Background There is conflicting evidence regarding the use of statins to reduce the risk of post-operative atrial fibrillation (POAF) in patients undergoing cardiac surgery. Purpose We sought to determine the effects of statin use on the burden of new-onset post-discharge POAF in the Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation (SEARCH-AF) CardioLink-1 randomized controlled trial. Methods In the SEARCH-AF trial, 336 patients with risk factors for stroke (CHA2DS2-VASc score ≥2) and no history of preoperative AF were randomized to usual care or continuous cardiac rhythm monitoring for 30 days after discharge from cardiac surgery with a wearable, patched-based device. The primary endpoint was the occurrence of cumulative atrial fibrillation/flutter (AF/AFL) lasting for ≥6 minutes detected by continuous monitoring or AF/AFL documented by a 12-lead electrocardiogram within 30 days of randomization. Using time-to-event analysis and Cox regression, we evaluated the association between the risk of post-operative AF in relation to statin use and dosing intensity (low, moderate, high) at the time of discharge. We excluded patients who experienced post-operative AF during hospitalization in this analysis. Results In the overall cohort (n=336), 260 (77.4%) patients were treated with statins at the time of hospital discharge. There were 18 (5.4%) patients who experienced post-operative AF during hospitalization. Patients prescribed with statins were more likely to be male (p=0.018), had lower CHA2DS2-VASc scores (p=0.011), and were more likely to undergo isolated coronary artery bypass grafting (CABG) (p=0.083). Baseline characteristics were otherwise similar between the 2 groups. Patients treated with statins at discharge had a 2-fold lower rate of post-operative AF than those who were not treated with statins in the overall cohort (17.6% vs. 8.2%, Log-Rank p=0.017) and among those who were randomized to continuous cardiac rhythm monitoring (31.6% vs. 16.0%, Log-Rank p=0.027) (Figure). After adjusting for surgery type (CABG vs. valve surgery) and the CHA2DS2-VASc score, statin use at discharge was associated with a lower risk of post-operative AF within 30 days after surgery (hazard ratio 0.48, 95% CI 0.24–0.97). Furthermore, increasing intensity of statin therapy was associated with lower risk of POAF (ptrend=0.0012) (Figure 1) Conclusion Among cardiac surgery patients with risk factors for stroke and no history of pre-operative AF, the use of statins was associated with a reduction in post-operative AF risk within 30 days of discharge. The routine use of high-intensity statin to prevent post-operative AF after cardiac surgery deserves further study. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Heart and Stroke Foundation of Canada