Sacubitril + valsartan
Sacubitril + valsartan has been studied in 35 papers since 2017: 5 trials and 11 observational studies in people, 3 in animals, 1 in cells, 12 reviews; 22 in the past year. It is an approved medicine. The newest paper, Nov 7, 2026: “Sacubitril/Valsartan versus Conventional Antihypertensive Therapy in Patients with Hypertension and Type 2 Diabetes”.
35 papers study it5 more mention it41 findingsUpdated
13 new papers in 30 daysSee all 40 papers on sacubitril + valsartan
At a glance
Independent labs found the same change in people. 14 independent labs in 8 countries; 53 trials, none about aging, 9 with no results posted.
“and 0.69 [95% CI: 0.51-0.95]), respectively (Pinteraction = 0.23).”
None of its findings points the other way.
- 14 independent labs in 8 countries
- 53 trials, none about aging, 9 with no results posted
- Funders: National Institute for Health Research and others
- 7 of 35 findings with company ties
- Human trial5
- Humans11
- Animals3
- Cells1
- In silico2
Studies in people
5 studies gave sacubitril + valsartan to people and measured what changed.
| What changed | Design | People | Source |
|---|---|---|---|
up: Increases time in target systolic blood pressure range7% (95% CI 5 to 9%) | Review of trialsfirst year | 18,823 people pooledBothmean age 72±9 yearsOlder adults; Heart failure with LVEF ≥45%; target systolic blood pressure 110–<130 mmHg | ESC Congress 2026 abstract, Oct 26, 2026 |
down: Decreases blood pressure-10.2 ± 9.3% down: Decreases NT-proBNP-18.3 ± 25.5% down: Decreases body weight-1.4 ± 4.4% | Trial6 months | 27 people48.1% of subjects were male74 ± 11 yearsHypertensive patients who had an office systolic BP of at least 140 mm Hg or diastolic BP of at least 90 mm Hg on at least two separate office visits despite receiving azilsartan treatment | Journal of clinical hypertension (Greenwich, Conn.), Mar 1, 2026 |
down: Decreases total heart failure hospitalizations or cardiovascular deathRR 0.69, 95% CI 0.51-0.95 | Randomized trial | 4,796 peopleClass 3 frailty (FI >=0.311) in HFpEF | Journal of the American College of Cardiology, Aug 29, 2022 |
down: Decreases systolic blood pressure22.71 vs. 16.11 mm Hg; P < 0.001 down: Decreases pulse pressure | Randomized trial10 weeks | 588 people≥65 yearsOlder adults; elderly Asian patients with systolic hypertension | American journal of hypertension, Oct 11, 2017 |
down: Decreases central aortic systolic blood pressure-3.7 mm Hg (P=0.010) down: Decreases 24-hour ambulatory systolic blood pressure-4.1 mm Hg brachial and -3.6 mm Hg central aortic, both P<0.001 down: Decreases requirement for add-on antihypertensive therapy32% versus 47% | Randomized trial12 weeks | 454 people≥60 yearsOlder adults; Patient cohorts | Hypertension (Dallas, Tex. : 1979), Jan 16, 2017 |
What did studies of sacubitril + valsartan find?
28Studies of sacubitril + valsartan measured 28 outcomes; the most studied are NT-proBNP (3 studies), mortality (3) and time in target systolic blood pressure range (1).
NT-proBNP
downin humans3
3 studies
NT-proBNP
downin humans3
Sacubitril + valsartan decreases NT-proBNP in humans after switching from azilsartan (-18.3 ± 25.5%).
“Sacubitril/valsartan treatment decreased BP, morning‐to‐nighttime decrease in home SBP, body mass index, body weight, and NT‐proBNP level, whereas other variables such as potassium and estimated glomerular filtration rate did not change significantly.”
Human trialafter switching from azilsartan6 monthsn = 27
Journal of clinical hypertension (Greenwich, Conn.)
Sacubitril + valsartan decreases NT-proBNP in humans after switching from azilsartan (188.2 [85.3-887.3] to 124.0 [83.6-696.2] pg/mL).
“median (IQR) NT-proBNP level (188.2 [85.3-887.3] to 124.0 [83.6-696.2] pg/mL) were observed.”
Human trialafter switching from azilsartan170±47 mg/day6 monthsn = 27
Journal of clinical hypertension (Greenwich, Conn.)
Sacubitril + valsartan decreases NT-proBNP in humans (heart failure with reduced ejection fraction).
“we observed a significant improvement in humoral and functional parameters of CGA, renal function, NTpro-BNP levels and echocardiographic parameters.”
Human trialheart failure with reduced ejection fraction6 monthsn = 61
Internal and emergency medicine
Sacubitril + valsartan is linked with lower NT-proBNP in humans (post-acute myocardial infarction heart failure; compared with enalapril).
“The sacubitril/valsartan group had bigger decreases in NT-proBNP (P < 0.001) and cTnI (P = 0.030).”
Humanspost-acute myocardial infarction heart failure; compared with enalaprilone yearn = 204
American journal of translational research
Mortality
downin humans3−22% all-cause mortality
3 studies
Mortality
downin humans3−22% all-cause mortality
Sacubitril + valsartan decreases mortality in humans (heart failure with reduced ejection fraction (HFrEF)) (-22% all-cause mortality).
“Sacubitril/valsartan demonstrated significant benefits in HFrEF patients, reducing cardiovascular death by 19%, all-cause mortality by 22%, and HHF by 22%.”
Reviewheart failure with reduced ejection fraction (HFrEF)
Frontiers in pharmacology
Sacubitril + valsartan decreases mortality in humans (HFrEF).
“associates lower risk of heart failure hospitalizations and mortality (also of arrhythmic origin).”
ReviewHFrEF
Cardiology
Sacubitril + valsartan decreases mortality in humans (heart failure).
“angiotensin receptor-neprilysin inhibitor (LCZ696), launched in August 2014 with an even greater reduction in mortality and morbidity of heart failure”
Reviewheart failure
Physical training in chronic heart failure: pathophysiology and clinical evolution
Medwave
Time in target systolic blood pressure range
upin humans1
1 study
Time in target systolic blood pressure range
upin humans1
Sacubitril + valsartan increases time in target systolic blood pressure range in humans (7% (95% CI 5 to 9%)).
“7% (5 to 9%) with sacubitril/valsartan”
Human trialHeart failure with LVEF ≥45%; compared with valsartan; target systolic blood pressure 110–<130 mmHgfirst year
ESC Congress 2026 abstract
Health status
no changein humans1
1 study
Health status
no changein humans1
Sacubitril + valsartan showed no clear effect on health status in humans (vs. dapagliflozin in symptomatic heart failure).
“In symptomatic HF, sacubitril-valsartan vs. dapagliflozin and torsemide vs. furosemide did not differ for health status at 6 mo”
Human trialvs. dapagliflozin in symptomatic heart failure6 mo
Annals of internal medicine
Heart failure
downin humans1
1 study
Heart failure
downin humans1
Sacubitril + valsartan decreases heart failure in humans.
“novel HF therapies, particularly sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan, has markedly improved clinical outcomes across HF phenotypes.”
Review
The Heart-Gut Axis in Heart Failure: The Role of Next-Generation Pharmacological Therapies
International journal of molecular sciences
Body weight
downin humans1
1 study
Body weight
downin humans1
Sacubitril + valsartan decreases body weight in humans after switching from azilsartan (-1.4 ± 4.4%).
“Sacubitril/valsartan treatment decreased BP, morning‐to‐nighttime decrease in home SBP, body mass index, body weight, and NT‐proBNP level, whereas other variables such as potassium and estimated glomerular filtration rate did not change significantly.”
Human trialafter switching from azilsartan6 monthsn = 27
Journal of clinical hypertension (Greenwich, Conn.)
Blood pressure
downin humans1
1 study
Blood pressure
downin humans1
Sacubitril + valsartan decreases blood pressure in humans after switching from azilsartan (-10.2 ± 9.3%).
“Sacubitril/valsartan treatment decreased BP, morning‐to‐nighttime decrease in home SBP, body mass index, body weight, and NT‐proBNP level, whereas other variables such as potassium and estimated glomerular filtration rate did not change significantly.”
Human trialafter switching from azilsartan6 monthsn = 27
Journal of clinical hypertension (Greenwich, Conn.)
Blood pressure
downin humans1
1 study
Blood pressure
downin humans1
Sacubitril + valsartan decreases blood pressure in humans after switching from azilsartan (144 ± 13/77 ± 13 to 128 ± 10/71 ± 9 mmHg).
“After 6 months, significant reductions in mean morning HBP (144 ± 13/77 ± 13 to 128 ± 10/71 ± 9 mmHg)”
Human trialafter switching from azilsartan170±47 mg/day6 monthsn = 27
Journal of clinical hypertension (Greenwich, Conn.)
Uric acid
downin humans1
1 study
Uric acid
downin humans1
Sacubitril + valsartan decreases uric acid in humans (MD -0.41 mg/dL, 95% CI -0.80 to -0.01).
“uric acid (MD -0.41 mg/dL; 95% CI -0.80 to -0.01)”
Reviewn = 11,093
BMC cardiovascular disorders
LDL cholesterol
downin humans1
1 study
LDL cholesterol
downin humans1
Sacubitril + valsartan decreases LDL cholesterol in humans (MD -12.1 mg/dL, 95% CI -20.37 to -3.82).
“lowdensity lipoprotein (MD -12.1 mg/dL; 95% CI - 20.37 to -3.82)”
Reviewn = 11,093
BMC cardiovascular disorders
Cognitive function
no changein humans1
1 study
Cognitive function
no changein humans1
Sacubitril + valsartan showed no clear effect on cognitive function in humans (heart failure with reduced ejection fraction).
“without adverse effects on cognitive performance.”
Human trialheart failure with reduced ejection fraction6 monthsn = 61
Internal and emergency medicine
Physical function
upin humans1
1 study
Physical function
upin humans1
Sacubitril + valsartan improves physical function in humans (heart failure with reduced ejection fraction).
“After 6 months follow-up, we observed a significant improvement in humoral and functional parameters of CGA, renal function, NTpro-BNP levels and echocardiographic parameters.”
Human trialheart failure with reduced ejection fraction6 monthsn = 61
Internal and emergency medicine
Total heart failure hospitalizations or cardiovascular death
downin humans1RR 0.69
1 study
Total heart failure hospitalizations or cardiovascular death
downin humans1RR 0.69
Sacubitril + valsartan decreases total heart failure hospitalizations or cardiovascular death in humans (class 3 frailty (FI >=0.311) in HFpEF) (RR 0.69, 95% CI 0.51-0.95).
“and 0.69 [95% CI: 0.51-0.95]), respectively (Pinteraction = 0.23).”
Human trialclass 3 frailty (FI >=0.311) in HFpEF
Sacubitril/Valsartan and Frailty in Patients With Heart Failure and Preserved Ejection Fraction
Journal of the American College of Cardiology
Pulse pressure
downin humans1
1 study
Pulse pressure
downin humans1
Sacubitril + valsartan decreases pulse pressure in humans (elderly Asian patients with systolic hypertension; compared with olmesartan).
“reductions from baseline in other BP and PP assessments were significantly greater with sacubitril/valsartan”
Human trialelderly Asian patients with systolic hypertension; compared with olmesartan100–400 mg once daily10 weeksn = 588
American journal of hypertension
Systolic blood pressure
downin humans1
1 study
Systolic blood pressure
downin humans1
Sacubitril + valsartan decreases systolic blood pressure in humans (elderly Asian patients with systolic hypertension; compared with olmesartan) (22.71 vs. 16.11 mm Hg; P < 0.001).
“sacubitril/valsartan provided superior msSBP reductions vs. olmesartan (22.71 vs. 16.11 mm Hg, respectively; P < 0.001)”
Human trialelderly Asian patients with systolic hypertension; compared with olmesartan100–400 mg once daily10 weeksn = 588
American journal of hypertension
All 28Fewer
What is sacubitril + valsartan linked with?
8Studies link sacubitril + valsartan with 8 measures, most often glycemic outcomes (1 study), estimated glomerular filtration rate (1) and composite cardiovascular events (1).
Glycemic outcomes
mixedin humans1
1 study
Glycemic outcomes
mixedin humans1
Sacubitril + valsartan is associated with glycemic outcomes in humans (Hypertension and type 2 diabetes; compared with conventional antihypertensive therapy).
“sacubitril/valsartan was associated with better blood pressure control and favorable renal and glycemic outcomes.”
HumansHypertension and type 2 diabetes; compared with conventional antihypertensive therapy200-400 mg/dayn = 212
Frontiers in cardiovascular medicine
Estimated glomerular filtration rate
upin humans1
1 study
Estimated glomerular filtration rate
upin humans1
Sacubitril + valsartan is associated with estimated glomerular filtration rate in humans (Hypertension and type 2 diabetes; compared with conventional antihypertensive therapy).
“The ARNI group had higher eGFR and more favorable renal and metabolic markers at 6 and 12 months”
HumansHypertension and type 2 diabetes; compared with conventional antihypertensive therapykidney200-400 mg/day6 and 12 monthsn = 212
Frontiers in cardiovascular medicine
Composite cardiovascular events
downin humans1HR 0.59
1 study
Composite cardiovascular events
downin humans1HR 0.59
Sacubitril + valsartan is associated with composite cardiovascular events in humans (HR 0.59, 95% CI 0.32–0.97; exploratory, unadjusted for multiple testing).
“In patients with uncontrolled baseline blood pressure (BP), ARNI was associated with a nominally lower risk of composite cardiovascular events”
HumansHypertension and type 2 diabetes with uncontrolled baseline blood pressure; exploratory subgroup analysis without multiple-testing adjustment200-400 mg/day
Frontiers in cardiovascular medicine
Blood pressure
downin humans1
1 study
Blood pressure
downin humans1
Sacubitril + valsartan is associated with blood pressure in humans (Hypertension and type 2 diabetes; compared with conventional antihypertensive therapy).
“At 6 months, greater reductions in systolic/diastolic blood pressure were observed in the ARNI group compared to conventional therapy”
HumansHypertension and type 2 diabetes; compared with conventional antihypertensive therapy200-400 mg/day6 monthsn = 212
Frontiers in cardiovascular medicine
Dementia-related adverse event reports
upin humans1
1 study
Dementia-related adverse event reports
upin humans1
Sacubitril + valsartan is associated with dementia-related adverse event reports in humans (Pharmacovigilance signal requiring prospective confirmation).
“exhibiting a potential association with dementia onset: Apixaban, Insulin glargine, Tafamidis, Insulin lispro, Sacubitril valsartan”
HumansPharmacovigilance signal requiring prospective confirmation
Drugs Associated with Dementia-Related Adverse Event Reports: A Real World Pharmacovigilance Study
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)
Transported treatment-effect hazard ratio
upin silico1HR 0.8
1 study
Transported treatment-effect hazard ratio
upin silico1HR 0.8
Sacubitril + valsartan is associated with transported treatment-effect hazard ratio in silico (HR 0.80→0.83).
“sacubitril/valsartan: HR 0.80→0.83)”
In silicoTransport from trial populations to a real-world heart failure target population; clinical endpoint not specified
AHA Scientific Sessions 2026 abstract
Hypotension
upin humans1
1 study
Hypotension
upin humans1
Sacubitril + valsartan raises the risk of hypotension in humans (heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF)).
“In contrast, sacubitril/valsartan substantially increased hypotension risk in HFmrEF/HFpEF patients.”
Reviewheart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF)
Frontiers in pharmacology
Systolic blood pressure
downin humans1
1 study
Systolic blood pressure
downin humans1
Sacubitril + valsartan is associated with systolic blood pressure in humans (Japanese patients with essential hypertension) (Systolic BP −15.6 mmHg; diastolic BP −6.1 mmHg).
“with significant mean reductions in systolic and diastolic BPs (-15.6 mmHg and -6.1 mmHg, respectively, p < 0.0001).”
HumansJapanese patients with essential hypertensionwithin 8 weeksn = 1,247
Hypertension research : official journal of the Japanese Society of Hypertension
Has sacubitril + valsartan been tested in people?
0 of 53 about agingYes: 5 trials and 11 observational studies in people have been published, and 53 trials are registered.
Approved
Jul 7, 2015Heart Failure, Chronic Heart Failure, left ventricular systolic dysfunction, cardiovascular death, hospitalization for heart failure, symptomatic heart failure
Nov 19, 2015Heart Failure, Chronic Heart Failure, Chronic Heart Failure With Reduced Ejection Fraction, left ventricular systolic dysfunction
May 26, 2016Heart Failure, Chronic Heart Failure, left ventricular systolic dysfunction
Apr 12, 2024Heart Failure, Chronic Heart Failure, left ventricular systolic dysfunction, cardiovascular death, hospitalization for heart failure, symptomatic heart failure
Repurposing
Phase 4Status unknown4 trials
Phase 4Status unknown5 trials
Phase 4Status unknown1 trial
Phase 4Recruiting1 trial
Phase 4Status unknown3 trials
Phase 4Terminated1 trial
All 30Fewer
Readouts due
- Apr 30, 2027
Stopped
NCT02787798TerminatedHeart failure
Today Entresto treatment has marketing authorization and is available for all patients, that is the reason why study was halted prematurely.
Who is developing sacubitril + valsartan?
2 companies: Novartis Pharmaceuticals and Viatris.
Trial sponsors
Novartis Pharmaceuticals Corporation
Company16 trialsPhase 413,645 people
Advanced Accelerator Applications
Company1 trialPhase 1/235 people
Company1 trialPhase 148 people
2 trialsPhase 4802 people
2 trialsPhase 4340 people
Sichuan Academy of Medical Sciences
1 trialPhase 4297 people
China National Center for Cardiovascular Diseases
1 trialPhase 4220 people
1 trialPhase 4200 people