Statin Therapy and Outcomes in Heart Failure with Mildly Reduced Ejection Fraction

BACKGROUND: This study investigates the association of statin therapy and prognosis in heart failure with mildly reduced ejection fraction (HFmrEF). While statins are routinely prescribed in patients with cardiovascular disease, their prognostic impact in HFmrEF remains unclear. METHODS: Consecutive HFmrEF patients hospitalized at the University Medical Centre Mannheim between 2016 and 2022 were retrospectively included. Endpoints were assessed based on the prescription of statin therapy at discharge in all patients with an indication for statin treatment, as well as stratified by ischemic vs. non-ischemic cardiomyopathy and in the setting of primary vs. secondary prevention. The primary endpoint was all-cause mortality at 30 months (median follow-up), key secondary endpoint was HF-related rehospitalization. RESULTS: Among 1,885 HFmrEF patients with a statin indication, 74% were discharged on a statin (atorvastatin: 64%). Statin use was associated with lower 30-month all-cause mortality (24.3% vs. 41.6%; log rank p=0.001), persisting after multivariable adjustment (adjusted hazard ratio (aHR)=0.704; 95% confidence interval (CI) 0.563-0.879; p=0.002) and propensity score matching. Subgroup analyses showed significantly lower long-term mortality with statin use in ischemic cardiomyopathy (aHR=0.596; 95% CI 0.438-0.811; p=0.001) and in primary (aHR=0.279; 95% CI 0.131-0.593; p=0.001) or secondary prevention settings (aHR=0.752; 95% CI 0.583-0.969; p=0.027), but not in non-ischemic cardiomyopathy (aHR=0.908; 95% CI 0.576-1.430; p=0.676). There was no association with the risk of HF-related rehospitalization (13.2% vs. 15.5%; log rank p=0.202). CONCLUSION: Statin therapy was associated with a significantly decreased risk of long-term all-cause mortality in patients with HFmrEF.