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

Gianluigi Savarese, Takuya Kishi, Orly Vardeny, Samuel Adamsson Eryd, Johan Bodegård, Lars H. Lund, Marcus Thuresson, Biykem Bozkurt

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59 Scopus citations


Background: Guidelines recommend early initiation of multiple guideline-directed medical therapies (GDMTs) to reduce mortality/rehospitalization in patients with heart failure and reduced ejection fraction. Understanding GDMT use is critical to improving clinical practice. Objectives: This study sought to describe GDMT use in Japan, Sweden, and the United States in contemporary real-world settings. Methods: EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational cohort study using routine-care databases. Patients initiating any GDMT within 12 months of a hospitalization for heart failure (hHF) discharge were included. Dapagliflozin (the only sodium-glucose cotransporter-2 inhibitor approved at study onset), sacubitril/valsartan, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were considered separately. Doses and discontinuation were assessed in the 12 months following initiation. Target dose was defined as ≥100% of the guideline-recommended dose. Results: Overall, 266,589 patients were included. Mean times from hHF to GDMT initiation were longer for novel GDMTs (dapagliflozin or sacubitril/valsartan) than for other GDMTs: 39 and 44 vs 12 to 13 days (Japan), 44 and 33 vs 22 to 31 days (Sweden), and 33 and 19 vs 18 to 24 days (United States). Pooled across countries, proportions of patients who discontinued therapy (not including switches from ACE inhibitor or ARB to sacubitril/valsartan) within 12 months were 23.5% (dapagliflozin), 26.4% (sacubitril/valsartan), 38.4% (ACE inhibitors), 33.4% (ARBs), 25.2% (beta-blockers), and 42.2% (MRAs). Corresponding target dose achievements were 75.7%, 28.2%, 20.1%, 6.7%, 7.2%, and 5.1%, respectively. Conclusions: Initiation of novel GDMTs is delayed compared with other GDMTs. Few patients received target doses of GDMTs requiring uptitration. Persistence was higher for dapagliflozin than other GDMTs.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalJACC: Heart Failure
Issue number1
StatePublished - Jan 2023

Bibliographical note

Funding Information:
EVOLUTION HF is funded by AstraZeneca. Dr Savarese has received grants from AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Merck, Novartis, Pharmacosmos, and Vifor; and personal fees from AstraZeneca, Cytokinetics, Medtronic, Pharmacosmos, Roche, Servier, and Vifor. Dr Kishi has reported that he has no relationships relevant to the contents of this paper to disclose. Dr Vardeny has received personal or institutional research support from AstraZeneca. Drs Adamsson Eryd and Bodegård are employees of AstraZeneca. Dr Lund has received grant support, lecture fees, and consulting fees from AstraZeneca. Dr Thuresson is an employee of Statisticon, which has received funding from AstraZeneca. Dr Bozkurt has received consulting fees from Amgen, AstraZeneca, Bristol Myers Squibb, scPharmaceuticals, Baxter, Sanofi, Relypsa, Vifor, Roche, and Boehringer Ingelheim; has served on the steering committees of Relypsa and Renovacor; has served on a Clinical Event Committee for Abbott Pharmaceuticals; and has served on the Data Safety Monitoring Board for LivaNova Pharmaceuticals.

Funding Information:
Medical writing support was provided by Caitlin Edgell, PhD, and Stéphane Pintat, PhD, of Oxford PharmaGenesis (Oxford, United Kingdom) and was funded by AstraZeneca. Medical writing support included aiding with the preparation of the manuscript outline and subsequent drafts, collating and incorporating author comments, and preparing tables and figures.

Publisher Copyright:
© 2022 The Authors


  • guideline-directed medical therapy
  • real-world data
  • treatment discontinuation
  • treatment initiation
  • treatment persistence

PubMed: MeSH publication types

  • Observational Study
  • Journal Article
  • Research Support, Non-U.S. Gov't


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