***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of 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 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 —Patent foramen ovale ( PFO ) is associated with stroke , but there are no r and omized studies to evaluate the efficacy of antithrombotic therapies . Methods and Results —The PFO in Cryptogenic Stroke Study was a 42-center study that evaluated transesophageal echocardiographic findings  in patients r and omly assigned to warfarin or aspirin in the Warfarin-Aspirin Recurrent Stroke Study . In this study , 630 stroke patients were enrolled , of whom 312 ( 49.5 % ) were r and omized to warfarin and 318 ( 50.5 % ) to aspirin .  Of these , 265 patients experienced cryptogenic stroke and 365 experienced known stroke subtypes . End points were recurrent ischemic stroke or death . PFO was present in 203 patients ( 33.8 % ) . There was no significant difference in the time to primary end points between those with and those without PFO in the overall population ( P = 0.84 ; hazard ratio 0.96 ; 95 % CI 0.62 to 1.48 ; 2-year event rates 14.8 % versus 15.4 % ) or in the cryptogenic subset ( P = 0.65 ; hazard ratio 1.17 ; 95 % CI 0.60 to 2.37 ; 2-year event rates 14.3 % versus 12.7 % ) . There was no significant difference among those with no , small , or large PFO ( P = 0.41 for small PFO and P = 0.16 for large PFO ; 2-year event rates for no , small , and large PFO , 15.4 % , 18.5 % , and 9.5 % , respectively ) . There was no significant difference between patients with isolated PFO and those with PFO in association with atrial septal aneurysm ( P = 0.84 ; 2-year event rates 14.5 % versus 15.9 % ) . In patients with PFO , there was no significant difference in the time to primary end points between those treated with warfarin and those treated with aspirin ( P = 0.49 ; hazard ratio 1.29 ; 95 % CI 0.63 to 2.64 ; 2-year event rates 16.5 % versus 13.2 % ) . Conclusions —On medical therapy , the presence of PFO in stroke 
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The BMJ Rapid Recommendations panel used a linked systematic review 1 triggered by three large r and omised trials published in September 2017 that suggested PFO closure might reduce the risk of ischaemic stroke more than alternatives.234 The panel felt that the studies , when considered in the context of the full body of evidence , might change current clinical practice .5 The linked systematic review finds that PFO closure prevents recurrent stroke relative to antiplatelet therapy , but possibly not relative to anticoagulants , and is associated with procedural complications and persistent atrial fibrillation.1 The review also presents evidence regarding the role of anticoagulants or antiplatelet therapy  when PFO closure is not acceptable or is contraindicated .