Newly diagnosed heart failure with reduced ejection fraction: timing, sequencing, and titration of guideline-recommended medical therapy

Abstract Background and Aims Despite guidelines recommending rapid initiation and up-titration of Guideline-recommended medical therapy (GRMT) for heart failure (HF) with reduced ejection fraction (HFrEF), its feasibility in daily practice remains unclear. TITRATE-HF studies the feasibility of rapid GRMT implementation in de novo HFrEF patients, investigating titration patterns and identifying barriers to effective treatment. Methods This analysis focuses on the de novo HFrEF patients included in the TITRATE-HF study, an ongoing prospective HF registry conducted in 48 Dutch hospitals. A detailed logbook for each GRMT drug class was recorded, from diagnosis to six months, including initiations, dose adjustments, discontinuations, and reasons for changes. Results The study included 1508 de novo HFrEF patients (median age: 70 years [inter-quartile ranges, IQR 62–77]; 31% women; median left ventricular ejection fraction: 30% [IQR 25–35]). At 6 weeks, 46% of patients were using quadruple therapy. Within 6 weeks post-HFrEF diagnosis, 50% of patients were prescribed quadruple therapy at some point, with 84% remaining on it after 180 days. At 6 months, 66.3% of patients were prescribed quadruple therapy, but only 1.3% achieved target doses for all four drug classes. While side effects accounted for 20%–37% of cases where target doses were not reached, a large proportion was attributed to physicians accepting suboptimal doses. Drug titrations occurred frequently in the first 60 days after diagnosis, fading afterwards. Discontinuation rates for angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, angiotensin receptor–neprilysin inhibitors, beta-blocker, mineralocorticoid receptor antagonists, and sodium–glucose cotransporter 2 inhibitors were 13%, 11%, 9%, 9%, 11%, and 9%, respectively, primarily due to side effects or intolerances. Rechallenging these drug classes was successful in over 83% of patients. Conclusions The TITRATE-HF study demonstrates that rapid initiation of GRMT for HFrEF is feasible in real-world clinical practice. Nonetheless, our results highlight the urgency for a proactive approach and ongoing dose titration of pharmacological therapy beyond the initial first months to fully optimize treatment.