Physicians' Academy for Cardiovascular Education

Initiation, uptitration, and discontinuation of HFrEF drugs after hospitalization for HF

Heart Failure Drug Treatment-Inertia, Titration, and Discontinuation: A Multinational Observational Study (EVOLUTION HF)

Literature - Savarese G, Kishi T, Vardeny O, et al. - JACC Heart Fail. 2022 Sep 7;S2213-1779(22)00508-X [Online ahead of print]. doi: 10.1016/j.jchf.2022.08.009

Introduction and methods


During and immediately after hospitalization for HF (HHF), patients are at high risk of death and rehospitalization [1,2]. For patients recently diagnosed with HFrEF, current European and American guidelines on HF recommend early initiation of multiple guideline-directed medical therapies (GDMTs) and subsequent uptitration of some of these drugs [3-5]. However, these recommendations are often not adequately implemented due to, for example, real or perceived risk of side effects or insufficient reimbursement.

Aim of the study

To improve clinical practice, the authors sought to describe the initiation GDMTs after HHF and their uptitration and discontinuation in contemporary real-world settings.



The EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) study is a multinational, observational, longitudinal cohort study that aims to provide insights into GDMT use after HHF. For this purpose, secondary data are extracted from well-established electronic health records or claims data sources in Japan, Sweden, and the USA. Patients who were new users of ≥1 GDMT for HFrEF within 12 months of an HHF discharge were included (n=266,589). Although LVEF measurements were not available, all patients were assumed to have an HFrEF indication based on the required initiation of ≥1 GDMT for HFrEF.

Initiation, uptitration, and discontinuation of the following drugs were assessed: (1) novel GDMTs: dapagliflozin (this was the only SGLT2i approved for HFrEF at study onset, in 2020) and sacubitril/valsartan; and (2) other GDMTs: ACEis, ARBs, beta-blockers, and MRAs. Doses and discontinuation were assessed in the 12 months following initiation of the GDMT. For the titration and discontinuation analyses (n=104,022 patients), only dose optimization after hospital discharge was considered. The target dose was defined as ≥100% of the dose recommended by local guidelines and a low dose as <50% of the recommended dose.

Main results

Time to GDMT initiation after recent HHF

GDMT initiation during treatment journey

GDMT titration and discontinuation


In HFrEF patients who had been hospitalized for HF in Japan, Sweden, or the USA, novel GDMTs (dapagliflozin and sacubitril/valsartan) were initiated later than the other GDMTs (ACEis, ARBs, beta-blockers, and MRAs). A year after GDMT initiation, most patients on dapagliflozin received the guideline-recommended dose, while few were prescribed the target dose of a GDMT that required uptitration. The discontinuation rate for dapagliflozin tended to be lower than that for the other GDMTs.


Show references

Find this article online at JACC Heart Fail.

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