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

Abstract

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.

Real-world effectiveness and safety of rivaroxaban versus warfarin among non-valvular atrial fibrillation patients with obesity in a US population

“…A post-hoc analysis of the ROCKET AF trial showed that both rivaroxaban and warfarin are effective in stroke prevention across various BMI subgroups with no significant difference among subgroups (interaction p ¼ .537) 36 . Subsequent observational studies, including the present study, further substantiated this evidence [17][18][19][20][21][22][23] 21 . However, these findings were evaluated over a relatively short follow-up period of $10 months, which may explain part of the differences with the current study when evaluating patients with morbid obesity.…”

“…However, since this advisement, growing evidence in support of the safety and efficacy of DOACs in obese patients has emerged. In particular, emerging evidence suggests that DOACs are associated with a similar or lower risk of stroke/SE or major bleeding relative to the vitamin K antagonist warfarin in morbidly obese [17][18][19][20][21][22] and obese 23 patients with AF. However, much of this evidence is based on pooled data from patients who initiated different DOACs 17,18,20 , despite evidence that not all DOACs have the same pharmacokinetic profile in obese patients 24 .…”

“…Currently, available evidence suggests that the pharmacokinetic profile of the DOAC rivaroxaban is not altered in patients with high body weight 31 . Although there is a growing body of literature regarding the clinical benefits associated with rivaroxaban in obese patients 23 , additional real-world evidence is needed. Real-world evidence is derived from observational data generated during routine clinical practice (e.g.…”

Direct Oral Anticoagulant Concentrations in Obese and High Body Weight Patients: A Cohort Study

“…23 These findings were consistent with those published by Costa el al on the effectiveness and safety of rivaroxaban for AF in obese patients across all BMI classes. 24 However, > 100 kg is commonly used to define high body weight with most of the patients falling between 100 kg and 120 kg. 25 For patients with BMI > 40 kg/m 2 , Kushnir et al recently demonstrated in a retrospective study including 795 patients receiving apixaban, rivaroxaban, or VKA for AF or VTE, similar efficacy and safety between FXa inhibitors and VKA.…”

Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism: Use in Patients with Advanced Renal Impairment, Obesity, or Other Weight-Related Special Populations

“…As a class, DOACs seem to maintain their efficacy and safety for the treatment of VTE in patients with obesity, with similar data in the setting of NVAF. 94,95 Individually, the extent of data supporting each agent varies. Dabigatran demonstrates a reduced PK/PD profile in patients with obesity.…”