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Background In event‐driven clinical trials, study termination is based on accrual of a target number of primary efficacy events. For noninferiority trials in which superiority is conditionally examined, the ideal cohort in which to track event accrual is unclear. We used data from the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial to determine the effect of primary efficacy‐event tracking in the per‐protocol cohort during the on‐treatment period versus the intention‐to‐treat (ITT) cohort during the ITT period. Methods and Results ROCKET AF was terminated after accruing 429 primary efficacy events (stroke or systemic embolism) in the per‐protocol cohort during the on‐treatment period for noninferiority. We identified the date on which 429 events occurred in the ITT cohort during the ITT period. We performed noninferiority and superiority analyses based on hypothetical study termination on this date. ROCKET AF would have terminated 226 days earlier if events were tracked during the ITT period. Similar to the main trial findings, rivaroxaban would have met noninferiority versus warfarin for the primary efficacy end point (hazard ratio [HR], 0.77; 95% CI, 0.62–0.96; P

Objective Patients with nonvalvular atrial fibrillation (AF) and renal disease (RD) who receive anticoagulation therapy appear to be at greater risk of major bleeding (MB) than AF patients without RD. As observed in past studies, anticoagulants are frequently withheld from AF patients with RD due to concerns regarding bleeding. The objective of this study was to evaluate the incidence and pattern of MB in those with RD, as compared to those without RD, in a population of rivaroxaban users with nonvalvular AF. Methods Electronic medical records of over 10 million patients from the Department of Defense Military Health System were queried to identify rivaroxaban users with nonvalvular AF. A validated algorithm was used to identify MB-related hospitalizations. RD was defined through diagnostic codes present within 6 months prior to the bleeding date for MB cases and end of study participation for non-MB patients. Data were collected on patient characteristics, comorbidities, MB management, and outcomes. Results Overall, 44,793 rivaroxaban users with nonvalvular AF were identified. RD was present among 6,921 patients (15.5%). Patients with RD had a higher rate of MB than those without RD, 4.52 per 100 person-years versus 2.54 per 100 person-years, respectively. The fatal bleeding outcome rate (0.09 per 100 person-years) was identical between those with and without RD. Conclusion In this post-marketing study of 44,793 rivaroxaban users with nonvalvular AF, RD patients experienced a higher MB rate than those without RD. The higher rate of MB among those with RD may be due to the confounding effects of comorbidities.