Timing of angiotensin receptor-neprilysin inhibitor initiation in patients with heart failure and reduced ejection fraction: data from the Swedish heart failure registry
Authors: Stolfo D , Lund L , Benson L , Kack O , Lindberg F , Sinagra G , Dahlstrom U , Savarese G 
Published: November 2023

Abstract

Background
International guidelines recommend early and fast optimization of the treatments for heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilyisin inhibitor (ARNI) reduced mortality/morbidity in HFrEF. However, despite early initiation of ARNI appeared safe and of potential benefit in randomized clinical trials, their early implementation is underutilized in real world.

Purpose
To explore the timing, modalities and predictors of ARNI initiation in a large, nationwide cohort of patients with HFrEF.

Methods
ARNI-naïve patients with HFrEF (EF&lt;40%) registered in the SwedeHF Registry from January 2017 to December-2021 were included. Separate analyses were performed to investigate ARNI initiation in terms of 1) course of the disease (duration of HF &lt;6 vs ≥6 months), 2) location (in hospital vs out-patient), 3) time from a previous HF hospitalization (in-hospital or ≤14 days from discharge vs 15-90 days vs &gt;90 days or no initiation).

Results
Analysis 1) Among 16,086 HFrEF patients registered in SwedeHF during the study period, 63% had an HF duration &lt;6 months. 5% vs. 9% of patients with HF duration &lt;6 vs. ≥6 initiated ARNI, respectively. Younger age and referral to specialty care were more strongly associated with ARNI initiation whether HF duration was ≥6 or &lt;6 months. In-patient status, lower EF, and hypertension were independently associated with initiation only if HF duration was &lt;6 months, and HF nurse-led clinic and higher income only if HF duration was ≥6 months. Previous ACEi/ARB use was associated with more likely ARNI initiation in HF duration ≥6 months and less likely initiation in HF duration &lt;6 months (Figure). Analysis 2) Of 1,065 HFrEF patients who initiated ARNI, 30% started as in-patients. Analysis 3) Among 3,892 patients registered as in-patients in SwedeHF, 8% initiated ARNI ≤14 days from the hospital discharge, 4% between 15-90 days, and 88% &gt;90 days or did not initiate. Important independent predictors of earlier initiation (≤14 days) were a more recent registration in SwedeHF, follow-up in specialty care and HF nurse-led clinic, lower EF, worse New York Heart Association class, previous use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB), use of mineralocorticoid receptor antagonist, ICD/CRT, and higher income, whereas older age, higher mean arterial pressure, atrial fibrillation (AF), chronic obstructive pulmonary disease (COPD), and living alone where associated with lower likelihood.

Conclusions
In this nationwide HFrEF cohort ARNI were rarely initiated early at/after an HF hospitalization discharge, initiation was more likely in the out-patient setting and in the later course of the HF disease. Key patient characteristics associated with early initiation were linked with more severe HF and follow-up in dedicated HF care. Overall our data highlight a delayed initiation of ARNI therapy and claim for better implementation in the early stage of HF.Predictors of ARNI initiation