Determinants of time to medication optimisation in heart failure with reduced ejection fraction: a real-world tertiary centre cohort

Background

Contemporary European Society of Cardiology (ESC) guidelines emphasise early initiation and rapid up-titration of the four pillars of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) [1]. Landmark trials have demonstrated that early initiation of all GDMT pillars at higher doses is associated with improved clinical outcomes [2]. Real-world implementation of guideline-recommended therapy remains heterogeneous, and factors influencing time to medication optimisation (TTMO) are incompletely understood.

Purpose

Evaluate real-world TTMO in patients with HFrEF and to identify clinical factors associated with delayed or accelerated optimisation of GDMT.

Methods

We conducted a retrospective observational chart review of 100 consecutive patients attending a tertiary-level heart failure unit in Ireland. TTMO was defined as the time from initial heart failure medication initiation to achievement of maximally tolerated doses of all four GDMT pillars.

A novel GDMT adherence score was used to quantify compliance with ESC recommendations: one point for prescription of each GDMT pillar, one additional point for each pillar at maximally tolerated or guideline-defined target dose, and four points for concurrent prescription of all four pillars (maximum score 12). Demographic characteristics, comorbidities, medication use, and adverse effects of therapy were recorded. Associations between clinical variables and TTMO were assessed using univariable linear regression analysis.

Results

Mean age was 69 ± 11.7 years, and 26% of patients were female. Median TTMO was 330 days. Multimorbidity (≥2 comorbid conditions) was present in 82% of the cohort.

A higher baseline GDMT score was associated with shorter TTMO (95% CI −71.1 to −17.6; p = 0.0014), figure 1. Greater comorbidity burden was associated with longer TTMO (95% CI 18.7 to 137.3; p = 0.0105), with a median TTMO of 202 days in patients with 0–1 comorbidity compared with 348 days in those with ≥2 comorbidities (figure 2).

Overall, 83% of patients experienced at least one adverse effect during GDMT optimisation, most commonly hypotension (54%), bradycardia (45%), and renal dysfunction (10%), frequently limiting dose escalation. 40% of patients achieved maximally tolerated doses of all four GDMT pillars, while only 3% achieved guideline-defined maximum doses. At final medication review, 92% received a beta-blocker, 89% an MRA, 90% an SGLT2 inhibitor, and 60% an ARNI.

Conclusion

In this real-world cohort of patients with HFrEF, TTMO was prolonged and strongly influenced by baseline GDMT intensity and comorbidity burden, although interpretation is limited by the retrospective, single-centre design. These findings support ESC guideline recommendations advocating early, comprehensive GDMT initiation to facilitate timely optimisation in routine clinical practice.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.