***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: BACKGROUND Trials of patent foramen ovale ( PFO ) closure to prevent recurrent stroke have been inconclusive . We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation , as compared with antiplatelet therapy . METHODS In a multicenter , r and omized , open‐label trial , we assigned , in a 1:1:1 ratio , patients 16 to 60 years of age who had had a recent stroke attributed to PFO , with an associated atrial septal aneurysm or large interatrial shunt , to transcatheter PFO closure plus long‐term antiplatelet therapy ( PFO closure group ) , antiplatelet therapy alone ( antiplatelet‐only group ) , or oral anticoagulation ( anticoagulation group ) ( r and omization group 1 ) . Patients with contraindications to anticoagulants or to PFO closure were r and omly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy ( r and omization groups 2 and 3 ) . The primary outcome was occurrence of stroke . The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from r and omization groups 1 and 2 , and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from r and omization groups 1 and 3 . RESULTS A total of 663 patients underwent r and omization and were followed for a mean ( ±SD ) of 5.3±2.0 years . In the analysis of r and omization groups 1 and 2 , no stroke occurred among the 238 patients in the PFO closure group , whereas stroke occurred in 14 of the 235 patients in the antiplatelet‐only group ( hazard ratio , 0.03 ; 95 % confidence interval , 0 to 0.26 ; P<0.001 ) . Procedural complications from PFO closure occurred in 14 patients ( 5.9 % ) . The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet‐only group ( 4.6 % vs. 0.9 % , P=0.02 ) . The number of serious adverse events did not differ significantly between the treatment groups ( P=0.56 ) . In the analysis of r and omization groups 1 and 3 , stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone . CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt , the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone . PFO closure was associated with an increased risk of atrial fibrillation . ( Funded by the French Ministry of Health ; CLOSE Clinical Trials.gov number , NCT00562289 . BACKGROUND Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown . METHODS In a multicenter , r and omized , open‐label trial , with blinded adjudication of end‐point events , we r and omly assigned patients 18 to 60 years of age who had a patent foramen ovale ( PFO ) and had had a cryptogenic ischemic stroke to undergo closure of the PFO ( PFO closure group ) or to receive medical therapy alone ( aspirin , warfarin , clopidogrel , or aspirin combined with extended‐release dipyridamole ; medical‐therapy group ) . The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke , fatal ischemic stroke , or early death after r and omization . The results of the analysis of the primary outcome from the original trial period have been reported previously ; the current analysis of data from the extended follow‐up period was considered to be exploratory . RESULTS We enrolled 980 patients ( mean age , 45.9 years ) at 69 sites . Patients were followed for a median of 5.9 years . Treatment exposure in the two groups was unequal ( 3141 patient‐years in the PFO closure group vs. 2669 patient‐years in the medical‐therapy group ) , owing to a higher dropout rate in the medical‐therapy group . In the intention‐to‐treat population , recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical‐therapy group , result ing in rates of 0.58 events per 100 patient‐years and 1.07 events per 100 patient‐years , respectively ( hazard ratio with PFO closure vs. medical therapy , 0.55 ; 95 % confidence interval [ CI ] , 0.31 to 0.999 ; P=0.046 by the log‐rank test ) . Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical‐therapy group ( hazard ratio , 0.38 ; 95 % CI , 0.18 to 0.79 ; P=0.007 ) . Venous thromboembolism ( which comprised events of pulmonary embolism and deep‐vein thrombosis ) was more common in the PFO closure group than in the medical‐therapy group . CONCLUSIONS Among adults who had had a cryptogenic ischemic stroke , closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow‐up . ( Funded by St. Jude Medical ; RESPECT Clinical Trials.gov number , NCT00465270 . BACKGROUND The efficacy of closure of a patent foramen ovale ( PFO ) in the prevention of recurrent stroke after cryptogenic stroke is uncertain . We investigated the effect of PFO closure combined with antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new brain infa rct ions . METHODS In this multinational trial involving patients with a PFO who had had a cryptogenic stroke , we r and omly assigned patients , in a 2:1 ratio , to undergo PFO closure plus antiplatelet therapy ( PFO closure group ) or to receive antiplatelet therapy alone ( antiplatelet‐only group ) . Imaging of the brain was performed at the baseline screening and at 24 months . The co primary end points were freedom from clinical evidence of ischemic stroke ( reported here as the percentage of patients who had a recurrence of stroke ) through at least 24 months after r and omization and the 24‐month incidence of new brain infa rct ion , which was a composite of clinical ischemic stroke or silent brain infa rct ion detected on imaging . RESULTS We enrolled 664 patients ( mean age , 45.2 years ) , of whom 81 % had moderate or large interatrial shunts . During a median follow‐up of 3.2 years , clinical ischemic stroke occurred in 6 of 441 patients ( 1.4 % ) in the PFO closure group and in 12 of 223 patients ( 5.4 % ) in the antiplatelet‐only group ( hazard ratio , 0.23 ; 95 % confidence interval [ CI ] , 0.09 to 0.62 ; P=0.002 ) . The incidence of new brain infa rct ions was significantly lower in the PFO closure group than in the antiplatelet‐only group ( 22 patients [ 5.7 % ] vs. 20 patients [ 11.3 % ] ; relative risk , 0.51 ; 95 % CI , 0.29 to 0.91 ; P=0.04 ) , but the incidence of silent brain infa rct ion did not differ significantly between the study groups ( P=0.97 ) . Serious adverse events occurred in 23.1 % of the patients in the PFO closure group and in 27.8 % of the patients in the antiplatelet‐only group ( P=0.22 ) . Serious device‐related adverse events occurred in 6 patients ( 1.4 % ) in the PFO closure group , and atrial fibrillation occurred in 29 patients ( 6.6 % ) after PFO closure . CONCLUSIONS Among patients with a PFO who had had a cryptogenic  stroke , the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone ; however , PFO closure was associated with higher rates of device complications and atrial fibrillation . ( Funded by W.L. Gore and Associates ; Gore REDUCE Clinical Trials.gov number , NCT00738894 . BACKGROUND The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source ( NAVIGATE-ESUS ) trial is a r and omized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS . AIMS We aim ed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups . METHODS We enrolled 7213 patients at 459 sites in 31 countries . Prespecified subgroups for primary safety and efficacy analyses included age , sex , race , global region , stroke or transient ischemic attack prior to qualifying event , time to r and omization , hypertension , and diabetes mellitus . RESULTS Mean age was 66.9 ± 9.8 years ; 24 % were under 60 years . Older patients had more hypertension , coronary disease , and cancer . Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infa rct ion . Women comprised 38 % of participants and were older than men . Patients from East Asia were oldest whereas those from Latin America were youngest . Patients in the Americas more frequently were on aspirin prior to the qualifying stroke . Acute cortical infa rct ion was more common in the United States , Canada , and Western Europe , whereas prior radiographic infa rct ions were most common in East Asia . Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke , with earliest enrollments in Asia and Eastern Europe . CONCLUSIONS NAVIGATE-ESUS is the largest r and omized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS . The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research BACKGROUND Recent reports showing the favorable role of patent foramen ovale ( PFO ) closure in patients with cryptogenic stroke have raised the issue of selecting optimal c and i date s. OBJECTIVES This study , DEFENSE-PFO ( Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale ) , evaluated whether the benefits of PFO closure can be determined on the basis of the morphologic characteristics of the PFO , as evaluated by transesophageal echocardiography . METHODS Patients with cryptogenic stroke and high-risk PFO were divided between a transcatheter PFO closure and a medication-only group . High-risk PFO included PFO with atrial septal aneurysm , hypermobility ( phasic septal excursion into either atrium ≥10 mm ) , or PFO size ( maximum separation of the septum primum from the secundum ) ≥2 mm . The primary endpoint was a composite of stroke , vascular death , or Thrombolysis In Myocardial Infa rct ion-defined major bleeding during 2 years of follow-up . RESULTS From September 2011 until October 2017 , 120 patients ( mean age : 51.8 years ) underwent r and omization . PFO size , frequency of septal aneurysm ( 13.3 % vs. 8.3 % ; p = 0.56 ) , and hypermobility ( 45.0 % vs. 46.7 % ; p > 0.99 ) were similar between the groups . All PFO closures were successful . The primary endpoint occurred exclusively in the medication-only group ( 6 of 60 patients ; 2-year event rate : 12.9 % [ log-rank p = 0.013 ] ; 2-year rate of ischemic stroke : 10.5 % [ p = 0.023 ] ) . The events in the medication-only group included ischemic stroke ( n = 5 ) , cerebral hemorrhage ( n = 1 ) , Thrombolysis In Myocardial Infa rct ion-defined major bleeding ( n = 2 ) , and transient ischemic attack ( n = 1 ) . Nonfatal procedural complications included development of atrial fibrillation ( n = 2 ) , pericardial effusion ( n = 1 ) , and pseudoaneurysm ( n = 1 ) . CONCLUSIONS PFO closure in patients with high-risk PFO characteristics result ed in a lower rate of the primary endpoint as well as stroke recurrence . ( Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale [ DEFENSE-PFO ] ; NCT01550588 ) BACKGROUND Studies to date have shown an association between the presence of patent foramen ovale and cryptogenic stroke in patients younger than 55 years of age . This association has not been established in patients 55 years of age or older . METHODS We prospect ively examined 503 consecutive patients who had had a stroke , and we compared the 227 patients with cryptogenic stroke and the 276 control patients with stroke of known cause . We examined the prevalences of patent foramen ovale and of patent foramen ovale with concomitant atrial septal aneurysm in all patients , using transesophageal ech 
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INTERPRETATION Among patients with ESUS who have PFO , anticoagulation might reduce the risk of recurrent stroke by about half , although substantial imprecision remains .