Independent and Joint Association of Statin Therapy with Adverse Outcomes in Heart Failure Patients with Atrial Fibrillation Treated with Cardiac Resynchronization Therapy

Background: The joint association of atrial fibrillation (AF) and statin therapy with adverse outcomes in heart failure (HF) patients with cardiac resynchronization therapy (CRT) has not been fully investigated so far. The purpose of this study was to explore the independent and joint association of AF and statin therapy with adverse outcomes. Methods: Study patients were divided into four groups according to AF status and statin use: Non-AF/Statin, Non-AF/Non-Statin, AF/Statin, and AF/Non-Statin. Multivariate Cox proportional hazards regression models were used to evaluate the independent and joint association of AF and statin therapy with poor prognosis. Results: Among 685 CRT patients, there were 180 deaths (26.5%) and 198 HF hospitalization (29.6%) during the 14 years of follow-up. AF was associated with a 46% increased risk of all-cause mortality (HR, 1.46; 95% CI, 1.03-2.07) and a 59% increased risk of HF hospitalization (HR, 1.59; 95% CI, 1.16-2.20) than those without AF. However, statin therapy failed to improve the prognosis. In the joint analysis, compared with the Non-AF/Statin group, the AF/Non-Statin group suffered a higher risk of all-cause mortality (HR, 1.75; 95% CI, 1.04-2.93) and HF hospitalization (HR, 1.76; 95% CI, 1.08-2.86). Furthermore, adding AF to the traditional risk factor model significantly improved the predictive value for death (C-statistic from 0.654 to 0.691) and HF (C-statistic from 0.613 to 0.675). Conclusion: AF was associated with poor prognosis, and statin use failed to improve the prognosis. Further analysis showed that statin therapy is ineffective in improving prognosis and fails to attenuate the adverse effects of AF.