Exploring the impact of age and comorbidities on quality-of-life improvements with empagliflozin: findings from a broad European real-world population

Background The ESC guidelines recommend empagliflozin (EMP) for heart failure (HF) with reduced (HFrEF), mildly reduced (HFmrEF), and preserved ejection fraction (HFpEF), after pivotal trials demonstrated reduced cardiovascular death, fewer HF hospitalizations, and improved quality of life (QoL). ESC guidelines identify QoL maintenance as a core goal in HF therapy, yet it is unclear if QoL benefits are consistent across key subgroups, since HF, type 2 diabetes mellitus (T2D), chronic kidney disease (CKD), and age collectively influence symptoms, progression, and patient-reported outcomes. Purpose Using data from 6 European countries (Bulgaria, Czech Republic, Hungary, Poland, Romania, Switzerland), we assessed QoL changes and, as a secondary objective, shifts in New York Heart Association (NYHA) class, in EMP-initiated patients with HF stratified by age (<65 vs ≥65), CKD status, and T2D status. Methods EMP-Activity is a multinational, prospective, non-interventional study enrolling 3,309 patients with chronic HF, receiving EMP as standard care. Patients were assessed at baseline and at 24 weeks. QoL was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ); a ≥5-point increase in the Overall Summary Score (OSS) was defined as clinically meaningful improvement, while a ≥5-point decrease was defined as worsening. All analyses are descriptive and exploratory. Results A total of 3,108 patients had evaluable KCCQ-OSS scores at baseline and week 24. The mean increase was 17.3±18.4 points in patients <65 years (N=900), and 16.1±19.1 points in those ≥65 years (N=2,208), with clinically meaningful improvement in 76.3% and 71.6%, respectively (Fig. 1). HF patients with T2D (N=530) had a slightly larger mean gain than those without T2D (N=2,578) (17.5±19.4 vs 16.3±18.7 points; 75.1% vs 72.5% improved, respectively) (Fig. 2A-B). HF patients with CKD (N=196) improved less than those without CKD (N=2,912) (9.2±15.8 vs 17.0±19.0 points; 56.1% vs 74.1% improved, while 13.3% vs 7.5% worsened, respectively) (Fig. 2C-D). Improvements in clinical status were seen across all subgroups; the proportion of patients in NYHA class I/II increased by approx. 15% from baseline to week 24 across all subgroups, but by only approx. 10% in patients with CKD. ConcLusions EMP achieved clinically meaningful QoL improvements in the majority of HF patients across all analysed subgroups, accompanied by consistent enhancements in NYHA class, underscoring its broad applicability. Improvements in QoL across age groups suggest consistent benefits among younger and older patients in routine practice. Improvements were slightly larger in patients with T2D, possibly due to dual glucose-lowering and haemodynamic benefits of EMP. In contrast, CKD markedly attenuated QoL improvements and doubled the risk of decline, suggesting that CKD may modify QoL trajectories under standard care.