Heart failure with reduced ejection fraction in Sweden: patient adherence and persistence to quadruple pharmacotherapy prescription

Abstract Background and Aims Real-world uptake of heart failure with reduced ejection fraction (HFrEF) treatments relies on physician prescriptions but also on patient adherence. This study assessed implementation of, patient adherence and persistence with quadruple HFrEF therapy in the contemporary setting, and associations with morbidity/mortality. Methods Patients with HFrEF enrolled in the Swedish Heart Failure Registry between January 2016 and December 2023 were included. Using pharmacy refills, patients with ≥80% proportion of days covered were categorized as adherent and with dispensations at 12 ± 2 months post-index as persistent. Results In 35 215 patients with HFrEF [median age 74 (interquartile range 64–80) years; 28% female], use of all four HFrEF foundational therapies increased between 2016 and 2023: in 2023, 93% used beta-blockers (BB), 95% renin–angiotensin–system inhibitors (RASi)/angiotensin receptor–neprilysin inhibitors (ARNi), 73% mineralocorticoid receptor antagonists (MRA), 83% sodium–glucose co-transporter 2 inhibitors (SGLT2i), and 60% quadruple therapy. The proportion of patients who were adherent and persistent, respectively, to BB was 95% and 90%, RASi/ARNi 95% and 89%, MRA 90% and 77%, SGLT2i 94% and 86%, and quadruple therapy 85% and 67%. Good adherence and persistence for BB, RASi/ARNi, and MRA and good adherence for SGLT2i were independently associated with lower heart failure hospitalization/cardiovascular death. Conclusions By 2023, use of quadruple therapy reached ∼60%, being mostly limited by lower adoption of MRA (∼73%). Patient adherence to foundational therapies was high and appeared associated with better prognosis. These data suggest that improvements in the uptake of and adherence to quadruple HFrEF pharmacotherapy are achievable in real-word heart failure care, although suboptimal dosing and frequent discontinuations remain important areas of further implementation.