A comprehensive meta-analysis of five randomized trials found edoxaban reduces stroke or systemic embolism by 42% in patients with prior myocardial infarction compared to warfarin, while also decreasing major adverse cardiovascular events by 10% overall. The factor Xa inhibitor proved particularly effective at reducing major bleeding in patients with less than 25% heart failure prevalence. However, the analysis revealed important patient-specific considerations: warfarin remained superior in high-risk patients with CHA2DS2VASc scores above 4, older adults over 65, and those with normal kidney function for preventing non-major bleeding complications. These findings illuminate the complexity of anticoagulant selection in atrial fibrillation management, moving beyond one-size-fits-all approaches. The results suggest clinicians should stratify patients based on stroke risk scores, heart failure status, age, and renal function when choosing between these medications. This preprint analysis awaits peer review, and the nuanced subgroup findings require validation in larger dedicated trials. While edoxaban shows promise as a safer alternative to warfarin's monitoring requirements, the data confirms that warfarin retains clinical relevance for specific high-risk populations, representing an incremental but clinically meaningful advancement in personalized anticoagulation therapy.