSSBP reductions were similar for valsartan and enalapril (primary endpoint of noninferiority, P < 0.0001). Least square mean BP reductions from baseline of -15.4/-9.4 mmHg were observed for valsartan compared with -14.1/-8.5 mmHg for enalapril. A similar proportion of patients achieved SBP control (valsartan: 67%; enalapril: 70%). In the subset of patients who underwent ambulatory BP assessments, valsartan provided greater reductions than enalapril in mean 24-h SBP (valsartan: -9.8 mmHg, enalapril: -7.2 mmHg: P = 0.03). The overall incidence of AEs was similar (valsartan 60%, enalapril 58%) with headache, cough, and nasopharyngitis reported most frequently. Valsartan and enalapril provided comparable BP reductions and effective BP control and were well tolerated in hypertensive children aged 6-17 years.
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