Temporal trends in incident heart failure medication use and clinical characteristics across guideline eras: a retrospective cohort study

Background Over the past decade, the management of incident heart failure (HF) has changed considerably with the introduction of angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Although these therapies are now incorporated into clinical guidelines, their uptake in everyday clinical practice across guideline eras remains unclear. Purpose We aimed to examine trends in patient characteristics and discharge medication use across successive HF guideline eras. Methods We conducted a multicenter retrospective cohort study of consecutive patients hospitalized with a confirmed diagnosis of heart failure (HF) across participating centers in Greece. To focus on incident cases, we excluded patients with a previously documented history of HF. The cohort was divided into three time periods reflecting major updates in HF treatment guidelines and the introduction of key therapies: pre-2016 (before the incorporation of angiotensin receptor–neprilysin inhibitors [ARNI] into routine practice), 2016–2021 (following the introduction of ARNI), and 2021 onward (after sodium–glucose cotransporter-2 inhibitors [SGLT2i] became guideline-recommended therapy). We analyzed demographics, comorbidities, presenting symptoms, laboratory findings, left ventricular ejection fraction (LVEF) categories, and discharge medications using descriptive statistics. Continuous variables were summarized as mean (SD) or median [IQR], and categorical variables as frequencies and percentages. Results The final cohort included 3,700 patients (mean age 74.4 ± 12 years; 61% male). Hypertension (49%), diabetes (36%), and coronary artery disease (28%) were common comorbidities. LVEF classification revealed 55% with HFrEF, 19% with HFmrEF, and 26% with HFpEF. Overall discharge prescription rates were 44.2% for RAS inhibitors, 8.1% for ARNI, 58.6% for beta-blockers, 57.7% for mineralocorticoid receptor antagonists (MRA), 9.4% for SGLT2i, and 73.1% for loop diuretics. Across eras, ARNI use increased from 4.1% in the pre-2016 era to 14.3% in 2021+, while SGLT2i utilization rose markedly to 42.3% in 2021+. Beta-blocker and MRA use also increased over time. In LVEF-stratified analyses, HFrEF patients had the highest uptake of RAS inhibitors (48.9%) and ARNI (13.2%), whereas HFpEF patients had the lowest utilization of disease-modifying therapies. Conclusions In this large real-world cohort, adoption of newer HF therapies increased across successive guideline eras, particularly for SGLT2 inhibitors. However, overall uptake of disease-modifying therapies remained modest, especially among patients with HFpEF. These findings highlight persistent gaps between guideline recommendations and real-world practice in contemporary heart failure management.