Comparison of Effects of Statin Use on Mortality in Patients With Heart Failure and Preserved Versus Reduced Left Ventricular Ejection Fraction

Randomized trials showed no survival benefit with statin therapy in heart failure (HF) patients with reduced ejection fraction (HFrEF). Whether these results are generalizable to HF patients with preserved ejection fraction (HFpEF) or with mid-range ejection fraction is unclear. In a cohort of 13,440 patients with HF, 9,903 (73.7%) were treated with statins. The association between statin use and all-cause mortality was assessed with Cox proportional hazard regression models and survival time inverse probability weighting propensity scores analyses. Multivariable Poisson regression models with robust error variance were applied to estimate the rate ratios (RR) for hospitalization. The association between statin treatment and clinical outcomes differed by ejection fraction group. In patients with HFpEF, statin use was associated with reduced mortality (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.66 to 0.81, p <0.001; average treatment effect [ATE] 0.48, 95% CI 0.13 to 0.84, p = 0.007) and reduced all-cause hospitalization (RR 0.82, 95% CI 0.76 to 0.89, p <0.001). In contrast, in patients with HFrEF, no significant association was observed between statin use and mortality (HR 0.86, 95% CI 0.74 to 1.0, p = 0.054; ATE 0.41, 95% CI −0.09 to 0.93, p = 0.11) or hospitalization (RR 0.92, 95% CI 0.82 to 1.04, p = 0.17). Similarly, in patients with mid-range ejection fraction, there was no significant association with reduced mortality (HR 0.76, 95% CI 0.60 to 0.95, p = 0.02, ATE 0.3, 95% CI −0.84 to 1.43, p = 0.61) or hospitalization (RR 1.07, 95% CI 0.9 to 1.27, p = 0.44). In conclusion, statin use was associated with improved clinical outcomes in patients with HFpEF but not in patients with HFrEF or mid-range ejection fraction.