Temporal Patterns of Antithrombotic Therapy and Clinical Outcomes After Atrial Fibrillation-Related Stroke

Temporal Patterns of Antithrombotic Therapy and Clinical Outcomes After Atrial Fibrillation-Related Stroke | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Temporal Patterns of Antithrombotic Therapy and Clinical Outcomes After Atrial Fibrillation-Related Stroke View ORCID Profile Keon-Joo Lee , Hoonji Oh , View ORCID Profile Han-Gil Jeong , View ORCID Profile Beom Joon Kim , View ORCID Profile Moon-Ku Han , View ORCID Profile Joon-Tae Kim , View ORCID Profile Kang-Ho Choi , View ORCID Profile Dong-Ick Shin , View ORCID Profile Jae-Kwan Cha , View ORCID Profile Dae-Hyun Kim , Dong-Eog Kim , View ORCID Profile Jong-Moo Park , View ORCID Profile Kyusik Kang , View ORCID Profile Soo Joo Lee , View ORCID Profile Jae Guk Kim , View ORCID Profile Mi-Sun Oh , View ORCID Profile Kyung-Ho Yu , View ORCID Profile Byung-Chul Lee , View ORCID Profile Keun-Sik Hong , View ORCID Profile Yong-Jin Cho , View ORCID Profile Jay Chol Choi , View ORCID Profile Tai Hwan Park , View ORCID Profile Kyungbok Lee , View ORCID Profile Jee-Hyun Kwon , View ORCID Profile Wook-Joo Kim , View ORCID Profile Jun Lee , View ORCID Profile Ji Sung Lee , Da Young Hong , View ORCID Profile Juneyoung Lee , View ORCID Profile Philip B. Gorelick , View ORCID Profile Hee-Joon Bae CRCS-K (Clinical Research Collaboration for Stroke in Korea) investigators doi: https://doi.org/10.1101/2025.08.01.25332685 Keon-Joo Lee 1 Department of Neurology, Korea University Guro Hospital , Seoul, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Keon-Joo Lee Hoonji Oh 2 Department of Biostatistics, Korea University College of Medicine , Seoul, Korea MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Han-Gil Jeong 3 Department of Neurology, Seoul National University Bundang Hospital , Seongnam, Korea MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Han-Gil Jeong Beom Joon Kim 3 Department of Neurology, Seoul National University Bundang Hospital , Seongnam, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Beom Joon Kim Moon-Ku Han 3 Department of Neurology, Seoul National University Bundang Hospital , Seongnam, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Moon-Ku Han Joon-Tae Kim 4 Department of Neurology, Chonnam National University Hospital , Gwangju, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Joon-Tae Kim Kang-Ho Choi 4 Department of Neurology, Chonnam National University Hospital , Gwangju, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kang-Ho Choi Dong-Ick Shin 5 Department of Neurology, Chungbuk National University & Hospital , Cheongju, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Dong-Ick Shin Jae-Kwan Cha 6 Department of Neurology, Dong-A University Hospital , Busan, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jae-Kwan Cha Dae-Hyun Kim 6 Department of Neurology, Dong-A University Hospital , Busan, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Dae-Hyun Kim Dong-Eog Kim 7 Department of Neurology, Dongguk University Ilsan Hospital , Goyang, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jong-Moo Park 8 Department of Neurology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine , Uijeongbu, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jong-Moo Park Kyusik Kang 9 Department of Neurology, Nowon Eulji Medical Center, Eulji University School of Medicine , Seoul, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kyusik Kang Soo Joo Lee 10 Department of Neurology, Daejeon Eulji Medical Center, Eulji University School of Medicine , Daejeon, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Soo Joo Lee Jae Guk Kim 10 Department of Neurology, Daejeon Eulji Medical Center, Eulji University School of Medicine , Daejeon, Korea MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jae Guk Kim Mi-Sun Oh 11 Department of Neurology, Hallym University Sacred Heart Hospital , Anyang, Korea MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mi-Sun Oh Kyung-Ho Yu 11 Department of Neurology, Hallym University Sacred Heart Hospital , Anyang, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kyung-Ho Yu Byung-Chul Lee 11 Department of Neurology, Hallym University Sacred Heart Hospital , Anyang, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Byung-Chul Lee Keun-Sik Hong 12 Department of Neurology, Inje University Ilsan Paik Hospital , Goyang, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Keun-Sik Hong Yong-Jin Cho 12 Department of Neurology, Inje University Ilsan Paik Hospital , Goyang, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Yong-Jin Cho Jay Chol Choi 13 Department of Neurology, Jeju National University Hospital , Jeju, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jay Chol Choi Tai Hwan Park 14 Department of Neurology, Seoul Medical Center , Seoul, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Tai Hwan Park Kyungbok Lee 15 Department of Neurology, Soonchunhyang University Hospital, College of Medicine , Seoul, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kyungbok Lee Jee-Hyun Kwon 16 Department of Neurology, Ulsan University Hospital, Ulsan University College of Medicine , Ulsan, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jee-Hyun Kwon Wook-Joo Kim 16 Department of Neurology, Ulsan University Hospital, Ulsan University College of Medicine , Ulsan, Korea MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Wook-Joo Kim Jun Lee 17 Department of Neurology, Yeungnam University Medical Center , Daegu, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jun Lee Ji Sung Lee 18 Clinical Research Center, Asan Medical Center , Seoul, Korea PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ji Sung Lee Da Young Hong 2 Department of Biostatistics, Korea University College of Medicine , Seoul, Korea MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Juneyoung Lee 2 Department of Biostatistics, Korea University College of Medicine , Seoul, Korea PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Juneyoung Lee Philip B. Gorelick 19 Davee Department of Neurology, Northwestern University Feinberg School of Medicine , Chicago, Illinois USA MD, MPH Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Philip B. Gorelick Hee-Joon Bae 3 Department of Neurology, Seoul National University Bundang Hospital , Seongnam, Korea MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Hee-Joon Bae For correspondence: braindoc{at}snu.ac.kr braindocbae{at}gmail.com Abstract Full Text Info/History Metrics Preview PDF Abstract Background There is clinical equipoise in relation to the optimal timing and strategy for antithrombotic therapy in acute ischemic stroke (AIS) patients with atrial fibrillation (AF) who may be eligible for non-vitamin K antagonist oral anticoagulants (NOACs). This study aimed to describe the temporal evolution of antithrombotic treatment strategies and associated clinical outcomes after AF-related AIS. Methods This multicenter prospective cohort study enrolled 2,965 patients with AIS and AF from 16 tertiary stroke centers across South Korea between February 2018 and January 2021, with follow-up completed by January 2022. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause death. Secondary outcomes included individual components of the primary outcome and major bleeding events. Results The median follow-up duration was 1.92 years. Among 2,965 patients (mean [SD] age, 75.3 [10.2] years; 54.1% male), antithrombotic strategies varied widely in the acute phase. Within 48 hours of admission, 50.9% received antiplatelet-only therapy (29.4% single, 21.5% dual), 23.2% received NOAC monotherapy, and 10.4% received a combination of antiplatelets and anticoagulants. By discharge, NOAC monotherapy had become the predominant treatment strategy (65.7%), and this pattern persisted throughout follow-up. This treatment heterogeneity coincided with distinct temporal patterns in clinical outcomes. The incidence of the primary endpoint was highest in the first two weeks (32.70 [95% CI, 29.64-36.06] per 100 person-months), and declined thereafter. Across all time periods, patients receiving NOAC monotherapy consistently had lower incidence rates (3-month rate: 4.95 [95% CI, 4.37-5.61] per 100 person-months) than those receiving antiplatelet-only therapy (11.98 [95% CI, 9.57-15.01]) or no antithrombotic therapy (18.44 [95% CI, 14.26-23.86]). Conclusions In this prospective cohort of patients with AF-related stroke, early antithrombotic treatment strategies were heterogeneous but evolved primarily toward use of NOAC monotherapy by the time of discharge from the hospital and during longitudinal follow-up. Treatment selection was associated with marked differences in outcomes, particularly during the early high-risk period. These findings underscore the need for safe and effective, time-sensitive antithrombotic strategies, especially in patients for whom immediate anticoagulation is deferred. What Is New? This nationwide prospective cohort study evaluated temporal trends in antithrombotic therapy and outcomes in patients with atrial fibrillation (AF)-related ischemic stroke. There was substantial heterogeneity in early treatment strategies, which converged toward NOAC (non–vitamin K antagonist oral anticoagulant) monotherapy by discharge. The risk of recurrent vascular events and death was highest during the first 2 weeks post-stroke and varied significantly by antithrombotic regimen. What Are the Clinical Implications? The early post-stroke period represents a critical window with elevated risk and variable treatment practices. NOAC monotherapy was consistently associated with the lowest event rates, supporting early initiation when feasible. Timely and individualized antithrombotic strategies are essential to improve outcomes, especially for patients in whom anticoagulation is initially deferred. Introduction Non-vitamin K antagonist oral anticoagulants (NOACs) are a cornerstone of stroke prevention in patients with atrial fibrillation (AF). 1 NOACs offer several advantages over vitamin K antagonists (VKAs) including predictable pharmacokinetics, rapid achievement of therapeutic drug levels, fewer drug-food interactions, lower rates of brain hemorrhage complications, and fixed dosing regimens that eliminate the need for routine coagulation monitoring. 2 , 3 Their rapid onset and offset of action also confer practical benefits in the context of urgent surgical interventions and management of bleeding. 4 , 5 Although NOACs have largely replaced warfarin in the management of AF-related stroke, 6 – 8 several key questions remain unresolved. These include: 1) what antithrombotic strategies are implemented during the acute and chronic phases after stroke; 2) when are the risks of recurrent vascular events and bleeding complications highest; and 3) how do clinical outcomes vary by treatment strategy. While recent clinical trials have investigated the timing of NOAC initiation after acute stroke, 9 , 10 the generalizability of these findings is limited by narrow inclusion criteria and short follow-up durations. Such questions are difficult to address through randomized clinical trials alone, due to restrictions of patient eligibility criteria and duration of follow-up. 11 , 12 Well-designed and implemented prospective registries can help to bridge this gap by capturing real-world treatment patterns across diverse populations. To address these knowledge gaps, we conducted a nationwide, prospective cohort study of patients with AF-related acute ischemic stroke (AIS), with up to 3 years of follow-up. Our aim was to characterize contemporary antithrombotic treatment practices, examine how these strategies evolve over time after stroke onset, and evaluate temporal trends in key clinical outcomes in real-world settings. Methods Study Design and Population This was a prospective cohort study of patients with atrial fibrillation (AF)-related AIS. Although the study population was derived from the Clinical Research Collaboration for Stroke in Korea (CRCS-K) registry, 13 – 15 this investigation was conducted independently, with a separate protocol and informed consent process. Of the 20 CRCS-K participating centers, 16 tertiary stroke centers contributed to this cohort study. Patient enrollment occurred between February 2018 and January 2021. Both the CRCS-K registry and this cohort study were approved by the institutional review boards of all participating centers, and written informed consent was obtained separately for each study. Eligible patients were adults (age >18 years) who presented with AIS within 7 days from symptom onset and had either a prior diagnosis of AF or new-onset AF identified during hospitalization. All participants had diffusion-weighted imaging (DWI) evidence of acute ischemic lesions corresponding to their clinical symptoms. Patients who were unable to provide informed consent were excluded. Data Collection and Baseline Assessment At enrollment, we collected demographic data and clinical characteristics, including stroke severity (National Institutes of Health Stroke Scale [NIHSS]), premorbid functional status (modified Rankin Scale [mRS]), and time from symptom onset to hospital arrival. Vascular risk factors and medical history—including hypertension, diabetes, hyperlipidemia, coronary heart disease, peripheral artery disease, current smoking status, and previous stroke or transient ischemic attack (TIA)—were also recorded. The presence of symptomatic steno-occlusion of relevant arteries was assessed at baseline using either CT or MR angiography. Antithrombotic medication use was documented at predefined time points: prior to admission, within 48 hours of admission, at discharge, and during follow-up visits at 3 months, 1 year, 2 years, and 3 years. We recorded the specific types of agents used, including anticoagulants (NOACs, warfarin) and antiplatelet agents, as well as combination regimens. Medication adherence was assessed at the 1-year follow-up visit using self-reported compliance questionnaires. Outcome Measures and Follow-up The primary outcome was a composite of stroke recurrence, myocardial infarction, and all-cause death. Secondary outcomes included individual components of the primary outcome, ischemic stroke recurrence, and bleeding events classified according to the Bleeding Academic Research Consortium (BARC) criteria, with major bleeding defined as type 3 or 5. 16 , 17 Stroke recurrence included both new neurological deficits and progression of the index ischemic lesion within the same vascular territory, consistent with definitions used in prior clinical trials of minor ischemic stroke. 18 – 20 Follow-up assessments were conducted at predefined intervals via in-person clinic visits or structured telephone interviews using standardized questionnaires. The final follow-up exams were completed in January 2022, ensuring a minimum follow-up of 1 year and a maximum of 3 years for all participants. All suspected outcome events were adjudicated by an independent clinical event committee blinded to patients’ antithrombotic treatment status. Statistical Analysis Baseline characteristics were summarized using means and standard deviations or medians with interquartile ranges for continuous variables, and frequencies with percentages for categorical variables. Follow-up time was calculated from the date of symptom onset (designated as time zero). Antithrombotic treatment was assessed at predefined intervals: within 48 hours of admission, at discharge, and at 3 months, 1 year, 2 years, and 3 years. Treatment regimens were initially categorized into 7 groups: no treatment, NOAC monotherapy, VKA monotherapy, other anticoagulants, single antiplatelet, dual antiplatelet, and combination of antiplatelet and anticoagulant agents. A Sankey diagram illustrated the transitions in treatment over time. Group comparisons of patient characteristics at each time point were performed using one-way ANOVA or Kruskal-Wallis tests for continuous/ordinal variables, and Pearson’s chi-square tests for categorical variables. Cumulative incidence and incidence rates of clinical outcomes were estimated for predefined intervals. To explore time-dependent risk patterns, landmark analyses were performed at 3 months, 1 year, 2 years, and 3 years. For each interval, only patients who were event-free at the preceding time point were included. The first 3-month interval was further subdivided at 2 weeks to capture early trends. Cumulative incidence was estimated using the Kaplan–Meier method, and incidence rates were expressed as events per 100 person-months with 95% confidence intervals. Kaplan–Meier curves and log-rank tests were used to compare cumulative event rates across discharge treatment groups. To enhance interpretability, treatment groups were consolidated into 5 categories for outcome comparisons: (1) NOAC monotherapy, (2) VKA or other anticoagulants, (3) antiplatelet-only (combining single and dual agents, with separate analysis for each within the first 48 hours), (4) combination therapy, and (5) no treatment. Subgroup analyses for the primary outcome were prespecified by age, sex, presence of symptomatic steno-occlusion, and coronary heart disease. To evaluate associations between treatment and clinical events, multivariable Cox proportional hazards models were constructed separately for initial therapy (within 48 hours, related to in-hospital events) and discharge therapy (related to post-discharge events). Incidence rates for in-hospital events were calculated per 1,000 person-hours. All models adjusted for age, sex, NIHSS score, premorbid mRS, hypertension, diabetes, coronary heart disease, prior stroke or TIA, and symptomatic steno-occlusion. NOAC monotherapy served as the reference group. All statistical tests were two-sided, with P values <0.05 considered statistically significant. Analyses were conducted using SAS version 9.4 (SAS Institute, Cary, NC) and R version 4.2.1 (R Foundation for Statistical Computing, Vienna, Austria). Ethics and Approvals The study protocol was approved by the Institutional Review Boards of all participating centers. Written informed consent was obtained from all participants or their legal representatives. The study was conducted in accordance with the Declaration of Helsinki. Data Availability The data that support the findings of this study are available from the corresponding author upon reasonable request. Deidentified participant data may be shared with qualified researchers for non-commercial academic purposes, subject to institutional and ethical approvals. Results Among 2,965 patients with AF-related AIS, the mean (SD) age was 75.3 (10.2) years, and 54.1% were men. The median follow-up duration was 1.92 years (IQR 0.99-2.08). Valvular AF was present in 1.8% of participants. At baseline, the median NIHSS score was 6 (IQR 2-14), and 70.2% had hypertension (Table S1). Symptomatic steno-occlusion of relevant arteries was observed in 55.6%, coronary heart disease in 15.2%, and had a prior history of stroke or TIA in 25.4%. Prior to the index stroke, 30.1% were receiving antiplatelet therapy, 20.0% NOACs, and 6.8% VKAs. Marked heterogeneity in antithrombotic strategies was observed during the acute phase. Within 48 hours of admission, 29.4% received single antiplatelet therapy, 21.5% dual antiplatelet therapy, and 23.2% NOAC monotherapy ( Figure 1 and Table S2). At discharge, a substantial shift toward NOAC monotherapy (65.7%) was observed, and this pattern remained stable during follow-up, with 76.8% of patients (excluding those with missing data) still on NOAC therapy at 3 years. The proportion of patients on combined therapy with antiplatelet and anticoagulant agents peaked at discharge (13.7%) and declined to 6.4% by the second year. Download figure Open in new tab Figure 1. Temporal Changes in Antithrombotic Strategies From Acute Period to 3-Year Follow-up Sankey diagram showing transitions in antithrombotic therapy across predefined time points. The width of the flow bands represents the proportion of patients on each therapy. NOAC indicates non-vitamin K antagonist oral anticoagulant; VKA, vitamin K antagonist. The acute period was defined as within 48 hours after admission. Antithrombotic strategies were categorized as NOAC only, VKA only, other anticoagulant, single antiplatelet, dual antiplatelet, antiplatelet + anticoagulant, no antithrombotics, and no information. Among 2252 patients prescribed NOAC therapy at discharge, 29.8% had received single antiplatelet therapy, 20.2% dual antiplatelet therapy, and 32.5% NOACs within the first 48 hours ( Figure 1 and Table S2). A notable proportion of patients initially treated with antiplatelet agents were administered combination therapy with antiplatelets and anticoagulants at discharge—11% of single and 17% of dual antiplatelet users. About 40% of those initially on combination therapy remained on it at discharge, but most transitioned to NOAC monotherapy during follow-up. VKA use remained stable at approximately 5.4%. Apixaban was the most prescribed NOAC therapy, followed by edoxaban (Table S3). Among 2,446 patients completing 1-year follow-up, 2,172 (88.8%) provided adherence data. These patients reported high medication compliance, taking their prescribed antithrombotic therapy for a mean of 97.5% of days in the preceding month. Patients discharged on single antiplatelet agents or no antithrombotic therapy had more severe strokes (median NIHSS, 12), and higher rates of symptomatic steno-occlusion (68.3% and 73.2%, respectively) ( Table ). Patients discharged on single antiplatelet agents or no antithrombotic therapy had more severe strokes (median NIHSS, 12) and higher rates of symptomatic steno-occlusion (68.3% and 73.2%, respectively) ( Table ). This severity-based treatment selection was evident from the acute phase and persisted during follow-up, with differences less pronounced at 2 and 3 years (Tables S4-S9). The observed pattern likely reflects clinical concerns about hemorrhagic transformation risk in patients with large infarcts, leading to conservative anticoagulation strategies despite the known benefits of stroke prevention in AF patients. In contrast, those discharged on combination therapy had milder strokes (median NIHSS, 3), but a higher prevalence of diabetes (41.3%), coronary heart disease (31.1%), peripheral artery disease (3.6%), and prior history of stroke or TIA (36.2%). Notably, 41.3% had received anticoagulant therapy prior to the index stroke.. View this table: View inline View popup Download powerpoint Table. Baseline characteristics according to antithrombotic strategy at discharge During the median follow-up of 1.92 years, the 3-year cumulative incidence of the primary outcome was 40.7%. For bleeding events, the 3-year cumulative incidence was 10.7% for any bleeding and 4.8% for major bleeding (BARC type 3 or 5) ( Figure 2 and Table S10). The primary outcome demonstrated a distinct temporal pattern, with the highest incidence rate during the first 2 weeks (32.70 events per 100 person-months), declining to 7.92 events per 100 person-months over the first 3 months, and further decreasing thereafter (0.81 between 3 months and 1 year) (Figure S1 and Table S11). Similar trends were observed for stroke recurrence, all-cause mortality, and any bleeding ( Figure 2 and Table S10). Download figure Open in new tab Figure 2. Cumulative Incidence of Primary and Secondary Outcomes Over 3-Year Follow-up A, Overall cumulative incidence curves for the primary composite outcome (recurrent stroke, myocardial infarction, and all-cause death), and individual components including ischemic stroke recurrence. B, Landmark analysis for the primary composite outcome (recurrent stroke, myocardial infarction, and all-cause death), and individual components including ischemic stroke recurrence at 3-month, 1-year, 2-year, and 3-year time points showing conditional cumulative incidence rates. C, Overall cumulative incidence curves for bleeding events. D, Landmark analysis for bleeding events at 3-month, 1-year, 2-year, and 3-year time points showing conditional cumulative incidence rates. Shaded areas represent 95% confidence intervals. Numbers below graphs indicate patients at risk at each time point. Subgroup analyses revealed that older age (75 years or above), female sex, coronary heart disease, and symptomatic steno-occlusion were associated with higher cumulative incidence of the primary outcome (log-rank P<0.05 for all comparisons) (Figure S2). Based on discharge antithrombotic treatment strategy, the 3-month incidence rate of the primary outcome was highest among patients without antithrombotic therapy (18.44 [95% CI 14.26-23.86] per 100 person-months), followed by antiplatelet-only therapy (11.98 [95% CI 9.57-15.01]), and lowest in those receiving NOAC monotherapy (4.95 [95% CI 4.37-5.61]). These differences persisted throughout the follow-up period: the 3-year cumulative incidence was 63.0% for no antithrombotic therapy, 47.9% for antiplatelet-only therapy, and 35.7% for NOAC therapy ( Figure 3A, B and Table S12). Secondary outcomes showed similar trends (Figures S3, S4 and Tables S13 to S18). Download figure Open in new tab Figure 3. Event Rates According to Different Antithrombotic Strategies A, Cumulative incidence curves for the primary outcome stratified by discharge antithrombotic strategy. B, Landmark analysis showing conditional cumulative incidence rates by discharge antithrombotic strategy. C, Incidence rates (per 1,000 person-hours) during hospitalization according to initial antithrombotic strategy. P values are from log-rank tests. Numbers below graphs indicate patients at risk at each time point. Regarding antithrombotic treatment within first 48 hours, in-hospital event rates (per 1,000 person-hours) were highest among patients who received no therapy, followed by those on combination or antiplatelet-only regimens, and lowest in those receiving NOAC monotherapy ( Figure 3C and Figure S5). In multivariable analyses adjusting for relevant covariates, initial treatment with dual antiplatelet therapy (hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.08-2.30), combination therapy (1.75 [1.18-2.60]), and no therapy (1.65 [1.05-2.19]) was associated with significantly higher in-hospital risk of the primary outcome compared with NOAC monotherapy. At discharge, when compared with NOAC monotherapy, no antithrombotic therapy was associated with a 2-fold increased risk of the primary outcome during follow-up (HR 2.05, 95% CI 1.60-2.62), while antiplatelet-only therapy (HR, 1.60 [95% CI, 1.31-1.96]) and VKA or other oral anticoagulants (HR, 1.36 [95% CI, 1.01-1.83]) were also associated with elevated risks ( Figure 4 ). Download figure Open in new tab Figure 4. Adjusted Hazard Ratios for Primary Outcome by Antithrombotic Strategy Forest plots showing adjusted hazard ratios with 95% confidence intervals for the primary outcome according to antithrombotic strategy: A, initial therapy within the first 48 hours and its association with in-hospital outcomes; B, discharge therapy and its association with post-discharge outcomes. NOAC monotherapy served as the reference group. Models were adjusted for age, sex, initial NIHSS score, premorbid mRS, hypertension, diabetes, coronary heart disease, previous stroke/TIA, and symptomatic steno-occlusion. NIHSS indicates National Institutes of Health Stroke Scale; mRS, modified Rankin Scale; TIA, transient ischemic attack. Discussion In this large prospective cohort of patients with AF-related AIS, we identified several key findings regarding contemporary antithrombotic practices and associated outcomes. First, substantial heterogeneity was observed in acute phase antithrombotic strategies, with nearly half of patients receiving antiplatelet therapy alone and only 23.2% receiving NOAC monotherapy. This variability diminished by discharge, with NOAC monotherapy becoming predominant (65.7%) and remaining stable over time. Second, adverse clinical events were highly concentrated in the early post-stroke period, particularly within the first two weeks—coinciding with the phase of greatest treatment heterogeneity. Third, antithrombotic regimens at both the acute and discharge stages were associated with clinical outcomes, with NOAC therapy consistently associated with lower event rates compared with antiplatelet-only therapy or no treatment. This early treatment heterogeneity occurring during a period of heightened vulnerability to recurrent events, suggests a critical gap between clinical need and the implementation of evidence-based care. Patients with more severe strokes were less likely to receive anticoagulant therapy and experienced higher rates of adverse outcomes, underscoring the challenges of optimal management in these high-risk individuals. Compared to recent clinical trials, our cohort exhibited a higher rate of early events. For instance, the ELAN trial reported a 30-day cumulative incidence of 3.5% following randomization, 9 whereas the cumulative incidence in our cohort reached 5.6% within the first two weeks after stroke onset. This discrepancy likely reflects the real-world nature of our study population and its Asian ancestry. Specifically, our study included a higher proportion of patients with symptomatic steno-occlusion of relevant cerebral arteries (55.6%)—a characteristic more commonly observed in Asian populations (Figure S3). 21 , 22 The high frequency of early events poses a significant therapeutic challenge. Although current guidelines often recommend delaying anticoagulation initiation, particularly in patients with large infarcts, due to concerns about hemorrhagic transformation, recent trials support early NOAC initiation. 1 , 23 , 24 The TIMING trial demonstrated that NOAC initiation within 4 days was noninferior to delayed initiation (5-10 days), while the ELAN trial showed that severity-guided early initiation reduced vascular events without increasing hemorrhagic risk. 9 , 10 Our findings reinforce the importance of re-evaluating the optimal timing of anticoagulation initiation. The severity-based treatment selection observed in our study, where patients with more severe strokes were less likely to receive anticoagulation, highlights the need for safer therapeutic alternatives. Emerging agents such as factor XIa inhibitors may offer a safer alternative for patients at high risk of bleeding. 25 The PACIFIC-AF trial showed that asundexian was associated with a lower bleeding risk than apixaban, while maintaining comparable antithrombotic efficacy. 26 These agents may prove valuable for patients deemed ineligible for currently used anticoagulant therapies. Several earlier cohort studies have explored antithrombotic use in AF-related stroke. The SAMURAI-NVAF and K-ATTENTION studies, conducted between 2011 and 2015, reported lower rates of NOAC therapy administration at discharge (41.7% and 26.9%, respectively) compared with our cohort (65.7%). 27 , 28 The Berlin Atrial Fibrillation Registry (2014-2016) showed similar adoption rates (68.1%) to our study, reflecting the global trend towards use of NOACs. 29 While earlier studies suggested comparable outcomes between NOAC and VKA therapy users, our findings demonstrate more favorable outcomes with NOACs, likely reflecting improvements in both patient selection for NOACs and stroke care practices in contemporary settings. 30 Notably, patients discharged on VKAs experienced higher rates of adverse events, despite multivariable adjustment—likely due to well-documented limitations of VKA therapy, including difficulty in maintaining adequacy of time in therapeutic range and the need for frequent INR monitoring. 2 , 31 These findings highlight the need for safer and more practical alternatives in patients who are ineligible for NOAC therapies but remain on VKAs. A substantial proportion of patients received combination therapy with antiplatelets and anticoagulants, particularly those with coronary artery disease or symptomatic cerebral arterial steno-occlusion. Although current guidelines recommend short-term combination therapy in the setting of acute coronary syndrome, 32 , 33 optimal strategies for patients with AF and concomitant atherosclerotic disease after stroke need to be clarified. The elevated event rates in patients with concomitant coronary artery disease or symptomatic steno-occlusion of relevant cerebral arteries (Figure S2C and S2D) suggest that the current approach may be inadequate for these subgroups of patients. This study has several limitations. First, because the cohort originated from tertiary centers in Korea and the participants were of Asian ancestry, the findings may not be generalizable to other populations or healthcare systems. However, consistency with national stroke audit data supports the broader applicability of our findings, at least in Korea. 34 Second, approximately 13% of eligible patients did not provide consent and were excluded from the study, which may introduce selection bias. Third, as an observational study, causal inferences regarding treatment effectiveness are limited, and residual confounding cannot be excluded. Fourth, while medication adherence assessed at 1-year follow-up showed high compliance rates (97.5%), this relied on self-reported data from a single time point with 11.2% missing responses, potentially overestimating actual adherence. In conclusion, this large, real-world cohort of patients from Korea with AF-related AIS demonstrates that early post-stroke adverse events were frequent and associated with initial and discharge choice of antithrombotic strategies. The concentration of risk in the early phase after AIS underscores the need for future trials targeting this critical window. Additionally, the suboptimal outcomes in patients not receiving anticoagulation highlight the need for safer, more personalized treatment options. Efforts to optimized early antithrombotic management, especially with NOAC therapies may improve outcomes in this high-risk population. Sources of Funding This study was supported in part by Bayer Korea and “Korea National Institute of Health"(KNIH) research project (project No. 2023-ER-1006-02). The funding sources did not participate in any part of the study, from conception to article preparation. Disclosures Hee-Joon Bae reports grants from Amgen Inc., Bayer Korea, Bristol Myers Squibb Korea, Celltrion, Dong-A ST, Otsuka Korea, Samjin Pharm, and Takeda Pharmaceuticals Korea Co., Ltd., roles as a principal investigator or co-investigator of clinical trials sponsored by Bayer, Bristol Myers Squibb, GNT Pharma, Korean Drug Co., Ltd., and Shinpoong Pharm. Co. Ltd, and personal fees from Amgen Korea, Bayer, Daewoong Pharmaceutical Co., Ltd., Daiichi Sankyo, Esai Korea, Inc., JW Pharmaceutical, and SK chemicals, outside the submitted work. Philip B. Gorelick reports grants from the Northwestern University Havey Institute for Global Health and US NIH and consultant fees from Amgen, Bristol Myers Squibb, Genentech, American Telephysicians/NeuroX, Quantal X, JLK, UCB, and AstraZeneca. Nonstandard Abbreviations and Acronyms AF Atrial fibrillation AIS Acute ischemic stroke NOAC Non–vitamin K antagonist oral anticoagulant VKA Vitamin K antagonist CRCS-K Clinical Research Collaboration for Stroke in Korea NIHSS National Institutes of Health Stroke Scale mRS Modified Rankin Scale TIA Transient ischemic attack BARC Bleeding Academic Research Consortium References 1. ↵ Kleindorfer DO , Towfighi A , Chaturvedi S , Cockroft KM , Gutierrez J , Lombardi-Hill D , Kamel H , Kernan WN , Kittner SJ , Leira EC , Lennon O , Meschia JF , Nguyen TN , Pollak PM , Santangeli P , Sharrief AZ , Smith SC , Turan TN , Williams LS . 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association . Stroke [Internet] . 2021 ; 52 : e364 – e467 . Available from: http://www.ncbi.nlm.nih.gov/pubmed/34024117 OpenUrl 2. ↵ Yeh CH , Hogg K , Weitz JI . Overview of the new oral anticoagulants: Opportunities and challenges . Arterioscler Thromb Vasc Biol . 2015 ; 35 : 1056 – 1065 . OpenUrl Abstract / FREE Full Text 3. ↵ Gelosa P , Castiglioni L , Tenconi M , Baldessin L , Racagni G , Corsini A , Bellosta S . Pharmacokinetic drug interactions of the non-vitamin K antagonist oral anticoagulants (NOACs) . Pharmacol Res . 2018 ; 135 : 60 – 79 . OpenUrl PubMed 4. ↵ Mekaj YH , Mekaj AY , Duci SB , Miftari EI . New oral anticoagulants: Their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events . Ther Clin Risk Manag . 2015 ; 11 : 967 – 977 . OpenUrl CrossRef PubMed 5. ↵ Benesch C , Glance LG , Derdeyn CP , Fleisher LA , Holloway RG , Messé SR , Mijalski C , Nelson MT , Power M , Welch BG . Perioperative Neurological Evaluation and Management to Lower the Risk of Acute Stroke in Patients Undergoing Noncardiac, Nonneurological Surgery: A Scientific Statement From the American Heart Association/American Stroke Association . Circulation . 2021 ; 143 : E923 – E946 . OpenUrl PubMed 6. ↵ Lee M , Lee BC , Yu KH , Oh MS , Kim BJ , Kim JY , Kang J , Lee KJ , Kim DY , Park JM , Kang K , Park TH , Lee KB , Hong KS , Park HK , Cho YJ , Kim DE , Lee SJ , Kim JG , Lee J , Cha JK , Kim DH , Kim JT , Choi KH , Choi JC , Sohn S Il , Hong JH , Lee SH , Kim C , Shin DI , Yum KS , Lee J , Lee JS , Gorelick PB , Bae HJ . Secular Trends in Outcomes and Impact of Novel Oral Anticoagulants in Atrial Fibrillation-Related Acute Ischemic Stroke . Stroke . 2024 ; 55 : 625 – 633 . OpenUrl PubMed 7. Weitz JI , Semchuk W , Turpie AGG , Fisher WD , Kong C , Ciaccia A , Cairns JA . Trends in Prescribing Oral Anticoagulants in Canada, 2008-2014 . Clin Ther . 2015 ; 37 : 2506 - 2514 .e4. OpenUrl CrossRef PubMed 8. ↵ Sur NB , Wang K , Di Tullio MR , Gutierrez CM , Dong C , Koch S , Gardener H , García-Rivera EJ , Zevallos JC , Burgin WS , Rose DZ , Goldberger JJ , Romano JG , Sacco RL , Rundek T . Disparities and Temporal Trends in the Use of Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation . Stroke . 2019 ; 50 : 1452 – 1459 . OpenUrl PubMed 9. ↵ Fischer U , Koga M , Strbian D , Branca M , Abend S , Trelle S , Paciaroni M , Thomalla G , Michel P , Nedeltchev K , Bonati LH , Ntaios G , Gattringer T , Sandset E-C , Kelly P , Lemmens R , Sylaja PN , Aguiar de Sousa D , Bornstein NM , Gdovinova Z , Yoshimoto T , Tiainen M , Thomas H , Krishnan M , Shim GC , Gumbinger C , Vehoff J , Zhang L , Matsuzono K , Kristoffersen E , Desfontaines P , Vanacker P , Alonso A , Yakushiji Y , Kulyk C , Hemelsoet D , Poli S , Paiva Nunes A , Caracciolo N , Slade P , Demeestere J , Salerno A , Kneihsl M , Kahles T , Giudici D , Tanaka K , Räty S , Hidalgo R , Werring DJ , Göldlin M , Arnold M , Ferrari C , Beyeler S , Fung C , Weder BJ , Tatlisumak T , Fenzl S , Rezny-Kasprzak B , Hakim A , Salanti G , Bassetti C , Gralla J , Seiffge DJ , Horvath T , Dawson J . Early versus Later Anticoagulation for Stroke with Atrial Fibrillation . New England Journal of Medicine . 2023 ; 388 : 2411 – 2421 . OpenUrl CrossRef PubMed 10. ↵ Oldgren J , Åsberg S , Hijazi Z , Wester P , Bertilsson M , Norrving B . Early Versus Delayed Non-Vitamin K Antagonist Oral Anticoagulant Therapy after Acute Ischemic Stroke in Atrial Fibrillation (TIMING): A Registry-Based Randomized Controlled Noninferiority Study . Circulation . 2022 ; 146 : 1056 – 1066 . OpenUrl CrossRef PubMed 11. ↵ Camm AJ , Fox KAA . Strengths and weaknesses of ‘real-world’ studies involving non-vitamin K antagonist oral anticoagulants . Open Heart . 2018 ; 5 : e000788 . OpenUrl Abstract / FREE Full Text 12. ↵ Azoulay L. Rationale , Strengths, and Limitations of Real-World Evidence in Oncology: A Canadian Review and Perspective . Oncologist . 2022 ; 27 : e731 – e738 . OpenUrl CrossRef PubMed 13. ↵ Kim BJ , Park J , Kang K , Lee J , Ko Y , Kim G , Cha J , Kim D , Nah H , Han M , Park H , Park S , Lee KB , Lee J , Hong K , Cho Y , Lee B , Yu K , Oh M , Kim D , Ryu W , Cho K , Kim J , Choi C. Case Characteristics, Hyperacute Treatment, and Outcome Information from the Clinical Research Center for Stroke-Fifth Division Registry in South Korea . J Stroke [Internet] . 2015 ; 17 : 38 – 53 . Available from: http://www.ncbi.nlm.nih.gov/pubmed/25692106 OpenUrl 14. Kim BJ , Han MK , Park TH , Park SS , Lee KB , Lee BC , Yu KH , Cha JK , Kim DH , Lee J , Lee SJ , Ko Y , Park JM , Kang K , Cho YJ , Hong KS , Cho KH , Kim JT , Kim DE , Lee J , Lee JS , Jang MS , Broderick JP , Yoon BW , Bae HJ . Current status of acute stroke management in Korea: A report on a multicenter, comprehensive acute stroke registry . International Journal of Stroke . 2014 ; 9 : 514 – 518 . OpenUrl PubMed 15. ↵ Bae HJ . David G . Sherman Lecture Award: 15-Year Experience of the Nationwide Multicenter Stroke Registry in Korea . Stroke . 2022 ; 53 : 2976 – 2987 . OpenUrl PubMed 16. ↵ Urban P , Mehran R , Colleran R , Angiolillo DJ , Byrne RA , Capodanno D , Cuisset T , Cutlip D , Eerdmans P , Eikelboom J , Farb A , Gibson CM , Gregson J , Haude M , James SK , Kim HS , Kimura T , Konishi A , Laschinger J , Leon MB , Magee PFA , Mitsutake Y , Mylotte D , Pocock S , Price MJ , Rao S V. , Spitzer E , Stockbridge N , Valgimigli M , Varenne O , Windhoevel U , Yeh RW , Krucoff MW , Morice MC . Defining high bleeding risk in patients undergoing percutaneous coronary intervention: А consensus document from the Academic Research Consortiumfor High Bleeding Risk . Ukrainian Journal of Cardiology . 2021 ; 28 : 53 – 72 . OpenUrl 17. ↵ Mehran R , Rao S V. , Bhatt DL , Gibson CM , Caixeta A , Eikelboom J , Kaul S , Wiviott SD , Menon V , Nikolsky E , Serebruany V , Valgimigli M , Vranckx P , Taggart D , Sabik JF , Cutlip DE , Krucoff MW , Ohman EM , Steg PG , White H . Standardized bleeding definitions for cardiovascular clinical trials: A consensus report from the bleeding academic research consortium . Circulation . 2011 ; 123 : 2736 – 2747 . OpenUrl FREE Full Text 18. ↵ Wang Y , Wang Y , Zhao X , Liu L , Wang D , Wang C , Wang C , Li H , Meng X , Cui L , Jia J , Dong Q , Xu A , Zeng J , Li Y , Wang Z , Xia H , Johnston SC . Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack . New England Journal of Medicine . 2013 ; 369 : 11 – 19 . OpenUrl CrossRef PubMed Web of Science 19. Claiborne Johnston S , Donald Easton J , Farrant M , Barsan W , Conwit RA , Elm JJ , Kim AS , Lindblad AS , Palesch YY . Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA . New England Journal of Medicine . 2018 ; 379 : 215 – 225 . OpenUrl CrossRef PubMed 20. ↵ Johnston SC , Amarenco P , Denison H , Evans SR , Himmelmann A , James S , Knutsson M , Ladenvall P , Molina CA , Wang Y . Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA . New England Journal of Medicine [Internet] . 2020 ; 383 : 207 – 217 . Available from: http://www.nejm.org/doi/10.1056/NEJMoa1916870 OpenUrl 21. ↵ Kim JS , Bonovich D . Research on Intracranial Atherosclerosis from the East and West: Why Are the Results Different? J Stroke . 2014 ; 16 : 105 . 22. ↵ Gutierrez J , Turan TN , Hoh BL , Chimowitz MI . Intracranial atherosclerotic stenosis: risk factors, diagnosis, and treatment . Lancet Neurol . 2022 ; 21 : 355 – 368 . OpenUrl CrossRef PubMed 23. ↵ Steffel J , Verhamme P , Potpara TS , Albaladejo P , Antz M , Desteghe L , Haeusler KG , Oldgren J , Reinecke H , Roldan-Schilling V , Rowell N , Sinnaeve P , Collins R , Camm AJ , Heidbüchel H. The 2018 European Heart Rhythm Association Practical Guide on the use of non-Vitamin K antagonist oral anticoagulants in patients with atrial fibrillation . Eur Heart J . 2018 ; 39 : 1330 – 1393 . OpenUrl 24. ↵ Andrade JG , Aguilar M , Atzema C , Bell A , Cairns JA , Cheung CC , Cox JL , Dorian P , Gladstone DJ , Healey JS , Khairy P , Leblanc K , McMurtry MS , Mitchell LB , Nair GM , Nattel S , Parkash R , Pilote L , Sandhu RK , Sarrazin JF , Sharma M , Skanes AC , Talajic M , Tsang TSM , Verma A , Verma S , Whitlock R , Wyse DG , Macle L. The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation . Canadian Journal of Cardiology . 2020 ; 36 : 1847 – 1948 . OpenUrl 25. ↵ Chan NC , Weitz JI . New Therapeutic Targets for the Prevention and Treatment of Venous Thromboembolism With a Focus on Factor XI Inhibitors . Arterioscler Thromb Vasc Biol . 2023 ; 43 : 1755 – 1763 . OpenUrl PubMed 26. ↵ Piccini JP , Caso V , Connolly SJ , Fox KAA , Oldgren J , Jones WS , Gorog DA , Durdil V , Viethen T , Neumann C , Mundl H , Patel MR , Auer J , Hubauer M , Pandzic S , Preishuber E , Primus-Grabscheit C , Reitgruber D , Schmalzer F , Adlbrecht C , Schober A , Hajos J , Keil C , Schratter A , Frick M , Benda MA , Mächler M , Mutschlechner B , Saely C , Sprenger L , Lichtenauer M , Eber M , Hoppe U , Kolbitsch T , Jirak PM , Mirna M , Schönbauer R , Bergler-Klein J , Hengstenberg C , Stojkovic S , Scherr D , Manninger-Wünscher M , Rohrer U , Stühlinger M , Schgoer W , Schwarzl J , Pürerfellner H , Derndorfer M , Ebner C , Eder V , Kollias G , Sturmberger T , Sieghartsleitner S , Vijgen J , Koopman P , Dujardin K , Anné W , De Ceuninck M , Tavernier R , Duytschaever M , Knecht S , Missault L , Vandekerckhove Y , Rossenbacker T , Ector B , Charlier F , Debruyne P , Dewilde W , Janssens L , Roosen J , Vankelecom B , Heidbuchel H , Delesie M , Vervoort G , Rombouts H , Vanassche T , Engelen M , Verhamme P , Willems R , Constance C , Pranno N , Cox J , Bata I , Macle L , Aguilar M , Tourigny JC , Dubuc M , Dyrda K , Guerra P , Khairy P , Mondésert B , Rivard L , Roy D , Tadros R , Talajic M , Thibault B , Nault I , Blier L , et al. Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study . The Lancet . 2022 ; 399 : 1383 – 1390 . OpenUrl 27. ↵ Yoshimura S , Koga M , Sato S , Todo K , Yamagami H , Kumamoto M , Itabashi R , Terasaki T , Kimura K , Yagita Y , Shiokawa Y , Kamiyama K , Okuda S , Okada Y , Takizawa S , Hasegawa Y , Kameda T , Shibuya S , Nagakane Y , Ito Y , Matsuoka H , Takamatsu K , Nishiyama K , Fujita K , Kamimura T , Ando D , Ide T , Yoshimoto T , Shiozawa M , Matsubara S , Yamaguchi Y , Kinoshita N , Matsuki T , Takasugi J , Tokunaga K , Higashida K , Homma K , Kario K , Arihiro S , Toyoda K . Two-year outcomes of anticoagulation for acute ischemic stroke with nonvalvular atrial fibrillation ― SAMURAI-NVAF study . Circulation Journal . 2018 ; 82 : 1935 – 1942 . OpenUrl PubMed 28. ↵ Song TJ , Baek IY , Woo HG , Kim YJ , Chang Y , Kim BJ , Heo SH , Jung JM , Oh K , Kim CK , Yu S , Park KY , Kim JM , Park JH , Choi JC , Park MS , Kim JT , Choi KH , Hwang YH , Chung JW , Bang OY , Kim GM , Seo WK . Characteristics and factors for short-term functional outcome in stroke patients with atrial fibrillation, nationwide retrospective cohort study . Front Neurol . 2019 ; 10 . 29. ↵ Haeusler KG , Tütüncü S , Kunze C , Schurig J , Malsch C , Harder J , Wiedmann S , Dimitrijeski B , Ebinger M , Hagemann G , Hamilton F , Honermann M , Jungehulsing GJ , Kauert A , Koennecke HC , Leithner C , MacKert BM , Masuhr F , Nabavi D , Rocco A , Schmehl I , Schmitz B , Sparenberg P , Stingele R , Von Brevern M , Völzke E , Dietzel J , Heuschmann PU , Endres M . Oral anticoagulation in patients with atrial fibrillation and acute ischaemic stroke: Design and baseline data of the prospective multicentre Berlin Atrial Fibrillation Registry . Europace . 2019 ; 21 : 1621 – 1632 . OpenUrl PubMed 30. ↵ Gu HQ , Yang X , Wang CJ , Zhao XQ , Wang YL , Liu LP , Meng X , Jiang Y , Li H , Liu C , Xiong YY , Fonarow GC , Wang D , Xian Y , Li ZX , Wang YJ . Assessment of Trends in Guideline-Based Oral Anticoagulant Prescription for Patients with Ischemic Stroke and Atrial Fibrillation in China . JAMA Netw Open . 2021 ; 4 . 31. ↵ Pokorney SD , Simon DN , Thomas L , Gersh BJ , Hylek EM , Piccini JP , Peterson ED. Stability of International Normalized Ratios in Patients Taking Long-term Warfarin Therapy . JAMA [Internet] . 2016 ; 316 : 661 – 3 . Available from: http://www.ncbi.nlm.nih.gov/pubmed/27532922 OpenUrl 32. ↵ Byrne RA , Rossello X , Coughlan JJ , Barbato E , Berry C , Chieffo A , Claeys MJ , Dan GA , Dweck MR , Galbraith M , Gilard M , Hinterbuchner L , Jankowska EA , Jüni P , Kimura T , Kunadian V , Leosdottir M , Lorusso R , Pedretti RFE , Rigopoulos AG , Gimenez MR , Thiele H , Vranckx P , Wassmann S , Wenger NK , Ibanez B . 2023 ESC Guidelines for the management of acute coronary syndromes . Eur Heart J . 2023 ; 44 : 3720 – 3826 . OpenUrl CrossRef PubMed 33. ↵ Virani SS , Newby LK , Arnold S V , Bittner V , Brewer LC , Demeter SH , Dixon DL , Fearon WF , Hess B , Johnson HM , Kazi DS , Kolte D , Kumbhani DJ , LoFaso J , Mahtta D , Mark DB , Minissian M , Navar AM , Patel AR , Piano MR , Rodriguez F , Talbot AW , Taqueti VR , Thomas RJ , van Diepen S , Wiggins B , Williams MS . 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines . Circulation [Internet] . 2023 ;Available from: http://www.ncbi.nlm.nih.gov/pubmed/37471501 34. ↵ Park TH , Ko Y , Lee SJ , Lee KB , Lee J , Han MK , Park JM , Kim DE , Cho YJ , Hong KS , Kim JT , Cho KH , Kim DH , Cha JK , Yu KH , Lee BC , Yoon BW , Lee JS , Lee J , Gorelick PB , Bae HJ . Gender differences in the age-stratified prevalence of risk factors in Korean ischemic stroke patients: A nationwide stroke registry-based cross-sectional study . International Journal of Stroke . 2014 ; 9 : 759 – 765 . OpenUrl PubMed View the discussion thread. Back to top Previous Next Posted August 06, 2025. Download PDF Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Temporal Patterns of Antithrombotic Therapy and Clinical Outcomes After Atrial Fibrillation-Related Stroke Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Temporal Patterns of Antithrombotic Therapy and Clinical Outcomes After Atrial Fibrillation-Related Stroke Keon-Joo Lee , Hoonji Oh , Han-Gil Jeong , Beom Joon Kim , Moon-Ku Han , Joon-Tae Kim , Kang-Ho Choi , Dong-Ick Shin , Jae-Kwan Cha , Dae-Hyun Kim , Dong-Eog Kim , Jong-Moo Park , Kyusik Kang , Soo Joo Lee , Jae Guk Kim , Mi-Sun Oh , Kyung-Ho Yu , Byung-Chul Lee , Keun-Sik Hong , Yong-Jin Cho , Jay Chol Choi , Tai Hwan Park , Kyungbok Lee , Jee-Hyun Kwon , Wook-Joo Kim , Jun Lee , Ji Sung Lee , Da Young Hong , Juneyoung Lee , Philip B. Gorelick , Hee-Joon Bae medRxiv 2025.08.01.25332685; doi: https://doi.org/10.1101/2025.08.01.25332685 Share This Article: Copy Citation Tools Temporal Patterns of Antithrombotic Therapy and Clinical Outcomes After Atrial Fibrillation-Related Stroke Keon-Joo Lee , Hoonji Oh , Han-Gil Jeong , Beom Joon Kim , Moon-Ku Han , Joon-Tae Kim , Kang-Ho Choi , Dong-Ick Shin , Jae-Kwan Cha , Dae-Hyun Kim , Dong-Eog Kim , Jong-Moo Park , Kyusik Kang , Soo Joo Lee , Jae Guk Kim , Mi-Sun Oh , Kyung-Ho Yu , Byung-Chul Lee , Keun-Sik Hong , Yong-Jin Cho , Jay Chol Choi , Tai Hwan Park , Kyungbok Lee , Jee-Hyun Kwon , Wook-Joo Kim , Jun Lee , Ji Sung Lee , Da Young Hong , Juneyoung Lee , Philip B. Gorelick , Hee-Joon Bae medRxiv 2025.08.01.25332685; doi: https://doi.org/10.1101/2025.08.01.25332685 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Neurology Subject Areas All Articles Addiction Medicine (568) Allergy and Immunology (863) Anesthesia (300) Cardiovascular Medicine (4435) Dentistry and Oral Medicine (444) Dermatology (382) Emergency Medicine (608) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1509) Epidemiology (15229) Forensic Medicine (30) Gastroenterology (1124) Genetic and Genomic Medicine (6600) Geriatric Medicine (668) Health Economics (997) Health Informatics (4538) Health Policy (1368) Health Systems and Quality Improvement (1613) Hematology (541) HIV/AIDS (1264) Infectious Diseases (except HIV/AIDS) (15916) Intensive Care and Critical Care Medicine (1103) Medical Education (623) Medical Ethics (146) Nephrology (667) Neurology (6599) Nursing (346) Nutrition (998) Obstetrics and Gynecology (1144) Occupational and Environmental Health (957) Oncology (3333) Ophthalmology (974) Orthopedics (369) Otolaryngology (420) Pain Medicine (436) Palliative Medicine (130) Pathology (663) Pediatrics (1693) Pharmacology and Therapeutics (691) Primary Care Research (711) Psychiatry and Clinical Psychology (5447) Public and Global Health (9232) Radiology and Imaging (2198) Rehabilitation Medicine and Physical Therapy (1370) Respiratory Medicine (1196) Rheumatology (593) Sexual and Reproductive Health (712) Sports Medicine (530) Surgery (712) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a00da4c4891f300f',t:'MTc3OTYzOTc5Mw=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();