However, there was marked study heterogeneity including the inability to account for major confounders such as the quality of anticoagulation control (TTR). One study reported that in AF patients on peritoneal dialysis, warfarin reduced stroke and thromboembolism compared with aspirin or no antithrombotic therapy, with no excess in serious bleeds (ICH).246 The lack of clinical trial data in severe CKD is a major evidence gap with the NOACs, even though some regulatory agencies such as the Food and Drug Administration have approved reduced-dosed NOACs for severe CKD and dialysis on the basis of Fortunately, the pivotal NOAC randomized trials have demonstrated noninferiority of NOACs to warfarin among patients with CrCl of 30 to All the NOACs have some degree of renal elimination, Cmax, and half-life, with the greatest renal dependency for excretion with dabigatran (80%) and the least with renal dependency for apixaban (27%). However, there are no head-to-head NOAC trials and therefore insuf cient evidence to recommend one agent over another. Given these limitations, treatment should be individualized, and the dose adapted on the basis of CrCl according to licensed indications437 (Fig 9). Recommendations 50. For mild CKD (Stage II, CrCl 60-89 mL/min), we suggest that oral anticoagulation clinical decision- making and treatment recommendations match that of patients without CKD (Weak recommendation, very low quality evidence). 51. For moderate CKD (Stage III, CrCl 30-59 mL/ min), we suggest oral anticoagulation in patients with a CHA2DS2-VASc 2 with label-adjusted NOACs or dose-adjusted vitamin K antagonists (Weak recommendation, very low quality evidence). Remark: With VKA, good quality anticoagulation control (TTR > 65-70%) is recommended. 52. 