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Rivaroxaban Precision Dosing Strategy for Real-World Atrial Fibrillation Patients.

ABSTRACT: Rivaroxaban is a direct-acting oral anticoagulant approved to prevent strokes in patients with atrial fibrillation. Dosage recommendations are approved for all adult patients to receive either 15 mg or 20 mg once daily depending upon renal function. There are a number of reasons to believe rivaroxaban dosing could be more effective and/or safer for more patients if increased dosing precision is available. Because real-world patients are more diverse than those studied in phase III clinical trials, we evaluated the extremes of creatinine clearance (CrCl) on rivaroxaban clearance using a published population pharmacokinetic model and applying exposure variation limits (±20%) based on published literature. The proposed dosing recommendations are 10 mg once daily (CrCl 15-29 ml/min), 15 mg once daily (CrCl 30-69 ml/min), 10 mg twice daily (CrCl 70-159 ml/min), and 15 mg twice daily (CrCl 160-250 ml/min). These new dosing recommendations should be prospectively tested for predictive accuracy and to assess the impact on AF patient efficacy and safety.

SUBMITTER: Konicki R

PROVIDER: S-EPMC7359950 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Rivaroxaban Precision Dosing Strategy for Real-World Atrial Fibrillation Patients.

Konicki Robyn R Weiner Daniel D Herbert Patterson J J Gonzalez Daniel D Kashuba Angela A Cao Yanguang Carter YC Gehi Anil K AK Watkins Paul P Powell J Robert JR

Clinical and translational science 20200507 4

Rivaroxaban is a direct-acting oral anticoagulant approved to prevent strokes in patients with atrial fibrillation. Dosage recommendations are approved for all adult patients to receive either 15 mg or 20 mg once daily depending upon renal function. There are a number of reasons to believe rivaroxaban dosing could be more effective and/or safer for more patients if increased dosing precision is available. Because real-world patients are more diverse than those studied in phase III clinical trial ...[more]

PMID: 32267996

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Project description:Direct oral anticoagulants (DOACs), such as rivaroxaban, reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). However, it is still unclear whether the stroke reduction benefit outweighs the bleeding risk in elderly Japanese patients with NVAF. The Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) was a real-world, prospective observational, post-marketing surveillance study on the safety and effectiveness of rivaroxaban in Japanese clinical practice. This sub-analysis evaluated the clinical outcomes of elderly patients aged???75 years. At the 1-year follow-up, there were 4,685 (48.91%) and 4,893 (51.09%) patients aged???75 and?<?75 years, respectively. Safety and effectiveness outcomes were compared between patients aged???75 years and those aged?<?75 years, and among 3 elderly sub-populations (age ranges: 75-79, 80-84, and???85 years). Patients aged???75 years had higher rates of major bleeding [2.22 vs. 1.35 events per 100 patient-years, hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.17-2.28] and composite of stroke (ischemic or hemorrhagic)/non-central nervous system (non-CNS) systemic embolism (SE)/myocardial infarction (MI) (2.41 vs. 1.21 events per 100 patient-years, HR 1.97, 95% CI 1.40-2.77) compared to patients aged?<?75 years. Intracranial hemorrhage rates were?<?1 event per 100 patient-years in both groups (0.85 vs. 0.59 events per 100 patient-years, HR 1.43, 95% CI 0.85-2.40). Kaplan-Meier curves of major bleeding and stroke/non-CNS SE/MI showed that no significant differences of cumulative event rates were identified among the 3 elderly sub-populations. Stepwise Cox regression analyses revealed that creatinine clearance (CrCl) (<50 mL/min), hepatic impairment, and hypertension were specific predictors for major bleeding and no specific predictors were found for stroke/non-CNS SE/MI in patients aged???75 years. In conclusion, safety and effectiveness event rates were higher in patients aged???75 years compared with those aged?<?75 years, yet, no distinct differences were observed among the 3 elderly sub-populations.

Project description:BackgroundReal-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment.Methods and resultsBetween January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines).ConclusionsThe RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world.Trial registrationUnique identifier: NCT02444221. Registerd 14 May 2015; Retrospectively Registered.

Project description:BackgroundThe Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) was designed to investigate safety and effectiveness during long-term follow-up of rivaroxaban treatment, using reduced doses compared with other global regions, in Japanese patients with non-valvular atrial fibrillation in real-world clinical practice.MethodsIn this prospective, open-label, single-arm, observational study, 11,308 patients with non-valvular atrial fibrillation newly prescribed rivaroxaban (15/10 mg once daily) at 1416 sites across Japan were enrolled and followed for a mean of 2.5 years.ResultsIn total, 10,664 and 10,628 patients were included in the safety and effectiveness analyses, respectively. In the safety population, mean (standard deviation) age was 73.1 (9.8) years and Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke/TIA (2 points) (CHADS2) score was 2.2 (1.3). Incidences (95% confidence intervals) of any and major bleeding were 3.77 (3.53-4.01) and 1.16 (1.03-1.29) events per 100 patient-years, respectively. Age ≥75 years, creatinine clearance <50 mL/min, diabetes mellitus, and vascular disease were independently associated with incidence of major bleeding. The primary composite effectiveness outcome of stroke, non-central nervous system systemic embolism, and myocardial infarction occurred at an incidence (95% confidence interval) of 1.32 (1.18-1.46) events per 100 patient-years. Age ≥75 years, hypertension, prior ischemic stroke/transient ischemic attack, and concomitant use of antiplatelets were independently associated with incidence of the composite outcome of stroke, non-central nervous system systemic embolism, and myocardial infarction.ConclusionIn the XAPASS, a large-scale study involving a broad range of patients with non-valvular atrial fibrillation newly prescribed rivaroxaban using Japan-specific dosage in real-world clinical practice, no unexpected safety or effectiveness concerns were detected during up to 5 years of follow-up.

Dataset Information

Rivaroxaban Precision Dosing Strategy for Real-World Atrial Fibrillation Patients.

Publications

Rivaroxaban Precision Dosing Strategy for Real-World Atrial Fibrillation Patients.

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