{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:29:57Z","timestamp":1791862197709,"version":"4.3.4"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,6,19]]},"abstract":"\n Background<\/jats:title>\n \n We conducted a systematic review and meta\u2010analysis of randomized controlled trials (\n RCT<\/jats:styled-content>\n s) comparing patent foramen ovale (\n PFO<\/jats:styled-content>\n ) closure, anticoagulation, and antiplatelet therapy to prevent stroke recurrence in patients with\n PFO<\/jats:styled-content>\n \u2010associated cryptogenic stroke.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We searched Medline, Cochrane Library, and EMBASE through March 2018. The primary outcome was stroke recurrence. Pooled incidences, hazard ratios, and risk ratios (\n RR<\/jats:styled-content>\n s) were calculated in random\u2010effects meta\u2010analyses.\n PFO<\/jats:styled-content>\n closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (antiplatelet therapy or anticoagulation: 3560 patients from 6\n RCT<\/jats:styled-content>\n s;\n RR<\/jats:styled-content>\n =0.36, 95%\n CI<\/jats:styled-content>\n : 0.17\u20130.79; I\n 2<\/jats:sup>\n =59%). The effect of\n PFO<\/jats:styled-content>\n closure on stroke recurrence was larger in patients with atrial septal aneurysm or large shunt (\n RR<\/jats:styled-content>\n =0.27, 95%\n CI<\/jats:styled-content>\n , 0.11\u20130.70; I\n 2<\/jats:sup>\n =42%) compared with patients without these anatomical features (\n RR<\/jats:styled-content>\n =0.80, 95%\n CI<\/jats:styled-content>\n , 0.43\u20131.47; I\n 2<\/jats:sup>\n =12%). Major complications occurred in 2.40% (95%\n CI<\/jats:styled-content>\n , 1.03\u20134.25; I\n 2<\/jats:sup>\n =77%) of procedures. New\u2010onset atrial fibrillation was more frequent in patients randomized to\n PFO<\/jats:styled-content>\n closure versus antithrombotic therapy (\n RR<\/jats:styled-content>\n =4.33, 95%\n CI<\/jats:styled-content>\n , 2.37\u20137.89; I\n 2<\/jats:sup>\n =14%). One\n RCT<\/jats:styled-content>\n compared\n PFO<\/jats:styled-content>\n closure versus anticoagulation (353 patients; hazard ratio=0.14, 95%\n CI<\/jats:styled-content>\n , 0.00\u20131.45) and 2\n RCT<\/jats:styled-content>\n s compared\n PFO<\/jats:styled-content>\n closure versus antiplatelet therapy (1137 patients; hazard ratio=0.18, 95%\n CI<\/jats:styled-content>\n , 0.05\u20130.63; I\n 2<\/jats:sup>\n =12%). Three\n RCT<\/jats:styled-content>\n s compared anticoagulation versus antiplatelet therapy, with none showing a significant difference.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n PFO<\/jats:styled-content>\n 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\u00a0years) in young and middle\u2010aged patients.\n PFO<\/jats:styled-content>\n closure was associated with an increased risk of atrial fibrillation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.008356","type":"journal-article","created":{"date-parts":[[2018,6,17]],"date-time":"2018-06-17T09:15:10Z","timestamp":1529226910000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":165,"title":["Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta\u2010Analysis, and New Insights From the CLOSE Study"],"prefix":"10.1161","volume":"7","author":[{"given":"Guillaume","family":"Turc","sequence":"first","affiliation":[{"name":"Department of Neurology H\u00f4pital Sainte\u2010Anne Paris France"},{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Paris France"},{"name":"NSERM U894 Paris France"},{"name":"DHU Neurovasc Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Calvet","sequence":"additional","affiliation":[{"name":"Department of Neurology H\u00f4pital Sainte\u2010Anne Paris France"},{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Paris France"},{"name":"NSERM U894 Paris France"},{"name":"DHU Neurovasc Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Gu\u00e9rin","sequence":"additional","affiliation":[{"name":"Department of Cardiology INSERM UMR 915 Institut du Thorax Nantes France"},{"name":"Institut du Thorax Centre Hospitalier Universitaire de Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Sroussi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Paris France"},{"name":"Department of Cardiology Cochin Hospital APHP Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Chatellier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Paris France"},{"name":"Epidemiology and Clinical Research Unit Georges Pompidou European Hospital APHP Paris France"},{"name":"INSERM CIC 1418 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Louis","family":"Mas","sequence":"additional","affiliation":[{"name":"Department of Neurology H\u00f4pital Sainte\u2010Anne Paris France"},{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Paris France"},{"name":"NSERM U894 Paris France"},{"name":"DHU Neurovasc Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the CLOSE Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410250410"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70310-7"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198805053181802"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.547828"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a08d59"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011503"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009639"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211716"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301440"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1610057"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707404"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1705915"},{"key":"e_1_3_1_14_2","article-title":"Cryptogenic stroke and high\u2010risk patent foramen ovale: the DEFENSE\u2010PFO trial","author":"Lee PH","year":"2018","unstructured":"Lee PH, Song JK, Kim JS, Heo R, Lee S, Kim DH, Song JM, Kang DH, Kwon SU, Kang DW, Lee D, Kwon HS, Yun SC, Sun BJ, Park JH, Lee JH, Jeong HS, Song HJ, Kim J, Park SJ. Cryptogenic stroke and high\u2010risk patent foramen ovale: the DEFENSE\u2010PFO trial. J Am Coll Cardiol. 2018. Available at: http:\/\/www.onlinejacc.org\/content\/early\/2018\/02\/28\/j.jacc.2018.02.046.full. Accessed May 9, 2018.","journal-title":"J Am Coll Cardiol"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyn188"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2007.03.013"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-017-0315-7"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2535"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.192218"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.13767"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90046-2"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jspi.2009.09.017"},{"key":"e_1_3_1_24_2","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [Updated March 2011]","author":"Higgins JPT","year":"2011","unstructured":"Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [Updated March 2011]. The Cochrane Collaboration; 2011. Available at: http:\/\/handbook.Cochrane.Org. Accessed May 6, 2018."},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.08.036"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2007.10.007"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1927.10502953"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/2049-3258-72-39"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-017-0875-8"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000017498.88393.44"},{"key":"e_1_3_1_32_2","first-page":"94","article-title":"Comparison of medical treatments in cryptogenic stroke patients with patent foramen ovale: a randomized clinical trial","volume":"18","author":"Shariat A","year":"2013","unstructured":"Shariat A, Yaghoubi E, Farazdaghi M, Aghasadeghi K, Borhani Haghighi A. Comparison of medical treatments in cryptogenic stroke patients with patent foramen ovale: a randomized clinical trial. J Res Med Sci. 2013;18:94\u201398.","journal-title":"J Res Med Sci"},{"key":"e_1_3_1_33_2","first-page":"CD009938","article-title":"Closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and a history of cryptogenic stroke or transient ischemic attack","author":"Li J","year":"2015","unstructured":"Li J, Liu J, Liu M, Zhang S, Hao Z, Zhang J, Zhang C. Closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and a history of cryptogenic stroke or transient ischemic attack. Cochrane Database Syst Rev. 2015:CD009938.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.12.023"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1177\/1747493016643551"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.31.10.2407"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.001773"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.018501"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.15420\/aer.2014.3.3.168"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.117.008356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:28:46Z","timestamp":1715599726000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.117.008356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,19]]},"references-count":38,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,6,19]]}},"alternative-id":["10.1161\/JAHA.117.008356"],"URL":"https:\/\/doi.org\/10.1161\/jaha.117.008356","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,19]]},"assertion":[{"value":"2017-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e008356"}}