Related Experiment Video
Updated: Aug 26, 2025
A Surgical Model of Heart Failure with Preserved Ejection Fraction in Tibetan Minipigs
Published on: February 18, 2022
Heart Failure Drug Treatment-Inertia, Titration, and Discontinuation: A Multinational Observational Study (EVOLUTION
Gianluigi Savarese1, Takuya Kishi2, Orly Vardeny3
1Cardiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden; Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.
Insights
Guideline-directed medical therapies (GDMTs) for heart failure are often delayed, especially newer treatments. Few patients reach target doses, though persistence is higher for dapagliflozin.
Area of Science:
- Cardiology
- Pharmacology
- Public Health
Background:
- Heart failure with reduced ejection fraction (HFrEF) guidelines emphasize early use of guideline-directed medical therapies (GDMTs) to improve outcomes.
- Understanding real-world GDMT utilization is crucial for enhancing clinical practice and patient management.
Purpose of the Study:
- To analyze the initiation patterns, dosing, and discontinuation of GDMTs in patients with heart failure across Japan, Sweden, and the United States.
- To compare the real-world use of novel GDMTs (dapagliflozin, sacubitril/valsartan) versus traditional therapies.
Main Methods:
- The EVOLUTION HF study utilized real-world, secondary data from routine care databases.
- Included patients initiated GDMT within 12 months post-hospitalization for heart failure (hHF).
- Assessed initiation times, adherence to target doses (≥100% of guideline dose), and 12-month discontinuation rates for dapagliflozin, sacubitril/valsartan, ACE inhibitors, ARBs, beta-blockers, and MRAs.
Main Results:
- Initiation of novel GDMTs (dapagliflozin, sacubitril/valsartan) was significantly delayed compared to traditional GDMTs across all countries.
- Achievement of target doses was low for most GDMTs, particularly for MRAs (5.1%) and ARBs (6.7%).
- Persistence rates at 12 months were highest for dapagliflozin (76.5%) compared to other GDMTs, excluding switches.
Conclusions:
- Real-world initiation of novel GDMTs for heart failure is suboptimal and delayed.
- Uptitration to target doses remains a significant challenge, with low achievement rates across most GDMT classes.
- Dapagliflozin demonstrated higher persistence compared to other GDMTs, suggesting potential benefits in long-term adherence.
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.
More Related Videos
09:20Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
14:35Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs
Published on: April 17, 2021
Related Concept Videos
01:26Heart Failure Drugs: Inotropic Agents
01:30Heart Failure V: Medical Management
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:22Heart Failure Drugs: β-Blockers
01:30Heart Failure IV: Classification and Diagnostic Evaluation
01:29Cardiomyopathy V: Interprofessional Care