Four pillars, uneven foundations: Impact of multimorbidity on guideline-directed medical therapy optimisation in a tertiary heart failure unit

Background

While guideline-directed medical therapy (GDMT) is foundational to heart failure management [1], real-world barriers, including multimorbidity with frailty and renal dysfunction, frequently limit optimal implementation in routine clinical practice.

Purpose

To evaluate real-world implementation and optimisation of GDMT in patients attending a tertiary heart failure unit, and to assess the impact of multimorbidity on achieved GDMT and left ventricular recovery.

Method

We performed a retrospective chart review of 100 consecutive patients with heart failure with reduced ejection fraction attending a tertiary heart failure unit in Ireland. Demographics, comorbidities, timing of diagnosis, and echocardiography were recorded.

A structured GDMT score was applied at first review and following optimisation: one point for prescription of each of the four pillars (ACE-i/ARB/ARNI, beta-blocker, mineralocorticoid receptor antagonist, SGLT2 inhibitor), one point for each agent at maximum or maximally tolerated dose, and four points for concurrent use of all four pillars (maximum 12 points). Changes in GDMT score, left ventricular ejection fraction (LVEF), and associations with multimorbidity were analysed.

Results

Mean age was 69 years ± 11.7. Twenty-six percent were female.

Overall, 83% of patients experienced at least one adverse effect during GDMT optimisation, most commonly hypotension (54%), bradycardia (45%), and renal dysfunction (10%). These adverse effects frequently limited dose escalation. Forty percent of patients achieved maximally tolerated doses of all four GDMT pillars, while only 3% achieved guideline-defined maximum doses.

Mean GDMT score increased from 6 at initial review (median 7) to 10 following optimisation (median 11), reflecting both increased prescription and dose up-titration. Sixty percent of patients were treated with an ARNI, with a median sacubitril/valsartan dose of 49/51 mg, while 28% received valsartan at a median dose of 80 mg.

Baseline mean LVEF was 27% (median 28%, SD 8%). Among the 80% of patients with repeat echocardiography, mean final LVEF was 42% (median 45%, SD 10%), representing a mean absolute improvement of 15%.

Multimorbidity, defined as two or more comorbid conditions, was present in 82% of the cohort. Advanced chronic kidney disease (52%), stratified by stage, was associated with significantly lower achieved GDMT scores compared with preserved or mildly impaired renal function (Figure 1). No other comorbidity demonstrated a significant association with achieved GDMT score or LVEF improvement.

Conclusion

In our cohort, most patients experienced treatment-limiting adverse effects, highlighting the gap between guideline-defined target doses and real-world tolerability. Renal dysfunction was the principal factor limiting achievement of optimal GDMT, highlighting the need for tailored strategies and structured models of care to optimise heart failure therapy in patients with chronic kidney disease.For image description, please refer to the figure legend and surrounding text.