, Volume 44, Issue 6, pp 534–540 | Cite as

Cognitive performance of patients with chronic heart failure on sacubitril/valsartan

A retrospective cohort study
  • R. De VecchisEmail author
  • C. Ariano
  • G. Di Biase
  • M. Noutsias
Original articles



Sacubitril, a neprilysin inhibitor in the combination molecule sacubitril/valsartan, slows down degradation of endogenous natriuretic peptides, thereby enhancing their beneficial cardiovascular effects. However, sacubitril might also promote neuronal dysfunction and cognitive impairment in patients with chronic heart failure (CHF) treated with sacubitril/valsartan, due to possible neprilysin inhibition at the level of Central Nervous System.


A retrospective cohort study was undertaken to detect the effects exerted by sacubitril/valsartan on cognitive function in CHF patients. The patients’ clinical data were examined for information provided in the Mini-Mental State Examination (MMSE), which was routinely administered during clinical visits at two centers from 15 March to 31 October 2017. Patients in the sacubitril/valsartan group had a clinical history of at least 3 months of continuous sacubitril/valsartan administration. The control group comprised CHF patients on conventional therapy not taking sacubitril/valsartan. In the between-group comparison, patients were matched for mean age, educational level, sex, NYHA class, and comorbidities. In the present retrospective study only patients in NYHA class II-III were enrolled.


The mean MMSE score was 22.72 ± 2.68 (mean ± standard deviation [SD]) in the sacubitril/valsartan group (n = 51 patients) vs. 21.96 ± 2.73 (mean ± SD) in the control group (n = 51; p = 0.1572, independent samples t-test). Thus, a similar mild-to-moderate impairment in cognitive performance was found in the comparison between the two groups.


In our study, we did not find any evidence of the alleged harmful influence of sacubitril/valsartan on cognitive function. Patients taking sacubitril/valsartan for at least 3 months had similar mean MMSE scores to control subjects.


Neprilysin inhibitor Cardiac insufficiency Adverse drug events Mini-Mental State Examination Neurologic manifestations 

Kognitive Leistungsfähigkeit unter Sacubitril/Valsartan bei Patienten mit chronischer Herzinsuffizienz

Eine retrospektive Kohortenstudie



Sacubitril, ein Neprilysin-Inhibitor in dem Kombinationsmolekül Sacubitril/Valsartan, verlangsamt den Abbau endogener natriuretischer Peptide und verstärkt somit deren günstige kardiovaskuläre Wirkungen. Jedoch könnte Sacubitril auch neuronale Funktionsstörungen und kognitive Beeinträchtigungen bei Patienten mit chronischer Herzinsuffizienz begünstigen, die mit Sacubitril/Valsartan behandelt werden.


Es wurde eine retrospektive Kohortenstudie durchgeführt, um die Wirkungen von Sacubitril/Valsartan auf die kognitiven Funktionen bei Patienten mit chronischer Herzinsuffizienz zu untersuchen. Dazu wurden die klinischen Daten der Patienten hinsichtlich Informationen zum Mini-Mental-Status-Test (MMST) ausgewertet, der routinemäßig in 2 Zentren bei der klinischen Visite zwischen 15. März und 31. Oktober 2017 durchgeführt wurde. Die Patienten in der Sacubitril/Valsartan-Gruppe wiesen eine klinische Vorgeschichte mit mindestens 3 Monate langer kontinuierlicher Gabe von Sacubitril/Valsartan auf. In der Kontrollgruppe befanden sich Patienten mit chronischer Herzinsuffizienz unter konventioneller Therapie ohne Sacubitril/Valsartan. Im Vergleich zwischen den beiden Gruppen wurden die Teilnehmer in Bezug auf Durchschnittsalter, Bildungsgrad, Geschlecht, Klasse gemäß NYHA (New York Heart Association) und Komorbiditäten abgeglichen.


Der durchschnittliche Wert im MMST betrug 22,72 ± 2,68 (Mittelwert, MW, ± Standardabweichung, „standard deviation“, SD) in der Sacubitril/Valsartan-Gruppe (n = 51 Patienten) vs. 21,96 ± 2,73 (MW ± SD) in der Kontrollgruppe (n = 51; p = 0,1572, t‑Test für unabhängige Stichproben). Somit stellte sich im Vergleich der beiden Gruppen eine ähnliche, leicht- bis mittelgradige Beeinträchtigung der kognitiven Leistungsfähigkeit heraus.


In der vorliegenden Studie fanden die Autoren keinen Beleg für die vermutete schädliche Wirkung von Sacubitril/Valsartan auf die kognitive Leistungsfähigkeit. Bei Patienten, die Sacubitril/Valsartan seit mindestens 3 Monaten einnahmen, waren die Durchschnittswerte im MMST ähnlich wie bei den Probanden der Kontrollgruppe.


Neprilysin-Inhibitor Herzinsuffizienz Unerwünschte Arzneimittelnebenwirkungen Mini-Mental-Status-Test Neurologische Manifestationen 



All authors certify that no funding has been received for the conduct of this study and/or preparation of this manuscript.

Compliance with ethical guidelines

Conflict of interest

R. DeVecchis, C. Ariano, and G. DiBiase declare that they have no competing interests. M. Noutsias has received grants from the Deutsche Forschungsgemeinschaft (DFG) through the Sonderforschungsbereich Transregio 19 “Inflammatory Cardiomyopathy” (SFB TR19) (TP B2), and by the University Hospital Giessen and Marburg Foundation Grant “T Cell Functionality” (UKGM 10/2009). M. Noutsias has been consultant to the IKDT (Institute for Cardiac Diagnosis and Therapy GmbH, Berlin) 06/2004-06/2008, and has received honoraria for presentations and/or participated in advisory boards from AstraZeneca, Bayer, Boehringer Ingelheim, Fresenius, Miltenyi Biotech, Novartis, Pfizer, and Zoll.

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  • R. De Vecchis
    • 1
    Email author
  • C. Ariano
    • 2
  • G. Di Biase
    • 3
  • M. Noutsias
    • 4
  1. 1.Preventive Cardiology and Rehabilitation UnitDSB 29 “S. Gennaro dei Poveri Hospital”NaplesItaly
  2. 2.Division of Geriatrics“Casa Sollievo della Sofferenza” HospitalSan Giovanni RotondoItaly
  3. 3.Division of GeriatricsClinic “S. Maria del Pozzo”Somma VesuvianaItaly
  4. 4.Mid-German Heart Center, Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital HalleMartin Luther University Halle-WittenbergHalleGermany

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