Valsartan+Sacubitril Efficacy and Safety in Hypertensive Disease in Adults: A Prospective Randomised Control Trial

INTRODUCTION. Valsartan+sacubitril (a combination of neprilysin inhibitor and angiotensin II receptor blocker) effectively reduces blood pressure (BP) and has the potential to improve metabolic parameters. However, despite this class of drugs being included in clinical guidelines, the specific indications in patients with arterial hypertension are not clearly defined, thus requiring a more detailed study. AIM. This study aimed to assess valsartan+sacubitril combination used for treatment of arterial hypertension in adults in outpatient settings, specifically regarding its efficacy, safety, and impact on overall clinical outcomes and quality of life. MATERIALS AND METHODS. The study is an open prospective longitudinal observation with active control. The study was conducted at State Autonomous Healthcare Institution “City Polyclinic No. 12” (city of Tyumen, Tyumen region). Patients were recruited from 01.10.2022 till 31.03.2025. For each patient, the observation period was 3 months for stage 1 ( n =550) and 1 year for stage 2 ( n =160). BP was controlled at the inclusion, at the end of stage 1, and after 3, 6, and 12 months of treatment. At stage 1, patients were divided into 4 groups: angiotensin-converting-enzyme inhibitor (ACE) + diuretic ( n =189), ACE inhibitor + calcium channel blocker (CCB) ( n =121), angiotensin II receptor blocker (ARB) + diuretic ( n =119), ARB + CCB ( n =121). At stage 2, patients not achieving target BP ≤140/90 mmHg ( n =160) were randomised into 2 groups: study group ( n =80), patients receiving valsartan+sacubitril + diuretic/CCB; and control group ( n =80), receiving a triple combination of ARB + diuretic + CCB or ACE inhibitor + diuretic + CCB. RESULTS. At stage 2, the rate of patients achieving target BP was 93% in the study group vs. 83% in the control group after 3 months; 94% vs. 88% after 6 months; and 99% vs. 98% after 12 months, respectively. Average daily systolic blood pressure and diastolic blood pressure after 3 months of treatment had a statistically significant difference in favour of the study group ( p <0.05). Noteworthy is the positive effect on the reduction of peak average daily systolic, diastolic, as well as pulse BP, and blood pressure load ( p <0.001). After 6 months, the difference between the groups remained the same for all the decreasing parameters (according to 24-h blood pressure monitoring). Only after 12 months did patients in the control group receive a comparable reduction in the parameters; no statistically significant differences were revealed ( p >0.05). EQ-5D showed higher quality of life in the study group after 12 months, the average score being 0.82±0.08 vs. 0.69±0.10 in the control group (change +0.17 vs. +0.05; p <0.05). All adverse reactions for valsartan+sacubitril were predictable; the differences in the frequency of treatment discontinuation between the groups were not statistically significant. CONCLUSIONS. Valsartan+sacubitril has demonstrated efficacy and safety in hypertension in adults. This combination can be recommended as a second-line treatment in case of ineffective two-component regimens of the first-line antihypertensive therapy.