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Efficacy and safety of sacubitril/valsartan compared with olmesartan in Asian patients with essential hypertension: A randomized, double-blind, 8-week study.

ABSTRACT: This study assessed the efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril/valsartan vs olmesartan in Asian patients with mild-to-moderate hypertension. Patients (N = 1438; mean age, 57.7 years) with mild-to-moderate hypertension were randomized to receive once daily administration of sacubitril/valsartan 200 mg (n = 479), sacubitril/valsartan 400 mg (n = 473), or olmesartan 20 mg (n = 486) for 8 weeks. The primary endpoint was reduction in mean sitting systolic blood pressure (msSBP) from baseline with sacubitril/valsartan 200 mg vs olmesartan 20 mg at Week 8. Secondary endpoints included msSBP reduction with sacubitril/valsartan 400 mg, and reductions in clinic and ambulatory BP and pulse pressure (PP) vs olmesartan. In addition, changes in msBP from baseline in the Chinese subpopulation, elderly (≥65 years), and in patients with isolated systolic hypertension (ISH) were assessed. Sacubitril/valsartan 200 mg provided a significantly greater reduction in msSBP than olmesartan 20 mg at Week 8 (between-treatment difference: -2.33 mm Hg [95% confidence interval (CI) -4.00 to -0.66 mm Hg], P < 0.05 for non-inferiority and superiority). Greater reductions in msSBP were also observed with sacubitril/valsartan 400 mg vs olmesartan 20 mg (-3.52 [-5.19 to -1.84 mm Hg], P < 0.001 for superiority). Similarly, greater reductions in msBP were observed in the Chinese subpopulation, in elderly patients, and those with ISH. In addition, both doses of sacubitril/valsartan provided significantly greater reductions from baseline in nighttime mean ambulatory BP vs olmesartan. Treatment with sacubitril/valsartan 200 or 400 mg once daily is effective and provided superior BP reduction than olmesartan 20 mg in Asian patients with mild-to-moderate hypertension and is generally safe and well tolerated.

SUBMITTER: Huo Y

PROVIDER: S-EPMC8030324 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAzilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has a well-characterized efficacy and safety profile in patients with hypertension. AZL-M is approved for use in over 40 countries globally; however, it is not yet approved in China. Therefore, a phase 3 registration study to assess the efficacy (antihypertensive effect), safety, and tolerability of AZL-M compared with valsartan in Chinese patients with essential hypertension was undertaken.MethodsThis multicenter, double-blind, randomized, 8-week phase 3 study compared AZL-M with valsartan in Chinese patients aged ≥18 years with essential hypertension. Endpoints included change from baseline to week 8 in trough sitting clinic systolic blood pressure (scSBP) and ambulatory blood pressure monitoring parameters.ResultsOverall, 612 patients (mean age, 57.1 years; 57.5% male) were randomized to AZL-M 80 mg (n = 209), AZL-M 40 mg (n = 199), or valsartan 160 mg (n = 204). Baseline mean scSBP was similar in all groups (157.9-158.5 mm Hg). The mean reduction in trough scSBP from baseline to week 8 was significantly greater with AZL-M 80 mg than with valsartan (-24.2 vs -20.6 mm Hg; P = .010), and noninferior with AZL-M 40 mg versus valsartan (-22.5 vs -20.6 mm Hg; P = .184). Mean reduction in 24-hour mean systolic blood pressure (n = 257) was significantly greater with both AZL-M 80 mg (-17.0 mm Hg; P < .001) and AZL-M 40 mg (-14.7 mm Hg; P = .014) than with valsartan (-9.4 mm Hg). Treatment-emergent adverse events had similar incidence (52.8%-56.5%) across the treatment groups and were generally mild or moderate. Dizziness was the most frequent treatment-related treatment-emergent adverse events (AZL-M 80 mg, 1.9%; AZL-M 40 mg, 1.5%; valsartan, 1.0%). The safety and tolerability of AZL-M were comparable with valsartan.ConclusionsAZL-M was noninferior to valsartan at the 40-mg dose and superior to valsartan at the 80-mg dose in reducing trough scSBP, and showed acceptable safety-consistent with the AZL-M safety profile in other populations-in Chinese adults with hypertension.Trial registration numberNCT02480764.

Project description:To assess the tolerability of initiating/uptitrating sacubitril/valsartan (LCZ696) from 50 to 200 mg twice daily (target dose) over 3 and 6 weeks in heart failure (HF) patients (ejection fraction ?35%).A 5-day open-label run-in (sacubitril/valsartan 50 mg twice daily) preceded an 11-week, double-blind, randomization period [100 mg twice daily for 2 weeks followed by 200 mg twice daily ('condensed' regimen) vs. 50 mg twice daily for 2 weeks, 100 mg twice daily for 3 weeks, followed by 200 mg twice daily ('conservative' regimen)]. Patients were stratified by pre-study dose of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEI/ARB; low-dose stratum included ACEI/ARB-naïve patients). Of 540 patients entering run-in, 498 (92%) were randomized and 429 (86.1% of randomized) completed the study. Pre-defined tolerability criteria were hypotension, renal dysfunction and hyperkalaemia; and adjudicated angioedema, which occurred in ('condensed' vs. 'conservative') 9.7% vs. 8.4% (P = 0.570), 7.3% vs. 7.6% (P = 0.990), 7.7% vs. 4.4% (P = 0.114), and 0.0% vs. 0.8% of patients, respectively. Corresponding proportions for pre-defined systolic blood pressure <95 mmHg, serum potassium >5.5 mmol/L, and serum creatinine >3.0 mg/dL were 8.9% vs. 5.2% (P = 0.102), 7.3% vs. 4.0% (P = 0.097), and 0.4% vs. 0%, respectively. In total, 378 (76%) patients achieved and maintained sacubitril/valsartan 200 mg twice daily without dose interruption/down-titration over 12 weeks (77.8% vs. 84.3% for 'condensed' vs. 'conservative'; P = 0.078). Rates by ACEI/ARB pre-study dose stratification were 82.6% vs. 83.8% (P = 0.783) for high-dose/'condensed' vs. high-dose/'conservative' and 84.9% vs. 73.6% (P = 0.030) for low-dose/'conservative' vs. low-dose/'condensed'.Initiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments. More gradual initiation/uptitration maximized attainment of target dose in the low-dose ACEI/ARB group.

Project description:IntroductionCentral blood pressure (BP), an important measure of cardiovascular risk, has been shown to be effectively reduced by calcium channel blockade with amlodipine (AML) plus renin-angiotensin system blockade by the angiotensin-converting enzyme inhibitor, perindopril (PER). The aim of the SEVITENSION study was to compare the central effects of PER/AML against renin-angiotensin system blockade with the angiotensin II receptor blocker olmesartan (OLM) plus AML.MethodsIn this multicenter, parallel group, non-inferiority study, patients received AML 10 mg during a 2- to 4-week run-in before randomization to 24 weeks of double-blind treatment with the fixed-dose combination of OLM/AML 40/10 mg or PER/AML 8/10 mg. Hydrochlorothiazide was added at Weeks 4, 8, or 12 in patients with inadequate BP control. The primary efficacy variable was the absolute change in central systolic BP (CSBP) from baseline to the final examination, measured by radial artery applanation tonometry and analyzed by parametric analysis of covariance. Secondary variables included 24-h ambulatory and seated BP measurements as well as BP normalization.ResultsOf 600 patients enrolled, 486 were randomized (244 to OLM/AML 40/10 mg, 242 to PER/AML 8/10 mg). The reduction in CSBP was larger with OLM/AML (14.5 ± 0.83 mmHg) than with PER/AML (10.4 ± 0.84 mmHg). The between-group difference was -4.2 ± 1.18 mmHg with 95% confidence intervals (-6.48 to -1.83 mmHg) within the predefined non-inferiority margin (2 mmHg). An integrated superiority test confirmed that OLM/AML was superior to PER/AML (p < 0.0001) in reducing CSBP. The superiority of OLM/AML over PER/AML was also established for the majority of secondary efficacy variables; at the final examination, 75.6% of OLM/AML recipients achieved BP normalization (mean seated systolic BP/diastolic BP <140/90 mmHg) compared with 57.5% of PER/AML recipients (p < 0.0001).ConclusionThe combination of OLM/AML was superior to PER/AML in reducing CSBP and other efficacy measures, including a significantly higher rate of BP normalization.

Project description:The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ?20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (-52.3% [2.8%] vs -0.6% [3.5%], P<0.0001), and the difference was -51.7% (4.1%) (95% confidence interval: -59.8% to -43.6%). The least square mean change (standard error) from baseline in diastolic blood pressure 8 weeks after treatment was significantly greater in the FDC group than in the rosuvastatin group (-10.4 [1.2] mmHg vs 0.1 [1.6] mmHg, P<0.0001), and the difference was -10.5 (1.8) mmHg (95% confidence interval: -14.1 to -6.9 mmHg). There were 50 adverse events in 41 patients (22.7%) and eight adverse drug reactions in five patients (2.8%). The study found that FDC therapy with olmesartan medoxomil and rosuvastatin is an effective, safe treatment for patients with hypertension and dyslipidemia. This combination may improve medication compliance in patients with a large pill burden.

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Efficacy and safety of sacubitril/valsartan compared with olmesartan in Asian patients with essential hypertension: A randomized, double-blind, 8-week study.

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