Authors

• Fran Rode — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0002-8787-2455
• Ana Jordan — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0001-5610-6259
• Ivan Zeljković — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0002-4550-4056
• Nikola Pavlović — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0001-9187-7681
• Ante Lisičić — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0002-4365-9652
• Aleksandar Blivajs — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0003-3404-3837
• Vanja Ivanović — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0001-6931-5404
• Jelena Kursar — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0001-8791-4910
• Danijela Grizelj — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0002-8298-7974
• Luka Antolković — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0002-5313-2213
• Domagoj Kobetić — Pakrac General Hospital and the Croatian Veterans Hospital, Pakrac, Croatia — ORCID: 0009-0000-2106-4933
• Ivan Skorić — University of Zagreb, Zagreb, Croatia — ORCID: 0000-0002-5201-2092
• Šime Manola — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0001-6444-2674
• Ivana Jurin — Dubrava University Hospital, Zagreb, Croatia — ORCID: 0000-0002-2637-9691

Keywords

heart failure with reduced ejection fraction, beta-blockers, SGLT2 inhibitors

DOI

Full Text

**Introduction:** Beta-blockers are one of the four major pillars of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF). The therapy has presented the best effects when up-titrated to evidence-based target doses. Despite their proven benefits, physicians have traditionally shown reluctance to up-titrate beta-blockers because of their negative inotropic and chronotropic effects. The effects of newly introduced sodium-glucose transporter 2 inhibitors (SGLT2I) in treating HFrEF might open more room for adequate beta-blockers up-titration (1). The goal of this study was to evaluate the up-titration practice, and impact of target doses of beta-blockers in patients with HFrEF receiving SGLT2I. **Patients and Methods:** This is a prospective cohort study involving patients with HFrEF receiving SGLT2I therapy. Up-titration to the evidence-based targets was examined. We compared the groups of patients receiving maximally titrated beta-blockers versus incompletely titrated. Primary outcome was composite of: 1) rehospitalization or revisit to emergency unit due to the heart failure; 2) all-cause death and major adverse cardiac events (MACE). Secondary outcomes were heart rate at rest, left ventricular ejection fraction, NT-proBNP and New York Heart Association (NYHA) status at 6 and 12 months of follow-up. Study endpoints were documented via telephone interviews, regular outpatient follow-up, or by electronic hospital records. **Results:** The study included 458 patients with median follow-up time of 365 (186-502) days. A total of 122 (26.6%) patients had maximally up-titrated beta-blockers. The results show adherence to maximal target doses of beta-blocker therapy significantly reduces hazard of death or MACE compared to not using maximal doses of beta-blocker (factor 0.43). Hazard reduction was not statistically significant for composite of rehospitalization or revisit to emergency unit due to HF. Maximal doses of beta-blockers did not result in a significant decrease in resting heart rate. **Conclusion:** Our real-world data have highlighted the prevalence of incomplete titration of beta-blockers. Although it has been shown that evidence-based target dosing of beta-blockers reduce death and MACE, there is still room for improvement with up-titrating beta-blockers in in eligible patients.

Literature

1. Niriayo YL, Asgedom SW, Demoz GT, Gidey K. Treatment optimization of beta-blockers in chronic heart failure therapy. Sci Rep. 2020 September 28;10(1):15903. https://doi.org/10.1038/s41598-020-72836-4