sacubitril and Essential-Hypertension

Sacubitril/valsartan has been demonstrated to reduce blood pressure in hypertensive patients, but the best dose remains unclear. We performed this network meta-analysis to determine the comparative efficacy and safety of three available doses of sacubitril/valsartan (i.e., 100, 200, and 400 mg).. We searched four databases for relevant studies published before January 2022. Mean systolic and diastolic blood pressures in the sitting position (msSBP and msDBP) and ambulatory condition (24-h maSBP and maDBP) and adverse events (AEs) were assessed. Nine randomized controlled trials (RCTs) involving 5474 patients were included. Sacubitril/valsartan 200 mg once daily was slightly better than 400 mg once daily in lowering 24-h maDBP (MD, 1.31 mmHg; 95% CI 0.61-2.01 mmHg), slightly better than 100 mg once daily in lowering 24-h maSBP (MD, - 3.70 mmHg; 95% CI  - 6.22 to - 1.18 mmHg) and 24-h maDBP (MD, - 2.98; 95% CI - 5.11 to - 0.85), and slightly better than Valsartan 160 mg once daily in lowering 24-h maSBP (MD, - 3.23 mmHg; 95% CI, - 5.25 to - 1.21). 400 mg once daily of sacubitril/valsartan was better than 200 mg once daily in lowering msDBP (MD, - 9.38 mmHg; 95% CI - 17.79 to - 0.97 mmHg). Interestingly, 400 mg once daily of sacubitril/valsartan had fewer trial-specified AEs than 200 mg once daily (OR, 0.74; 95%CI 0.55-0.99). There was no statistical difference for the remaining comparisons.. In hypertensive patients, 200 mg once daily of sacubitril/valsartan may exert a greater reduction in ambulatory blood pressure than 100 mg once daily and 200 mg once daily may not be inferior to 400 mg once daily. Moreover, it is not clear that sacubitril/valsartan lowers blood pressure more than an angiotensin receptor blocker. Further trials are required to determine the incremental value of sacubitril/valsartan as an anti-hypertensive agent.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Drug Combinations; Essential Hypertension; Humans; Hypertension; Network Meta-Analysis; Randomized Controlled Trials as Topic; Tetrazoles; Valsartan

Since sacubitril/valsartan (LCZ696) has neprilysin inhibition and angiotensin receptor-blocking properties, it is anticipated to have strong antihypertensive effects. However, there is not enough evidence to compare the safety and efficacy of sacubitril/valsartan to those of olmesartan in patients with hypertension.. To compare the efficacy and safety of sacubitril/valsartan versus olmesartan in patients with hypertension.. This study follows the guidelines of the Cochrane Handbook. We searched MEDLINE, Cochrane Central, Scopus, and Web of Science databases for relevant clinical trials. We extracted outcome endpoints regarding mean ambulatory systolic/diastolic blood pressure (maSBP/maDBP), mean sitting systolic/diastolic blood pressure (msSBP/msDBP), mean ambulatory/mean sitting pulse pressure (maPP/msPP), the proportion of patients achieving blood pressure control (< 140/90 mmHg), and adverse events. We used Review Manager Software for the conduction of the analysis of this study. The effect estimates of the studies were pooled as Mean difference or risk ratio and 95% confidence interval. We also conducted a subgroup analysis based on the dose of sacubitril/valsartan.. A total of six clinical trials were included. The studies showed an overall low risk of bias. The pooled effect estimate revealed that sacubitril/valsartan significantly reduces maSBP, maDBP, maPP, msSBP, and msDBP measurements compared with olmesartan (p < 0.001). A significantly higher portion of patients achieved blood pressure control in the sacubitril/valsartan group (p < 0.001). The test of subgroup difference showed that 400 mg dose is significantly more effective than 200 mg dose in reducing maSBP. Regarding the safety profile, olmesartan was associated with more side effects due to drug discontinuation and more serious side effects.. Sacubitril/valsartan or LCZ696 is more effective and safer than olmesartan for controlling blood pressure in patients with hypertension.

Topics: Aminobutyrates; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Blood Pressure; Drug Combinations; Essential Hypertension; Humans; Hypertension; Tetrazoles; Valsartan

The aim of this study was to model the potential long-term disease progression and pharmacoeconomic value of sacubitril/valsartan for the treatment of essential hypertension from a Chinese healthcare system perspective.. A Markov cohort model with five health states was constructed to simulate the incidence of acute cardiovascular events and cost per quality-adjusted life-year (QALY) gained with sacubitril/valsartan compared with allisartan isoproxil and valsartan over a lifetime horizon with an annual cycle. Multivariable risk regression models derived from China-PAR data accompanied by hazard ratios were used to transform the dual mechanism of sacubitril/valsartan to lower blood pressure and left ventricular mass index into long-term fatal and non-fatal cardiovascular risks. Efficacy data were calculated using a network meta-analysis integrated by the results of clinical trials. Healthcare costs were determined from a real-world study and published literature, supplemented by expert opinion. Utilities were derived from literature. Both costs and health outcomes were discounted at 5.0% annually, and prices corresponded to 2021. Model validation, deterministic and probabilistic sensitivity analyses were conducted to test the robustness of results.. For simulated patients with hypertension, sacubitril/valsartan reduced the rates of myocardial infarction by 6.67% and 6.39%, stroke by 9.38% and 8.98%, and heart failure hospitalization by 9.92% and 9.62% relative to allisartan isoproxil and valsartan, respectively. It was also associated with gains in life expectancy among hypertensive individuals of 0.362-0.382 years. Eventually, lifetime costs per patient were CN¥59,272 (US$9187) for sacubitril/valsartan, CN¥54,783 (US$8492) for allisartan isoproxil, and CN¥56,714 (US$8791) for valsartan; total QALYs were 11.38, 11.24, and 11.25, respectively. The incremental cost-effectiveness ratio was CN¥31,805/QALY (US$4930/QALY) compared with allisartan isoproxil, and CN¥19,247/QALY (US$2983/QALY) compared with valsartan, both of which are below the one time per-capita GDP of CN¥80,976/QALY (US$12,551/QALY) in China. Similar results were obtained in various extensive sensitivity analysis scenarios.. This was the first study to evaluate the cost effectiveness of sacubitril/valsartan in the treatment of hypertension. Sacubitril/valsartan compares favorably with allisartan isoproxil and valsartan in the Chinese setting, which is mainly due to its higher efficacy resulting in fewer cardiovascular events and ultimately less related mortality over time. The results could inform deliberations regarding reimbursement and access to this treatment in China and may provide reference for facilitating more reasonable and efficient allocation of limited resources in such low- and middle-income countries.

Topics: Cost-Benefit Analysis; Drug Combinations; Essential Hypertension; Humans; Valsartan

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; East Asian People; Essential Hypertension; Humans; Hypertension; Tetrazoles; Valsartan

This randomized, double-blind phase 2 study assessed the efficacy and safety of sacubitril/allisartan, an angiotensin receptor neprilysin inhibitor, compared with placebo in Chinese patients with mild to moderate hypertension. Eligible patients aged 18-75 years (n = 235) with mild to moderate hypertension were randomized to receive sacubitril/allisartan 120 mg (n = 52), sacubitril/allisartan 240 mg (n = 52), sacubitril/allisartan 480 mg (n = 52), placebo (n = 26) or olmesartan 20 mg (n = 53) once daily for 8 weeks. The primary end point was a reduction in clinic systolic blood pressure from baseline with different doses of sacubitril/allisartan versus placebo at 8 weeks. Secondary efficacy variables included clinic diastolic blood pressure and 24-h ambulatory blood pressure for the comparison between sacubitril/allisartan and placebo at 8 weeks. Safety assessments included all adverse events and serious adverse events. Sacubitril/allisartan 480 mg/day provided a significantly greater reduction in clinic systolic blood pressure than placebo at 8 weeks (between-treatment difference: -9.1 mmHg [95% confidence interval -1.6 to -16.6 mmHg], P = 0.02). There were also significant reductions in 24-h, daytime and nighttime systolic and diastolic blood pressure for sacubitril/allisartan 480 mg/day compared with placebo (P ≤ 0.03). Similarly, a greater reduction in daytime systolic blood pressure was observed for sacubitril/allisartan 240 mg/day compared with placebo (between-treatment difference: -7.3 mmHg [95% confidence interval -0.5 to -14.0 mmHg], P = 0.04). Sacubitril/allisartan was well tolerated, and no cases of angioedema were reported. Sacubitril/allisartan is effective for the treatment of hypertension in Chinese patients and is well tolerated.

Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Drug Combinations; Essential Hypertension; Humans; Middle Aged; Tetrazoles; Treatment Outcome; Young Adult

This phase III study assessed the efficacy and safety of sacubitril/valsartan compared with those of olmesartan in Japanese patients with essential hypertension. Patients (n = 1161, aged ≥20 years) with mild to moderate hypertension (mean sitting systolic blood pressure [msSBP] ≥150 to <180 mmHg) were randomized to receive sacubitril/valsartan 200 mg (n = 387), sacubitril/valsartan 400 mg (n = 385), or olmesartan 20 mg (n = 389) once daily for 8 weeks. The primary assessment was a reduction in msSBP from baseline with sacubitril/valsartan 200 mg vs. olmesartan 20 mg at Week 8. Secondary assessments included msSBP reduction with sacubitril/valsartan 400 mg vs. olmesartan at Week 8 and reductions in mean sitting diastolic blood pressure (msDBP), mean sitting pulse pressure (msPP), and overall blood pressure (BP) control rate for all treatment groups at Week 8. Sacubitril/valsartan 200 mg provided a significantly greater reduction in msSBP from baseline than olmesartan at Week 8 (between-treatment difference: -5.01 mmHg [95% confidence interval: -6.95 to -3.06 mmHg, P < 0.001 for noninferiority and superiority]). Greater reductions in msSBP with sacubitril/valsartan 400 mg vs. olmesartan, as well as in msDBP and msPP with both doses of sacubitril/valsartan vs. olmesartan (P < 0.05 for all), were also observed. Patients treated with sacubitril/valsartan achieved an overall higher BP control rate. The safety and tolerability profiles of sacubitril/valsartan were generally comparable to those of olmesartan. The adverse event rate with sacubitril/valsartan was not dose-dependent. Treatment with sacubitril/valsartan was effective and provided superior BP reduction, with a higher proportion of patients achieving target BP goals than treatment with olmesartan in Japanese patients with mild to moderate essential hypertension.

Topics: Aminobutyrates; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Double-Blind Method; Essential Hypertension; Humans; Hypertension; Imidazoles; Japan; Tetrazoles; Treatment Outcome; Valsartan