Sacubitril/valsartan and Quality of Life Assessed Using the EuroQol 5-Dimension 3-Level Questionnaire Level Sum Score (EQ-5D-3L-LSS) in Patients with HFrEF and HFmrEF/HFpEF

Objectives To investigate the EQ-5D-3L Level Sum Score (LSS) in patients with heart failure (HF) and reduced (HFrEF) and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and the effect of sacubitril/valsartan on this score using patient-level data from the PARADIGM-HF and PARAGON-HF trials. Methods The LSS was calculated by summating the 3 levels (1-3) for each of the 5 domains (minimum sum score=5; maximum sum score=15). Patient characteristics and outcomes were compared across LSS tertiles (T1-T3) at baseline. Cox models were used to evaluate the primary endpoint (first HF hospitalization or cardiovascular death) according to tertiles of LSS. Changes in LSS severity at 8 months were analysed using ordinal logistic regression models to estimate the effect of sacubitril/valsartan versus enalapril or valsartan. Results Of 13,195 patients, 12,974 had a baseline LSS. Compared to lower LSS, patients with higher (worse) scores were older, more often women and White, and had more comorbidities and more severe HF. At 8 months, patients assigned to sacubitril/valsartan experienced more improvement and less worsening of LSS versus the comparator: OR:1.16 (95%CI: 1.08-1.24). Sacubitril/valsartan also reduced the risk of the primary outcome across LSS tertiles: T1: HR: 0.87 (95%CI: 0.75-1.00); T2: 0.80 (95%CI: 0.71-0.90); T3: 0.87 (95%CI: 0.77-0.97); Pinteraction=0.59. Higher LSS was independently associated with a greater risk of the primary endpoint, and the achieved LSS at 8 months may be more strongly associated with subsequent outcomes. Conclusions Sacubitril/valsartan significantly reduced the risk of HF events and improved health status across the LSS spectrum in HFrEF and HFmrEF/HFpEF. Clinical Trial Registration https://www.clinicaltrials.gov. Unique identifiers: NCT01920711 (PARAGON-HF), NCT01035255 (PARADIGM-HF).