Left atrial appendage occlusion using the LAmbre device in atrial fibrillation patients with a history of ischemic stroke: 1-Year outcomes from a multicenter study in China.

BACKGROUND: Patients with non-valvular atrial fibrillation (NVAF) and previous stroke have a significantly higher risk of stroke recurrence. This study aimed to examine the safety and efficacy of the LAmbre left atrial appendage occlusion device in NVAF patients with a history of stroke. METHODS: We examined 103 consecutive NVAF patients in 11 Chinese medical centers who had a history of stroke or transient ischemic attacks (TIA) and underwent placement of the LAmbre device. Follow-up was conducted 1, 3, 6, and 12 months after the procedure. The primary endpoints were the incidence of new ischemic or hemorrhagic stroke, TIA, systemic embolism, or cardiac death. Secondary endpoints were serious perioperative or device-related complications and cerebral, gastrointestinal, or other bleeding events requiring transfusion of at least 2 units of packed red blood cells. RESULTS: Mean patient age was 67.63 ± 7.14 years; mean CHA2DS2-VASc score was 4.72 ± 1.18 and mean HAS-BLED score was 1.90 ± 1.00. LAmbre device placement was successful in 101 patients (98.05%). Mean follow-up was 12.2 months. Five patients (4.95%) developed a new pericardial effusion after the procedure; none required treatment. Eighty-six patients (85.15%) exhibited no peri-device leak (PDL). However, 13 (12.8%) had a small (0-3 mm) PDL and two (2.3%) had a moderate PDL (3-5 mm). One recurrent stroke occurred during follow-up (1.1%). No other complications occurred. CONCLUSIONS: This multicenter study shows the safety and efficacy of LAmbre left atrial appendage occlusion for NVAF patients with a history of stroke or TIA.

High-intensity training in patients with lacunar stroke: A one-year follow-up.

OBJECTIVES: Physical inactivity is a major risk factor for stroke. It is a challenge for patients to initiate and adhere to regular exercise post-stroke. Early initiation of home-based high-intensity interval training (HIIT) may engage patients in physical activity, improve cardiorespiratory fitness, and reduce risk of recurrent stroke. MATERIALS AND METHODS: Post-intervention follow-up of patients with lacunar stroke, randomized to three-months HIIT including weekly motivational calls, or usual care. At follow-up (six- and 12-months post-stroke), we investigated changes in cardiorespiratory fitness, physical activity, fatigue, depression, mental well-being, stress, cognition, cardiovascular function, and recurrent stroke. RESULTS: We included 71 patients of whom 59 patients (mean age: 63.9 ± 8.8 years) completed six- and 12-month follow-up. No change was detected in cardiorespiratory fitness between groups from baseline to 12-months follow-up. At six months, vigorous-intensity activity (median hours/week [interquartile range]) was maintained in the intervention group (baseline, 0[0;2]; post-intervention, 2[0;3]; six-month, 2[0;4]) and increased in the usual care group (baseline, 0[0;1]; post-intervention, 1[0;2]; six-month, 1[0;3]), with no difference between groups. Vigorous-intensity activity declined to baseline levels at 12-months in both groups. Secondary outcomes improved from baseline to 12-months with no significant differences between groups. Similar rate of recurrent stroke (n=3) occurred in each group with a three-month delay in the intervention group. CONCLUSIONS: Early initiated HIIT did not increase long-term cardiorespiratory fitness, but increased time spent doing vigorous-intensity activities post-stroke. Decline to baseline activity level at 12 months warrants identification of motivators to initiate and sustain physical activity post-stroke.

Prediction of occult atrial fibrillation in patients after cryptogenic stroke and transient ischaemic attack: PROACTIA.

AIMS: Studies with implantable cardiac monitors (ICMs) show that one-third of patients with cryptogenic stroke/transient ischaemic attack (TIA) have episodes of subclinical atrial fibrillation (SCAF) and benefit switching from antiplatelet- to anticoagulant therapy. However, ICMs are costly and resource demanding. We aimed to build a score based on participant's baseline characteristics that could assess individual risk of SCAF. METHODS AND RESULTS: In a prospective study, 236 eligible patients with a final diagnosis of cryptogenic stroke/TIA had an ICM implantated during the index hospitalization. Pre-specified evaluated variables were: CHA2DS2-VASc, P-wave duration, P-wave morphology, premature atrial beats (PAC)/24 h, supraventricular tachycardia/24 h, left atrial end-systolic volume index (LAVI), Troponin-T, NT-proBNP, and D-dimer. SCAF was detected in 84 patients (36%). All pre-specified variables were significantly associated with SCAF detection in univariate analysis. P-wave duration, followed by PAC/24 h, NT-proBNP, and LAVI, had the largest ratio of SCAF prevalence between its upper and lower quartiles (3.3, vs. 3.2, vs. 3.1 vs. 2.8, respectively). However, in a multivariate analysis, only PAC/24t, P-wave duration, P-wave morphology, and LAVIs remained significant predictors and were included in the PROACTIA score. Subclinical atrial fibrillation prevalence was 75% in the highest vs. 10% in the lowest quartile of the PROACTIA score with a 10-fold higher number of patients with an atrial fibrillation burden >6 h in the highest vs. the lowest quartile. CONCLUSION: The PROACTIA score can identify patients with cryptogenic stroke/TIA at risk of subsequent SCAF detection. The large difference in SCAF prevalence between groups may provide a basis for future tailored therapy. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration: ClinicalTrials.gov; NCT02725944.

Cost-Effectiveness of Using LDL-Direct Versus Lipid-Panel as Part of the Inpatient Stroke Workup.

OBJECTIVE: To investigate whether utilizing a LDL-direct laboratory test rather than a lipid panel to determine LDL-C as part of the inpatient stroke and TIA workup is more cost-effective to the patient and hospital system. A retrospective analysis was conducted on all patients admitted to UCSD La Jolla and Hillcrest Hospital and discharged with a final diagnosis of ischemic stroke or transient ischemic attack between 7/2016 and 6/2019. A cost-analysis was extrapolated based on the current cost of each test as provided by the UCSD hospital billing department as of June 2020. Patients started on a statin, who were not on one prior to admission, were also analyzed to highlight the importance of an accurate LDL-C on management of dyslipidemia. RESULTS: A total of 1245 patients were included in the study with 87% representing Ischemic strokes and 13% transient ischemic attacks. Over the three-year period, a total savings of $77,545 would be achieved if LDL-direct were used in place of a lipid-panel, representing an overall cost savings of 33%. Over the same time-frame, 536 (43%) patients were started on a statin that were not previously on one. CONCLUSIONS: Ordering a LDL-direct test should be considered over a lipid panel to evaluate LDL-C as it may prove to be the most cost effective approach to both the patient and Healthcare system.

Non-vitamin K oral anticoagulants for secondary stroke prevention in patients with atrial fibrillation.

The aims of this article are to review the evidence regarding the use of non-vitamin K oral anticoagulants (NOACs) for secondary stroke prevention as compared to vitamin K antagonists in patients with atrial fibrillation (AF) and in patients with embolic strokes of uncertain source (ESUS), and when to initiate or resume anticoagulation after an ischaemic stroke or intracranial haemorrhage. Four large trials compared NOACs with warfarin in patients with AF. In our meta-analyses, the rate of all stroke or systemic embolism (SE) was 4.94% with NOACs vs. 5.73% with warfarin. Among the patients with AF and previous transient ischaemic attack or ischaemic stroke, the rate of haemorrhagic stroke was halved with a NOAC vs. warfarin, and the rate of major bleeding was 5.7% with a NOAC vs. 6.4% with warfarin. There was no significant difference in mortality. In a trial comparing apixaban with aspirin in patients with AF, the rate of stroke or SE was 2.4% at 1 year with apixaban vs. 9.2% at 1 year with aspirin and the rates of major bleeding were 4.1% with apixaban vs. 2.9% with aspirin. Data from registries confirmed the results from the randomized trials. Initiation or resumption of anticoagulation after ischaemic stroke or cerebral haemorrhage depends on the size and severity of stroke and the risk of recurrent bleeding. Two large trials tested the hypothesis that NOACs are more effective than 100 mg aspirin in patients with ESUS. Neither trial showed a significant benefit of the NOAC over aspirin. In the meta-analysis, the rate all stroke or SE was 4.94% with NOACs vs. 5.73% with warfarin and the rate of haemorrhagic stroke was halved with a NOAC. The four NOACs had broadly similar efficacy for the major outcomes in secondary stroke prevention.

Dabigatran for Japanese Patients with Atrial Fibrillation and Prior Stroke: A Subgroup Analysis of the J-Dabigatran Surveillance Program.

BACKGROUND: The study objective was to evaluate long-term safety and effectiveness of dabigatran 110 mg and 150 mg twice daily (bid) in patients with nonvalvular atrial fibrillation (NVAF) with a focus on secondary stroke prevention. METHODS: In J-Dabigatran Surveillance, 6772 patients newly initiated on dabigatran to prevent ischemic stroke and systemic embolism were enrolled in Japan (1042 sites, December 2011 to November 2013). This subgroup analysis included patients with (1302) and without (5071) previous stroke/transient ischemic attack (TIA). Case report forms were reviewed to determine incidence of outcome events. RESULTS: In patients with previous stroke/TIA, the incidence rate for recurrent stroke/TIA was 2.48/100 patient-years (ischemic stroke 2.22, hemorrhagic stroke 0.18, TIA 0.12) and for major bleeding was 1.79/100 patient-years, including intracranial bleeding (0.55). Event rates for recurrent stroke/TIA or major bleeding were 1.2% (for both) for patients who started dabigatran less than 30 days after stroke onset and 0.3% (for both) for patients who started dabigatran more than or equal to 30 days after stroke onset, and were independent of dabigatran dose. For patients with previous stroke/TIA, 17% who received 110 mg bid did not meet dose reduction recommendations (DRRs) and 28% who received 150 mg bid met at least 1 DRR, but the dabigatran dose was not reduced. Use of DRRs did not have a major impact on the incidence rates of recurrent stroke/TIA and major bleeding. CONCLUSION: Findings from this subgroup analysis support the real-world safety and effectiveness of long-term dabigatran in Japan, particularly for patients with NVAF in secondary prevention settings.

Temporal Trends in Pharmacological Stroke Prevention in Patients with Acute Ischemic Stroke and Known Atrial Fibrillation.

INTRODUCTION: Oral anticoagulation (OAC) substantially reduces stroke risk in patients with atrial fibrillation (AF) at risk for stroke. Whether non-vitamin K-dependent oral anticoagulants (NOACs) improve OAC use in stroke prevention requires investigation. METHODS: To investigate temporal trends of OAC use in patients with known AF pre-stroke, we retrospectively analyzed records of 6,803 stroke patients admitted in 2003-2004 (n=1,496), 2008-2010 (n=1,638) or 2013-2015 (n=3,669) to the Charité-Universitätsmedizin Berlin, Germany. Adjusted regression models were used to identify factors associated with OAC use. RESULTS: Of 1,209 AF patients (mean age 79 years, 55.9% female) with given indication for OAC according to the CHADS2/CHA2DS2-VASc score, 484 (40.0%) were anticoagulated prior to the index stroke, 458 (37.9%) received antiplatelets and 236 (19.5%) had no antithrombotic medication. Compared to 2003-2004 and 2008-2010, there was a higher rate of pre-admission OAC in 2013-2015 (28.2% vs. 49.6%, p<0.001). After adjustment for possible confounders, factors associated with OAC pre-admission were young age (OR 0.74 per decade [95%CI 0.64-0.85]), previous stroke/TIA (OR 1.29 [95%CI 1.00-1.67]), absence of heart failure (OR 0.63 [95%CI 0.47-0.85]) and admission in 2013-2015 (OR 2.45 [95%CI 1.91-3.15]). Prescription of OAC at hospital discharge increased from 2003-2010 compared to 2013-2015 (45.2% vs. 69.5%, p < 0.001). CONCLUSIONS: Irrespective of temporal trends and despite given indication, more than half of all patients with known AF were not anticoagulated prior to the index stroke. In the NOAC era, there was an increase in OAC intake pre-stroke and a higher rate of OAC prescription at hospital discharge in stroke survivors with known AF.

Secondary stroke prevention with apixaban in nonvalvular atrial fibrillation: A subgroup analysis of the STANDARD study.

BACKGROUND: Data on independent risk factors for stroke recurrence in Japanese patients with nonvalvular atrial fibrillation are limited. METHODS: We performed a subgroup analysis of a postmarketing surveillance study of apixaban (STroke prevention ANticoagulant Drug Apixaban Real-world Data study) in Japanese patients with nonvalvular atrial fibrillation receiving oral apixaban (5 mg/2.5 mg twice daily) in routine clinical practice. Patients were categorized into primary and secondary prevention groups based on the absence or presence of a history of ischemic stroke/transient ischemic attack, respectively. RESULTS: Patients in the secondary prevention group (1101 of 6306 patients [17.5%] analyzed; mean observation period, 15.7 months) had a higher risk of ischemic stroke or hemorrhage than those in the primary prevention group. The incidence rates of major (3.92%/year vs 2.06%/year), intracranial (1.87%/year vs 0.55%/year), and cerebral (1.14%/year vs 0.37%/year) hemorrhage and effectiveness outcomes (ischemic stroke/systemic embolism/transient ischemic attack, 3.25%/year vs 0.57%/year) were significantly higher (all P < 0.001) in the secondary prevention group than in the primary prevention group. Multivariate analysis identified no independent risk factors in the secondary prevention group, while prior major bleeding, alcohol abuse, advanced age, male sex, lower body weight, higher serum creatinine, and antiplatelet drug use were identified as risk factors for major hemorrhage, and advanced age and antiplatelet drug use for effectiveness outcomes in the primary prevention group. CONCLUSIONS: Among Japanese patients with nonvalvular atrial fibrillation who received apixaban, presence of a history of ischemic stroke/transient ischemic attack was associated with higher incidence rates of hemorrhage and thromboembolic events.

[Use of smartphone apps in secondary stroke prevention]. / Apps in der Sekundärprävention nach Schlaganfall.

Modifiable risk factors such as hypertension, obesity or smoking have been reported to explain up to 90% of risk for ischemic stroke. Treatment of these risk factors is known to decrease the risk of recurrent stroke events. We performed a computer-based literature research from June to August 2018 using the electronic database PubMed to investigate the effect of smartphone apps on risk factor control for secondary stroke prevention as well as feasibility and patient satisfaction with mobile health. Studies evaluating interventions by smartphone or tablet devices in stroke patients and reported results regarding risk factors, feasibility or patient satisfaction were considered (n = 10). Identified data showed significant improvement regarding the control of risk factors hypertension and diabetes as well as significant improvements of the lifestyle risk factors physical inactivity and obesity. Stroke patients perceive smartphone apps mostly as useful and are open-minded regarding mHealth, provided that these complement rather than replace personal medical care.

Stroke prevention in patients with acute ischemic stroke and atrial fibrillation in Germany - a cross sectional survey.

BACKGROUND: Atrial fibrillation (AF) is present in 15-20% of patients with acute ischemic stroke. Oral anticoagulation reduces the risk of AF-related recurrent stroke but clinical guideline recommendations are rather vague regarding its use in the acute phase of stroke. We aimed to assess the current clinical practice of medical stroke prevention in AF patients during the acute phase of ischemic stroke. METHODS: In April 2017, a standardized anonymous questionnaire was sent to clinical leads of all 298 certified stroke units in Germany. RESULTS: Overall, 154 stroke unit leads participated (response rate 52%). Anticoagulation in the acute phase of stroke is considered feasible in more than 90% of AF patients with ischemic stroke. Clinicians assume that about two thirds of all AF patients (range 20-100%) are discharged on oral anticoagulation. According to local preferences, acetylsalicylic acid is given orally in the majority of patients with delayed initiation of oral anticoagulation. A non-vitamin K-dependent oral anticoagulant (NOAC) is more often prescribed than a vitamin K-dependent oral anticoagulant (VKA). VKA is more often chosen in patients with previous VKA intake than in VKA naive patients. In the minority of patients, stroke unit leads discuss the prescription of a specific oral anticoagulant with the treating general practitioner. Adherence to medical stroke prevention after hospital discharge is not assessed on a regular basis in any patient by the majority of participating stroke centers. CONCLUSIONS: Early secondary stroke prevention in AF patients in German stroke units is based on OAC use but prescription modalities vary in clinical practice.

Early Secondary Prevention in Transient Ischemic Attack (TIA) and Minor Stroke.

PURPOSE OF REVIEW: The purpose of this study was to review recent literature on the early secondary prevention in transient ischemic attack (TIA) and minor stroke. RECENT FINDINGS: The result of Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events and the secondary analysis of Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) have shown that treatment with clopidogrel and aspirin for 21 days reduced the risk of recurrent stroke with no significant increase in bleeding risk. Triple antiplatelet therapy with aspirin, clopidogrel, and dipyridamole resulted in a significant increase in major (including fatal) bleeding with no significant reduction in the recurrent stroke or TIA. The early treatment of patients with TIA or minor stroke with clopidogrel and aspirin for 21 days was effective in reducing the risk of recurrent stroke with no significant increase in bleeding risk. Most stroke guidelines have been updated to reflect this recommendation.

Self-Reported Physical Activity and Cardiovascular Disease Risk Factors in Patients with Lacunar Stroke.

BACKGROUND: Physical inactivity is a major modifiable risk factor for stroke. The aim was to explore if stroke patients admitted with lacunar stroke adhere to the international recommendations on physical activity prestroke (≥150 minutes of moderate-intensity activity, or ≥75 minutes of vigorous-intensity activity, or an equivalent combination). Further, to assess association between prestroke physical activity and cardiovascular disease (CVD) risk factors. METHODS: A cross-sectional study, including patients with lacunar stroke according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Data collected included prestroke physical activity using the self-reported Physical Activity Scale. Cardiorespiratory fitness was estimated as the power output from the Graded Cycling Test with Talk Test and sociodemographic factors including age, sex, education, and CVD risk factors including pre-existing diabetes, history of hypertension, body mass index, and lipids were assessed. RESULTS: We included 19 women and 52 men (mean age 64 years). Overall, 79% of the recruited patients adhered to the physical activity recommendations prestroke, but only 35% did vigorous-intensity activity. Prestroke physical activity was associated with a history of hypertension. CONCLUSIONS: A high proportion of the lacunar stroke patients reported to adhere to the recommendations on physical activity prestroke; however, only one third engaged in vigorous-intensity activity. Studies are warranted to investigate if vigorous-intensity activity is effective as secondary prevention in patients with a lacunar stroke.

Diagnostics, treatment and secondary prevention of ischemic stroke in the Silesian Province, Poland between 2009 and 2015.

BACKGROUND: The available data on diagnostics and treatment of ischemic stroke (IS) in Poland come mainly from non-representative cohorts or are outdated. OBJECTIVE: Therefore, the current study was done to access the most recent data on IS in the industrial region that covers 12% of the country's population. MATERIALS & METHODS: Analysis of the data from stroke questionnaires, obligatory for all patients hospitalized due to acute stroke and administered by the National Health Fund (the only public health insurer in Poland) between 2009 and 2015 (n=81,193). RESULTS: The number of hospitalizations due to IS in the Silesian Province was 69,403 and constituted 85.5% of all stroke cases reported to the NHF between 2009 and 2015. Neuroimaging of the brain (CT/MRI) was performed in 68,696 (99%) subjects, while ultrasonography of extra- and/or intracranial arteries in 57,886 (83.4%). The rtPA therapy was applied in 3282 patients (4.7% of all IS subjects). The rate of patients treated with rtPA gradually increased (1.2% in 2009, 9.3% in 2015). Among all patients with IS, 57,636 (83.1%) subjects were administered antiplatelet drugs, 16,199 (23.3%) - oral anticoagulants, and 55,971 (80.7%) - antihypertensive drugs. Also, 2260 (3.3%) patients were referred for vascular intervention. In subjects with cardioembolic stroke etiology, 37.8% were treated with anticoagulants. CONCLUSIONS: There has been observed a significant improvement in the quality of diagnosis and treatment of acute ischemic stroke during recent years. However, further actions are required both in terms of reperfusion treatment (thrombolysis and/or thrombectomy) and secondary prevention of stroke.

Secondary Stroke Prevention in Cryptogenic Stroke and Embolic Stroke of Undetermined Source (ESUS).

PURPOSE OF THE REVIEW: The purpose of the study was to review the literature on cryptogenic stroke and embolic stroke of undetermined stroke (ESUS). Cryptogenic stroke according to TOAST criteria is a stroke which is not due to cardiogenic embolism, small vessel disease with lacunes or large vessel disease of brain supplying arteries. In the context of secondary stroke prevention studies, cryptogenic stroke is not operationally defined. RECENT FINDINGS: The new concept of "embolic stroke of undetermined source" (ESUS) provides an operational definition. ESUS is diagnosed as a non-lacunar stroke on cerebral imaging and exclusion of large vessel atherosclerosis by CTA, MRA or ultrasound. Cardiogenic embolism is made less likely by ECG monitoring and echocardiography. At present, aspirin is used for secondary stroke prevention in patients with cryptogenic stroke. Based on the construct that ESUS might be caused by undetected atrial fibrillation or other embolic mechanisms, ongoing randomised secondary stroke prevention trials are comparing non-vitamin K oral anticoagulants (NOACs) with aspirin.

Three-Case Report of Embolic Stroke of Undetermined Source.

BACKGROUND: Embolic stroke of undetermined source (ESUS) is a new clinical construct. It signifies that the embolus in the thromboembolic ischemic stroke is of unknown origin. The anticoagulants are usually prescribed for antithrombotic prophylaxis, but whether it is appropriate for all patients with ESUS is still unknown. METHODS AND RESULTS: In this article, we describe 3 cases of ESUS, all of whose antithrombotic therapy was antiplatelet medication, and the 3 patients had no recurrence on 3- to 7-month follow-up. CONCLUSIONS: Because there was no obvious risk factor found in these ESUS cases, the recurrence risk is difficult to evaluate, and the optimum means of secondary prevention are still unknown. Hence, many aspects warrant resolution.

Recurrent cerebral ischemia after patent foramen ovale percutaneous closure in older patients: A two-center registry study.

OBJECTIVES: The aim of this study is to describe the cerebral ischemia recurrence rate after percutaneous patent foramen ovale (PFO) closure in patients older than 55 years and their outcomes, compared with younger patients. BACKGROUND: The registries data and the recent randomized trials about PFO closure are focused on patients younger than 55 years. Little is known about older patients' long-term outcome. METHODS: In total, 458 patients underwent PFO closure for cryptogenic cerebral ischemia and were stratified into an "older" (≥ 55 years, 151 patients) and a "younger" (<55 years, 307 patients) group. RESULTS: Older patients had mean age of 63 ± 6 years and more atrial septum aneurysm (P = 0.05), hypertension, diabetes, and dyslipidemia (P = 0.001). Mean followup was 4.5 ± 2.8 years. Older patients had a higher rate of ischemic recurrence (0.3 vs. 4.0%, P = 0.002), after a mean time of 3.1 ± 2.6 years. The Kaplan-Meier curve confirmed higher event-free survival in the youngers (P = 0.008). None of the patients with ischemic recurrence had significant residual shunt. Age and hypertension were correlated to ischemic recurrence, but age was the only independent predictor at multivariate analysis. CONCLUSIONS: Recurrent cerebral ischemia after PFO closure is more frequent in older patients and could most likely be associated to conditions related to age (atherosclerosis, atrial fibrillation), than to paradoxical embolism. The procedure is as safe as in younger patients.

The Role of Nonvitamin K Antagonist Oral Anticoagulants (NOACs) in Stroke Prevention in Patients with Atrial Fibrillation.

Anticoagulation is important in stroke prevention in patients with atrial fibrillation. Until recently, heparins and vitamin K antagonists were the only available therapy for stroke reduction in atrial fibrillation (AF) patients. Non-vitamin K antagonist oral anticoagulants (NOACs) including direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are now available and offer new options for stroke prevention. This article reviews the available data on the use of NOACs for primary and secondary stroke prevention in AF patients and describes specific patient populations to guide clinician in making the informed decision regarding appropriate use of those agents. It also addresses the use of NOACs early after acute stroke and use of thrombolysis while on NOAC.

Anticoagulant vs. antiplatelet therapy in patients with cryptogenic stroke and patent foramen ovale: an individual participant data meta-analysis.

AIMS: The preferred antithrombotic strategy for secondary prevention in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) is unknown. We pooled multiple observational studies and used propensity score-based methods to estimate the comparative effectiveness of oral anticoagulation (OAC) compared with antiplatelet therapy (APT). METHODS AND RESULTS: Individual participant data from 12 databases of medically treated patients with CS and PFO were analysed with Cox regression models, to estimate database-specific hazard ratios (HRs) comparing OAC with APT, for both the primary composite outcome [recurrent stroke, transient ischaemic attack (TIA), or death] and stroke alone. Propensity scores were applied via inverse probability of treatment weighting to control for confounding. We synthesized database-specific HRs using random-effects meta-analysis models. This analysis included 2385 (OAC = 804 and APT = 1581) patients with 227 composite endpoints (stroke/TIA/death). The difference between OAC and APT was not statistically significant for the primary composite outcome [adjusted HR = 0.76, 95% confidence interval (CI) 0.52-1.12] or for the secondary outcome of stroke alone (adjusted HR = 0.75, 95% CI 0.44-1.27). Results were consistent in analyses applying alternative weighting schemes, with the exception that OAC had a statistically significant beneficial effect on the composite outcome in analyses standardized to the patient population who actually received APT (adjusted HR = 0.64, 95% CI 0.42-0.99). Subgroup analyses did not detect statistically significant heterogeneity of treatment effects across clinically important patient groups. CONCLUSION: We did not find a statistically significant difference comparing OAC with APT; our results justify randomized trials comparing different antithrombotic approaches in these patients.