Background: This study investigates the association of statin therapy and prognostic outcomes 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%). Despite a formal indication, statin prescription was significantly less frequent in the setting of primary compared to secondary prevention. Statin therapy at discharge 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 (28.7% vs. 37.7%; log-rank p = 0.009). After multivariable adjustment, subgroup analyses also showed significantly lower long-term all-cause 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) as well as 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. Similar results were found in subgroup analyses in ICM and in the setting of primary as well as secondary prevention but not in NICM. Prospective studies are warranted to clarify the prognostic effects of statins in patients with HF, particularly in specific patient populations (e.g., with/without CAD, systemic inflammatory conditions and other forms of metabolic disease).
