Abstract Background Clinical trials have shown that dapagliflozin, a sodium–glucose cotransporter-2 inhibitor (SGLT-2i), reduces cardiovascular mortality and worsening heart failure (HF). Adoption of new therapies has historically been slow despite robust evidence. Furthermore, treatment profiles of patients in real-world settings are scarce. Purpose EVOLUTION HF is a multinational study programme that aims to describe clinical characteristics and treatment patterns among patients initiating dapagliflozin for HF with reduced ejection fraction (HFrEF) in routine clinical practice. Methods The EVOLUTION HF primary data study programme consists of prospective, observational, descriptive studies of new users of dapagliflozin for HFrEF in 12 countries (Italy, Portugal, UK and the Central and Eastern Europe and Baltic [CEEBA] region [Bulgaria, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania and Slovenia]). Patients with type 1 diabetes or prior SGLT-2i treatment were excluded. Clinical characteristics were obtained from electronic health records. A total of 2170/2555 (85%) patients were enrolled from November 2021 to November 2023; 1736 patient profiles were assessed using descriptive statistics in this interim analysis. Results In total, 256, 228, 125 and 1127 new dapagliflozin users were analysed from Italy, Portugal, the UK and the CEEBA region, respectively (Table 1). Across the 12 countries, mean patient age in the studies was 65–70 years. Patients were predominantly male (67–76%) and generally had HF with an ischaemic aetiology (35–56%) and New York Heart Association functional class II (52–85%). Mean left ventricular ejection fraction in the studies was 29–32% and estimated glomerular filtration rate was 61–77 mL/min/1.73m². Hypertension and atrial fibrillation were common comorbidities. Mean time between HF diagnosis and dapagliflozin initiation in the studies was 23–52 months. Background therapy included angiotensin receptor-neprilysin inhibitors (36–72%), angiotensin receptor blockers (4–12%) and angiotensin-converting enzyme inhibitors (9–33%). At 6 and 12 months after dapagliflozin initiation, respectively, treatment discontinuation rates across the CEEBA region were 5.22% (59/1131) and 4.66% (50/1072). Conclusions The EVOLUTION HF primary data study programme provides novel insights into clinical characteristics and treatment patterns in patients with HFrEF initiating dapagliflozin in real-world practice across a broad European population. At dapagliflozin initiation, a large proportion of patients were receiving other HF therapeutics, suggesting dapagliflozin is one of the later therapies to be initiated. Indeed, this study identified a substantial delay (23–52 months) in dapagliflozin initiation following HF diagnosis. Treatment discontinuation rates following dapagliflozin initiation were also low, reinforcing the findings of the EVOLUTION HF secondary data studies.