Abstract 505: Incidence of Major Bleeding in a Real-World Population of 57,070 Nonvalvular Atrial Fibrillation Patients Treated With Rivaroxaban

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Frank Peacock ◽  
Manesh Patel ◽  
Zhong Yuan ◽  
Nicholas Sicignano ◽  
Kathleen Hopf ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Factor Xa ◽  
Patient Characteristics ◽  
World Population ◽  
Nonvalvular Atrial Fibrillation ◽  
Military Health ◽  
Bleeding Management ◽  
Fatal Bleeding ◽  
Registration Trial

Introduction: Rivaroxaban, a direct factor Xa inhibitor approved in 2011, reduces the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). Phase 3 results from the registration trial showed a major bleeding (MB) rate of 3.6 per 100 person-years. Objective: To evaluate MB incidence among NVAF patients taking rivaroxaban in a post-approval clinical setting. Methods: From January 1, 2013 to June 30, 2016, over 10 million electronic medical records from the Department of Defense Military Health System were queried. A validated MB case-finding algorithm (Cunningham) was used to identify MB-related hospitalizations. Major bleeding incidence, patient characteristics, comorbid conditions, concomitant medications, bleeding management, and fatal bleeds were assessed. Results: Of 57,070 rivaroxaban users with NVAF, 1,914 experienced a MB event, with incidence of 2.60 (95% CI 2.49-2.72) per 100 person-years. Patient characteristics and subgroup bleeding rates are displayed in Table 1. There were 62 patients who experienced fatal bleeding, and the mean (SD) age at time of death was 79.3 (7.6) years. Among those who died, 74.2% had intracranial hemorrhage, 22.6% had gastrointestinal hemorrhage, and 3.2% had bleeding in other sites. Conclusion: The incidence, pattern, and management of MB in rivaroxaban users with NVAF in a large and diverse population were generally consistent with the findings from the registration trial. Fatal bleeding was rare.

scholarly journals Comparison of the Efficacy and Safety Outcomes of Edoxaban in 8040 Women Versus 13 065 Men With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial

Circulation ◽  
2021 ◽  
Vol 143 (7) ◽  
pp. 673-684
Author(s):  
Thomas A. Zelniker ◽  
Maddalena Ardissino ◽  
Felicita Andreotti ◽  
Michelle L. O’Donoghue ◽  
Ophelia Yin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Hemorrhagic Stroke ◽  
Factor Xa ◽  
Efficacy And Safety ◽  
Similar Reduction ◽  
Similar Treatment ◽  
Endogenous Factor ◽  
Fatal Bleeding ◽  
Artery Disease

Background: Female sex is an independent risk factor for stroke and systemic embolic events in patients with atrial fibrillation. This study aimed to examine the efficacy and safety profile of edoxaban in women versus men. Methods: The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) randomly assigned 21 105 patients (8040 women) with atrial fibrillation and CHADS 2 score ≥2 either to a higher-dose edoxaban regimen, a lower-dose edoxaban regimen, or warfarin. The primary end points of the trial were the composite of stroke or systemic embolic events (efficacy), and International Society on Thrombosis and Haemostasis–defined major bleeding (safety). Results: In comparison with men, women were older, had lower body weight, were more likely to have hypertension and renal dysfunction, but less likely to smoke, drink alcohol, or have diabetes or coronary artery disease. Pretreatment endogenous factor Xa activity was significantly higher in women than in men (92.5% versus 86.1%, P <0.001). Treatment with edoxaban in women resulted in greater peak edoxaban concentration and inhibition of endogenous factor Xa in comparison with men, resulting in similar endogenous factor Xa activity between the sexes 2 to 4 hours after dose. Treatment with higher-dose edoxaban regimen (versus warfarin) resulted in similar reduction in the risk of stroke/systemic embolic events (women: hazard ratio [HR], 0.87 [0.69–1.11], men: HR, 0.87 [0.71–1.06]; P -interaction=0.97) and major bleeding (women: HR, 0.74 [0.59–0.92], men: HR, 0.84 [0.72–0.99]; P -interaction=0.34) in women and men. However, women assigned to higher-dose edoxaban regimen experienced greater reductions in hemorrhagic stroke (HR, 0.30 [95% CI, 0.15–0.59] versus HR, 0.70 [95% CI, 0.46–1.06]), intracranial bleeding (HR, 0.20 [95% CI, 0.10–0.39] versus HR, 0.63 [95% CI, 0.44–0.89]), and life-threatening or fatal bleeding (HR, 0.25 [95% CI, 0.15–0.42] versus HR, 0.72 [95% CI, 0.54–0.96]) than men (each P -interaction<0.05). Conclusions: Despite many differences in baseline characteristics between women and men and higher baseline endogenous factor Xa levels in women, the intensity of anticoagulation achieved with edoxaban between the sexes was similar. Treatment with higher-dose edoxaban regimen resulted in an even greater reduction in hemorrhagic stroke and several serious bleeding outcomes in women than in men, whereas the efficacy profile was similar between sexes.

scholarly journals Apixaban-Calibrated Anti-FXa Activity in Relation to Outcome Events and Clinical Characteristics in Patients with Atrial Fibrillation: Results from the AVERROES Trial

TH Open ◽  
2017 ◽  
Vol 01 (02) ◽  
pp. e139-e145 ◽  
Author(s):  
Vinai Bhagirath ◽  
John Eikelboom ◽  
Jack Hirsh ◽  
Michiel Coppens ◽  
Jeffrey Ginsberg ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Clinical Characteristics ◽  
Factor Xa ◽  
Entire Group ◽  
Minor Bleeding ◽  
Systemic Embolism ◽  
Nonvalvular Atrial Fibrillation ◽  
Clinical Trial Registration

Background In patients with nonvalvular atrial fibrillation (AF), apixaban is given in doses of 5 or 2.5 mg twice daily, according to clinical characteristics. The usual on-treatment range of apixaban drug levels, as determined by apixaban-calibrated anti-factor Xa (anti-Xa) activity, has previously been measured in small cohorts; however, the association between anti-Xa activity and clinical outcomes and the predictors of variability in anti-Xa activity have not been well studied in the AF population. Methods and Results Anti-Xa activity was measured before taking the morning dose, 3 months after enrollment in the AVERROES study using a calibrated anti-Xa assay (Rotachrom). Patients with two of the following criteria—age >80; weight <60 kg; or creatinine >133 μg/L—received 2.5 mg twice daily (n = 145), while all others received 5 mg twice daily (n = 2,247). A total of 2,392 patients were included, with median follow-up of 1.1 years. Median apixaban anti-Xa activity was 122 ng/mL (interquartile range [IQR]: 63–198 ng/mL) for the entire group; 99 ng/mL (IQR: 60–146 ng/mL) for the 2.5-mg group; and 125 ng/mL (IQR: 64–202 ng/mL) for the 5-mg group (p = 0.003). A relationship was evident between bleeding and anti-Xa activity (p = 0.01), which was driven by minor bleeding. No relationship was evident between major bleeding or stroke/systemic embolism and anti-Xa activity. In those receiving the 5-mg dose, estimated glomerular filtration rate, sex, and age had the strongest association with anti-Xa activity. Conclusion There is considerable variability in anti-Xa activity among AF patients receiving apixaban. Rates of major bleeding and stroke/systemic embolism were low irrespective of anti-Xa activity. Clinical Trial Registration ClinicalTrials.gov NCT00496769; https://clinicaltrials.gov/ct2/show/NCT00496769.

scholarly journals Patient characteristics and stroke and bleeding events in nonvalvular atrial fibrillation patients treated with apixaban and vitamin K antagonists: a Spanish real-world study

2019 ◽  
Vol 8 (14) ◽  
pp. 1201-1212 ◽  
Author(s):  
Sreeram V Ramagopalan ◽  
Antoni Sicras-Mainar ◽  
Carlos Polanco-Sanchez ◽  
Robert Carroll ◽  
Jaime F de Bobadilla
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Medical Records ◽  
Vitamin K Antagonists ◽  
Patient Characteristics ◽  
Minor Bleeding ◽  
Thromboembolic Events ◽  
Systemic Embolism ◽  
Bleeding Events ◽  
Nonvalvular Atrial Fibrillation

Aim: To compare the risk of stroke, systemic thromboembolism and bleeding, in patients initiating apixaban or acenocoumarol for the treatment of nonvalvular atrial fibrillation. Methods: An observational, retrospective study was performed using medical records of patients who initiated apixaban or acenocoumarol between 2015 and 2017. Propensity score matching was used to match patients; stroke, systemic thromboembolism, major and minor bleeding events were compared between the matched patients. Results: Patients who were prescribed apixaban had a lower rate of systemic embolism/stroke (hazard ratio [HR] = 0.54; 95% CI: 0.38–0.78; p = 0.001), minor bleeding (HR = 0.64; 95% CI: 0.52–0.79; p < 0.001) and major bleeding (HR = 0.51; 95% CI: 0.37–0.72; p < 0.001). Conclusion: Patients prescribed apixaban for the treatment of nonvalvular atrial fibrillation had lower rates of thromboembolic events and minor/major bleeding than patients on acenocoumarol.

Long-term outcomes of Japan-specific dosage of rivaroxaban in high-risk patients with non-valvular atrial fibrillation: analysis from the XAPASS

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Ikeda ◽  
S Ogawa ◽  
T Kitazono ◽  
J Nakagawara ◽  
K Minematsu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Risk ◽  
Major Bleeding ◽  
Factor Xa ◽  
Incidence Rates ◽  
Funding Source ◽  
High Risk Patients ◽  
Reduced Dose ◽  
Risk Patients

Abstract Background XAPASS is a real-world, prospective, single-arm, observational study conducted as a post-marketing surveillance mandated by the health authority in Japan. Nowadays, direct oral anticoagulant therapy using factor Xa or thrombin inhibitor has been the standard of care for patients with non-valvular atrial fibrillation (NVAF) to prevent ischemic stroke. However, the clinical impact of reduced dosage (approved dose of 15 or 10 mg once daily in Japan is relatively reduced compared to global dosage) factor Xa inhibitor rivaroxaban in high-risk patients remains unclear. Purpose The present sub-analysis of XAPASS was carried out to assess long-term safety and effectiveness of reduced-dose rivaroxaban in high-risk NVAF patients for bleeding and thromboembolism. Methods All patients with NVAF who were newly started on rivaroxaban were eligible for surveillance. The principal safety outcome was a composite of major and non-major bleeding events, and the primary effectiveness outcome was a composite of ischaemic stroke, haemorrhagic stroke, non-central nervous system systemic embolism (non-CNS SE), and myocardial infarction (MI). In this present sub-analysis, high-risk patients were defined as those who had two of the following three risk factors: elderly (≥75 years old), low body weight (≤50 kg), and renal impairment (CrCl &lt;50 mL/min). Results In total, 11,308 patients were enrolled between April 2012 and June 2014 from 1,419 hospitals, and overall data were analysed from 10,664 patients from whom data were collected. Among them, 3,694 patients matched the criteria for the high-risk patients defined in this sub-analysis, and 6,970 patients did not match the criteria (non-high-risk patients). The mean treatment duration was 791±673 days in the high-risk patients and 944±709 days in the non-high-risk patients. Mean patient age was 80.9±5.5 years and 69.0±9.0 years at baseline, respectively. Mean CHADS2 score was 2.8 and 1.8, and CHA2DS2-VASc score was 4.4 and 2.9, respectively. The rates of CHADS2 component comorbidities were lower in the non-high-risk patients except for diabetes mellitus. The incidence rates of any bleeding, major bleeding, and the primary effectiveness outcomes were 4.8, 1.6, and 2.1%/patient-year in the high-risk patients. The incidence rates of these clinical events in the non-high-risk patients were 3.3, 0.9, and 1.0%/patient-year, respectively. Conclusions Incidence rates of long-term bleeding and thromboembolism were higher in the high-risk patients than in the non-high-risk patients. However, the rates of these outcomes using the Japan-specific reduced dose were not so high. Furthermore, the balance between safety and effectiveness outcomes was within an acceptable range. The present study provides useful information for physicians to stratify high-risk patients using the reduced dose in daily clinical practice. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer Yakuhin Ltd.

Probable Rivaroxaban-Induced Full Body Rash: A Case Report

2017 ◽  
Vol 31 (5) ◽  
pp. 503-506 ◽  
Author(s):  
Evan Sasson ◽  
Marian James ◽  
Mark Russell ◽  
Darko Todorov ◽  
Henry Cohen
Keyword(s):  
Atrial Fibrillation ◽  
Adverse Drug Events ◽  
Factor Xa ◽  
Similar Reaction ◽  
Medication Regimen ◽  
Nonvalvular Atrial Fibrillation ◽  
Novel Oral Anticoagulant ◽  
History Of ◽  
Potential Issue ◽  
Full Body

Introduction: Rivaroxaban is a novel oral anticoagulant with several indications, one of which is for stroke prevention in nonvalvular atrial fibrillation. We present a case of probable rivaroxaban-induced rash. Case Summary: A 79-year-old female with a medical history of atrial fibrillation experienced a stroke, after which she was prescribed rivaroxaban 20 mg. After several days, she developed a rash requiring admission to the emergency department and several days of treatment. The rash resolved and she was switched from rivaroxaban to apixaban and did not experience any adverse drug events. Discussion: Onset of symptoms occurred within days of rivaroxaban initiation. The patient had no allergy history and never reported a similar reaction while on concurrent home medication regimen. The resolution of rash and toleration of apixaban suggest a rivaroxaban-specific reaction. The mechanism of this rash is currently unclear. Conclusion: We report one of the first cases of probable rivaroxaban-induced rash, whereas the patient tolerated apixaban. Further investigation is warranted, but prescribers should be cognizant of this potential issue when choosing a factor Xa inhibitor for anticoagulation.

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

2020 ◽  
Vol 26 ◽  
pp. 107602962095491
Author(s):  
Olivia S. Costa ◽  
Jan Beyer-Westendorf ◽  
Veronica Ashton ◽  
Dejan Milentijevic ◽  
Kenneth Todd Moore ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
African Americans ◽  
Major Bleeding ◽  
Cox Regression ◽  
Cohort Analysis ◽  
Bleeding Risk ◽  
Nonvalvular Atrial Fibrillation ◽  
Thrombotic Risk ◽  
Hazard Ratios

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.

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