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. 2020 Dec 11;23(3):556–567. doi: 10.1111/jch.14120

Table 3.

Global studies on sacubitril/valsartan in hypertension

Title Conditions Age Ethnicity Enrollment Study design Intervention Length of follow up Results
Blood pressure reduction with LCZ696, a novel dual‐acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double‐blind, placebo‐controlled, active comparator study (Ruilope et al, 31 2010)

  1. Treatment naïve, msDBP 95‐109 mmHg, or

  2. Previously treated, msDBP 90‐109 mmHg after washout

 18‐75 Multi‐ethnic; 87% white 1328 Multicenter, randomized, double‐blind

Sacubitril/valsartan 100 mg vs sacubitril/valsartan 200 mg vs sacubitril/valsartan 400 mg vs

80 mg valsartan vs

160 mg valsartan vs

320 mg valsartan vs

200 mg sacubitril vs

placebo

 13 weeks (8 weeks of treatment) Sacubitril/valsartan significantly decreased msDBP compared to valsartan only (mean reduction: –2.17 mm Hg, 95% CI –3.28 to –1.06; P < .0001); 200 mg of sacubitril/valsartan was superior also to 160 mg valsartan (msDBP reduction –2.97 mm Hg, 95% CI –4.88 to –1.07, P = .0023), as was 400 mg sacubitril/valsartan to 320 mg valsartan (msDBP reduction –2.70 mm Hg, –4.61 to –0.80, P = .0055).
Efficacy and Safety of Crystalline Valsartan/Sacubitril (LCZ696) Compared With Placebo and Combinations of Free Valsartan and Sacubitril in Patients With Systolic Hypertension: The RATIO Study (Izzo et al, 32 2017)

  1. Office SBP ≥ 150 and < 180 mmHg, and

  2. Office DBP ≥ 70 mmHg

 ≥18 Multi‐ethnic; 68.4% white 907 Multicenter, randomized, double‐blind Sacubitril/valsartan 400 mg QD vs free valsartan 320 mg QD with placebo or increasing doses of free sacubitril (50, 100, 200, or 400 mg QD) 8 weeks Sacubitril/valsartan 400 mg resulted in greater reductions in sitting office SBP and 24‐hour ambulatory SBP than with valsartan 320 mg (−5.7 and −3.4 mmHg, respectively, P < .05 each)
Effects of Sacubitril/Valsartan Versus Olmesartan on Central Hemodynamics in the Elderly With Systolic Hypertension: The PARAMETER Study (Williams et al, 65 2017)

  1. Treatment naïve, msSBP ≥ 150 and < 180 mmHg, or

  2. Previously treated, msSBP ≥ 140 and < 180 mmHg, and ≥ 150 and < 180 mmHg after washout

 ≥60 Multi‐ethnic; 64.3% white 432 Multicenter, randomized, double‐blind Sacubitril/valsartan 200 mg vs olmesartan 20 mg for 4 weeks, then doubled doses. If msSBP > 140 mmHg or msDBP > 90 mmHg after 12 weeks, amlodipine (2.5‐5 mg) followed by hydrochlorothiazide (6.25‐25 mg) were added every 4 weeks up to week 24 52 weeks Sacubitril/valsartan resulted in greater reductions of central aortic systolic pressure than olmesartan at week 12 by a difference of − 3.7 mmHg (P = .010). At week 52, there were no differences between blood pressure parameters of the two groups; however, more patients required add‐on antihypertensive therapy with olmesartan (47%) versus sacubitril/valsartan (32%; P < .002).
Efficacy and safety of sacubitril/valsartan in patients with essential hypertension uncontrolled by olmesartan: A randomized, double‐blind, 8‐week study (Cheung et al, 66 2018)

  1. Treatment naïve, msSBP ≥ 150 and < 180 mmHg, or

  2. Previously treated, msSBP ≥ 145 and < 180 mmHg after washout

 ≥18 Multi‐ethnic; 57.6% white 376 Multicenter, randomized, double‐blind Addition of sacubitril/valsartan 200 mg QD to uncontrolled hypertension under Olmesartan 20 mg QD 8 weeks Addition of sacubitril/valsartan led to superior reductions in 24‐hour mean ambulatory systolic BP vs olmesartan alone (−4.3 mm Hg vs − 1.1 mm Hg, P < .001); sacubitril/valsartan was also superior for reductions in 24‐hour mean ambulatory DBP, pulse pressures and office SBP and DBP.