Twenty‐Four‐Hour Blood Pressure‐Lowering Efficacy of Sacubitril/Valsartan Versus Olmesartan in Japanese Patients With Essential Hypertension Based on Nocturnal Blood Pressure Dipping Status: A Post Hoc Analysis of Data From a Randomized, Double‐Blind Multicenter Study

Abstract

Background Nighttime blood pressure (BP) and an abnormal nocturnal BP dipping profile are important cardiovascular risk factors in patients with hypertension. This post hoc analysis investigated the effects of sacubitril/valsartan on 24‐hour BP in patients with mild‐to‐moderate hypertension and in patient subgroups based on nocturnal BP dipping status. Methods and Results Data from a randomized clinical trial comparing the BP‐lowering effects of 8 weeks of treatment with sacubitril/valsartan (200 or 400 mg/d) and olmesartan (20 mg/d) in Japanese patients with mild‐to‐moderate hypertension were analyzed. The primary end point was change in 24‐hour, daytime, and nighttime BP in patient subgroups based on nocturnal BP dipping status (dipper, nondipper). Six hundred thirty‐two patients with baseline and follow‐up ambulatory BP data were included. Both sacubitril/valsartan dosages reduced 24‐hour, daytime, and nighttime systolic BP, and 24‐hour and daytime diastolic BP, to a significantly greater extent than olmesartan in the dipper and nondipper groups. However, between‐group differences in nighttime systolic BP were more significant in the nondipper group (difference [95% CI] for sacubitril/valsartan 200 and 400 mg/d versus olmesartan 20 mg/d: –4.6 [95% CI, −7.3 to −1.8] and −6.8 [95% CI, −9.5 to −4.1] mm Hg, respectively; P <0.01 and P <0.001). Between‐group differences in the BP control rate were greatest in the nondipper subgroup (systolic BP control rate of 34.4% and 42.6% with sacubitril/valsartan 200 and 400 mg/d versus 23.1% with olmesartan 20 mg/d). Conclusions This analysis highlights the value of sacubitril/valsartan therapy in patients with a nondipper profile of nocturnal BP and confirms this agent's potent 24‐hour BP‐lowering effect in Japanese populations with hypertension. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01599104.

Comparison of sacubitril/valsartan with olmesartan for hypertension: A meta-analysis of randomized controlled trials

“…Among the 7 studies included here, 5 studies reported SBP and DBP, [ 12 , 17 , 24 – 26 ] 3 studies reported PP, [ 12 , 24 , 26 ] 4 studies reported SBP control and DBP control, [ 12 , 17 , 18 , 23 ] and 4 studies reported adverse events. [ 12 , 18 , 23 , 25 ] Jadad scores of the 7 included studies varied from 4 to 5, and all 7 studies were considered to have high quality according to quality assessment.…”

“…Five studies were included for the meta-analysis of SBP and DBP. [ 12 , 17 , 24 – 26 ] Compared to olmesartan treatment for hypertension, sacubitril/valsartan treatment resulted in significantly reduced SBP (MD = −4.58; 95% CI = −7.90 to −1.25; P = .007) with significant heterogeneity among the studies ( I 2 = 99%, heterogeneity P < .00001; Fig. 2 ) and DBP (MD = −1.70; 95% CI = −3.24 to −0.17; P = .03) with significant heterogeneity among the studies ( I 2 = 97%, heterogeneity P < .00001; Fig.…”

“…[ 14 – 16 ] Several randomized controlled trials (RCTs) compared the efficacy of sacubitril/valsartan with olmesartan on the control of hypertension, but the results were not well established. [ 12 , 17 , 18 ] With accumulating evidence, we therefore performed this systematic review and meta-analysis of RCTs to explore the efficacy of sacubitril/valsartan versus olmesartan for the control after hypertension.…”

Management of nocturnal hypertension: An expert consensus document from Chinese Hypertension League

“… 80 In a post hoc analysis of Japanese RCT, 24‐h BP reduction with sacubitril/valsartan was compared to olmesartan, the between‐group differences in nighttime systolic BP were more significant in the nondipper group. 81 …”

Clinical Benefit of Sacubitril/Valsartan for Hypertensive Patients in Daily Practice and Predictors of Its Antihypertensive Effect

“…Sacubitril/valsartan (Sac/Val), a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) that provides simultaneous neutral endopeptidase (neprilysin) inhibition and angiotensin II receptor-1 blockade, 1 – 3 has been currently approved in Japan not only for the treatment of chronic heart failure, 4 , 5 but also as an antihypertensive drug. 6 – 8 Many studies have shown that the antihypertensive effect of Sac/Val is greater than that of angiotensin II receptor blockers (ARBs), 9 – 13 which is probably derived from the natriuretic/diuretic and direct vasodilatory effects of sacubitril enhancing the biological activity of natriuretic peptides. 1 , 2 In real-world clinical practice of hypertension management, Sac/Val is used not only for switching from ARBs, but also for switching from other classes of antihypertensive drugs, including combination drugs, and as an additional drug for patients whose blood pressure (BP) is not adequately controlled.…”