Rate Of Recurrent Ischemic Stroke Research Articles

Abstract WP110: DEVIATING: Determining Variability in Antiplatelet Timing in Stroke by Gender

Background: Antiplatelet administration within 48 hours of acute stroke presentation is standardized as it reduces mortality and recurrent ischemic stroke rate. Gender disparities have been noted in acute stroke care, including IV tPA and thrombectomy. Limited data exists for gender disparities in antiplatelet administration by day 2 of hospitalization. Methods: In an IRB-approved analysis, we retrospectively assessed patients admitted with acute ischemic strokes from the prospectively collected UC San Diego Stroke Registry from 2013 to 2023. We reviewed baseline demographics, whether an antiplatelet agent was initiated by hospital day 2, and choice of antiplatelet agent. We grouped patients based on their gender identification: male versus female. Patients who transitioned to comfort care, had an embolic source, were treated with a therapeutic dose of anticoagulation, had hemorrhagic conversion of infarct, or had a contraindication to antiplatelet use were excluded. Chi-squared, Kruskal-Wallis and Fisher tests were utilized. Results: 471 patients were included in this analysis (179 female, 292 male). We found no significant differences in medical history except diabetes (60 female, 69 male, p = 0.03). We found a significant difference in age (female 69.3 years, male 64.3 years, p < 0.01). We found a significant difference in patient race (p = 0.01). There was no significant difference in antiplatelet administration by hospital day 2 (171 female, 287 male, p = 0.14) or choice of antiplatelet (aspirin p = 0.29, clopidogrel p = 0.12, ticagrelor p = 0.67, dual antiplatelet p = 0.22). Conclusions: These findings suggest equality of care in antiplatelet administration for acute ischemic stroke between genders, which is reassuring. This data was collected at an academic comprehensive stroke center. Further studies should be completing including patients who were treated at various levels of stroke centers.

Changing or Retaining Direct Oral Anticoagulant After Ischemic Stroke Despite Direct Oral Anticoagulant Treatment.

The optimal antithrombotic strategies for patients with atrial fibrillation who experience ischemic stroke (IS) despite direct oral anticoagulant (DOAC) therapy remain inconclusive. This study compared outcomes for patients with DOAC treatment failure who changed or retained their prestroke DOAC. This retrospective cohort study analyzed data from the National Health Insurance Research Database from 2012 to 2020. Patients with atrial fibrillation who experienced IS during DOAC therapy were assigned to either (1) the DOAC-change group: changing prestroke DOAC or (2) the DOAC-retain group: retaining prestroke DOAC. The primary outcome was a composite of recurrent IS and transient ischemic attack. The secondary outcomes included intracranial hemorrhage, major bleeding, systemic thromboembolism, and all-cause death. Propensity score-based inverse probability of treatment weighting was applied to balance the baseline characteristics between the DOAC-change and DOAC-retain groups. The Cox proportional hazards model compared the risk of outcomes between the 2 groups. In total, 1979 patients were enrolled (609 DOAC-change patients and 1370 DOAC-retain patients). The incidence rates of recurrent IS or transient ischemic attack were 7.20 and 6.56 per 100 person-years in the DOAC-change and DOAC-retain groups, respectively (hazard ratio [HR], 1.07 [95% CI, 0.87-1.30]). A nonsignificantly higher incidence rate of intracranial hemorrhage was observed in the DOAC-change group compared with the DOAC-retain group (0.75 versus 0.53 per 100-person-years; HR, 1.49 [95% CI, 0.78-2.83]). The systemic thromboembolism, major bleeding, and death rates were comparable between the DOAC-change and DOAC-retain groups. Changing prestroke DOAC does not reduce the risk of recurrent cerebral ischemia in patients with atrial fibrillation who develop IS during DOAC therapy. However, future studies should continue to observe the potential trends of increased intracranial hemorrhage risk.

OUTCOMES OF WARFARIN THERAPY FOR SECONDARY PREVENTION OF ISCHEMIC STROKE: A RETROSPECTIVE, FOLLOW-UP STUDY

Aim: Anticoagulant prophylaxis is recommended because cardioembolic ischemic stroke is associated with worse functional outcomes, increased recurrence rates, and higher mortality. This study aimed to investigate the rates of recurrent ischemic attacks and bleeding complications in patients receiving warfarin following ischemic stroke. Method: In this retrospective analysis, a total of 181 individuals who were initiated on warfarin therapy following an ischemic stroke were included in the study. These patients were subsequently monitored for a duration spanning from 1 month to as long as 16 years. The acute ischemic stroke diagnosis was established using the Trial of Org 10172 in Acute Stroke Treatment classification criteria. Patient follow-up periods, international normalized ratio (INR) levels, ischemic events, and bleeding were recorded and evaluated. Results: In the patient cohort, 97 (53.6%) were women and 84 (46.4%) were men. The recurrent ischemic stroke rate was 7.2%, major bleeding rate was 3.3%, and minor bleeding rate was 12.7%. While the average INR value during recurrent ischemic stroke was 1.69±0.31, the average INR value during bleeding complications was observed to be 3.15±1.38. The rate of minor bleeding was related to duration of warfarin use and non-valvular atrial fibrillation. Conclusion: Our results show that long-term warfarin use and non-valvular atrial fibrillation are risk factors for bleeding.

Short- and long-term outcomes of patients with minor stroke and nonvalvular atrial fibrillation

Background and purposeNonvalvular atrial fibrillation (NVAF) is a risk factor for stroke. This study was undertaken to determine the influence of NVAF on the mortality and recurrent stroke after a minor stroke event.MethodsData were derived from the Third China National Stroke Registry (CNSR-III) which enrolled 15,166 subjects during August 2015 through March 2018 in China. Patients with minor stroke (NIHSS ≤ 5) within 24 h after onset were included. Clinical outcomes including all-cause mortality, cardiovascular death, recurrent ischemic stroke, and recurrent hemorrhagic stroke were collected. The Cox proportional hazards models were used to determine the association between NVAF and clinical outcomes.ResultsA total of 4,753 patients were included in our study. Of them, 222 patients had NVAF (4.7%) (mean age, 71.1 years) and 4,531 patients were without AF (95.3%) (mean age, 61.4 years). NVAF was associated with 12-month cardiovascular mortality in both univariate (hazards ratio [HR], 4.13; 95% confidence interval [CI], 1.84 to 9.31; P < 0.001) and multivariate analyses (HR, 4.66; 95% CI, 1.79 to 12.15; P = 0.001). There was no difference in the in-hospital ischemic stroke recurrence rate between the two groups (HR, 0.45 [95% CI, 0.19 to 1.05] P = 0.07 at discharge). However, patients with NVAF had a lower rate of recurrent ischemic stroke at medium- (3 months and 6 months) and long-term (12 months) follow-up (HR, 0.33 [95% CI, 0.16 to 0.68] P = 0.003 at 3 months; 0.49 [95% CI, 0.27 to 0.89] P = 0.02 at 6 months; 0.55 [95% CI, 0.32 to 0.94] P = 0.03 at 12 months, respectively) compared with those without. There was no difference in all-cause mortality and hemorrhagic stroke between the two groups during follow-up.ConclusionsMinor stroke patients with NVAF were at higher risk of cardiovascular death but had a lower rate of recurrent ischemic stroke compared to those without during the subsequent year after stroke event. A more accurate stroke risk prediction model for NVAF is warranted for optimal patient care strategies.

Effectiveness of Transcatheter Closure of Patent Foramen Ovale in Clinical Practice.

Background Transcatheter closure of patent foramen ovale (PFO) has reduced the risk of recurrent stroke in patients with cryptogenic strokes in randomized clinical trials. Whether PFO closure in clinical practice is associated with similar benefit remains unknown. Methods and Results We identified patients with PFO and a history of ischemic stroke or transient ischemic attack who were treated with PFO closure or medical therapy in the OptumLabs database. The primary end point was recurrent ischemic stroke or systemic embolization. Secondary outcomes included mortality, all stroke, transient ischemic attack, and major bleeding. A total of 6668 propensity-matched patients were included (PFO closure n=4111; medical therapy n=2557). The incidence of stroke or systemic embolization per 100 person-years was 2.38 after PFO cohort and 2.99 with medical therapy (hazard ratio [HR], 0.85 [95% CI, 0.68-1.05], P=0.13). Mortality was lower in the PFO closure cohort (1.78 versus 2.59 per 100 person-years: HR, 0.69 [95% CI, 0.55-0.87], P=0.002). Falsification end points showed that this difference is unlikely to be completely explained by residual confounders. There were no significant differences between the groups in secondary end points including intracranial hemorrhage and major bleeding except for an increase in nonintracranial hemorrhage bleeding among patients treated with oral anticoagulation (1.42 versus 2.16 per 100 person-years: HR, 0.69 [95% CI, 0.48-0.99], P=0.043). The main end point was consistent in subanalyses including patients <60 years of age, patients with prior stroke, and those treated after the publication of the positive PFO trials in 2017. Conclusions In contemporary US practice, PFO closure is not associated with lower rates of recurrent ischemic stroke or systemic embolization compared with medical therapy. Potential reasons for this discrepancy warrant further investigation.

Comparative effectiveness of dual to single antiplatelet therapy after one year versus seven years in patients with acute ischemic stroke combined with cerebral microbleeds

BackgroundCerebral microbleeds (CMBs) were thought to be associated with stroke. The relationship CMBs, antiplatelet therapy and prognosis is still unclear. Our aim here was to compare the long-term risk of stoke between dual and single antiplatelet therapies in patients of acute ischemic stroke (IS) combined with CMBs. MethodWe conducted a retrospective cohort study of 1017 acute IS patients received susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) sequences. We constructed a sample of patients received short-term dual antiplatelet therapy (DAPT) (n = 154) and received single antiplatelet therapy (SAPT) (n = 125), followed them for up to 7 years (median 33 months). DAPT was prescribed for at least 3 weeks, followed by using SAPT. The primary endpoint was a composite of all-cause death, recurrence IS or intracerebral hemorrhage (ICH). Secondary endpoints were a composite of recurrent IS or ICH, and the recurrent IS. ResultAt last follow-up, rated of the endpoints were similar in patients treated with SAPT and DAPT (P > 0.05). The IS risk was higher in patients treated with SAPT in the first year after the occurrence of acute IS (P = 0.035). And in 0–1 year or in 1–7 year, the risk of primary endpoint and main secondary endpoint were similar among patients treated with SAPT and DAPT (P > 0.05). ConclusionThe study is limited due to different baseline characteristics. We initially consider that the short-term DAPT may be considered to potentially reduce the rate of recurrent IS in the first year. In patients of IS combined with CMBs, the short-term DAPT may be recommended to reduce the recurrent IS.

Association of Shunt Size and Long-Term Clinical Outcomes in Patients with Cryptogenic Ischemic Stroke and Patent Foramen Ovale on Medical Management.

Patent foramen ovale (PFO) is a potential source of cardiac embolism in cryptogenic ischemic stroke, but it may also be incidental. Right-to-left shunt (RLS) size may predict PFO-related stroke, but results have been controversial. In this cohort study of medically-managed PFO patients with cryptogenic stroke, we aimed to investigate the association of shunt size with recurrent stroke, mortality, newly detected atrial fibrillation (AF), and to identify predictors of recurrent stroke. Patients with cryptogenic stroke who screened positive for a RLS using a transcranial Doppler bubble study were included. Patients who underwent PFO closure were excluded. Subjects were divided into two groups: small (Spencer Grade 1, 2, or 3; n = 135) and large (Spencer Grade 4 or 5; n = 99) shunts. The primary outcome was risk of recurrent stroke, and the secondary outcomes were all-cause mortality and newly detected AF. The study cohort included 234 cryptogenic stroke patients with medically-managed PFO. The mean age was 50.5 years, and 31.2% were female. The median period of follow-up was 348 (IQR 147-1096) days. The rate of recurrent ischemic stroke was higher in patients with large shunts than in those with small shunts (8.1% vs. 2.2%, p = 0.036). Multivariate analyses revealed that a large shunt was significantly associated with an increased risk of recurrent ischemic stroke [aOR 4.09 (95% CI 1.04-16.0), p = 0.043]. In our cohort of cryptogenic stroke patients with medically managed PFOs, those with large shunts were at a higher risk of recurrent stroke events, independently of RoPE score and left atrium diameter.

Association of distal hyperintense vessel sign and recurrent stroke in patients with symptomatic intracranial stenosis

ObjectiveThe distal hyperintense vessel sign (DHV) on fluid-attenuated inversion recovery magnetic resonance image (MRI) is an imaging biomarker of slow leptomeningeal collateral flow in the presence of large artery stenosis or occlusion reflecting impaired cerebral hemodynamics. In this study, we aim to investigate the significance of the DHV sign in patients with symptomatic ≥ 70% intracranial atherosclerotic stenosis. MethodsWe retrospectively reviewed patients with ischemic stroke or transient ischemic attack admitted to a single center from January 2010 to December 2017. Patients were included if they had symptomatic ≥ 70% atherosclerotic stenosis of the intracranial internal carotid artery or middle cerebral artery. The presence of the DHV sign was evaluated by blinded neuroradiologist and vascular neurologists. Recurrent ischemic stroke in the vascular territory of symptomatic intracranial artery was defined as new neurological deficits with associated neuroimaging findings during the follow up period. ResultsA total of 109 patients were included in the study, of which 55 had DHV sign. Average duration of follow up was 297 ± 326 days. Four patients were lost during follow up. Patients with the DHV sign had a higher rate of recurrent ischemic stroke (38%), compared to patients without the DHV sign (17%; p=0.018). In multivariate regression analysis, the presence of DHV sign was an independent predictor of recurrent ischemic stroke. A DHV score of ≥ 2 had a 63% sensitivity and 69% specificity for recurrent ischemic stroke. InterpretationIn patients with severe symptomatic intracranial atherosclerotic stenosis, those with a DHV sign on MRI are at higher risk of recurrent ischemic stroke.

Post-Treatment Plasma D-Dimer Levels Are Associated With Short-Term Outcomes in Patients With Cancer-Associated Stroke.

Background and ObjectiveHypercoagulability is associated with increased risks of ischemic stroke and subsequent mortality in patients with active cancer. This study investigated the relationships between plasma D-dimer levels after stroke treatment and short-term outcomes in patients with cancer-associated stroke.MethodsThis retrospective, observational, multicenter study analyzed consecutive patients with cancer-associated ischemic stroke. Hypercoagulability was assessed by plasma D-dimer levels before and after stroke treatment. Short-term outcomes were assessed in terms of poor outcomes (a modified Rankin Scale score >3), cumulative rates of recurrent ischemic stroke, and mortality at 30 days after admission.ResultsOf 282 patients, 135 (47.9%) showed poor outcomes. Recurrent ischemic stroke was observed in 28 patients (9.9%), and the cumulative mortality rate was 12.4%. Multivariate analysis showed that post-treatment plasma D-dimer levels ≥10 μg/ml were independently associated with both poor outcomes (adjusted odds ratio [OR], 9.61; 95% confidence interval [CI], 3.60–25.70; P < 0.001) and mortality (adjusted OR, 9.38; 95% CI, 3.32–26.44; P < 0.001). Pre-treatment plasma D-dimer levels ≥10 μg/ml were not associated with these outcomes. Patients who received heparin had higher pre-treatment plasma D-dimer levels than those treated with other anticoagulants. Heparin produced a significant reduction in D-dimer levels from pre- to post-treatment without increasing the incidence of hemorrhagic events.ConclusionA high plasma D-dimer level after stroke treatment was associated with poor short-term outcomes in patients with cancer-associated stroke. Using anticoagulants to reduce D-dimer levels may improve short-term outcomes in these patients.

Angioplasty And stenting For symptomatic intracranial atherosclerotic disease: How I Do It.

Intracranial atherosclerotic disease (ICAD) is a common cause of acute ischemic stroke. ICAD has a high rate of recurrent ischemic stroke despite recommended adequate medical treatment. Endovascular treatment of ICAD has been controversial due to high periprocedural complication in historic randomized clinical trials (RCTs). Recently, a multicenter prospective study of stent placement in patients with high grade intracranial stenosis that evaluated safety and efficacy of Balloon-mounted stents (BMS) in symptomatic ICAD showed low rates of periprocedural stroke (5.6%) than the SAMMPRIS (14.7%) and VISSIT (21.4%) trials. This review highlights the recent evolution of endovascular therapy for symptomatic ICAD.

Evaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source

Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients. Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). The mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22). In this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.

The efficacy and safety of insertable cardiac monitor on atrial fibrillation detection in patients with ischemic stroke: a systematic review and meta-analysis.

Atrial fibrillation (AF) leads to a high risk of recurrent stroke, and the insertable cardiac monitor (ICM), as a new kind of electrocardiographic monitoring device, has been proven to enhance the recognition rate of AF. The aim of this systematic review was to evaluate the efficacy and safety of the ICM use in AF detection of patients with stroke. We pooled 1233 patients from three randomized controlled trials (RCTs). The detection rate of AF was superior in the ICM group to that in the control group at 6months (risk ratio [RR], 4.63; P < 0.0001; 95% confidence interval [CI], 2.17-9.90) and 12months (RR, 5.04; P < 0.00001; 95% CI, 2.93 to 8.68). Patients in the ICM group had a higher rate of oral anticoagulant usage (RR, 2.76; P < 0.00001; 95% CI, 1.89-4.02). However, there was no difference in the time to first detection of AF within 12months (mean difference, - 8.28; P = 0.82; 95% CI, - 77.84-61.28) or the rate of recurrent ischemic stroke or transient ischemic attack (RR, 0.88; P = 0.51; 95% CI, 0.60-1.28) between the ICM and control groups. In addition, the ICM group experienced more adverse events than the control group within 12months (RR, 4.42; P = 0.002; 95% CI, 1.69-11.55). To conclude, the sensitivity of ICM is superior to that of conventional external cardiac monitoring. Reducing adverse reactions will be a new development direction of ICM.

Intracranial Atherosclerotic Disease: Current Concepts in Medical and Surgical Management.

This article reviews the current concepts in intracranial atherosclerotic disease (ICAD) as a common etiology of ischemic stroke; pathophysiologic mechanisms of ischemic stroke; diagnostic evaluation; and therapeutic modalities, including maximal medical therapy (MMT), percutaneous transluminal angioplasty and stenting (PTAS), and bypass surgery. Data from recent studies demonstrate that proper patient selection and timing of procedure and standardized PTAS techniques by experienced operators resulted in acceptably low periprocedural adverse events for patients who failed MMT. ICAD is a common cause of ischemic stroke. Complex pathology and high rates of recurrent and disabling ischemic strokes despite currently available treatments make ICAD the most challenging to treat of all ischemic stroke etiologies. Randomized trials previously showed that MMT, which involves the use of combinations of antiplatelet medications, targeted control of hypertension and serum low-density lipoprotein cholesterol, and adequate management of body weight through lifestyle modification, was superior to PTAS in decreasing rates of recurrent ischemic strokes from symptomatic ICAD. MMT performed better than expected, while periprocedural complications were significantly higher than expected in PTAS. Meanwhile, high rates of recurrent ischemic stroke despite MMT remain a great challenge. New clinical evidence continues to emerge on a safer application of PTAS, which is currently offered to a subset of patients who present with recurrent ischemic strokes despite MMT.

Therapeutic efficacy of heparin and direct factor Xa inhibitors in cancer-associated cryptogenic ischemic stroke with venous thromboembolism

BackgroundAnticoagulation therapy, especially using heparin or recently developed oral direct factor Xa inhibitors (DiXals), is recommended as first-line treatment for cancer-related venous thromboembolism (VTE). However, the preventive efficacy of these anticoagulants for cancer-associated ischemic stroke is still unknown. We retrospectively investigated the efficacy of subcutaneous unfractionated heparin (UFH) and DiXals for preventing the recurrence of cancer-associated cryptogenic ischemic stroke with VTE. MethodsWe retrospectively studied consecutive patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE who received subcutaneous UFH or oral DiXaIs at 9 hospitals. ResultFifty-three patients (24 treated with UFH and 29 treated with DiXaIs) were enrolled. Of these, 47 demonstrated systemic metastasis (cancer stage IV). During 30-day follow-up after initiation of anticoagulation therapy, recurrent ischemic stroke was observed in only 1 patient (4%) in the UFH group and in 9 patients (31%) in the DiXal group. The incidence of major bleeding complications was similar between the 2 groups (4% and 10%, respectively). The cumulative risk of ischemic stroke recurrence within 30 days was lower with UFH than with DiXals (competing risk analysis, p = 0.008). In the DiXal group, patients who experienced recurrence showed significantly higher D-dimer levels than those without recurrence. ConclusionIn patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE, UFH demonstrated a lower rate of recurrent ischemic stroke than DiXaIs, and there were no differences in bleeding risk between the 2 treatments. D-dimer levels at stroke onset increased the risk of recurrence in the DiXal group but not in the UFH group.

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76-1.14]; P=0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P=0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P=0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P=0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P=0.64) at 12 months. Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/; Unique identifier: ACTRN12611000774921.

Closure or medical therapy of patent foramen ovale in cryptogenic stroke: prospective case series

BackgroundResults of randomized controlled trials (RCT) do not provide definite guidance for secondary prevention after ischemic stroke (IS)/transient ischemic attack (TIA) attributed to patent foramen ovale (PFO). No recommendations can be made for patients > 60 years. We aimed to compare interventional and medical PFO-management in cryptogenic IS/TIA patients, including patients > 60 years.MethodsProspective case series including consecutive cryptogenic IS/TIA patients with PFO at Tuebingen university stroke unit, Germany. ‘PFO-closure’ was recommended in patients ≤70 years when featuring high-risk PFO (i.e., with atrial septal aneurysm, spontaneous, or high-grade right-to-left shunt during Valsalva). Primary (recurrent IS/intracranial hemorrhage) and secondary endpoints (e.g., disability) were assessed during ≥1-year follow-up; planned subgroup analyses of patients ≤60/> 60 years.ResultsAmong 236 patients with median age of 58 (range 18–88) years, 38.6% were females and median presenting National Institutes of Health Stroke Scale score was 1 (IQR 0–4). Mean follow-up was 2.8 ± 1.3 years. No intracranial hemorrhage was observed. Recurrent IS rate after ‘PFO-closure’ was 2.9% (95%CI 0–6.8%) and 7% (4–16.4) in high-risk PFO patients ≤60 (n = 103) and > 60 years (n = 43), respectively, versus 4% (0–11.5) during ‘medical therapy alone’ MTA (n = 28). 42 low-risk PFO patients treated with MTA experienced no recurrent IS/TIA.ConclusionsIn our real-world study, IS recurrence rate in ‘PFO-closure’ high-risk PFO patients ≤60 years was comparable to that observed in recent RCT. High-risk PFO patients > 60 years who underwent PFO-closure had similar IS recurrence rates than those who received MTA. MTA seems the appropriate treatment for low-risk PFO.Trial registrationClinicalTrials.gov, registration number: NCT04352790, registered on: April 20, 2020 – retrospectively registered.

Economic evaluation of extended electrocardiogram monitoring for atrial fibrillation in patients with cryptogenic stroke.

Timely identification of occult atrial fibrillation following cryptogenic stroke facilitates consideration of oral anticoagulation therapy. Extended electrocardiography monitoring beyond 24 to 48 h Holter monitoring improves atrial fibrillation detection rates, yet uncertainty remains due to upfront costs and the projected long-term benefit. We sought to determine the cost-effectiveness of three electrocardiography monitoring strategies in detecting atrial fibrillation after cryptogenic stroke. A decision-analytic Markov model was used to project the costs and outcomes of three different electrocardiography monitoring strategies (i.e. 30-day electrocardiography monitoring, three-year implantable loop recorder monitoring, and conventional Holter monitoring) in acute stroke survivors without previously documented atrial fibrillation. The lifetime discounted costs and quality-adjusted life years were $206,385 and 7.77 quality-adjusted life years for conventional monitoring, $207,080 and 7.79 quality-adjusted life years for 30-day extended electrocardiography monitoring, and $210,728 and 7.88 quality-adjusted life years for the implantable loop recorder strategy. Additional quality-adjusted life years could be attained at a more favorable incremental cost per quality-adjusted life year with the implantable loop recorder strategy, compared with the 30-day electrocardiography monitoring strategy, thereby eliminating the 30-day strategy by extended dominance. The implantable loop recorder strategy was associated with an incremental cost per quality-adjusted life year gained of $40,796 compared with conventional monitoring. One-way sensitivity analyses indicated that the model was most sensitive to the rate of recurrent ischemic stroke. An implantable loop recorder strategy for detection of occult atrial fibrillation in patients with cryptogenic stroke is more economically attractive than 30-day electrocardiography monitoring compared to conventional monitoring and is associated with a cost per quality-adjusted life year gained in the range of other publicly funded therapies. The value proposition is improved when considering patients at the highest risk of recurrent ischemic stroke. However, the implantable loop recorder strategy is associated with increased health care costs, and the opportunity cost of wide scale implementation must be considered.

Anticoagulation and Risk of Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source Having No Potential Source of Embolism

Background: This study aimed to determine whether use of oral anticoagulants (OACs) was associated with a reduced risk of recurrent stroke compared with use of antiplatelets (APs) in patients with embolic stroke of undetermined source (ESUS) having no potential source of embolism. Methods: Of 8,790 patients with acute ischemic stroke registered at 7 centers in the Fukuoka Stroke Registry from June 2007 to May 2017, we included 681 patients (mean age 69.7 [SD 14.1] years, 48.3% men) who experienced ESUS without a potential source of embolism and received OAC alone or AP alone. We estimated hazard ratios (HRs) and 95% confidential intervals (CIs) of recurrent ischemic stroke or any stroke after discharge using a Cox proportional hazards model and Fine and Gray model. Results: During a mean follow-up of 3.4 (SD 1.7) years, event rates of recurrent ischemic stroke were 4.4 per 100 person-years in 489 patients treated with AP and 2.0 per 100 person-years in 192 patients treated with OAC. OAC use was associated with a reduced risk of recurrent ischemic stroke, even after adjusting for potential confounding factors (multivariable-adjusted HR [95% CI], 0.42 [0.23–0.80]) and when additionally considering death as a competing risk (0.45 [0.24–0.85]). The reduced risk of recurrent ischemic stroke was still observed in patients treated with OAC (0.32 [0.15–0.67]) in reference to propensity score-matched patients treated with AP. These associations were maintained for all types of stroke, including ischemic and hemorrhagic stroke. Conclusions: This nonrandomized observational study suggests that anticoagulation therapy might be associated with a reduced risk of recurrent stroke compared with antiplatelet therapy in patients with ESUS in whom no potential source of embolism was identified. Further study should be performed in consideration of a potential source of embolism even in patients with ESUS.

Intracranial and systemic atherosclerosis in the NAVIGATE ESUS trial: Recurrent stroke risk and response to antithrombotic therapy

BackgroundNon-stenotic intracranial and systemic atherosclerosis are associated with ischemic stroke. We report frequency and response to anticoagulant vs. antiplatelet prophylaxis of patients with embolic stroke of undetermined source (ESUS) who have non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis. MethodsExploratory analysis of the international NAVIGATE ESUS randomized trial comparing rivaroxaban 15mg daily with aspirin 100mg daily in 7213 patients with recent ESUS. Among participants with results of intracranial arterial imaging with either computed tomographic angiography (CTA) or magnetic resonance angiography (MRA), the frequency and predictors of non-stenotic intracranial and systemic atherosclerosis and responses to antithrombotic therapy were assessed. ResultsAmong 4723 participants with available intracranial CTA or MRA results (65% of the trial cohort), the prevalence of intracranial atherosclerosis was 16% (n=739). Patient features independently associated with intracranial atherosclerosis included East Asian region (odds ratio 2.7, 95%CI 2.2,3.3) and cervical carotid plaque (odds ratio 2.3, 95%CI 1.9,2.7), among others. The rate of recurrent ischemic stroke averaged 4.8%/year among those with intracranial atherosclerosis vs. 5.0.%/year for those without (HR 0.95, 95%CI 0.65, 1.4). Among those with intracranial atherosclerosis, the recurrent ischemic stroke rate was higher if assigned to rivaroxaban (5.8%/year) vs. aspirin (3.7%/year), but the difference was not statistically significant (HR 1.6, 95%CI 0.78, 3.3). There was trend for the effect of antithrombotic treatments to be different according to the presence or absence of intracranial atherosclerosis (pinteraction=0.09). Among participants with evidence of systemic atherosclerosis by either history or imaging (n=3820), recurrent ischemic stroke rates were similar among those assigned to rivaroxaban (5.5%/year) vs. aspirin (4.9%/year)(HR 1.1, 95%CI 0.84, 1.5). ConclusionsEast Asia region was the strongest factor associated with intracranial atherosclerosis. There were no statistically significant differences between rivaroxaban and aspirin prophylaxis for recurrent ischemic stroke in patients with non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis.

Abstract TMP18: Early versus Late Start of Direct Oral Anticoagulants After an Ischemic Stroke Related to Atrial Fibrillation - An Individual Patient Data Analysis

Background: The optimal timepoint of starting DOAC after an acute ischemic stroke (IS) related to atrial fibrillation (AF) remains unclear. We aimed to compare an early (≤ 5 days of IS) versus late (&gt;5 days of IS) DOAC-start. Methods: Individual patient data analysis of 7 European and Japanese prospective observational cohort studies. We included patients with IS or TIA related to non-valvular AF where a DOAC was started within 30 days. We excluded patients with an intracranial bleeding (ICH) after the index event but prior to DOAC-start. We compared the 30-day rates of recurrent IS and ICH between the groups of early versus late DOAC-start with a landmark analysis at day 5. Results: Overall, 2550 patients were included. Median age was 77 years (IQR 70-84). DOAC were started early in 1362 (53%) patients, late in 1188 (47%). In the whole cohort, 37 patients suffered from a recurrent IS (1.5%), 16 patients (43%) of whom before any DOAC was started. 6 patients (0.2%) had an ICH. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent IS after DOAC-start and within 30 days; two patients (0.1%) suffered from ICH after DOAC-start. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent IS before DOAC was started; 4 patients (0.3%) suffered from ICH after DOAC-start. In the comparison of late versus early DOAC-groups, no difference in the hazard ratios was observed for the endpoint of recurrent IS (HR = 1.15, 95%CI 0.48-2.73, p=0.76) and ICH (HR = 4.71, 95%CI 0.51-43.10, p=0.17). Conclusion: Our results do not corroborate the concern that early anticoagulation - at least when performed with DOACs - increases the risk of hemorrhagic transformation of the brain infarct compared to late anticoagulation. Given the seven times higher risk of recurrent IS - with almost half of recurrent IS occurring before any DOAC-start - an early DOAC-start after AF-related IS may be reasonable, if inclusion in the ongoing trials (the recommended option) is not possible.