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.