scholarly journals Effectiveness and Safety of Contemporary Oral Anticoagulants Among Asians With Nonvalvular Atrial Fibrillation

Stroke ◽  
2019 ◽  
Vol 50 (8) ◽  
pp. 2245-2249 ◽  
Author(s):  
So-Ryoung Lee ◽  
Eue-Keun Choi ◽  
Soonil Kwon ◽  
Kyung-Do Han ◽  
Jin-Hyung Jung ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Gastrointestinal Bleeding ◽  
Intracranial Hemorrhage ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Asian Population ◽  
Nonvalvular Atrial Fibrillation ◽  
Observational Cohort

Background and Purpose— Limited evidence exists on the effectiveness and safety of warfarin and all 4 available non-vitamin K antagonist oral anticoagulants (NOACs) from current clinical practice in the Asian population with nonvalvular atrial fibrillation. We aimed to evaluate the comparative effectiveness and safety of warfarin and 4 NOACs. Methods— We studied a retrospective nonrandomized observational cohort of oral anticoagulant naïve nonvalvular patients with atrial fibrillation treated with warfarin or NOACs (rivaroxaban, dabigatran, apixaban, or edoxaban) from January 2015 to December 2017, based on the Korean Health Insurance Review and Assessment database. For the comparisons, warfarin to 4 NOACs and NOAC to NOAC comparison cohorts were balanced using the inverse probability of treatment weighting. Ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, and a composite clinical outcome were evaluated. Results— A total of 116 804 patients were included (25 420 with warfarin, 35 965 with rivaroxaban, 17 745 with dabigatran, 22 177 with apixaban, and 15 496 with edoxaban). Compared with warfarin, all NOACs were associated with lower risks of ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, and composite outcome. Apixaban and edoxaban showed a lower rate of ischemic stroke compared with rivaroxaban and dabigatran. Apixaban, dabigatran, and edoxaban had a lower rate of gastrointestinal bleeding and major bleeding compared with rivaroxaban. The composite clinical outcome was nonsignificantly different for apixaban versus edoxaban. Conclusions— In this large contemporary nonrandomized Asian cohort, all 4 NOACs were associated with lower rates of ischemic stroke and major bleeding compared with warfarin. Differences in clinical outcomes between NOACs may give useful guidance for physicians to choose drugs to fit their particular patient clinical profile.

P4782Direct comparison of dabigatran, apixaban, rivaroxaban and edoxaban for effectiveness and safety among patients with non-valvular atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E.-K Choi ◽  
S R Lee ◽  
S R Lee ◽  
S Kwon ◽  
S Kwon ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Asian Population ◽  
Treatment Groups ◽  
Observational Cohort ◽  
Asian Cohort ◽  
Baseline Covariates

Abstract Background Although the prescription of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) has been rapidly increasing in Asian countries since their introduction, limited evidence exists on the effectiveness and safety of warfarin and all 4 available NOACs from current clinical practice in the Asian population. We aimed to evaluate comparative effectiveness and safety of warfarin and all 4 available NOACs Methods We studied a retrospective observational cohort of oral anticoagulant (OAC) naïve non-valvular AF patients treated with warfarin or NOACs (rivaroxaban, dabigatran, apixaban, or edoxaban) from January 2015 to December 2017, based on the Korean Health Insurance Review and Assessment database. For the comparisons, warfarin to 4 NOACs and NOAC to NOAC comparison cohorts were balanced using inverse probability of treatment weighting (IPTW). Ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), major bleeding (MB) and a composite clinical outcome were evaluated. Results A total of 116,804 patients were included (25,420 with warfarin, 35,965 with rivaroxaban, 17,745 with dabigatran, 22,177 with apixaban, and 15,496 with edoxaban). Patients treated with warfarin were younger (mean age 67 years) compared to NOAC users (71 to 73 years) and had lower mean CHA2DS2-VASc score (3.18) than the NOAC groups (3.58 to 3.76). Among the NOAC users, patients prescribed apixaban were older (mean age 73 years) than other NOAC groups (71 to 72 years), had higher mean CHA2DS2-VASc score (3.76) than others (3.55 to 3.63) and higher burden of comorbidities. More than half of patients were prescribed reduced dose regimes. After IPTW, all baseline covariates were well balanced across 5 treatment groups. Compared with warfarin, all NOACs were associated with lower risks of ischemic stroke, ICH, GIB, MB and composite outcome (Figure A). Apixaban and edoxaban showed a lower rate of ischemic stroke compared with rivaroxaban and dabigatran (Figure B). Apixaban, dabigatran and edoxaban had a lower rate of GIB and MB compared with rivaroxaban. The composite clinical outcome was non-significantly different for apixaban vs edoxaban. Conclusions In this large contemporary observational Asian cohort, all 4 NOACs were associated with lower rates of ischemic stroke and major bleeding compared to warfarin. Differences in clinical outcomes between NOACs may give useful guidance for physicians to choose drugs to fit their particular patient clinical profile.

scholarly journals Early Initiation of Direct Oral Anticoagulants After Onset of Stroke and Short- and Long-Term Outcomes of Patients With Nonvalvular Atrial Fibrillation

Stroke ◽  
2020 ◽  
Vol 51 (3) ◽  
pp. 883-891 ◽  
Author(s):  
Tadataka Mizoguchi ◽  
Kanta Tanaka ◽  
Kazunori Toyoda ◽  
Sohei Yoshimura ◽  
Ryo Itabashi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Hazard Ratio ◽  
Interquartile Range ◽  
Systemic Embolism ◽  
Nonvalvular Atrial Fibrillation ◽  
Ischemic Attack

Background and Purpose— We aimed to compare outcomes of ischemic stroke patients with nonvalvular atrial fibrillation between earlier and later initiation of direct oral anticoagulants (DOACs) after stroke onset. Methods— From data for 1192 nonvalvular atrial fibrillation patients with acute ischemic stroke or transient ischemic attack in a prospective, multicenter, observational study, patients who started DOACs during acute hospitalization were included and divided into 2 groups according to a median day of DOAC initiation after onset. Outcomes included stroke or systemic embolism, major bleeding, and death at 3 months, as well as those at 2 years. Results— DOACs were initiated during acute hospitalization in 499 patients in median 4 (interquartile range, 2–7) days after onset. Thus, 223 patients (median age, 74 [interquartile range, 68–81] years; 78 women) were assigned to the early group (≤3 days) and 276 patients (median age, 75 [interquartile range, 69–82] years; 101 women) to the late (≥4 days) group. The early group had lower baseline National Institutes of Health Stroke Scale score and smaller infarcts than the late group. The rate at which DOAC administration persisted at 2 years was 85.2% overall, excluding patients who died or were lost to follow-up. Multivariable Cox shared frailty models showed comparable hazards between the groups at 2 years for stroke or systemic embolism (hazard ratio, 0.86 [95% CI, 0.47–1.57]), major bleeding (hazard ratio, 1.39 [95% CI, 0.42–4.60]), and death (hazard ratio, 0.61 [95% CI, 0.28–1.33]). Outcome risks at 3 months also did not significantly differ between the groups. Conclusions— Risks for events including stroke or systemic embolism, major bleeding, and death were comparable whether DOACs were started within 3 days or from 4 days or more after the onset of nonvalvular atrial fibrillation–associated ischemic stroke or transient ischemic attack. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01581502.

scholarly journals Direct Oral Anticoagulants versus Warfarin in Octogenarians with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (22) ◽  
pp. 5268
Author(s):  
Clara Bonanad ◽  
Sergio García-Blas ◽  
Javier Torres Llergo ◽  
Rosa Fernández-Olmo ◽  
Pablo Díez-Villanueva ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Intracranial Bleeding ◽  
Significant Heterogeneity ◽  
Nonvalvular Atrial Fibrillation ◽  
Warfarin Group

Direct oral anticoagulants (DOACs) have been demonstrated to be more effective and safer than vitamin-K antagonist (VKA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). This meta-analysis aims to assess the effect of DOACS vs. VKA in patients ≥ 80 and AF. Primary endpoints were stroke or systemic embolism and all-cause death. Secondary endpoints included major bleeding, intracranial bleeding, and gastrointestinal bleeding. A random-effects model was selected due to significant heterogeneity. A total of 147,067 patients from 16 studies were included, 71,913 (48.90%) treated with DOACs and 75,154 with VKA (51.10%). The stroke rate was significantly lower in DOACs group compared with warfarin group (Relative risk (RR): 0.72; 95% confidence interval (CI): 0.63–0.82; p < 0.001). All-cause mortality was significantly lower in DOACs group compared with warfarin group (RR: 0.82; 95% CI: 0.70–0.96; p = 0.012). Compared to warfarin, DOACs were not associated with reductions in major bleeding (RR: 0.85, 95% CI 0.69–1.04; p = 0.108) or gastrointestinal bleeding risk (RR: 1.08, 95% CI 0.76–1.53; p = 0.678) but a 43% reduction of intracranial bleeding (RR: 0.47, IC 95% 0.36–0.60; p < 0.001) was observed. Our meta-analysis demonstrates that DOACs are effective and safe with statistical superiority when compared with warfarin in octogenarians with AF.

scholarly journals Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Prior Gastrointestinal Bleeding

Stroke ◽  
2021 ◽  
Author(s):  
Soonil Kwon ◽  
So-Ryoung Lee ◽  
Eue-Keun Choi ◽  
Euijae Lee ◽  
Jin-Hyung Jung ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Hazard Ratio ◽  
Composite Outcome ◽  
Inverse Probability ◽  
Secondary Outcomes

Background and Purpose: Limited data support the benefits of non–vitamin K oral anticoagulants (NOACs) among atrial fibrillation patients with prior gastrointestinal bleeding (GIB). We aimed to evaluate the effectiveness and safety of NOACs compared with those of warfarin among atrial fibrillation patients with prior GIB. Methods: Oral anticoagulant–naive individuals with atrial fibrillation and prior GIB between January 2010 and April 2018 were identified from the Korean claims database. NOAC users were compared with warfarin users by balancing covariates using the inverse probability of treatment weighting method. The primary outcomes were ischemic stroke, major bleeding, and the composite outcome (combined ischemic stroke and major bleeding). Fatal events from each outcome were evaluated as secondary outcomes. Results: A total of 42 048 patients were included (24 781 in the NOAC group and 17 267 in the warfarin group). The mean time from prior GIB to the initiation of oral anticoagulant was 3.1±2.6 years. After inverse probability of treatment weighting, baseline characteristics were balanced between the two groups (mean age, 72 years; men, 56.8%; and mean CHA 2 DS 2 -VASc score, 3.7). Lower risks of ischemic stroke, major bleeding, and the composite outcome were associated with NOAC use than with warfarin use (weighted hazard ratio, 0.608 [95% CI, 0.543–0.680]; hazard ratio, 0.731 [95% CI, 0.642–0.832]; and hazard ratio, 0.661 [95% CI, 0.606–0.721], respectively). For all secondary outcomes, NOACs showed greater risk reductions compared with warfarin. Conclusions: NOACs were associated with lower risks of ischemic stroke and major bleeding than warfarin among atrial fibrillation patients with prior GIB.

Abstract 63: Three-month Outcomes in Japanese Stroke /TIA Patients With Non-valvular Atrial Fibrillation After Initiating Oral Anticoagulants: The SAMURAI-NVAF Study

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Shoji Arihiro ◽  
Kenichi Todo ◽  
Masatoshi Koga ◽  
Hiroshi Yamagami ◽  
Tadashi Terasaki ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Recurrent Stroke ◽  
Oral Anticoagulants ◽  
Bleeding Events ◽  
Nonvalvular Atrial Fibrillation ◽  
Fatal Bleeding ◽  
Index Stroke ◽  
Ischemic Events

Backgound and Purpose: Recently, three non-vitamin K antagonist oral anticoagulants (NOACs) became available for patients with nonvalvular atrial fibrillation (NVAF) in Japan. We aimed to determine 3-month outcomes in ischemic stroke/TIA patients receiving NOACs or warfarin from a multicenter prospective registry (SAMURAI-NVAF registry, NCT01581502). Methods: Among 1,191 acute ischemic stroke /TIA patients enrolled between September 2011 and March 2014, we studied 916 patients (389 women, 77±10 y) who took oral anticoagulants (OACs) after index stroke and completed 3-month follow-up survey. Primary outcome measures were ischemic events, including recurrent stroke/TIA and thromboembolism, and major bleedings events, such as fatal bleeding and/or symptomatic bleeding in a critical area or organ according to the International Society on Thrombosis and Haemostasis statement. We assessed the incidence and clinical factors associated with primary outcomes within 90 days after initiating OACs. Results: NOACs were given for 370 patients (126 women, 74±9 y; dabigatran 168, rivaroxaban 183 and apixaban 19) and warfarin for 546 (263 women, 79±10 y). NOAC users had lower scores of CHADS2 (median 3 in NOAC, 4 in warfarin, p<0.001) and HAS-BLED (3, 3, p<0.001) than warfarin users. Ischemic events occurred in 14 NOAC users (3.8%; 2 women, 76±6 y, including 8 lower dose users between two approved dose for each NOAC) and 25 warfarin users (4.6%; 13 women, 81±9 y). Of these, 13 NOAC users (3.5%) and 16 warfarin users (2.9%) developed ischemic stroke/TIA. Among NOAC users, patients with ischemic events had lower body weights (53±11 vs 60±11kg, p= 0.017), more frequently had congestive heart failure (36 vs 10%, p = 0.003) and intracardiac thrombus (27 vs 4%, p < 0.001) than those without. Major bleeding events occurred in 5 NOAC users (1.4%, all using lower dose), and 14 warfarin users (2.6%). Of these, one NOAC user (0.3%) and 4 warfarin users (0.7%) developed intracranial hemorrhage. Conclusion: The 3-month incidence of ischemic events in stroke/TIA patients with NVAF was approximately 4% in both NOAC and warfarin users. Intracranial hemorrhage was relatively infrequent in NOAC users.

Safety of early anticoagulation in patients treated with urgent reperfusion for acute ischemic stroke related to non-valvular atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Giustozzi
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Major Bleeding ◽  
Oral Anticoagulation ◽  
Primary Outcome ◽  
Oral Anticoagulants ◽  
Early Recurrence ◽  
Optimal Timing ◽  
Hemorrhagic Event

Abstract Background The optimal timing for starting anticoagulation after an acute ischemic stroke related to non-valvular atrial fibrillation (AF) remains a challenge, especially in patients treated with systemic thrombolysis or mechanical thrombectomy. Purpose We aimed to assess the rates of early recurrence and major bleeding in patients with acute ischemic stroke and AF treated with thrombolytic therapy and/or thrombectomy who received oral anticoagulants for secondary prevention. Methods We combined the dataset of the RAF and the RAF-NOACs studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and AF treated with either vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Results A total of 2,159 patients were included in the RAF and RAF-NOACs trials, of which 564 patients (26%) were treated with urgent reperfusion therapy. After acute stroke, 505 (90%) patients treated with reperfusion and 1,287 out of the 1,595 (81%) patients not treated with reperfusion started oral anticoagulation. Timing of starting oral anticoagulation was similar in reperfusion-treated and untreated patients (13.5±23.3 vs 12.3±18.3 days, respectively, p=0.287). At 90 days, the composite rate of recurrence and major bleeding occurred in 37 (7%) of patients treated with reperfusion treatment and in 139 (9%) of untreated patients (p=0.127). Twenty-four (4%) reperfusion-treated patients and 82 (5%) untreated patients had early recurrence while major bleeding occurred in 13 (2%) treated and in 64 (4%) untreated patients, respectively. Seven patients in the untreated group experienced both an ischemic and hemorrhagic event. Figure 1 shows the risk of early recurrence and major bleeding over time in patients treated and not treated with reperfusion treatments. The use of NOACs was associated with a favorable rate of the primary outcome compared to VKAs (Odd ratio 0.4, 95% Confidence Interval 0.3–0.7). Conclusions Reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with AF-related acute ischemic stroke who started anticoagulant treatment. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals The Number of Concomitant Drugs and the Safety of Direct Oral Anticoagulants in Routine Care Patients with Atrial Fibrillation

TH Open ◽  
2020 ◽  
Vol 04 (04) ◽  
pp. e417-e426
Author(s):  
Carline J. van den Dries ◽  
Sander van Doorn ◽  
Patrick Souverein ◽  
Romin Pajouheshnia ◽  
Karel G.M. Moons ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Routine Care ◽  
P Value ◽  
Risk Of Mortality ◽  
Mortality Effect

Abstract Background The benefit of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) on major bleeding was less prominent among atrial fibrillation (AF) patients with polypharmacy in post-hoc randomized controlled trials analyses. Whether this phenomenon also exists in routine care is unknown. The aim of the study is to investigate whether the number of concomitant drugs prescribed modifies safety and effectiveness of DOACs compared with VKAs in AF patients treated in general practice. Study Design Adult, nonvalvular AF patients with a first DOAC or VKA prescription between January 2010 and July 2018 were included, using data from the United Kingdom Clinical Practice Research Datalink. Primary outcome was major bleeding, secondary outcomes included types of major bleeding, nonmajor bleeding, ischemic stroke, and all-cause mortality. Effect modification was assessed using Cox proportional hazard regression, stratified for the number of concomitant drugs into three strata (0–5, 6–8, ≥9 drugs), and by including the continuous variable in an interaction term with the exposure (DOAC vs. VKA). Results A total of 63,600 patients with 146,059 person-years of follow-up were analyzed (39,840 person-years of DOAC follow-up). The median age was 76 years in both groups, the median number of concomitant drugs prescribed was 7. Overall, the hazard of major bleeding was similar between VKA-users and DOAC-users (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.87–1.11), though for apixaban a reduction in major bleeding was observed (HR 0.81; 95% CI 0.68–0.98). Risk of stroke was comparable, while risk of nonmajor bleeding was lower in DOAC users compared with VKA users (HR 0.92; 95% CI 0.88–0.97). We did not observe any evidence for an impact of polypharmacy on the relative risk of major bleeding between VKA and DOAC across our predefined three strata of concomitant drug use (p-value for interaction = 0.65). For mortality, however, risk of mortality was highest among DOAC users, increasing with polypharmacy and independent of the type of DOAC prescribed (p-value for interaction <0.01). Conclusion In this large observational, population-wide study of AF patients, risk of bleeding, and ischemic stroke were comparable between DOACs and VKAs, irrespective of the number of concomitant drugs prescribed. In AF patients with increasing polypharmacy, our data appeared to suggest an unexplained yet increased risk of mortality in DOAC-treated patients, compared with VKA recipients.

Abstract 160: Impact of Medication Adherence on Risk of Stroke, Major Bleeding and Other Outcomes in Atrial Fibrillation Patients Using Novel Oral Anticoagulants (Dabigatran and Rivaroxaban)

2017 ◽  
Vol 10 (suppl_3) ◽  
Author(s):  
Chinmay G Deshpande ◽  
Cynthia Willey Temkin ◽  
Robert Laforge ◽  
Stephen Kogut
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Drug Use ◽  
Propensity Score ◽  
Major Bleeding ◽  
Cox Regression ◽  
Oral Anticoagulants ◽  
Cox Models ◽  
Adherence Assessment ◽  
The Impact

Introduction: Dabigatran and Rivaroxaban have shown better or similar efficacy to lower stroke risk compared to warfarin in clinical trials. Evidence suggests adherence to cardiac drugs tend to reduce outcomes and cost. Our study is the first to examine the impact of atleast 6 to 12 month adherence to NOACs on ischemic stroke, major bleeding, Deep Vein Thrombosis and Pulmonary Embolism (DVTPE) risk in a propensity score based matched sample. Methods: A retrospective cohort study utilized de-identified data from Optum® Clinformatics™ Data Mart database (OptumInsight, Eden Prairie, MN) (Jan 1, 2010 and Dec 31, 2012). Adult patients with ≥ 1 diagnosis of atrial fibrillation or flutter (ICD9 427.31/32), >1 prescription of NOACs, 6 months pre-index continuous enrollment and CHA2DS2VASC score >1 were included. Adherence was calculated using Proportion of Days Covered (PDC ≥80%) for atleast 6 and 12 months of NOAC use and cohorts (adherent vs. non adherent) were matched on propensity score using Inverse Probability Treatment Weighting (IPTW) controlling for demographic and clinical characteristics at baseline. The risk of ischemic stroke, major bleeding (primary outcomes) and DVTPE (exploratory outcome) was evaluated for the matched cohorts post adherence assessment using Cox regression. Results: Out of 25,150 NOAC patients, a total of 3,629 and 1,946 patients with atleast 6 and 12 months of NOAC use were included. Across 2 cohorts, the mean age of the sample was 65 years, 65% were males and >60% had a moderate-high risk of stroke (CHA2DS2VASC>2). Adherence (PDC ≥80%) was 77% and 76% for patients with 6 and 12 month drug use. Post 12 months of drug use, the overall incidence of bleeding, stroke, and DVTPE in the follow-up period was 4.42%, 1.80%, and 0.82% respectively. Each outcome was analyzed separately to avoid calculation of competing risks. Using Cox models with IPTW balanced cohorts, non-adherence was significantly (p ≤0.05) associated with an increase in stroke (≥ 1.5 fold) and DVTPE (≥ 2 fold) risk in both 6 and 12 month users. The risk of bleeding was not significantly different across adherent vs. non adherent users (Table). Conclusion: In our sample, adherence to NOACs was associated with a reduction in stroke and DVTPE risk but did not substantially increase bleeding risk. Further studies with newer NOACs are warranted.

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