Dataset Information

Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a pharmacovigilance study of 27 467 patients taking rivaroxaban.

ABSTRACT:

Background

In nonvalvular atrial fibrillation (NVAF), rivaroxaban is used to prevent stroke and systemic embolism.

Objective

To evaluate major bleeding (MB) in NVAF patients treated with rivaroxaban in a real-world clinical setting.

Methods

From January 1, 2013, to March 31, 2014, US Department of Defense electronic health care records were queried to describe MB rates and demographics. Major bleeding was identified using a validated algorithm.

Results

Of 27 467 patients receiving rivaroxaban, 496 MB events occurred in 478 patients, an incidence of 2.86 per 100 person-years (95% confidence interval: 2.61-3.13). The MB patients were older, mean (SD) age of 78.4 (7.7) vs 75.7 (9.7) years, compared with non-MB patients. Patients with MB had higher rates of hypertension (95.6% vs 75.8%), coronary artery disease (64.2% vs 36.7%), heart failure (48.5% vs 23.7%), and renal disease (38.7% vs 16.7%). Of MB patients, 63.2% were taking 20 mg, 32.2% 15 mg, and 4.6% 10 mg of rivaroxaban. Four percent of MB patients took warfarin within the prior 30 days. Major bleeding was most commonly gastrointestinal (88.5%) or intracranial (7.5%). Although 46.7% of MB patients received a transfusion, none had sufficient evidence of receiving any type of clotting factor. Fourteen died during their MB hospitalization, yielding a fatal bleeding incidence rate of 0.08 per 100 person-years (95% confidence interval: 0.05-0.14). Mean age at death was 82.4 years.

Conclusions

In this large observational study, the MB rate was generally consistent with the registration trial results, and fatal bleeds were rare.

SUBMITTER: Tamayo S

PROVIDER: S-EPMC6685471 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Publications

Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a pharmacovigilance study of 27 467 patients taking rivaroxaban.

Tamayo Sally S Frank Peacock W W Patel Manesh M Sicignano Nicholas N Hopf Kathleen P KP Fields Larry E LE Sarich Troy T Wu Shujian S Yannicelli Daniel D Yuan Zhong Z

Clinical cardiology 20150114 2

<h4>Background</h4>In nonvalvular atrial fibrillation (NVAF), rivaroxaban is used to prevent stroke and systemic embolism.<h4>Objective</h4>To evaluate major bleeding (MB) in NVAF patients treated with rivaroxaban in a real-world clinical setting.<h4>Methods</h4>From January 1, 2013, to March 31, 2014, US Department of Defense electronic health care records were queried to describe MB rates and demographics. Major bleeding was identified using a validated algorithm.<h4>Results</h4>Of 27 467 pati ...[more]

PMID: 25588595

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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:ImportanceMany patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age >65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions.ObjectiveTo compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non-vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin.Design, setting, and participantsThis retrospective cohort study included patients with NVAF who were 75 years and older; had stage III to V CKD; had an HAS-BLED score of 3 or greater; used corticosteroids, antiplatelets, or NSAIDs; or had GI conditions. Data were collected from the Centers for Medicare & Medicaid Services and 4 commercial insurance databases between January 1, 2012, and September 30, 2015. Data analysis was conducted from January 2012 to September 2015.ExposuresNew prescription for apixaban, dabigatran, rivaroxaban, or warfarin between January 1, 2013, and September 30, 2015 (identification period).Main outcomes and measuresSix propensity score-matched cohorts were created to compare between study drugs. For the primary objective, Cox models were used to estimate stroke and/or SE and MB hazard ratios (HRs).ResultsA total of 381 054 patients (187 489 [49.2%] women) with NVAF and at least 1 high-risk GI bleeding factor were identified (HAS-BLED score ≥3: 284 527 [74.7%]; aged ≥75 years: 252 835 [66.4%]; corticosteroid, antiplatelet, or NSAID therapy: 107 675 [28.3%]; prior GI bleeding conditions: 74 818 [19.6%]; and stage III-V CKD: 56 892 [14.9%]). All NOACs were associated with a lower risk of stroke and/or SE vs warfarin (apixaban: HR, 0.60; 95% CI, 0.52-0.68; dabigatran: HR, 0.75; 95% CI, 0.64-0.88; rivaroxaban: HR, 0.79; 95% CI, 0.73-0.86). Compared with warfarin, apixaban and dabigatran were associated with a lower risk of MB (apixaban: HR, 0.59; 95% CI, 0.56-0.63; dabigatran: HR, 0.78; 95% CI, 0.70-0.86), while rivaroxaban was associated with a higher risk (HR, 1.11; 95% CI, 1.05-1.16).Conclusions and relevanceIn this study of patients with NVAF and high risk of GI bleed, NOACs were associated with lower rates of stroke and/or SE, but NOACs had varying risks of MB compared with warfarin. These results may help inform treatment options in this patient population.

Project description:IntroductionNew target-specific oral anticoagulants may have benefits, such as shorter hospital length of stay, compared to warfarin in patients with nonvalvular atrial fibrillation (NVAF). This study aimed to assess, among patients with NVAF, the effect of rivaroxaban versus warfarin on health care costs in a cohort of rivaroxaban users and matched warfarin users.MethodsHealth care claims from the Humana database from 5/2011 to 12/2012 were analyzed. Adult patients newly initiated on rivaroxaban or warfarin with ≥2 atrial fibrillation (AF) diagnoses (The International Classification of Diseases, Ninth Revision, Clinical Modification: 427.31) and without valvular AF were identified. Based on propensity score methods, warfarin patients were matched 1:1 to rivaroxaban patients. Patients were observed up to end of data, end of insurance coverage, death, a switch to another anticoagulant, or treatment nonpersistence. Health care costs [hospitalization, emergency room (ER), outpatient, and pharmacy costs] were evaluated using Lin's method.ResultsMatches were found for all rivaroxaban patients, and characteristics of the matched groups (n = 2253 per group) were well balanced. Estimated mean all-cause and AF-related hospitalization costs were significantly lower for rivaroxaban versus warfarin patients (all-cause: $5411 vs. $7427, P = 0.047; AF-related: $2872 vs. $4147, P = 0.020). Corresponding estimated mean all-cause outpatient visit costs were also significantly lower, but estimated mean pharmacy costs were significantly higher for rivaroxaban patients ($5316 vs. $2620, P < 0.001). Although estimated mean costs of ER visits were higher for rivaroxaban users compared to those of warfarin users, differences were not statistically significant. Including anticoagulant costs, mean overall total all-cause costs were comparable for rivaroxaban versus warfarin users due to cost offset from a reduction in the number and length of hospitalizations and number of outpatient visits ($17,590 vs. $18,676, P = 0.542).ConclusionDespite higher anticoagulant cost, mean overall total all-cause and AF-related cost remains comparable for patients with NVAF treated with rivaroxaban versus warfarin due to the cost offset from reduced health care resource utilization.

Project description:Background Reducing major bleeding events is a challenge when managing anticoagulation in patients with atrial fibrillation. This study evaluated the impact of modifiable and nonmodifiable bleeding risk factors in patients with atrial fibrillation receiving rivaroxaban and estimated the impact of risk factor modification on major bleeding events. Methods and Results Modifiable and nonmodifiable risk factors associated with major bleeding events were identified from the XANTUS (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation) prospective registry data set (6784 rivaroxaban-treated patients). Parameters showing univariate association with bleeding were used to construct a multivariable model identifying independent risk factors. Modeling was used to estimate attributed weights to risk factors. Heavy alcohol use (hazard ratio [HR]=2.37; 95% CI 1.24-4.53); uncontrolled hypertension (HR after parameter-wise shrinkage=1.79; 95% CI 1.05-3.05); and concomitant treatment with antiplatelets, nonsteroidal anti-inflammatory drugs, or paracetamol (HR=1.80; 95% CI 1.24-2.61) were identified as modifiable, independent bleeding risk factors. Increasing age (HR=1.25 [per 5-year increment]; 95% CI 1.12-1.38); heart failure (HR=1.97; 95% CI 1.36-2.86); and vascular disease (HR=1.91; 95% CI 1.32-2.77) were identified as nonmodifiable bleeding risk factors. Overall, 128 (1.9%) patients experienced major bleeding events; of these, 11% had no identified bleeding risk factors, 50% had nonmodifiable bleeding risk factors only, and 39% had modifiable bleeding risk factors (with or without nonmodifiable risk factors). The presence of 1 modifiable bleeding risk factor doubled the risk of major bleeding. Conclusions Elimination of modifiable bleeding risk factors is a potentially effective strategy to reduce bleeding risk in atrial fibrillation patients receiving rivaroxaban. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01606995.

Dataset Information

Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a pharmacovigilance study of 27 467 patients taking rivaroxaban.

Background

Objective

Methods

Results

Conclusions

Publications

Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a pharmacovigilance study of 27 467 patients taking rivaroxaban.

Similar Datasets

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