Physicians' Academy for Cardiovascular Education

Recent hospitalizations for HF may identify HFpEF at higher risk that may benefit from ARNI

Prior Heart Failure Hospitalization, Clinical Outcomes, and Response to Sacubitril/Valsartan Compared with Valsartan in HFpEF

Literature - Vaduganathan M, Claggett BL, Desai AS et al., - J Am Coll Cardiol. 2019.

Introduction and methods

The period shortly after hospitalization for heart failure (HF) is a high-risk window for recurrent clinical events, including rehospitalization or death [1,2]. The angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan was found to be safe when initiated during hospitalization for HF with reduced ejection fraction (HFrEF) and it led to short-term reductions in natriuretic peptides (NP) [3] and clinical events [4], when compared with enalapril.

Limited therapeutic progress is seen for patients with preserved ejection fraction (HFpEF). Recently, modest reductions in the risk of total HF hospitalizations (HFH) and CV death was seen upon treatment with sacubitril/valsartan compared with valsartan monotherapy in ambulatory patients with HFpEF in the PARAGON-HF trial (HR: 0.87, 95%CI: 0.75-1.005, P=0.058)[5]. Clinical trials in HFpEF are challenged by the disease heterogeneity and confounding of HF diagnosis by comorbid medical illness. In PARAGON-HF, patients could be screened during hospitalization for HFpEF (but not during an episode of acute decompensated HF). Recent hospitalization may identify patients with congestion, who are at higher risk of disease progression. Their phenotype may be more modifiable.

This posthoc analysis of PARAGON-HF evaluated whether the risk of clinical events and response to sacubitril/valsartan varies in relation to whether their HFH was closer in time or not or to the burden (number of visits) of HFH in the prior year. PARAGON-HF included patients ≥50 years of age with chronic HF, LVEF ≥45% within the 6 months prior to screening, NYHA class II-IV symptoms, elevated NP levels evidence of structural heart disease and use of diuretics for at least 30 days. Median follow-up was 35 months (IQR: 30-41), in which 1083 first primary endpoints (HFH and CV death) occurred and 1903 total primary endpoints.

Main results


This post-hoc analysis shows that HFpEF patients who have recently been hospitalized, and particularly those with multiple recent HFHs, have a 2 – 3-fold higher risk of rehospitalization and CV death. A gradient was seen in relative treatment effects with sacubitril/valsartan with declining treatment effect if the hospitalization was more remote in time. Timing of prior HFH did not affect the rate of patients who discontinued drug due to adverse events.


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Find this article online at J Am Coll Cardiol.

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