Associations between Ischemic Stroke Follow-Up, Socioeconomic Status, and Adherence to Secondary Preventive Drugs in Southern Sweden: Observations from the Swedish Stroke Register (Riksstroke)

Background: Currently, the knowledge that one has on adequate stroke follow-up practices is limited. We report associations between 90-day stroke follow-up, socio-economy and adherence to secondary prevention in southern Sweden. Methods: Data on 5,602 patients with ischemic stroke January 1, 2008-December 31, 2010, were obtained from Riksstroke and linked to official registers for information on education, birth country, doctor's follow-ups, and secondary prevention. Primary adherence at 4 months and persistence at 14 months post-stroke were calculated for warfarin, statins, antihypertensive, and antiplatelet drugs. Results: The 90-day follow-up rate was 75%. Patients not receiving a 90-day follow-up had lower age-adjusted OR of persistent drug use at 14 months for antihypertensive agents (OR = 0.74, 95% CI 0.60-0.91) and for antiplatelet drugs (OR = 0.72, 95% CI 0.60-0.87). Drug adherence rates 14 months post-stroke were 85% for antiplatelet drugs, 69% for warfarin, 88% for antihypertensive agents, and 76% for statins. One in three patients discontinued using one or more drug class within 14 months, and nonadherence was associated with activities of daily living dependency at 3 months (age-adjusted OR 0.63, 95% CI 0.57-0.69), but not with age, gender, or educational status. Conclusions: The use of secondary preventive drugs decreases over the first year after stroke and remains suboptimal. Specific reasons for nonadherence warrant further study.

Download Full-text

Red Blood Cell Indices in Relation to Post-stroke Psychiatric Disorders: A Longitudinal Study in a Follow-up Stroke Clinic

Current Neurovascular Research ◽

10.2174/1567202617666200423090958 ◽

2020 ◽

Vol 17 (3) ◽

pp. 218-223

Author(s):

Haichao Wang ◽

Li Gong ◽

Xiaomei Xia ◽

Qiong Dong ◽

Aiping Jin ◽

...

Keyword(s):

Regression Analysis ◽

Ischemic Stroke ◽

Blood Cell ◽

Cox Regression ◽

Depression And Anxiety ◽

Cox Regression Analysis ◽

Post Stroke ◽

Rbc Indices ◽

Post Stroke Depression

Background: Depression and anxiety after stroke are common conditions that are likely to be neglected. Abnormal red blood cell (RBC) indices may be associated with neuropsychiatric disorders. However, the association of RBC indices with post-stroke depression (PSD) and poststroke anxiety (PSA) has not been sufficiently investigated. Methods: We aimed to investigate the trajectory of post-stroke depression and anxiety in our follow- up stroke clinic at 1, 3, and 6 months, and the association of RBC indices with these. One hundred and sixty-two patients with a new diagnosis of ischemic stroke were followed up at 1, 3, and 6 months, and underwent Patient Health Questionnaire-9 (PHQ-9) and the general anxiety disorder 7-item (GAD-7) questionnaire for evaluation of depression and anxiety, respectively. First, we used Kaplan-Meier analysis to investigate the accumulated incidences of post-stroke depression and post-stroke anxiety. Next, to explore the association of RBC indices with psychiatric disorders after an ischemic stroke attack, we adjusted for demographic and vascular risk factors using multivariate Cox regression analysis. Results: Of the 162 patients with new-onset of ischemic stroke, we found the accumulated incidence rates of PSD (1.2%, 17.9%, and 35.8%) and PSA (1.2%, 13.6%, and 15.4%) at 1, 3, and 6 months, respectively. The incident PSD and PSA increased 3 months after a stroke attack. Multivariate Cox regression analysis indicated independent positive associations between PSD risk and higher mean corpuscular volume (MCV) (OR=1.42, 95% CI=1.16-1.76), older age (OR=2.63, 95% CI=1.16-5.93), and a negative relationship between male sex (OR=0.95, 95% CI=0.91-0.99) and PSA. Conclusion: The risks of PSD and PSA increased substantially 3 months beyond stroke onset. Of the RBC indices, higher MCV, showed an independent positive association with PSD.

Download Full-text

Abstract TMP83: Long-term Risk of Venous Thromboembolism After Stroke

Stroke ◽

10.1161/str.48.suppl_1.tmp83 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Santosh B Murthy ◽

Alexander E Merkler ◽

Gino Gialdini ◽

Abhinaba Chatterjee ◽

Costantino Iadecola ◽

...

Keyword(s):

Ischemic Stroke ◽

Venous Thromboembolism ◽

Proportional Hazards ◽

Cox Regression ◽

Multivariable Analysis ◽

First Year ◽

Cumulative Rate ◽

Incident Cases

Background: There are few data on the long-term risk of venous thromboembolism (VTE) among stroke survivors. We aimed to compare the incidence of VTE amongst patients with ischemic stroke versus those with intracerebral hemorrhage (ICH). Methods: We identified all adults discharged from nonfederal acute care hospitals in CA, NY, and FL between 2005 and 2012 with previously validated ICD-9-CM codes for ischemic stroke and ICH. Our primary outcome of VTE was defined as pulmonary embolism or deep vein thrombosis. To capture incident cases of VTE, we excluded patients with a VTE prior to or during the index stroke. Kaplan-Meier survival statistics were used to calculate the cumulative rate of incident VTE. Cox regression was used to compare the risk of VTE after stroke while adjusting for demographics, vascular risk factors, and Elixhauser comorbidity index. As there was a violation of the proportional-hazards assumption, we calculated separate hazard ratios (HR) for each year of follow-up. Results: We identified 834,660 patients with stroke, of whom 712,440 (85.3%) had ischemic stroke and 112,220 (14.7%) had ICH. Over a mean follow-up of 2.8 (+/-2.4) years, 19,937 (2.4%) developed VTE. After 7 years, the cumulative rate of VTE was 4.7% (95% confidence interval [CI], 4.5-4.9%) in patients with ICH and 4.4% (95% CI, 4.3-4.5%) in patients with ischemic stroke. In multivariable analysis, VTE risk was higher in the first year after ICH compared to ischemic stroke (HR 1.51; 95% CI, 1.43-1.58). However, following the first year, the hazard of VTE was higher among patients with ischemic stroke versus those with ICH (Figure). Conclusions: The risk of VTE after stroke varies by stroke type and time. Patients with ICH have a higher risk of VTE in the first year after stroke as compared to those with ischemic stroke while patients with ischemic stroke have a higher risk beyond 1 year.

Download Full-text

Abstract TP149: Aphasia Recovery After Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp149 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Angelina Gronberg ◽

Ingrid Henriksson ◽

Arne Lindgren

Keyword(s):

Ischemic Stroke ◽

Treatment Plan ◽

Drop Out ◽

Stroke Patients ◽

Speech And Language Pathologists ◽

Aphasia Treatment ◽

Aphasia Recovery ◽

Stroke Register

Background: Establishing aphasia prevalence and outcome after ischemic stroke can facilitate strategies for treatment of aphasia. Few studies of aphasia recovery after ischemic stroke have included consecutive, unselected patients. Our aim was to identify acute and chronic prevalence of aphasia in an unselected consecutive cohort of patients with ischemic stroke. Methods: 218 patients with first-ever acute ischemic stroke were included prospectively and consecutively in the Lund Stroke Register Study. Patients with 1) dementia or psychiatric disorders; 2) non-native Swedish language; or 3) decreased consciousness were not included. Language assessment was made at baseline (within 6 days, median 3 days) after stroke onset by trained research nurses using the NIHSS sub-item 9, “Best Language” to screen for aphasia. Patients with aphasia (score of 1-3 on NIHSS item 9) were re-assessed with NIHSS item 9 by speech and language pathologists at 1 month, 3 months and 12 months after stroke. Results: Of 218 first-ever ischemic stroke patients 52 patients (24%) had aphasia according to NIHSS item 9 (median age 75 years; n=25 female). The distribution of the scores 1-3 at baseline were n=32, n=11, and n=9, respectively. At the 1 year follow-up, 31 patients (67%; n=5 deceased, n=1 drop out) had recovered from aphasia (n=28 with initial NIHSS item 9 score of 1, n=2 with initial NIHSS item 9 score of 2), even though all patients with initial global aphasia (NIHSS item 9 score of 3) had remaining aphasia (NIHSS item 9 score ≥ 1). Figure 1shows aphasia recovery (n=52) according to NIHSS item 9. Conclusions: A majority of patients with mild aphasia recover substantially from aphasia within 1 year after stroke. Patients with initial global aphasia all suffer from remaining aphasia 1 year after stroke. This suggests that this population might especially benefit from an early onset comprehensive, long-term aphasia treatment plan.

Download Full-text

Abstract TMP92: Higher Risk of Ischemic Events in Secondary Prevention for Patients With Persistent Versus Paroxysmal Atrial Fibrillation: The SAMURAI-NVAF Study

Stroke ◽

10.1161/str.47.suppl_1.tmp92 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Masatoshi Koga ◽

Sohei Yoshimura ◽

Yasuhiro Hasegawa ◽

Satoshi Shibuya ◽

Yasuhiro Ito ◽

...

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Clinical Outcomes ◽

Chads2 Score ◽

Multicenter Observational Study ◽

Hemorrhagic Events ◽

Anticoagulated Patients ◽

Prospective Multicenter Observational Study ◽

Ischemic Events

Background and purpose: The discrimination between paroxysmal and persistent atrial fibrillations (AF) has not been considered to guide secondary stroke prevention, because it remains unclear whether patients with persistent AF are at higher risk compared with paroxysmal AF, particularly in secondary prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with persistent vs. paroxysmal AF who had ischemic stroke or TIA. Methods: Using interim data of 1192 nonvalvular AF (NVAF) patients with acute ischemic stroke or TIA who were registered in the SAMURAI-NVAF study (an ongoing prospective, multicenter, observational study) to determine choice of anticoagulantion therapy and clinical outcomes, we divided patients into those with paroxysmal AF and those with persistent AF. We compared clinical outcomes between the 2 groups. Results: The median follow-up period was 1.0 year (IQR 0.3-2.0). Of the 1192 patients, 434 (191 women, 77.3±10.0 y.o.) and 758 (336, 77.9±9.9) were assigned to the paroxysmal AF group and persistent AF group, respectively. Of each group, 220 (50.7%) and 442 (58.3%) were anticoagulated with warfarin and 199 (45.9%) and 276 (36.4%) were so with non-vitamin K antagonist oral anticoagulant (NOAC) (p=0.004). As for primary outcomes, 30 (6.2%/person-year) and 78 (9.9) ischemic events, respectively [hazard ratio adjusted for sex, age, initial NIHSS, CHADS2 score, creatinine clearance, anticoagulation with warfarin (vs. NOAC) (HR) 0.65; 95% CI 0.42-0.98], and 18 (4.9%/person-year) and 31 (3.8) hemorrhagic events, respectively (HR 0.97, 0.52-1.75), occurred during follow-up. As for secondary outcomes, the person-year rate of ischemic stroke or TIA was 3.9% and 8.4%, respectively (HR 0.46, 0.27-0.76), that of intracranial hemorrhage was 1.6% and 1.7%, respectively (HR 0.97, 0.36-2.37), and that of death was 11.1% and 15.7%, respectively (HR 0.90, 0.64-1.26). Conclusions: Among patients with prior ischemic stroke or TIA, those with persistent AF had a higher risk of ischemic events, and ischemic stroke or TIA compared with those with paroxysmal AF. The prevention of progress to persistent AF from paroxysmal AF may be beneficial for secondary prevention in patients with NVAF.

Download Full-text

Abstract TP150: Effects of Pre-existing Psychotropic Medication Use on a Cohort of Patients With Ischemic Stroke Outcome

Stroke ◽

10.1161/str.51.suppl_1.tp150 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Dilip Jayaraman ◽

Nils Henninger ◽

Brian Silver ◽

Majaz Moonis ◽

Anthony Rothschild ◽

...

Keyword(s):

Ischemic Stroke ◽

Psychotropic Medication ◽

Medication Use ◽

Female Gender ◽

Control Group ◽

Stroke Outcome ◽

Stroke Registry ◽

Post Stroke ◽

Significant Difference

Background: Although SSRI use for ischemic stroke related motor recovery has been studied with mixed results, the effects of the pre-existing psychotropic medication use (PPMU), such as antidepressants, on a long-term ischemic stroke outcome is unknown. Objective: We sought to determine the prevalence of PPMU, and the clinical outcome in a cohort of patients presenting with acute ischemic strokes. Methods: We retrospectively analyzed 323 consecutive patients who presented with an acute ischemic stroke that were included in an institutional stroke registry between January 2015 and December 2017. Baseline characteristics, functional outcome measured by mRS, cardiovascular complications and death within 90 days and 365 days were recorded. The control was defined as a group of ischemic stroke patients that were not on psychotropic medications pre- and/or post-ischemic stroke. Results: The prevalence of PPMU in the studied cohort was 21.4% (69/323). The prevalence of female gender in PPMU was higher compared to the control and post stroke-psychotropic medication use groups (P<0.001), and the patients with PPMU had similar vascular risk factors compared to the control (NS), except for an increased presence of hyperlipidemia (68.1% vs. 57.5%, p<0.05). Among the patients with an available 90-day follow-up (n=175) and 365-day follow-up (n=246), there was no statistically significant difference in outcome events of MI, stroke, death, and dementia. The mRS was higher on PPMU and poststroke-psychotropic medication use groups compared to the control group within the 365-day follow-up (P=0.013). Conclusion: The prevalence of PPMU is common in ischemic stroke, and it is not associated with worsened post-stroke complications within 1 year.

Download Full-text

Abstract 15360: Prolonged P Wave Duration is Not Associated With New Onset Atrial Fibrillation During 10-year Follow-up After First-ever Ischemic Stroke in Lund Stroke Register

Circulation ◽

10.1161/circ.130.suppl_2.15360 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Maria A Baturova ◽

Arne Lindgren ◽

Jonas Carlson ◽

Yuri V Shubik ◽

Bertil Olsson ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

P Wave ◽

Stroke Patients ◽

Wave Duration ◽

Control Subjects ◽

P Wave Duration ◽

Stroke Register ◽

New Onset

Introduction: Prolonged P-wave duration (PWD) is associated with paroxysmal atrial fibrillation (AF), which might be underdiagnosed in ischemic stroke patients, in whom it might be pivotal for initiation of secondary prevention oral anticoagulation therapy. We aimed to assess whether PWD predicts new-onset AF during 10-year follow-up in ischemic stroke patients compared to control subjects enrolled in the Lund Stroke Register (LSR). Methods: Study sample comprised of 227 first-ever ischemic stroke patients without AF (mean age 72±12 y, 92 female) and 1:1 age- and gender- matched control subjects without stroke and AF enrolled in LSR from Mar 2001 to Feb 2002. The date of new-onset AF during follow-up was assessed by the date of first AF ECG in the regional ECG database and by record linkage with the Swedish National Patient Register. The available standard snapshot 12-lead sinus rhythm ECGs at baseline were retrieved from electronic database and digitally processed. Results: Patients with ischemic stroke compared to controls more often had hypertension (57% vs 31%), diabetes (15% vs 7%) and vascular diseases (42% vs 13%, all p < 0.005). New-onset AF was detected in 39 (17%) stroke patients and in 30 (13%) controls, p=0.296. In the multivariate Cox regression analysis, new onset AF in the stroke group was associated with age>65 years (HR=3.78, 95%CI 1.32-10.85, p=0.013) and hypertension (HR=2.42, 95%CI 1.09-5.40, p=0.030), but not with PWD. On the contrary, PWD>120 ms was the only independent predictor of new onset AF in the control group after adjustment for age and cardiovascular risk factors (HR=3.36, 95%CI 1.41-8.01, p=0.006, Figure 1). Conclusions: Prolonged P-wave duration is the strongest predictor of AF incidence during 10-year follow-up in stroke-free population. However, in ischemic stroke patients the developing of AF is more likely associated with more advanced cardiovascular comorbidities than with electrical abnormalities in the heart.

Download Full-text

Abstract W P29: Tissue Plasminogen Activator Mediated Reperfusion, and Subsequent Improvement in Resting State Connectivity Correlates with Functional Outcome in Acute Ischemic Stroke Patients

Stroke ◽

10.1161/str.46.suppl_1.wp29 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Souvik Sen ◽

Johann Fridriksson ◽

Taylor Hanayik ◽

Christopher Rorden ◽

Isabel Hubbard ◽

...

Keyword(s):

Ischemic Stroke ◽

Functional Connectivity ◽

Functional Outcome ◽

Resting State ◽

Network Connectivity ◽

Stroke Patients ◽

Post Stroke ◽

Resting State Network ◽

Tissue Plasminogen

Background: Intravenous Tissue Plasminogen Activator (TPA) is the only FDA approved medical therapy for acute ischemic stroke (AIS). Prior study suggests that early recanalization is associated with better stroke outcome. Our aim was to correlate task-negative and task-positive (TN/TP) resting state network activity with tissue perfusion and functional outcome, in stroke patients who received TPA. Method: AIS patients were consented and underwent NIH stroke scale (NIHSS) assessment and magnetic resonance imaging (MRI) scans during TPA infusion (baseline) and six hours post stroke. The MRI sequences include contrast-enhanced perfusion weighted image (PWI) and resting state Blood Oxygen Level-Dependent or BOLD (RSB) images acquired using a Siemens Treo 3T MRI scanner. Additionally, the RSB scan and the NIHSS were obtained at a 30-day follow up visit. Results: Fourteen patients (mean age ± SD=63 ±14, 50% male, 50% white, 43% black and 7% others) who qualified for TPA completed the study at baseline and 6 hours post stroke. Of these, 6 patients had valid follow up data at 30 days. Three patients without cerebral ischemia were excluded. A paired samples t-test comparing baseline and 6h post stroke showed a significantly improved TP network t(10)= -4.24 p< 0.05. The resting network connectivity improved from 6 hours post stroke to 30-days follow up, t(5)= -5.35 p< 0.01. Similarly, NIHSS, at 6h post stroke t(10)= 3.62 p< 0.01 and at 30-days follow up t(5)= -3.4 p< 0.01 were significantly better than the NIHSS at baseline. The 6-hours post-stroke perfusion correlated with the resting network connectivity in both the damaged (r=-0.56 p= 0.07) and intact hemispheres (r= -0.57 p= 0.06). Differences in functional connectivity and NIHSS scores from baseline to 6 h were positively correlated (r= 0.56 p=0.07). Conclusion: In this pilot study we found that TPA led to changes in MRI based resting state networks and associated functional outcome. Correlations were found between perfusion, functional connectivity and NIHSS. This suggests that the improvement of resting state network means improved efficiency of brain activity indicated by functional outcome and may be a potential predictive MRI biomarker for TPA response. A larger study is needed to verify this finding.

Download Full-text

Trial design and pilot phase results of a cluster-randomised intervention trial to improve stroke care after hospital discharge – The structured ambulatory post-stroke care program (SANO)

European Stroke Journal ◽

10.1177/2396987320910596 ◽

2020 ◽

pp. 239698732091059 ◽

Cited By ~ 2

Author(s):

Felizitas A Eichner ◽

Christopher J Schwarzbach ◽

Moritz Keller ◽

Karl Georg Haeusler ◽

Gerhard F Hamann ◽

...

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Hospital Discharge ◽

Complex Intervention ◽

Trial Design ◽

National Level ◽

Stroke Care ◽

Pilot Phase ◽

Post Stroke ◽

Hospitalised Patients

Introduction Previous studies showed insufficient control of cardiovascular risk factors (CVRF) and high stroke recurrence rates among ischemic stroke patients in Germany. Currently, no structured secondary prevention program exists in clinical routine. We present the trial design and pilot phase results of a complex intervention to improve stroke care after hospital discharge in Germany. Patients and methods SANO is a cluster-randomized trial with 30 participating regions across Germany aiming to enrol 2,790 patients (drks.de, DRKS00015322). Study intervention combines both structural and patient-centred elements. Study development was based on the Medical Research Council framework for complex interventions. In 15 intervention regions, a cross-sectoral multidisciplinary network is established to enhance CVRF control as well as detection and treatment of post-stroke complications. Recommendations on CVRF are based on high-quality secondary prevention guidelines. Study physicians use motivational interviewing and agree with patients on therapeutic targets. While hospitalised, patients also receive dietary counselling and a health-passport to track their progress. During regular visits, CVRF management and potential complications are monitored. The intervention is compared to 15 regions providing usual care. The primary endpoint is the combination of recurrent stroke, myocardial infarction and death assessed 12 months after enrolment and adjudicated in a blinded manner. Results Eighteen patients were enrolled in a pilot phase that demonstrated feasibility of patient recruitment and study procedures. Conclusion SANO is investigating a program to reduce outcome events after ischemic stroke by implementing a complex intervention. If successful, the program may be implemented in routine care on national level in Germany.

Download Full-text

Residual Risk and Its Risk Factors for Ischemic Stroke with Adherence to Guideline-Based Secondary Stroke Prevention

Journal of Stroke ◽

10.5853/jos.2020.03391 ◽

2021 ◽

Vol 23 (1) ◽

pp. 51-60

Author(s):

Yuesong Pan ◽

Zixiao Li ◽

Jiejie Li ◽

Aoming Jin ◽

Jinxi Lin ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Secondary Prevention ◽

Acute Ischemic Stroke ◽

Stroke Prevention ◽

Recurrent Stroke ◽

Antihypertensive Agents ◽

Residual Risk ◽

Stroke Recurrence ◽

Secondary Stroke Prevention

Background and Purpose Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk.Methods Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months.Results Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk.Conclusions There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.

Download Full-text

Apixaban for treatment of embolic stroke of undetermined source (ATTICUS) randomized trial – update of patient characteristics and study timeline after interim analysis

European Heart Journal ◽

10.1093/eurheartj/ehab724.2070 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

S Poli ◽

C Meissner ◽

H J Baezner ◽

A Kraft ◽

F Hillenbrand ◽

...

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Embolic Stroke ◽

High Rate ◽

Cardiac Monitoring ◽

Severe Bleeding ◽

Current Standard ◽

Private Company ◽

The Impact

Abstract Background Secondary prevention after embolic stroke of undetermined source (ESUS) has not yet been established. ESUS is associated with high risk of recurrent ischemic stroke and clinically silent ischemic lesions. Secondary prevention with aspirin is the current standard therapy in ESUS patients, despite high prevalence of occult atrial fibrillation (AF). Purpose To determine whether the direct oral factor Xa inhibitor apixaban, started within 28 days after index stroke, is superior to aspirin in preventing new ischemic lesions in subjects with remote cardiac monitoring. Primary endpoint was detection of new ischemic lesions in flair and diffusion-weighted (DWI) MR imaging at 12 months follow-up. Methods The study enrolled ESUS patients with risk profile for cardiac thromboembolism (i.e., left atrium (LA) size >45 mm, spontaneous echo contrast in LA appendage, LA appendage flow velocity ≤0.2 cm/s, atrial high rate episodes, CHA2DS2-Vasc score ≥4, patent foramen ovale). Patients were randomized 1:1 into the aspirin and apixaban arms. Study drug was initiated within 3–28 days after minor/moderate stroke and 14–28 days after major stroke. MRI (Flair/DWI) was conducted within 7 days of AF detection by remote cardiac monitors and at 12 months. ClinicalTrials.gov Identifier: NCT02427126. Funding: The trial is supported by BMS-Pfizer Alliance. Results Enrollment was stopped after interims analysis (including 200 patients) due to futility. Overall, 373 patients were screened with 353 being enrolled (178 and 175 in apixaban and ASA arms, respectively). So far, 130 (73.0%) and 120 (68.6%) subjects from apixaban and ASA arms, respectively, completed the study. 2% death, 1.7% withdrawal, and 1.7% were lost to follow-up. 3.9% did not completed the study for other reasons. Mean age of the ATTICUS population was 68.5 years with 51% males. 80% of the subjects suffered from hypertension. Mean systolic blood pressure at enrollment was 132 mmHg, BMI was 27.7, and CHA2DS-VASc-Score was 4.9. So far, adverse events (AE) occurred in 63% of the subjects, 30% was documented as severe. 6.8% cases of recurrent ischemic stroke and no case of hemorrhagic stroke were reported. Only 1 case of severe bleeding was reported in the aspirin arm. Newly detected AF was reported in 80 patients (23%), 42 occurring in the aspirin arm. As required by protocol, latter were immediately switched from aspirin to apixaban. Due to ongoing data clearing, numbers and % will change until presentation. Conclusions In contrast to the recently published NAVIGATE and RESPECT ESUS trials, patients enrolled in ATTICUS need to exhibit additional AF predicting factors. Furthermore, mandatory cardiac remote monitoring will help to elucidate the impact of AF and the effects of early oral anticoagulation with apixaban compared to antiplatelet therapy with aspirin on the incidence of new ischemic lesions after ESUS. Preliminary data will be presented and discussed in the context of current literature. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): The trial is supported by BMS-Pfizer Alliance.

Download Full-text