***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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    ***EXAMPLES*** 
    Input: BACKGROUND Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown . We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age . METHODS In this prospect i ve , multicenter , r and omized , event-driven trial , we r and omly assigned patients , in a 1:1 ratio , to medical therapy alone or closure of the patent foramen ovale . The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated . RESULTS We enrolled 980 patients ( mean age , 45.9 years ) at 69 sites . The medical-therapy group received one or more antiplatelet medications ( 74.8 % ) or warfarin ( 25.2 % ) . Treatment exposure between the two groups was unequal ( 1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group , P=0.009 ) owing to a higher dropout rate in the medical-therapy group . In the intention-to-treat cohort , 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke ( hazard ratio with closure , 0.49 ; 95 % confidence interval [ CI ] , 0.22 to 1.11 ; P=0.08 ) . The between-group difference in the rate of recurrent stroke was significant in the prespecified per- protocol cohort ( 6 events in the closure group vs. 14 events in the medical-therapy group ; hazard ratio , 0.37 ; 95 % CI , 0.14 to 0.96 ; P=0.03 ) and in the as-treated cohort ( 5 events vs. 16 events ; hazard ratio , 0.27 ; 95 % CI , 0.10 to 0.75 ; P=0.007 ) . Serious adverse events occurred in 23.0 % of the patients in the closure group and in 21.6 % in the medical-therapy group ( P=0.65 ) . Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group ( 4.2 % ) , but the rate of atrial fibrillation or device thrombus was not increased . CONCLUSIONS In the primary intention-to-treat analysis , there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic  ischemic stroke . However , closure was superior to medical therapy alone in the prespecified per- protocol and as-treated analyses , with a low rate of associated risks . ( Funded by St. Jude Medical ; RESPECT Clinical Trials.gov number , NCT00465270 . ) 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 and Purpose — We sought to evaluate the real-world rate of safety outcomes after patent foramen ovale ( PFO ) closure in patients with ischemic stroke or transient ischemic attack ( TIA ) . Methods — We performed a retrospective cohort study using administrative cl aims data on all hospitalizations from 2005 to 2013 in New York , California , and Florida . Using International Classification of Diseases , Ninth Revision , Clinical Modification codes , we identified patients who underwent percutaneous transcatheter PFO closure within 1 year of ischemic stroke or TIA . Our outcome was an adverse event occurring during the hospitalization for PFO closure , defined as in prior studies as atrial fibrillation or flutter , cardiac tamponade , pneumothorax , hemothorax , a vascular access complication , or death . Crude rates were reported with exact confidence intervals . Results — We identified 1887 patients who underwent PFO closure after ischemic stroke or TIA . The rate of any adverse outcome during the hospitalization for PFO closure was 7.0 % ( 95 % confidence interval [ CI ] , 5.9%–8.2 % ) . Rates of adverse outcomes varied by age and type of preceding cerebrovascular event . In patients > 60 years of age , the rate of adverse outcomes was 10.9 % ( 95 % CI , 8.6%–13.6 % ) versus 4.9 % ( 95 % CI , 3.8%–6.3 % ) in patients ⩽60 years of age . The rate of adverse outcomes was 9.9 % ( 95 % CI , 7.3%–12.5 % ) in patients with preceding ischemic stroke versus 5.9 % ( 95 % CI , 4.7%–7.1 % ) after TIA . Conclusions — Approximately 1 in 14 patients who underwent percutaneous transcatheter PFO closure after ischemic stroke or TIA experienced a serious periprocedural adverse outcome or death . The risk of adverse outcomes was highest in older patients and in those with preceding ischemic stroke 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 
    Output:
    
PFO closure is superior to antithrombotic therapy to prevent stroke recurrence after cryptogenic stroke .
The annual absolute risk reduction of stroke was low , but it has to be tempered by a substantial time at risk ( at least 5 years ) in young and middle-aged patients .
PFO closure was associated with an increased risk of atrial fibrillation