GDMT prescription and dosing in contemporary, real-world HF population


ESC Heart Failure 2024 - The Dutch TITRATE-HF study showed that 44% of the HFrEF patients were treated with quadruple GDMT, of whom 1% was on all 4 target doses.

This summary is based on the presentation of Jasper Brugts, MD, PhD (Rotterdam, the Netherlands) at the ESC Heart Failure Congress 2024 - Contemporary guideline-directed medical therapy sequencing and titration in de novo, worsening, and chronic heart failure: first data from the TITRATE-HF study.

Introduction and methods

The 2021 ESC HF Guidelines recommend initiating treatment with 4 drug classes (RAASi/ARNI, beta-blocker (BB), MRA, and SGLT2 inhibitor) in all patients with HFrEF, with rapid uptitration and close follow-up in the first 6 weeks following HF hospitalization (the latter is listed in the 2023 Focused Update). Yet, information on real-world implementation of these recommendations is lacking.

The TITRATE-HF study is an ongoing, prospective, longitudinal, observational, multicenter HF registry study conducted in the Netherlands that investigates GDMT sequencing and titration patterns in real-world HF patients, thereby also aiming to identify implementation barriers. From June 2022 through February 2024, 4288 patients with LVEF <50% (HFrEF, HFmrEF, or HF with improved EF) from 48 hospitals were consecutively included in the study. Of them, 1732 presented with de novo HF (confirmed HF diagnosis ≤3 months prior to enrollment), 2240 with chronic HF (diagnosis ≥6 months prior), and 316 with worsening HF (diagnosis ≥6 months prior plus HF-related event).

Main results

  • Of the patients with de novo HF, 49.1% were already prescribed ≥1 GDMT drug classes for indications other than HF, such as hypertension (ACEi, ARNI, BB), coronary artery disease (BB), and atrial rhythm disorder (BB).
  • Among patients with chronic or worsening HFrEF (n=1860), 44.4% were on quadruple GDMT, with 0.8% at the target dose for all drug classes. Reasons for non-GDMT prescription were side effects (such as hypotension, hyperkalemia, worsening renal function, or urogenital infection), intolerance, contraindication, or other or not specified reason. 
  • The prescription rate for quadruple therapy in patients with chronic or worsening HFrEF varied from 20% to 79% across participating sites with ≥50 enrolled patients. At a dedicated HF outpatient clinic, 47.2% of these patients received quadruple therapy (RAASi, BB, MRA, SGLT2 inhibitor) compared with 32.5% at a general cardiology outpatient clinic (P<0.001).
  • Of the patients admitted for worsening HF, 73.9% had a change in diuretic prescription or dosing, 34.2% were started on an SGLT2 inhibitor, and 13.7% were switched from ACEi/ARB to ARNI.


This first analysis of the TITRATE-HF study showed that in a Dutch, contemporary, real-world HF population, 44% of the HFrEF patients were treated with quadruple GDMT, of whom 1% was on all 4 target doses. According to Dr. Brugts, the findings indicate the implementation of treatment with new drug classes takes time. He also pointed out that the GDMT prescription rate among HFrEF patients has improved in the Netherlands over the past decade. In the CHECK-HF registry study, which ran from 2013 through 2016, 39% were on triple therapy (RAASi, BB, MRA).

- Our reporting is based on the information provided at the ESC Heart Failure Congress 2024 -

The findings of this study were simultaneously published in Eur J Heart Fail.

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