There is limited evidence to support definite clinical outcomes of direct oral anticoagulant (DOAC) therapy in chronic kidney disease (CKD). By identifying the important variables associated with clinical outcomes following DOAC administration in patients in different stages of CKD, this study aims to assess this evidence gap. An anonymised dataset comprising 97,413 patients receiving DOAC therapy in a tertiary health setting was systematically extracted from the multidimensional electronic health records and prepared for analysis. Machine learning classifiers were applied to the prepared dataset to select the important features which informed covariate selection in multivariate logistic regression analysis. For both CKD and non-CKD DOAC users, features such as length of stay, treatment days, and age were ranked highest for relevance to adverse outcomes like death and stroke. Patients with Stage 3a CKD had significantly higher odds of ischaemic stroke (OR 2.45, 95% Cl: 2.10-2.86; p = 0.001) and lower odds of all-cause mortality (OR 0.87, 95% Cl: 0.79-0.95; p = 0.001) on apixaban therapy. In patients with CKD (Stage 5) receiving apixaban, the odds of death were significantly lowered (OR 0.28, 95% Cl: 0.14-0.58; p = 0.001), while the effect on ischaemic stroke was insignificant. A positive effect of DOAC therapy was observed in advanced CKD. Key factors influencing clinical outcomes following DOAC administration in patients in different stages of CKD were identified. These are crucial for designing more advanced studies to explore safer and more effective DOAC therapy for the population.