Thromboembolism, bleeding and vascular death in nonvalvular atrial fibrillation patients with type 2 diabetes receiving rivaroxaban or warfarin.

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.

Effectiveness and safety of rivaroxaban versus warfarin in obese patients with acute venous thromboembolism: analysis of electronic health record data.

There is limited data evaluating clinical outcomes of rivaroxaban versus warfarin in obese patients with venous thromboembolism (VTE). Our objective was to evaluate the effectiveness and safety of rivaroxaban versus warfarin in obese VTE patients. We performed a cohort analysis using Optum® De-Identified Electronic Health Record data from 11/1/2012 to 9/30/2018. Patients with a body mass index (BMI) ≥ 30 kg/m2 admitted to the hospital, emergency department or observation unit for VTE, prescribed rivaroxaban or warfarin as their first oral anticoagulant (OAC) within 7-days and had ≥12-months of EHR activity prior were included. We excluded patients with OAC use at baseline or cancer. Patients were 1:1 matched (standard differences<0.10). Primary outcomes were recurrent VTE and major bleeding at 3-, 6- and 12-months using an intent-to-treat approach. Subanalyses of BMI 30.0-34.9, 35.0-39.9 and ≥ 40 kg/m2 were performed. Risk was compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CI). We identified 6755 rivaroxaban and 6755 warfarin users with BMI ≥ 30 kg/m2 and incident VTE. At 3-, 6- and 12-months, rivaroxaban was associated with a reduced hazard of recurrent VTE compared to warfarin (HR 0.61, 95%CI 0.51-0.72; HR 0.65, 95%CI 0.55-0.77; HR 0.63, 95%CI 0.54-0.74) with no difference in major bleeding (HR 0.99, 95%CI 0.68-1.44; HR 0.90, 95%CI 0.64-1.26; HR 1.00, 95%CI 0.73-1.36). No statistical difference was found across BMI categories for either recurrent VTE (p-interaction≥0.43) or major bleeding (p-interaction ≥ 0.58) at any time point. In obese VTE patients, prescription of rivaroxaban was associated with a significantly reduced risk of recurrent VTE versus warfarin, without impacting major bleeding. Our findings remained consistent across BMI classes.

Rivaroxaban Versus Warfarin for Management of Obese African Americans With Non-Valvular Atrial Fibrillation or Venous Thromboembolism: A Retrospective Cohort Analysis.

African Americans (AAs) and obese individuals have increased thrombotic risk. This study evaluated the effectiveness and safety of rivaroxaban versus warfarin in obese, AAs with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Optum® De-Identified Electronic Health Record (EHR) data was used to perform separate propensity-score matched analyses of adult, oral anticoagulant (OAC)-naïve AAs with NVAF or acute VTE, respectively; who had a body mass index≥30kg/m2 and ≥12-months EHR activity with ≥1-encounter before OAC initiation. Cox regression was performed and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). For the NVAF analysis, 1,969 rivaroxaban- and 1,969 warfarin-users were matched. Rivaroxaban was not associated with a difference in stroke/systemic embolism versus warfarin (HR = 0.88, 95%CI = 0.60-1.28), but less major bleeding (HR = 0.68, 95%CI = 0.50-0.94) was observed. Among 683 rivaroxaban-users with VTE, 1:1 matched to warfarin-users, rivaroxaban did not alter recurrent VTE (HR = 1.36, 95%CI = 0.79-2.34) or major bleeding (HR = 0.80, 95%CI = 0.37-1.71) risk versus warfarin at 6-months (similar findings observed at 3- and 12-months). Rivaroxaban appeared to be associated with similar thrombotic, and similar or lower major bleeding risk versus warfarin in these obese, AA cohorts.

Effectiveness and safety of rivaroxaban versus warfarin in obese nonvalvular atrial fibrillation patients: analysis of electronic health record data.

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/m2 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/m2) 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 = 1.2-4.1). Rivaroxaban was associated with a reduced risk of SSE (HR = 0.83, 95%CI = 0.73-0.94) and major bleeding (HR = 0.82, 95%CI = 0.75-0.89) compared to warfarin. Subanalysis did not show a statistically significant interaction across BMI categories for SSE (p-interaction = .58) or major bleeding (p-interaction = .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.