Dataset Information

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation-Related Mild Ischemic Stroke: A Randomized Clinical Trial.

ABSTRACT:

Importance

In atrial fibrillation (AF)-related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear.

Objective

To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke.

Design, setting, and participants

A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis.

Interventions

Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks.

Main outcomes and measures

The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length.

Results

Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001).

Conclusions and relevance

In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy.

Trial registration

clinicaltrials.gov Identifier: NCT02042534.

SUBMITTER: Hong KS

PROVIDER: S-EPMC5710243 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation-Related Mild Ischemic Stroke: A Randomized Clinical Trial.

Hong Keun-Sik KS Kwon Sun U SU Lee Sang Hun SH Lee Ji Sung JS Kim Yong-Jae YJ Song Tae-Jin TJ Kim Young Dae YD Park Man-Seok MS Kim Eung-Gyu EG Cha Jae-Kwan JK Sung Sang Min SM Yoon Byung-Woo BW Bang Oh Young OY Seo Woo-Keun WK Hwang Yang-Ha YH Ahn Seong Hwan SH Kang Dong-Wha DW Kang Hyun Goo HG Yu Kyung-Ho KH

JAMA neurology 20171001 10

<h4>Importance</h4>In atrial fibrillation (AF)-related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear.<h4>Objective</h4>To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke.<h4>Design, setting, and participants</h4>A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December ...[more]

PMID: 28892526

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Project description:ImportanceThe comparative effectiveness of rivaroxaban and apixaban, the most frequently prescribed oral anticoagulants for ischemic stroke prevention in patients with atrial fibrillation, is uncertain.ObjectiveTo compare major ischemic and hemorrhagic outcomes in patients with atrial fibrillation treated with rivaroxaban or apixaban.Design, setting, and participantsRetrospective cohort study using computerized enrollment and claims files for US Medicare beneficiaries 65 years or older. Between January 1, 2013, and November 30, 2018, a total of 581 451 patients with atrial fibrillation began rivaroxaban or apixaban treatment and were followed up for 4 years, through November 30, 2018.ExposuresRivaroxaban (n = 227 572) and apixaban (n = 353 879), either standard or reduced dose.Main outcomes and measuresThe primary outcome was a composite of major ischemic (stroke/systemic embolism) and hemorrhagic (intracerebral hemorrhage/other intracranial bleeding/fatal extracranial bleeding) events. Secondary outcomes were nonfatal extracranial bleeding and total mortality (fatal ischemic/hemorrhagic event or other death during follow-up). Rates, hazard ratios (HRs), and rate differences (RDs) were adjusted for baseline differences in comorbidity with inverse probability of treatment weighting.ResultsStudy patients (mean age, 77.0 years; 291 966 [50.2%] women; 134 393 [23.1%] receiving reduced dose) had 474 605 person-years of follow-up (median [IQR] of 174 [62-397] days). The adjusted primary outcome rate for rivaroxaban was 16.1 per 1000 person-years vs 13.4 per 1000 person-years for apixaban (RD, 2.7 [95% CI, 1.9-3.5]; HR, 1.18 [95% CI, 1.12-1.24]). The rivaroxaban group had increased risk for both major ischemic events (8.6 vs 7.6 per 1000 person-years; RD, 1.1 [95% CI, 0.5-1.7]; HR, 1.12 [95% CI, 1.04-1.20]) and hemorrhagic events (7.5 vs 5.9 per 1000 person-years; RD, 1.6 [95% CI, 1.1-2.1]; HR, 1.26 [95% CI, 1.16-1.36]), including fatal extracranial bleeding (1.4 vs 1.0 per 1000 person-years; RD, 0.4 [95% CI, 0.2-0.7]; HR, 1.41 [95% CI, 1.18-1.70]). Patients receiving rivaroxaban had increased risk of nonfatal extracranial bleeding (39.7 vs 18.5 per 1000 person-years; RD, 21.1 [95% CI, 20.0-22.3]; HR, 2.07 [95% CI, 1.99-2.15]), fatal ischemic/hemorrhagic events (4.5 vs 3.3 per 1000 person-years; RD, 1.2 [95% CI, 0.8-1.6]; HR, 1.34 [95% CI, 1.21-1.48]), and total mortality (44.2 vs 41.0 per 1000 person-years; RD, 3.1 [95% CI, 1.8-4.5]; HR, 1.06 [95% CI, 1.02-1.09]). The risk of the primary outcome was increased for rivaroxaban in both those receiving the reduced dose (27.4 vs 21.0 per 1000 person-years; RD, 6.4 [95% CI, 4.1-8.7]; HR, 1.28 [95% CI, 1.16-1.40]) and the standard dose (13.2 vs 11.4 per 1000 person-years; RD, 1.8 [95% CI, 1.0-2.6]; HR, 1.13 [95% CI, 1.06-1.21]) groups.Conclusions and relevanceAmong Medicare beneficiaries 65 years or older with atrial fibrillation, treatment with rivaroxaban compared with apixaban was associated with a significantly increased risk of major ischemic or hemorrhagic events.

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 and purposeComparative effectiveness and safety of oral anticoagulants in patients with atrial fibrillation and high polypharmacy are unknown.MethodsWe used Medicare administrative data to evaluate patients with new atrial fibrillation diagnosis from 2015 to 2017, who initiated an oral anticoagulant within 90 days of diagnosis. Patients taking ≤3, 4 to 8, or ≥9 other prescription medications were categorized as having low, moderate, or high polypharmacy, respectively. Within polypharmacy categories, patients receiving apixaban 5 mg twice daily, rivaroxaban 20 mg once daily, or warfarin were matched using a 3-way propensity score matching. Study outcomes included ischemic stroke, bleeding, and all-cause mortality.ResultsThe study cohort included 6985 patients using apixaban, 3838 using rivaroxaban, and 6639 using warfarin. In the propensity-matched cohorts there was no difference in risk of ischemic stroke between the 3 drugs in patients with low and moderate polypharmacy. However, among patients with high polypharmacy, the risk of ischemic stroke was higher with apixaban compared with warfarin (adjusted hazard ratio 2.34 [95% CI, 1.01-5.42]; P=0.05) and similar to rivaroxaban (adjusted hazard ratio, 1.38 [95% CI, 0.67-2.84]; P=0.4). There was no difference in risk of death between the 3 drugs in patients with low and moderate polypharmacy, but apixaban was associated with a higher risk of death compared with rivaroxaban (adjusted hazard ratio, 2.03 [95% CI, 1.01-4.08]; P=0.05) in the high polypharmacy group. Apixaban had lower bleeding risk compared with warfarin in the low polypharmacy group (adjusted hazard ratio, 0.54 [95% CI, 0.32-0.90]; P=0.02), but there was no difference in bleeding between the 3 drugs in the moderate and high polypharmacy groups.ConclusionsOur study suggests that among patients with significant polypharmacy (>8 drugs), there may be a higher stroke and mortality risk with apixaban compared with warfarin and rivaroxaban. However, differences were of borderline significance.

Dataset Information

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation-Related Mild Ischemic Stroke: A Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation-Related Mild Ischemic Stroke: A Randomized Clinical Trial.

Similar Datasets

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