Magnitude of and outcome associated with inappropriate prescribing in heart failure with reduced ejection fraction: an analysis of 50 348 patients from the Swedish Heart Failure Registry

AIMS: Patients with heart failure and reduced ejection fraction (HFrEF) are frequently exposed to polypharmacy, placing them at risk of potentially inappropriate prescribing (PIP)-defined as use of drugs that may worsen HF prognosis, counteract guideline-directed medical therapies (GDMTs), or increase harmful interactions. The prevalence, predictors, and prognostic impact of PIP in HFrEF remain unclear. Therefore, the aim was to investigate the prevalence, predictors, and outcomes of PIP in a large, real-world HFrEF population. METHODS: Patients with HFrEF enrolled in the Swedish HF Registry (2005-20) were included. The European Society of Cardiology position statement of PIP-HFrEF was used to retrieve PIP from the National Prescribed Drugs Register. Associations between PIP and outcomes were assessed using Cox proportional hazards and negative binomial regression for recurrent events. RESULTS: Among 50 348 patients (median age 75 years, 29% female), 23 583 (47%) were prescribed ≥1 PIP. The most frequent agents were neuroleptics (29%), systemic steroids (10%), and NSAIDs (6%). Independent predictors included rheumatoid arthritis [odds ratio (OR) 3.39; 95% CI, 2.92-3.94], depression (OR 3.06; 95% CI, 2.74-3.42), chronic obstructive pulmonary disease (OR 1.86; 95% CI, 1.76-1.98), and gout (OR 1.48; 95% CI, 1.35-1.62). Patients on PIP were less likely to receive GDMT. Presence of ≥1 PIP was independently associated with increased 3-year risk of HF death (HR, 1.13; 95% CI, 1.04-1.23), all-cause and cardiovascular death, first and recurrent HF hospitalizations. CONCLUSION: Nearly half of HFrEF patients received PIP medications, particularly those with multimorbidity, which was independently associated with worse outcomes and less GDMT use. Our data underscore the need for targeted strategies to reduce inappropriate prescribing in HFrEF.