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Background: Although rivaroxaban has demonstrated consistent drug levels in normal weight and obese patients, sufficient confirmation of equal clinical effectiveness and safety is currently lacking. Purpose: To evaluate the effectiveness and safety of rivaroxaban versus warfarin for prevention of stroke and systemic embolism (SSE) in obese nonvalvular atrial fibrillation (NVAF) patients. Methods: Using Optum de-identified Electronic Health Record (EHR) data from November 2011 to September 2018,we evaluated NVAF patients with a body mass index (BMI)!30 kg/m 2 newly initiated on rivaroxaban or warfarin (index date), with !12-months of EHR activity and !1 encounter before the index date. We excluded patients with valvular disease or evidence of oral anticoagulant (OAC) use at baseline. Patients who were prescribed rivaroxaban were 1:1 propensity-score matched to patients who were prescribed warfarin (standard differences <0.10 achieved for all covariates). Outcomes included SSE and major bleeding using an intent-to-treat approach. Subanalyses stratified by BMI (30.0-34.9, 35.0-39.9 and !40 kg/m 2) were performed. Cox regression was performed and reported as hazard ratios (HRs) and 95% confidence intervals (CIs). Results: We included 35,613 rivaroxaban and 35,613 warfarin users with NVAF. Patients were followed for a median of 2.6 years (25%-75% range ¼ 1.2-4.1). Rivaroxaban was associated with a reduced risk of SSE (HR ¼ 0.83, 95%CI ¼ 0.73-0.94) and major bleeding (HR ¼ 0.82, 95%CI ¼ 0.75-0.89) compared to warfarin. Subanalysis did not show a statistically significant interaction across BMI categories for SSE (p-interaction ¼ .58) or major bleeding (p-interaction ¼ .44) outcomes. Conclusions: Among obese NVAF patients, prescription of rivaroxaban was associated with a reduced risk of SSE and major bleeding compared to warfarin, which remained consistent across BMI classes.

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Background Andexanet alfa is approved (FDA “accelerated approval”; EMA “conditional approval”) as the first specific reversal agent for factor Xa (FXa) inhibitor-associated uncontrolled or life-threatening bleeding. Four-factor prothrombin complex concentrates (4F-PCC) are commonly used as an off-label, non-specific, factor replacement approach to manage FXa inhibitor-associated life-threatening bleeding. We evaluated the effectiveness and safety of andexanet alfa versus 4F-PCC for management of apixaban- or rivaroxaban-associated intracranial hemorrhage (ICH). Methods This two-cohort comparison study included andexanet alfa patients enrolled at US hospitals from 4/2015 to 3/2020 in the prospective, single-arm ANNEXA-4 study and a synthetic control arm of 4F-PCC patients admitted within a US healthcare system from 12/2016 to 8/2020. Adults with radiographically confirmed ICH who took their last dose of apixaban or rivaroxaban < 24 h prior to the bleed were included. Patients with a Glasgow Coma Scale (GCS) score < 7, hematoma volume > 60 mL, or planned surgery within 12 h were excluded. Outcomes were hemostatic effectiveness from index to repeat scan, mortality within 30 days, and thrombotic events within five days. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using propensity score-overlap weighted logistic regression. Results The study included 107 andexanet alfa (96.6% low dose) and 95 4F-PCC patients (79.3% receiving a 25 unit/kg dose). After propensity score-overlap weighting, mean age was 79 years, GCS was 14, time from initial scan to reversal initiation was 2.3 h, and time from reversal to repeat scan was 12.2 h in both arms. Atrial fibrillation was present in 86% of patients. Most ICHs were single compartment (78%), trauma-related (61%), and involved the intracerebral and/or intraventricular space(s) (53%). ICH size was ≥ 10 mL in volume (intracerebral and/or ventricular) or ≥ 10 mm in thickness (subdural or subarachnoid) in 22% of patients and infratentorial in 15%. Andexanet alfa was associated with greater odds of achieving hemostatic effectiveness (85.8% vs. 68.1%; OR 2.73; 95% CI 1.16–6.42) and decreased odds of mortality (7.9% vs. 19.6%; OR 0.36; 95% CI 0.13–0.98) versus 4F-PCC. Two thrombotic events occurred with andexanet alfa and none with 4F-PCC. Conclusions In this indirect comparison of patients with an apixaban- or rivaroxaban-associated ICH, andexanet alfa was associated with better hemostatic effectiveness and improved survival compared to 4F-PCC. Trial registration NCT02329327; registration date: December 31, 2014.

Guidelines provide differing recommendations regarding direct-acting oral anticoagulants vs low-molecular-weight heparin (LMWH) for treatment of cancer-associated thrombosis (CAT). This study was undertaken to evaluate the effectiveness and safety of rivaroxaban vs LMWH for treatment of CAT. Using US Surveillance, Epidemiology and End Results-Medicare–linked data from 2013 through 2016, we evaluated adults with active breast, lung, ovarian, or pancreatic cancer, who were admitted to the hospital or treated in the emergency department for CAT and were prescribed rivaroxaban or LMWH for outpatient anticoagulation. Patients with luminal gastrointestinal or genitourinary cancers were excluded. Rivaroxaban and LMWH users were 1:1 propensity score matched. Outcomes included the composite of recurrent thrombosis or major bleeding, each outcome separately, and mortality at 6 months, using an intent-to-treat approach. On-treatment analysis after 12 months was also performed. Proportional hazards models for the subdistribution of competing risk were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 529 rivaroxaban- and 529 LMWH-treated patients with CAT. Rivaroxaban was not associated with differences in risk of the composite outcome (HR, 0.71; 95% CI, 0.41-1.22), major bleeding (HR, 1.01; 95% CI, 0.50-2.01), or mortality (HR, 0.87; 95% CI, 0.70-1.07) vs LMWH, but it reduced recurrent thrombosis (HR, 0.37; 95% CI, 0.15-0.95). On-treatment analysis at 12 months showed similar results. Rivaroxaban may be a reasonable alternative to LMWH for patients with CAT without gastrointestinal or genitourinary cancer.

Background Diabetes increases a patient’s risk of developing atrial fibrillation by 49%. Patients with nonvalvular atrial fibrillation are at a fivefold increased risk of stroke and die more frequently from vascular causes. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with type 2 diabetes. Methods This was an analysis of Optum® De-Identified electronic health record data from 11/2010 to 12/2019. We included adults with nonvalvular atrial fibrillation and type 2 diabetes, newly started on rivaroxaban or warfarin and with ≥ 12-months of prior electronic health record activity. Patients who were pregnant, had alternative indications for oral anticoagulation or valvular heart disease were excluded. We evaluated the incidence rate (%/year) of developing the composite outcome of stroke/systemic embolism or vascular death and major or clinically relevant nonmajor bleeding as well as each endpoint individually. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted proportional hazards regression. Results We included 32,078 rivaroxaban (31% initiated on 15 mg dose) and 83,971warfarin users (time-in-therapeutic range = 47 ± 28%). Rivaroxaban was associated with a reduced risk of stroke/systemic embolism or vascular death (3.79 vs. 4.19; hazard ratio = 0.91, 95% confdience interval = 0.88–0.95), driven mostly by reductions in vascular death (2.81 vs 3.18, hazard ratio = 0.90, 95% confidence interval = 0.86–0.95) and systemic embolism (0.13 vs. 0.16; hazard ratio = 0.82, 95% confidence interval = 0.66–1.02). Major/clinically relevant nonmajor bleeding was less frequent with rivaroxaban versus warfarin (2.17 vs. 2.31; hazard ratio = 0.94, 95% confidence interval = 0.89–0.99) due to decreased critical organ bleeding (including intracranial hemorrhage) (0.35 vs. 0.54; hazard ratio = 0.63, 95% confidence interval = 0.55–0.72). Conclusions In nonvalvular atrial fibrillation patients with type 2 diabetes, rivaroxaban was associated with an ~ 10% relative reduction in vascular mortality and fewer bleeding-related hospitalizations versus warfarin.

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Introduction A paucity of contemporary data examining bleeding-related hospitalization outcomes in atrial fibrillation (AF) patients exists. Methods Adults in the Nationwide Readmissions Database (January 2016–November 2016) with AF and hospitalized for intracranial hemorrhage (ICH), gastrointestinal, genitourinary, or other bleeding were identified. Association between bleed types and outcomes were assessed using multivariable regression (gastrointestinal defined as referent) and reported as crude incidences and adjusted odds ratios (ORs) or mean differences with 95% confidence intervals (CIs). Results In total, 196,878 index bleeding-related hospitalizations were identified in this AF cohort (CHA2DS2VASc score ≥2 in 95.1%), with 70.8% classified as gastrointestinal. The overall incidences of in-hospital mortality, need for post-discharge out-of-home care, and 30-day readmission were 4.9, 50.8, and 18.2%, respectively. Multivariable regression suggested traumatic and nontraumatic ICHs were associated with higher odds of in-hospital mortality (OR = 3.99, 95% CI = 3.79, 4.19; OR = 13.09, 95% CI = 12.24, 13.99) and need for post-discharge out-of-home care (OR = 2.92, 95% CI = 2.83, 3.01; OR = 2.74, 95% CI = 2.59, 2.90), and increases in mean index hospitalization length-of-stay (8.31 days, 95% CI = 8.03, 8.60, 6.27 days, 95% CI = 5.97, 6.57) versus gastrointestinal bleeding. Genitourinary and other bleeds were associated with lower mortality (OR = 0.37, 95% CI = 0.25, 0.55; OR = 0.59, 95% CI = 0.53, 0.64) and reduced length-of-stays (−2.84 days, 95% CI =  − 2.91, −2.76; −2.06 days, 95% CI =  − 2.11, −2.01) versus gastrointestinal bleeding. Genitourinary bleeds were also associated with a reduced need for post-discharge out-of-home care (OR = 0.86, 95% CI = 0.77, 0.97). Conclusion The burden of bleeding-related hospitalizations was notably driven by relatively rare but severe and life-threatening ICH, and less morbid but more frequent gastrointestinal bleeding. There is need for continued research on bleeding risk factors and mitigation techniques to avoid bleeding-related patient hospitalizations.