Trial reportCardiovascular therapeutics2016
Pharmacodynamic and Pharmacokinetic Profiles of Sacubitril/Valsartan (LCZ696) in Patients with Heart Failure and Reduced Ejection Fraction.
Trial report in Cardiovascular therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00913653 (An Open Label, Non-randomised Study to Explore Safety/Tolerability, Pharmacokinetics and Pharmacodynamics of LCZ696 in Patients With Stable Heart Failure), which is not on this map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open Label, Non-randomised Study to Explore Safety/Tolerability, Pharmacokinetics and Pharmacodynamics of LCZ696 in Patients With Stable Heart Failure
Who cites it
48 citing papers in PubMed, 79 citations in OpenAlex.
- Combined effects of ARNI and SGLT2 inhibitors in diabetic patients with heart failure with reduced ejection fraction.Scientific reports · 2021Trial
- Safety, Pharmacokinetics, and Pharmacodynamics of TD-0714, a Novel Potent Neprilysin Inhibitor in Healthy Adult and Elderly Subjects.Clinical and translational science · 2020Trial
- Pharmacodynamic interaction between intravenous nitroglycerin and oral sacubitril/valsartan (LCZ696) in healthy subjects.European journal of clinical pharmacology · 2018Trial
- Evaluation of Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild-to-Moderate Hypertension.Clinical pharmacology and therapeutics · 2018Trial
- Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension.Hypertension (Dallas, Tex. : 1979) · 2018Trial
- Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial.The lancet. Diabetes & endocrinology · 2017 · on this mapTrial
- Effects of heart failure pharmacotherapy on natriuresis and diuresis: A narrative review.Heart failure reviews · 2026Review
- Sacubitrilat exerts potent antiarrhythmic effects through activation of natriuretic peptide receptor-C.ESC heart failure · 2026Article
- Population Pharmacokinetics of Sacubitril/Valsartan in Patients with Heart Failure and End-Stage Renal Disease Undergoing Peritoneal Dialysis.Clinical pharmacokinetics · 2026Observational
- Dose optimization of sacubitril/valsartan in Chinese chronic heart failure patients: integration of physiologically based pharmacokinetic modeling and real-world data.Frontiers in pharmacology · 2026Article
- A sensitive green HPLC-fluorescence method for simultaneous analysis of sacubitril and valsartan in pure forms, pharmaceutical dosage form and human plasma.Scientific reports · 2025Article
- Divergent Electrophysiologic Effects of Sacubitril in Digitalis- and Pinacidil-Related Shortened Repolarization: Experimental Evidence for Harmful Effects of Digitalis Glycosides.Pharmaceutics · 2025Article
- Impact of Combined Treatment with ARNi and SGLT2i on Clinical and Echocardiographic Outcomes in Patients with CRT During Mid-term Period.Current cardiology reviews · 2025Article
- Sympathetic overactivation and catecholamine toxicity: mechanisms and therapeutic strategies for neurogenic heart injury following acute ischemic stroke.Frontiers in cardiovascular medicine · 2025Review
- Addition of Sacubitril/Valsartan to Mineralocorticoid Receptor Antagonist Therapy in Primary Aldosteronism: Effects on Plasma Aldosterone Concentration and Plasma Renin Activity.Journal of clinical medicine research · 2024Article
- Advances in the Insulin-Heart Axis: Current Therapies and Future Directions.International journal of molecular sciences · 2024Review
- Sacubitril/valsartan reduces proteasome activation and cardiomyocyte area in an experimental mouse model of hypertrophy.Journal of molecular and cellular cardiology plus · 2024Article
- The concentration of maternal sacubitril/valsartan transferred into human milk is negligible.Frontiers in public health · 2024Article
- Severe Refractory Vasoplegic Shock Syndrome after OPCABG Successfully Treated with Hydroxycobalamin: A Case Report and Review of the Literature.Journal of clinical medicine · 2023Review
- Effect of sacubitril/valsartan on natriuretic peptide in patients with compensated heart failure.Heart and vessels · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsConcomitant renin-angiotensin-aldosterone system blockade and natriuretic peptide system enhancement may provide unique therapeutic benefits to patients with heart failure and reduced ejection fraction (HFrEF). This study assessed the pharmacodynamics and pharmacokinetics of LCZ696 in patients with HFrEF.
methodsThis was an open-label, noncontrolled single-sequence study. After a 24-h run-in period, patients (n = 30) with HFrEF (EF ≤ 40%; NYHA class II-IV) received LCZ696 100 mg twice daily (bid) for 7 days and 200 mg bid for 14 days, along with standard treatment for heart failure (HF) (except angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs]).
resultsOn Day 21, significant increases were observed in the plasma biomarkers indicative of neprilysin and RAAS inhibition (ratio-to-baseline: cyclic guanosine monophosphate [cGMP], 1.38; renin concentration and activity, 3.50 and 2.27, respectively; all, P < 0.05). Plasma NT-proBNP levels significantly decreased at all the time points on Days 7 and 21; plasma aldosterone and endothelin-1 levels significantly decreased on Day 21 (all, P < 0.05). Following administration of LCZ696, the Cmax of sacubitril (neprilysin inhibitor prodrug), LBQ657 (active neprilysin inhibitor), and valsartan were reached within 0.5, 2.5, and 2 h. Between 100- and 200-mg doses, the Cmax and AUC0-12 h for sacubitril and LBQ657 were approximately dose-proportional while that of valsartan was less than dose-proportional.
conclusionsTreatment with LCZ696 for 21 days was well tolerated and resulted in plasma biomarker changes indicative of neprilysin and RAAS inhibition in patients with HF. The pharmacokinetic exposure of the LCZ696 analytes in patients with HF observed in this study is comparable to that observed in the pivotal Phase III study.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.