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Use of sacubitril/valsartan in patients with heart failure in primary care in Germany: the AURORA-HF noninterventional study

Anwendung von Sacubitril/Valsartan bei Patienten mit Herzinsuffizienz in der Primärversorgung in Deutschland: die nichtinterventionelle AURORA-HF-Studie

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Abstract

Background

Sacubitril/valsartan (Sac/Val) is the first angiotensin receptor-neprilysin inhibitor indicated for symptomatic chronic heart failure (HF) with reduced ejection fraction (HFrEF). Given most patients with HF in Germany are managed by general practitioners, AURORA-HF investigated the baseline characteristics and 1‑year follow-up of patients starting Sac/Val in primary care in Germany.

Methods

This was a prospective, multicenter, observational study, with all treatment decisions independent of participation. The only inclusion criteria were adults (age ≥ 18 years) with symptomatic HFrEF. The study comprised four groups, depending on therapy on entry: initiation of (1) Sac/Val or (2) other HF therapy; and no change in HF regimen that (3) included or (4) did not include Sac/Val. Baseline data were captured for all groups; 1‑year follow-up was recorded in groups 1 and 2.

Results

Of 1278 patients in the baseline analyses, 513 (40.1%) had newly started Sac/Val (449 [87.5%] completing the 1‑year follow-up), 265 (20.7%) had newly started other HF regimens (245, 92.5%) with 1‑year follow-up, while 249 with Sac/Val (19.5%) and 251 without Sac/Val (19.6%) patients had unchanged therapies. Patients treated with Sac/Val had a higher New York Heart Association (NYHA) class at baseline and more often a left ventricular ejection fraction (LVEF) < 35%. The only baseline parameter significantly correlating with Sac/Val discontinuation during the 1‑year follow-up was diabetes mellitus (odds ratio: 2.44; 95% confidence interval: 1.14–5.24). In the Sac/Val group, 30.7% of patients were in NYHA class I/II on study entry, improving to 51.0% at 1‑year follow-up. In the no Sac/Val group, the corresponding rates of NYHA I and II classes were 49.8% and 58.2%, respectively. The overall adverse event profile of Sac/Val was good, with only 6.0% patients experiencing serious adverse events leading to permanent discontinuation.

Conclusion

In patients with symptomatic HFrEF treated in primary care, the group in whom Sac/Val was initiated was characterized by a higher NYHA class and lower LVEF compared to patients in whom Sac/Val was not initiated. Sac/Val was well tolerated, with a high proportion completing 1 year of therapy.

Zusammenfassung

Hintergrund

Sacubitril/Valsartan (Sac/Val) ist der erste Angiotensin-Rezeptor-Neprilysin-Inhibitor mit Indikation für symptomatische Herzinsuffizienz (HF) mit verminderter Ejektionsfraktion (HFrEF). Angesichts dessen, dass die meisten Patienten mit HF in Deutschland von Hausärzten behandelt werden, wurden in der AURORA-HF-Studie die Merkmale zu Studienbeginn und nach einem Jahr Follow-up bei Patienten untersucht, bei denen eine Therapie mit Sac/Val in der Primärversorgung in Deutschland begonnen wurde.

Methoden

Bei der vorliegenden Studie handelt es sich um eine prospektive Multizenter-Beobachtungs-Studie, wobei alle Therapieentscheidungen unabhängig von der Studienteilnahme waren. Einzige Einschlusskriterien waren Erwachsene (Alter ≥ 18 Jahre) mit symptomatischer HFrEF. Die Studie umfasst 4 Gruppen, je nach Therapie bei Studieneintritt: Beginn mit (1) Sac/Val oder (2) anderer HF-Therapie; und keine Änderung des HF-Regimes, das Sac/Val (3) einschloss oder (4) nicht einschloss. Ausgangsdaten wurden für alle Gruppen erhoben, das Follow-up nach einem Jahr nur für die Gruppen 1 und 2.

Ergebnisse

Von 1278 Patienten in der Baseline-Analyse hatten 513 (40,1%) neu mit einer Sac/Val-Therapie begonnen (449; 87,5% vollendeten die einjährige Nachbeobachtung), 265 (20,7%) hatten bei einjährigem Follow-up neu mit anderen HF-Regimen begonnen (245; 92,5%), während bei 249 Patienten mit Sac/Val (19,5%) und bei 251 ohne Sac/Val (19,6%) keine Änderung der Therapie erfolgte. Patienten, die mit Sac/Val behandelt wurden, wiesen eine höhere Klasse gemäß New York Heart Association (NYHA) zu Beginn auf und häufiger eine linksventrikuläre Ejektionsfraktion (LVEF) < 35%. Der einzige Ausgangsparameter, der signifikant mit einer Unterbrechung der Sac/Val-Gabe während der einjährigen Nachbeobachtung korrelierte, war Diabetes mellitus (Odds Ratio: 2,44; 95%-Konfidenzintervall: 1,14–5,24). In der Sac/Val-Gruppe waren 30,7% der Patienten bei Studieneintritt in NYHA-Klasse I/II, was sich nach einjährigem Follow-up auf 51,0% verbesserte. In der Gruppe ohne Sac/Val betrugen die entsprechenden Raten der NYHA-Klasse I und II 49,8% bzw. 58,2%. Das gesamte Nebenwirkungsprofil von Sac/Val war gut, denn nur 6,0% der Patienten wiesen schwere Nebenwirkungen auf, die zum dauerhaften Absetzen der Therapie führten.

Schlussfolgerung

Bei Patienten mit symptomatischer HFrEF, die in der Primärversorgung behandelt wurden, zeichnete sich die Gruppe, bei der eine Sac/Val-Therapie begonnen worden war, durch eine höhere NYHA-Klasse und eine geringere LVEF im Vergleich zu Patienten aus, bei denen keine Sac/Val-Therapie begonnen worden war. Sac/Val wurde gut vertragen, ein großer Anteil der Patienten vollendete ein Jahr dieser Therapie.

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Acknowledgements

The authors would like to thank the investigators and patients at the investigative sites for their support of this study.

Funding

Writing support was provided by David Young of Young Medical Communications and Consulting Ltd. This study was funded by Novartis Pharma GmbH.

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Authors and Affiliations

  1. Institut für Herzinfarktforschung, Klinikum Ludwigshafen, Bremserstraße 79, 67063, Ludwigshafen, Germany

    Uwe Zeymer

  2. Institut für Herzinfarktforschung Ludwigshafen, Ludwigshafen, Germany

    Uwe Zeymer

  3. Novartis Pharma GmbH, Nuremberg, Germany

    Robert Groves & Stephan Hupfer

Authors
  1. Uwe Zeymer
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  2. Robert Groves
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  3. Stephan Hupfer
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Corresponding author

Correspondence to Uwe Zeymer.

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Conflict of interest

U. Zeymer declares the receipt of payment or honoraria for lectures, presentations, speakers bureaus: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Novartis, Pfizer, and Sanofi. R. Groves is an employee of Novartis Pharma GmbH, the funder of the study. S. Hupfer is an employee of Novartis Pharma GmbH, the funder of the study, and holds shares in Novartis.

For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case.

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Supplementary Information

Table S1 Main outcomes during the 1‑year follow-up period (full analysis aet)

59_2024_5248_MOESM2_ESM.docx

Table S2 Overview of adverse events in the sacubitril/valsartan-initiated treatment group (adverse events in ≥ 2.5% patients; and serious adverse events, related adverse events, adverse events resulting in discontinuation and deaths in ≥ 1% of patients)

Table S3 Concomitant medication during the study by substance class and study arm (FAS)

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Zeymer, U., Groves, R. & Hupfer, S. Use of sacubitril/valsartan in patients with heart failure in primary care in Germany: the AURORA-HF noninterventional study. Herz (2024). https://doi.org/10.1007/s00059-024-05248-z

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