Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) comprising ARNI/RAAS inhibitors, β-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors—markedly improves survival and reduces hospitalizations. However, real-world data indicate persistent underuse, particularly in patients with chronic kidney disease (CKD), where renal impairment often limits the prescription of three of these four therapeutic pillars despite their nephroprotective potential.

This study aimed to evaluate the impact of CKD on GDMT prescription patterns, in-hospital outcomes, and one-year mortality in a real-world Eastern European HFrEF cohort.

We conducted a retrospective observational cohort study including adults with heart failure (LVEF ≤40%) who were hospitalized for acute decompensated heart failure in Cardiology Department of the County Emergency Hospital Timișoara, Romania, between January 2022 and December 2023. Baseline demographic, clinical, and laboratory data were extracted from medical records. Discharge therapy was categorized according to the number of GDMT pillars prescribed (0–4). A predefined 90-day post-discharge exposure period was used to evaluate GDMT optimization, followed by a 12-month follow-up to assess all-cause mortality. Patients were stratified according to the number of GDMT pillars received (0–1, 2, 3, or 4). Kaplan–Meier curves were used to estimate survival probability, with group comparisons by log-rank test. Multivariable Cox proportional hazards models identified independent predictors of mortality, adjusting for age, sex, baseline ejection fraction, renal function, and comorbidities.

A two-tailed p-value <0.05 was considered statistically significant. All analyses were performed using R (version X.X.X).

The study inculded 439 patients (mean age: 70 ± 12 years; mean LVEF: 29 ± 8%). CKD was present in 34.2% of patients, diabetes in 37%, and prior stroke in 18.2%. Patients with CKD had a nearly 3-fold higher risk of acute kidney injury (AKI) compared with non-CKD patients (21.8% vs. 8.3%; OR 2.9, 95% CI 1.6–5.3; p = 0.0002), while in-hospital mortality (3.6% overall; 4% in CKD) and hyperkalemia rates were similar between groups.

At discharge, CKD patients were less likely to receive RAAS inhibitors (2.4% vs. 5.3%, p < 0.0001), MRAs (64% vs. 76.8%, p = 0.005), or ARNI (12% vs. 19%, p = 0.07), whereas β-blocker and SGLT2 inhibitor use did not differ significantly.

At discharge, GDMT adoption improved between 2022 and 2023, with the proportion of patients receiving ≥3 therapeutic pillars rising from 22% to 31%, largely driven by wider use of SGLT2 inhibitors. However, at one-year reassessment, treatment patterns showed a marked decline in the intensity of GDMT. Therapy de-escalation occurred in 187 patients (57%), whereas only 11 patients (3%) were up titrated and 44 (13%) remained unchanged. The percentage of patients receiving three or more GDMT pillars dropped from 31% at the start to 18% at the end. Among individual drug classes, RAAS inhibitors (27% to 13%) and MRAs (72% to 19%) showed the steepest reductions, while β-blocker (91% to 78%) and SGLT2 inhibitor (30% to 10%) use also declined significantly.

Survival increased progressively with the number of GDMT pillars prescribed (log-rank p < 0.01) (Figure 1).

Figure 1. Survival by GDMT pillars (0–1–2–3–4)

            At one-year follow-up (n = 328), 39% of patients had died. CKD and diabetes emerged as independent predictors of mortality in multivariate Cox analysis. Kaplan–Meier analysis further demonstrated stepwise reductions in one-year survival across CKD/DM subgroups. The lowest survival was observed in patients presenting both CKD and diabetes (log-rank p < 0.01; Figure 2).

Figure 2. Kaplan–Meier survival curves according to the presence CKD and DM at one-year follow-up.