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Sacubitril/valsartan for heart failure with reduced left ventricular ejection fraction

A retrospective cohort study

Sacubitril/Valsartan bei Herzinsuffizienz mit verminderter linksventrikulärer Ejektionsfraktion

Eine retrospektive Kohortenstudie

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Abstract

Background

The combination drug sacubitril/valsartan was reported to be superior to enalapril in reducing all-cause death, cardiovascular mortality, and heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction (HFREF) with NYHA class II–IV.

Methods

Our retrospective cohort study aimed to assess the effects of sacubitril/valsartan in addition to a beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients with NYHA class II–III HF vs. conventional therapy (ACE inhibitor or angiotensin II receptor blocker added to a beta-blocker plus an MRA) administered to a control group of HFREF patients with comparable clinical features. In both groups, treatment was supplemented by a loop diuretic, usually furosemide, at variable doses. The primary outcomes were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia, and worsening renal function.

Results

Mortality at 6 months was 6.8% in patients taking sacubitril/valsartan vs. 34% in those on conventional therapy (odds ratio [OR] = 0.14; 95% CI: 0.04–0.49). Moreover, there was a 4.5% rate of HF hospitalizations in the sacubitril/valsartan group vs. 59% in the control group (OR = 0.03; 95% CI: 0.01–0.14). Safety outcomes were comparable in the two groups, although hypotension (systolic blood pressure < 100 mm Hg) was found in 15.9% of patients in the sacubitril/valsartan group vs. 5.7% in the control group (OR = 3.14; 95% CI: 0.94–10.55).

Conclusion

Sacubitril/valsartan offered strong protection against all-cause death and HF hospitalizations at 6 months without any significant side effects. To validate this efficacious molecule, further postmarketing observational studies, focusing mainly on hypotension and angioedema are warranted.

Zusammenfassung

Hintergrund

Das Kombinationspräparat Sacubitril/Valsartan erwies sich der Literatur zufolge der Gabe von Enalapril als überlegen – hinsichtlich der Senkung der Gesamtmortalität, der kardiovaskulären Mortalität und der Rate herzinsuffizienzbedingter stationärer Aufnahmen bei Patienten mit Herzinsuffizienz und verminderter linksventrikulärer Ejektionsfraktion (HFREF), wobei es sich um eine Herzinsuffizienz der Klasse II–IV nach New York Heart Association (NYHA) handelte.

Methoden

Ziel der vorliegenden retrospektiven Kohortenstudie war es, die Wirkung von Sacubitril/Valsartan zusätzlich zu einem Betablocker und einem Mineralokortikoidrezeptorantagonisten (MRA) in einer Gruppe von Patienten mit HFREF bei Herzinsuffizienz der Klasse II–III nach NYHA zu untersuchen – im Vergleich zu konventioneller Therapie (ACE-Hemmer oder Angiotensin-II-Rezeptorblocker plus Betablocker plus MRA), die einer Kontrollgruppe von HFREF-Patienten mit vergleichbaren klinischen Merkmalen verabreicht wurde. In beiden Gruppen wurde die Therapie ergänzt durch ein Schleifendiuretikum, gewöhnlich Furosemid, in variabler Dosierung. Primäre Endpunkte waren Gesamtmortalität und stationäre Aufnahme wegen Herzinsuffizienz. Sicherheitsbezogene Endpunkte waren symptomatische Hypotonie, Angioödem, Hyperkaliämie und Verschlechterung der Nierenfunktion.

Ergebnisse

Die Mortalität betrug nach 6 Monaten 6,8 % bei Patienten unter Sacubitril/Valsartan vs. 34 % in der Gruppe mit konventioneller Therapie (Odds Ratio, OR = 0,14; 95 %-Konfidenzintervall, 95 %-KI: 0,04–0,49). Darüber hinaus lag die Rate an stationären Aufnahmen wegen Herzinsuffizienz bei 4,5 % in der Gruppe mit Sacubitril/Valsartan vs. 59 % in der Kontrollgruppe (OR = 0,03; 95 %-KI: 0,01–0,14). Die sicherheitsbezogenen Endpunkte waren in beiden Gruppen vergleichbar, jedoch fand sich eine Hypotonie (systolischer Blutdruck < 100 mm Hg) bei 15,9 % der Patienten in der Gruppe mit Sacubitril/Valsartan vs. 5,7 % in der Kontrollgruppe (OR = 3,14; 95 %-KI: 0,94–10,55).

Schlussfolgerung

Mit Sacubitril/Valsartan ließ sich ohne signifikante Nebenwirkungen nach 6 Monaten eine deutliche Wirkung in Bezug auf die Gesamtmortalität und die Rate stationärer Aufnahmen wegen Herzinsuffizienz erzielen. Um dieses wirksame Molekül zu validieren, sind weitere Postmarketing-Beobachtungsstudien erforderlich, die den Fokus hauptsächlich auf die Hypotonie und das Angioödem richten.

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Authors and Affiliations

  1. Preventive Cardiology and Rehabilitation Unit, DSB 29 “S. Gennaro dei Poveri Hospital”, via S.Gennaro dei Poveri 25, 80136, Napoli, Italy

    R. De Vecchis MD & C. Ariano

  2. Division of Geriatrics, Casa di Cura “Sollievo della Sofferenza”, viale Cappuccini 2, 71013, San Giovanni Rotondo, Italy

    C. Ariano

  3. Division of Geriatrics, Clinic “S. Maria del Pozzo”, via Pomigliano 40, 80049, Somma Vesuviana, Italy

    G. Di Biase

  4. Mid-German Heart Center, Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle, Ernst Grube-Straße 40, 06120, Halle, Germany

    M. Noutsias

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Correspondence to R. De Vecchis MD.

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Conflict of interest

R. De Vecchis, C. Ariano, and G. Di Biase declare that they have no competing interests. M. Noutsias has received grants by 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.

For this type of study (retrospective study) formal consent by Ethical Committees is not required. This article does not contain any studies with animals performed by any of the authors.

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De Vecchis, R., Ariano, C., Di Biase, G. et al. Sacubitril/valsartan for heart failure with reduced left ventricular ejection fraction. Herz 44, 425–432 (2019). https://doi.org/10.1007/s00059-017-4671-1

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