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. 2025 Jun;12(3):1703-1713.
doi: 10.1002/ehf2.15188. Epub 2025 Feb 19.

Up-titration of medication in patients with new-onset heart failure with and without atrial fibrillation

Arietje J L Zandijk  1 , Bernadet T Santema  1 , Friso D J Inkelaar  1 , Martje H L van der Wal  1 , Janke Warink-Riemersma  1 , Michiel Rienstra  1 , Adriaan A Voors  1
Affiliations

Up-titration of medication in patients with new-onset heart failure with and without atrial fibrillation

Arietje J L Zandijk et al. ESC Heart Fail. 2025 Jun.

Abstract

Aims: Differences in guideline-directed medical therapy (GDMT) and clinical outcomes have been observed between heart failure (HF) patients with atrial fibrillation (AF) versus those in sinus rhythm. This study evaluated the effects of up-titration of HF therapies, consisting of beta-blockers, angiotensin-converting-enzyme inhibitors (ACEis)/angiotensin-receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRAs), in patients with new-onset HF with and without AF.

Methods: Among 607 patients with new-onset HF (<3 months) from a specialized nurse-led HF clinic in the Netherlands, 187 (31%) patients had AF, and 420 (69%) patients were in sinus rhythm at baseline electrocardiogram. After an up-titration period of 9 months, achieved doses and reasons for not reaching target doses were documented.

Results: Patients with AF were older, less likely to have ischaemic heart disease and had higher baseline N-terminal B-type natriuretic peptide levels (all P < 0.05). Left ventricular ejection fraction (LVEF) at baseline was similar between patients with AF and those in sinus rhythm (37% vs. 36%, P = 0.453). Prescription of GDMT was comparable between patients with AF and those in sinus rhythm, except for a lower ACEi/ARB prescription and higher use of diuretics in patients with AF (79% vs. 86%; P = 0.038; 86% vs. 59%, P < 0.001, respectively, compared with sinus rhythm). Up-titration to guideline-recommended target doses of beta-blocker, ACEi/ARB and MRA therapy was similar between patients with and without AF (31% vs. 24%, P = 0.096; 32% vs. 40%, P = 0.098; 23.7% vs. 30.5%, P = 0.125, respectively). Reasons for not further up-titrating to recommended target doses were consistent across patients with AF and sinus rhythm. LVEF improvement of ≥5% and ≥10% after up-titration was more common in patients with AF than those in sinus rhythm (67% vs. 53%, P = 0.017; 48% vs. 36%, P = 0.043). Achieving target doses of ACEi/ARB and MRA therapies was associated with lower mortality and HF rehospitalization rates at 3 years in both patients with AF and those in sinus rhythm.

Conclusions: In patients with new-onset HF, up-titration to recommended doses of GDMT was similar in patients with and without AF, but was associated with a greater improvement in LVEF in patients with AF.

Keywords: atrial fibrillation; guideline‐directed medical therapy; heart failure; left ventricular ejection fraction; up‐titration.

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Conflict of interest statement

None declared.

Figures

Figure 1
Figure 1
Association between reaching target dose (≥100%) of beta‐blockers, ACEi/ARB and MRA and the primary outcomes (i.e., all‐cause mortality and combined endpoint of mortality and HF rehospitalization). The results are stratified by AF and sinus rhythm. Reference category 0% target dose. P for interaction with AF is shown. AF, atrial fibrillation; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HR, hazard ratio.
See this image and copyright information in PMC

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