A new model to predict ischemic stroke in patients with atrial fibrillation using warfarin or direct oral anticoagulants

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.

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Direct oral anticoagulants in the early phase of non valvular atrial fibrillation-related acute ischemic stroke: focus on real life studies

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-018-1775-2 ◽

2018 ◽

Vol 47 (2) ◽

pp. 292-300 ◽

Cited By ~ 3

Author(s):

Luca Masotti ◽

Elisa Grifoni ◽

Alessandro Dei ◽

Vieri Vannucchi ◽

Federico Moroni ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Early Phase ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Real Life

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Abstract P146: Comparative Effectiveness Of Direct Oral Anticoagulants Versus Warfarin Among Medicare Beneficiaries With Atrial Fibrillation

Circulation ◽

10.1161/circ.143.suppl_1.p146 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Shirin Ardeshirrouhanifard ◽

Huijun An ◽

Ravi Goyal ◽

Mukaila Raji ◽

Caleb Alexander ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Cancer Patients ◽

Risk Model ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Competing Risk ◽

Secondary Outcome ◽

Systemic Embolism ◽

Competing Risk Model

Objective: Post-hoc analysis of three pivotal clinical trials suggests no difference in risk of ischemic stroke or systemic embolism among cancer patients with atrial fibrillation treated with direct oral anticoagulants (DOACs) vs. warfarin. However, these studies were underpowered and also do not reflect the context of real-world use. We compared the effectiveness of DOACs versus warfarin for the risk of stroke or systemic embolism and all-cause death in patients with NVAF. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2009 to 2016 and included patients aged ≥66 years diagnosed with cancer (breast, bladder, colorectal, esophagus, lung, ovary, kidney, pancreas, prostate, stomach or uterus) and NVAF. We limited the cohort to patients who newly initiated warfarin or DOACs (from 2010 to 2016) with no history of ischemic stroke or systemic embolism. The primary outcome was hospitalization due to ischemic stroke or systemic embolism and the secondary outcome was all-cause death. We used Fine and Gray’s competing risk model, while treating death as a competing risk, to determine the association of oral anticoagulants with the incidence of stroke or systemic embolism. We also adjusted the analysis using inverse probability of treatment weighted (IPTW). Additionally, an IPTW-adjusted Cox proportional hazards regression model was constructed for all-cause death. Results: Of 1,028,784 patients with cancer, 158,744 (15.4%) were diagnosed with atrial fibrillation. After applying all inclusion criteria, the final study cohort included 7,334 cancer patients diagnosed with incident NVAF who newly initiated warfarin or DOACs, of which 3,194 (43.6%) used warfarin and 4,140 (56.4%) used DOACs. The unadjusted rate of stroke or systemic embolism was similar among warfarin and DOACs users (1.20 vs. 1.32 cases per 100 person-years, p=0.27). In the IPTW weighted competing risk model, the use of DOACs was not associated with an increased risk of stroke or systemic embolism compared with warfarin users (Hazard Ratio [HR] 1.41, 95% confidence intervals [CI] 0.90-2.20). However, DOACs users had a significantly lower risk of all-cause death compared with warfarin users (HR 0.82, CI 0.74-0.91). Conclusion: Among cancer patients diagnosed with NVAF, DOACs had a similar risk for stroke or systemic embolism compared to warfarin, although DOAC use was associated with reduced risk of all-cause mortality.

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Abstract WMP85: Clinical Effectiveness of Direct Oral Anticoagulants (DOACs) vs. Warfarin in Older Ischemic Stroke Patients With Atrial Fibrillation: Findings From Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study

Stroke ◽

10.1161/str.50.suppl_1.wmp85 ◽

2019 ◽

Vol 50 (Suppl_1) ◽

Author(s):

Ying Xian ◽

Haolin Xu ◽

Emily C O’Brien ◽

Shreyansh Shah ◽

Laine Thomas ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Clinical Effectiveness ◽

Effectiveness Research ◽

Stroke Patients ◽

Patient Centered

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Rates and Determinants for the Use of Anticoagulation Treatment before Stroke in Patients with Known Atrial Fibrillation

Cerebrovascular Diseases Extra ◽

10.1159/000506923 ◽

2020 ◽

Vol 10 (2) ◽

pp. 44-49

Author(s):

Michela Giustozzi ◽

Giancarlo Agnelli ◽

Silvia Quattrocchi ◽

Monica Acciarresi ◽

Andrea Alberti ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Medical Information ◽

Treatment Guidelines ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Antiplatelet Agents ◽

Anticoagulant Treatment ◽

Anticoagulation Treatment

Introduction and Objective: Even though the introduction of less cumbersome anticoagulant agents has improved, the rates ofoverall anticoagulant treatment in eligible patients with atrial fibrillation (AF) remain to be defined. We aimed to assess the rates of and determinants for the use of anticoagulation treatment before stroke in patients with known AF since the introduction of direct oral anticoagulants (DOAC) in clinical practice. Methods: Consecutive patients admitted to an individual stroke unit, from September 2013 through July 2019, for acute ischemic stroke or transient ischemic attack (TIA) with known AF before the event were included in the study. Logistic regression analysis was used to identify independent predictors of the use of anticoagulant treatment. Results: Overall, 155 patients with ischemic stroke/TIA and known AF were included in this study. Among 152 patients with a CHA2DS2-VASc score >1, 43 patients were not receiving any treatment, 47 patients were receiving antiplatelet agents, and the remaining 62 patients were on oral anticoagulants. Among 34 patients on DOAC, 13 were receiving a nonlabeled reduced dose and 18 out of 34 patients on vitamin K antagonists had an INR value <2 at the time of admission. Before stroke, only 34 out of 155 patients (21.9%) were adequately treated according to current guidelines. Previous stroke/TIA was the only independent predictor of the use of anticoagulant therapy. Conclusions: Only 21.9% of the patients hospitalized for a stroke or TIA with known AF before the event were adequately treated according to recent treatment guidelines. It is important to improve medical information about the risk of AF and the efficacy of anticoagulants in stroke prevention.

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Comparative risks of bleeding, ischemic stroke and mortality with direct oral anticoagulants versus phenprocoumon in patients with atrial fibrillation

European Journal of Clinical Pharmacology ◽

10.1007/s00228-018-2504-7 ◽

2018 ◽

Vol 74 (10) ◽

pp. 1317-1325 ◽

Cited By ~ 11

Author(s):

Mariam Ujeyl ◽

Ingrid Köster ◽

Hans Wille ◽

Thomas Stammschulte ◽

Rebecca Hein ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants

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Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation

Annals of Neurology ◽

10.1002/ana.25489 ◽

2019 ◽

Vol 85 (6) ◽

pp. 823-834 ◽

Cited By ~ 29

Author(s):

David J. Seiffge ◽

Maurizio Paciaroni ◽

Duncan Wilson ◽

Masatoshi Koga ◽

Kosmas Macha ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants

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Efficacy and Safety of Direct Oral Anticoagulants in Patients with Diabetes and Nonvalvular Atrial Fibrillation: Meta-Analysis of Observational Studies

Cardiovascular Therapeutics ◽

10.1155/2021/5520027 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Bo Cao ◽

Xingcan Yao ◽

Lifang Zhang ◽

Xiaobo Hu ◽

Min Chen ◽

...

Keyword(s):

Myocardial Infarction ◽

Atrial Fibrillation ◽

Ischemic Stroke ◽

Observational Studies ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Efficacy And Safety ◽

Nonvalvular Atrial Fibrillation ◽

Patients With Diabetes

Background. This meta-analysis was performed to compare the efficacy and safety of direct oral anticoagulants (DOACs) with vitamin K antagonists (VKAs) for stroke prevention in real-world patients with diabetes and nonvalvular atrial fibrillation (NVAF) through observational studies. Methods. PubMed, Embase, and Web of Science databases were searched up to August 2020 for eligible studies. Outputs were presented as risk ratios (RRs) and corresponding 95% confidence intervals (CIs) by using a random-effect model. Results. Seven observational studies involving 249,794 diabetic NVAF patients were selected. Compared with VKAs, the use of DOACs was associated with significantly reduced risks of stroke ( RR = 0.56 , 95% CI 0.45-0.70; p < 0.00001 ), ischemic stroke ( RR = 0.61 , 95% CI 0.48-0.78; p < 0.0001 ), stroke or systemic embolism (SSE) ( RR = 0.81 , 95% CI 0.68-0.95; p = 0.01 ), myocardial infarction ( RR = 0.69 , 95% CI 0.55-0.88; p = 0.002 ), major bleeding ( RR = 0.75 , 95% CI 0.63-0.90; p = 0.002 ), intracranial hemorrhage ( RR = 0.50 , 95% CI 0.44-0.56; p < 0.00001 ), and major gastrointestinal bleeding ( RR = 0.77 , 95% CI 0.62-0.95; p = 0.02 ), and a borderline significant decrease in major adverse cardiac events ( RR = 0.87 , 95% CI 0.75-1.00; p = 0.05 ) in NVAF patients with diabetes. Conclusion. For patients with NVAF and diabetes in real-world clinical settings, DOACs showed superior efficacy and safety profile over VKAs and significantly reduced risks of stroke, ischemic stroke, SSE, myocardial infarction, major bleeding, intracranial hemorrhage, and major gastrointestinal bleeding.

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

Stroke ◽

10.1161/strokeaha.119.028118 ◽

2020 ◽

Vol 51 (3) ◽

pp. 883-891 ◽

Cited By ~ 2

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.

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Oral Anticoagulants in Atrial Fibrillation Patients With Recent Stroke Who Are Dependent on the Daily Help of Others

Stroke ◽

10.1161/strokeaha.120.033862 ◽

2021 ◽

Author(s):

Louisa Meya ◽

Alexandros A. Polymeris ◽

Sabine Schaedelin ◽

Fabian Schaub ◽

Valerian L. Altersberger ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Proportional Hazards ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Cox Proportional Hazards ◽

Composite Outcome ◽

Unique Identifier ◽

The Individual

Background and Purpose: Data on the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with stroke attributable to atrial fibrillation (AF) who were dependent on the daily help of others at hospital discharge are scarce. Methods: Based on prospectively obtained data from the observational Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-longterm registry from Basel, Switzerland, we compared the occurrence of the primary outcome—the composite of recurrent ischemic stroke, major bleeding, and all-cause death—among consecutive patients with AF-stroke treated with either VKAs or DOACs between patients dependent (defined as modified Rankin Scale score, 3–5) and patients independent at discharge. We used simple, adjusted, and weighted Cox proportional hazards regression to account for potential confounders. Results: We analyzed 801 patients (median age 80 years, 46% female), of whom 391 (49%) were dependent at discharge and 680 (85%) received DOACs. Over a total follow-up of 1216 patient-years, DOAC- compared to VKA-treated patients had a lower hazard for the composite outcome (hazard ratio [HR], 0.58 [95% CI, 0.42–0.81]), as did independent compared to dependent patients (HR, 0.54 [95% CI, 0.40–0.71]). There was no evidence that the effect of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome differed between dependent (HR dependent , 0.68 [95% CI, 0.45–1.01]) and independent patients (HR independent , 0.44 [95% CI, 0.26–0.75]) in the simple model ( P interaction =0.212). Adjusted (HR dependent , 0.74 [95% CI, 0.49–1.11] and HR independent , 0.51 [95% CI, 0.30–0.87]; P interaction =0.284) and weighted models (HR dependent , 0.79 [95% CI, 0.48–1.31] and HR independent , 0.46 [95% CI, 0.26–0.81]; P interaction =0.163) yielded concordant results. Secondary analyses focusing on the individual components of the composite outcome were consistent to the primary analyses. Conclusions: The benefits of DOACs in patients with atrial fibrillation with a recent stroke were maintained among patients who were dependent on the help of others at discharge. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03826927.

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