Application of guideline-directed medical therapy in patients with HFrEF in the Netherlands

In patients with heart failure (HF) in the Netherlands, the use of guideline-directed medical therapy (GDMT) is relatively high, as reported in the first cross-sectional results of the prospective TITRATE-HF study. Among patients with HF with reduced ejection fraction (HFrEF), 44% were treated with quadruple GDMT, with 1% receiving all 4 target doses. A large variation in HF medication use was observed between sites.

In all patients with HFrEF, the 2021 ESC Guidelines for HF recommend treatment with 4 drug classes: renin‐angiotensin system inhibitors/angiotensin receptor-neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors [1]. Rapid up-titration and close follow-up in the first 6 weeks following HF hospitalisation is also recommended, based on recent findings of the STRONG-AF trial [2]. Dr Jasper Brugts (Erasmus University Medical Center, the Netherlands) explained that the ongoing TITRATE-HF study aimed to longitudinally study GDMT sequencing and titration patterns in real-world HF patients, to assess the extent to which guideline recommendations have been implemented.

Between June 2022 and February 2024, 4,288 participants were consecutively enrolled with left ventricular EF <50% (HFrEF, HF with mid-range EF, or HF with improved EF) from 48 Dutch medical centres. Of these, 1,732 participants presented with de novo HF, 2,240 with chronic HF, and 316 with worsening HF. The median age was 71 years, 29% were women, and the median EF was 35%.

Dr Brugts and colleagues observed that 44% of participants with chronic and worsening HFrEF were prescribed quadruple therapy (see also Figure). However, only 0.8% in this group achieved the target dose for all 4 drug classes. Reasons for not applying GDMT were adverse events (such as hypotension, hyperkalaemia, or worsening renal function), intolerance, contraindication, or other reasons, often unknown.

In addition, there were large variations in prescription of HF therapy between different sites, as well as between general cardiology and dedicated HF outpatient clinics. The prescription rate for quadruple therapy in participants with chronic or worsening HFrEF ranged from 20% to 79%. At general cardiology outpatient clinics, 32.5% of participants received quadruple therapy, compared with 47.2% at dedicated HF outpatient clinics.

Among participants admitted for worsening HF, 73.9% had a change in diuretic prescription or dosing, 34.2% initiated an SGLT2 inhibitor, and 13.7% switched from an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker to an angiotensin receptor-neprilysin inhibitor.

Figure: Percentage of patients with chronic and worsening HFrEF using GDMT [3]



ARNI, angiotensin receptor-neprilysin inhibitor; BB, beta blocker; GDMT, guideline-directed medical therapy; MRA, mineralocorticoid receptor antagonist; RASi, renin‐angiotensin system inhibitor; SGLT2i, sodium-glucose cotransporter-2 inhibitor.

Dr Brugts observed that significant gaps in GDMT use and dosing remain in patients with HFrEF. He added that the implementation of treatment with new drug classes takes time, as the results of this study illustrate.

1. 
   
   1. McDonagh TA, et al. Eur J Heart Fail. 2022;24:4–131.
   2. Mebazaa A, et al. Lancet. 2022;400:1938–52.
   3. Brugts J, et al. Contemporary guideline-directed medical therapy sequencing and titration in de novo, worsening, and chronic heart failure: first data from the TITRATE-HF study. Late breaking clinical trials: Drugs and disease management, Heart Failure 2024, 11–14 May, Lisbon, Portugal.

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Posted on 16 July 2024