allisartan-isoproxil and Essential-Hypertension

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

Allisartan isoproxil is a selective nonpeptide angiotensin II (AT1) receptor blocker developed by China, this study aimed to assess its clinical efficacy for essential hypertension (EH).. Patients with mild-to-moderate EH, selected at 44 sites in China from September 9, 2016, to December 7, 2018, were administered 240 mg allisartan isoproxil daily for 4 weeks. Patients with controlled blood pressure (BP) continued monotherapy for 8 weeks, others were randomly assigned (1:1) to A + D group (allisartan isoproxil 240 mg + indapamide 1.5 mg) or A + C group (allisartan isoproxil + amlodipine besylate 5 mg) for 8 weeks. BP were measured at week 4, 8 and 12.. 2,126 patients were included in the analysis. After 12 weeks of treatment, systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased by 19.24 ± 12.02 and 10.63 ± 8.89 mm Hg, respectively, and the overall BP control rate was 78.56%. The sitting blood pressures (SBP/DBP) decreased by 19.12 ± 11.71/10.84 ± 8.73 mm Hg in patients with 12 weeks allisartan isoproxil monotherapy (both P < 0.0001). The BP reductions and control rates were comparable between A + D and A + C groups. 48 patients with monotherapy-controlled BP underwent ambulatory BP monitoring, with a mean decrease in ambulatory BP of 10.04 ± 10.87/5.50 ± 8.07 mm Hg after 12 weeks of treatment, and consistent reductions between day and night. SBP and DBP had trough-to-peak ratios of 64.64% and 62.63% and smoothness indices of 3.82 and 2.92, respectively.. An allisartan isoproxil-based antihypertensive regimen can effectively control BP in patients with mild-to-moderate EH.. CTR20160138 (Registration and Information Disclosure Platform for China Drug Clinical Studies, http://www.chinadrugtrials.org.cn/index.html).

Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Essential Hypertension; Humans; Hypertension; Imidazoles; Tetrazoles; Treatment Outcome

Evidence has shown that angiotensin II type 1 receptor antagonists have lower blood pressure and have target organ protective effects, but this is not the case for the drug allisartan isoproxil. The aim of this study was to evaluate the effects of allisartan isoproxil on blood pressure and target organ injury in patients with mild to moderate essential hypertension.In total, 80 essential hypertensive participants were randomly divided into an allisartan group and a nifedipine group (n = 40 per group), and their blood pressure was measured once per month for 6 months. A 2-dimensional echocardiogram was performed at baseline and at the end of the study. The serum levels of renal injury indexes, endothelial function markers, inflammatory factors, blood biochemical assays and urinary measurements were determined at baseline and at 6 months.At the end of the study, both systolic and diastolic blood pressure were significantly decreased in the allisartan group compared with baseline and showed the same antihypertensive effect as the nifedipine group. Meanwhile, the left ventricular remodeling, 24-hours levels of urinary microalbumin, endothelial dysfunction, and arterial stiffness were all significantly improved compared with that of the baseline and the nifedipine group (all P < .05).The present study showed that allisartan isoproxil had favorable blood pressure lowering and heart, renal, and endothelial protective effects in patients with mild to moderate essential hypertension.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Endothelium, Vascular; Essential Hypertension; Hematologic Tests; Humans; Imidazoles; Inflammation Mediators; Kidney Function Tests; Male; Middle Aged; Nifedipine; Severity of Illness Index; Urinalysis; Vascular Stiffness; Ventricular Remodeling

Angiotensin II receptor blockers (ARBs) is a well-tolerated class of antihypertensive agents, exhibiting effective antihypertensive and cardiovascular protective function. The objective of the study was to examine the efficacy and safety of Allisartan Isoproxil, a newly developed, selective, nonpeptide blocker of the angiotensin II type 1 receptor (AT1R), in essential hypertensive patients at low-medium risk.. A Phase II prospective, randomized, double-blind, placebo-controlled, multicenter trial comparing Allisartan Isoproxil 240mg versus placebo was conducted in essential hypertensive patients at low-medium risk at 8 sites in China. After a 2-week placebo baseline period, 275 patients received once-daily treatment with Allisartan Isoproxil 240mg or placebo randomly for 8 weeks. Systolic/diastolic blood pressure (SBP/DBP) was measured at week 2, 4 and 8. By the end of treatment, mean reductions from baseline of SBP and DBP in Allisartan Isoproxil and placebo groups were 14.5/10.4 and 8.3/7.7 mmHg, respectively (P<0.01). The rate of effective blood pressure control in Allisartan Isoproxil group was significantly higher than in placebo group at week 4 (61.3% vs 50.0%, P<0.05) and week 8 (67.2% vs 48.6%, P<0.01). In terms of safety and tolerability, there were no report of death and serious adverse event (SAE) in all subjects. There was no difference of frequency between two groups in adverse event (AE) and adverse drug reaction (ADR) (P>0.05). No one withdraw because of an ADR in two groups. 124 patients received additional 56 weeks treatment with Allisartan Isoproxil and 84 of them completed the study. The rate of effective BP control kept up to 80% since week 24. No significant clinical change was observed and ADRs were generally mild or moderate during the long-term study.. Allisartan Isoproxil 240mg was effective and safe for essential hypertension patients at low-medium risk.. http://www.chictr.org/cn/ ChiCTR-TRC-10000886.

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Biphenyl Compounds; Double-Blind Method; Endpoint Determination; Essential Hypertension; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Placebos; Risk; Safety