Statin therapy and mortality in septic patients with new-onset atrial fibrillation: a retrospective database study

New-onset atrial fibrillation (NOAF) significantly worsens the prognosis of sepsis, yet effective disease-modifying therapies remain limited. Statins possess pleiotropic anti-inflammatory properties that may counteract the inflammatory-arrhythmogenic cascade in sepsis.

To evaluate the association between statin therapy and all-cause mortality in septic patients with NOAF and explore the impact of initiation timing, statin agent, and dosage.

This retrospective cohort study utilized the MIMIC-IV database to identify septic patients with NOAF. Statin exposure was modeled as a time-varying covariate to mitigate immortal time bias. Primary outcomes were 28-day, 90-day, and 1-year all-cause mortality. Propensity score matching (PSM) and multivariable time-dependent Cox regression were employed for robustness.

Among 4,392 patients, 1,327 (30.2%) received statins. After propensity score matching (n=2,654), statin therapy was independently associated with significantly reduced mortality at 28 days (HR 0.677, 95% CI: 0.589-0.779), 90 days (HR 0.678, 95% CI: 0.601-0.765), and 1 year (HR 0.690, 95% CI: 0.622-0.767; all P<0.001). The survival benefit was primarily driven by de novo initiation after ICU admission rather than chronic continuation. Agent-specific analyses revealed that simvastatin and pravastatin demonstrated the most consistent protective signals across all time points, while both low- and high-intensity regimens yielded improved survival.

Statin therapy, particularly with simvastatin or pravastatin, is independently associated with improved short- and long-term survival in septic patients with NOAF. These hypothesis-generating findings support the conduct of prospective, biomarker-guided randomized trials to validate targeted statin interventions in this high-risk subpopulation.