Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke
Jean-Louis Mas, Geneviève Derumeaux, Benoît Guillon, Evelyne Massardier, Hassan Hosseini, Laura Mechtouff, Caroline Arquizan, Yannick Béjot, Fabrice Vuillier, Olivier Detante, Céline Guidoux, Sandrine Canaple, Claudia Vaduva, Nelly Dequatre-Ponchelle, Igor Sibon, Pierre Garnier, Anna Ferrier, Serge Timsit, Emmanuelle Robinet-Borgomano, Denis Sablot, Jean-Christophe Lacour, Mathieu Zuber, Pascal Favrole, Jean-François Pinel, Marion Apoil, Peggy Reiner, Catherine Lefebvre, Patrice Guérin, Christophe Piot, Roland Rossi, Jean-Luc Dubois-Randé, Jean-Christophe Eicher, Nicolas Meneveau, Jean-René Lusson, Bernard Bertrand, Jean-Marc Schleich, François Godart, Jean-Benoit Thambo, Laurent Leborgne, Patrik Michel, Luc Pierard, Guillaume Turc, Martine Barthelet, Anaïs Charles-Nelson, Christian Weimar, Thierry Moulin, Jean-Michel Juliard, Gilles Chatellier, CLOSE Investigators, V Domigo, V Guiraud, E Touzé, D Calvet, C Lamy, E Teiger, J-L Dubois-Randé, P Aubry, O Varenne, S Menacer, M Sroussi, A Nana, L Cabanes, A Schunck, F Herisson, S De Gaalon, M Sevin, J-M Langlard, N Piriou, P Jaafar, B d'Héré, D Stepowski, F Bauer, A-M Duval, P Lim, N Nighoghossian, L Derex, T Cho, G Rioufol, H Thibaut, S Thivolet, I Mourand, C Sportouch, S Cade, F Cransac, M Giroud, I L’Huillier, R Chopard, V Descotes-Genon, K Garambois, C Saunier, E Brochet, M Mazighi, E Meseguer, D Messika-Zeitoun, L Cabrejo, P Lavallée, L Lepage, P Amarenco, J-M Bugnicourt, O Godefroy, C Rey, M-P Guillaumont, F Trojette, D Malaquin, G Couvreur, V Golfier, F Plurien, G Taldir, C Lucas, C Cordonnier, H Henon, F Dumont, D Leys, M Richardson, A-S Polge, D Montaigne, A Coisne, F Rouanet, P Renou, P Réant, S Laffite, R Roudaut, C Comtet, D Delsart, N Bourgois, P Clavelou, F Rouhart, E Le Cadet, A Tirel, Y Mocquard, Y Jobic, F Le Ven, M-C Pouliquen, L Milandre, N Laksiri, A Fraisse, G Habib, V Chalvignac, F Thuny, F Targosz, G Runavot, P Chopat, P Sultan, S Richard, X Ducrocq, F Marcon, M C Selton-Suty, O Huttin, M Bruandet, R Tamazyan, Y Antakly, P Garçon, J Serfaty, N Hammoudi, E Donal, B Lelong, C Chabanne, F Viader, J Cogez, F Labombarda, E Saloux, F Buffon, M Baudet, D Logeart, M Bataille, F Godard, F Biausque, Y Lefetz, M Clément–Dupont, V Zegarac, T Schmitz, B Plicht, M Eissmann, A Mahabadi, M Obadia, N Iglesias Benyounes, F Macian, N Darodes, B Tanguy, D Mohty, F Vuillemet, R Onea, S Greciano, O Roth, J-P Neau, L Quillet, L Christiaens, D Saudeau, F Patat, O Singer, S Fichtlscherer, F Pico, C Charbonnel, I Durand-Zaleski, F Woimant, G Finet, F Mounier-Vehier, G Rodier, L Ernande, M Lièvre, Chantal Andrieux, Isabelle Sauret, Clémence Bruyère, Romain Chenu, Ludovic Trinquart, Khaled Alsaleh, Djennat Bousry, Sonia Branco, Maxime Brussieux, Cécile Gréaud, Zineb Kacher, Laurie Loret, Mahendran Niranjani, Audrey Olivier, Romain Pigeat, Karen Sahuc, Juliette Djadi-Prat, Jean-Louis Mas, Geneviève Derumeaux, Benoît Guillon, Evelyne Massardier, Hassan Hosseini, Laura Mechtouff, Caroline Arquizan, Yannick Béjot, Fabrice Vuillier, Olivier Detante, Céline Guidoux, Sandrine Canaple, Claudia Vaduva, Nelly Dequatre-Ponchelle, Igor Sibon, Pierre Garnier, Anna Ferrier, Serge Timsit, Emmanuelle Robinet-Borgomano, Denis Sablot, Jean-Christophe Lacour, Mathieu Zuber, Pascal Favrole, Jean-François Pinel, Marion Apoil, Peggy Reiner, Catherine Lefebvre, Patrice Guérin, Christophe Piot, Roland Rossi, Jean-Luc Dubois-Randé, Jean-Christophe Eicher, Nicolas Meneveau, Jean-René Lusson, Bernard Bertrand, Jean-Marc Schleich, François Godart, Jean-Benoit Thambo, Laurent Leborgne, Patrik Michel, Luc Pierard, Guillaume Turc, Martine Barthelet, Anaïs Charles-Nelson, Christian Weimar, Thierry Moulin, Jean-Michel Juliard, Gilles Chatellier, CLOSE Investigators, V Domigo, V Guiraud, E Touzé, D Calvet, C Lamy, E Teiger, J-L Dubois-Randé, P Aubry, O Varenne, S Menacer, M Sroussi, A Nana, L Cabanes, A Schunck, F Herisson, S De Gaalon, M Sevin, J-M Langlard, N Piriou, P Jaafar, B d'Héré, D Stepowski, F Bauer, A-M Duval, P Lim, N Nighoghossian, L Derex, T Cho, G Rioufol, H Thibaut, S Thivolet, I Mourand, C Sportouch, S Cade, F Cransac, M Giroud, I L’Huillier, R Chopard, V Descotes-Genon, K Garambois, C Saunier, E Brochet, M Mazighi, E Meseguer, D Messika-Zeitoun, L Cabrejo, P Lavallée, L Lepage, P Amarenco, J-M Bugnicourt, O Godefroy, C Rey, M-P Guillaumont, F Trojette, D Malaquin, G Couvreur, V Golfier, F Plurien, G Taldir, C Lucas, C Cordonnier, H Henon, F Dumont, D Leys, M Richardson, A-S Polge, D Montaigne, A Coisne, F Rouanet, P Renou, P Réant, S Laffite, R Roudaut, C Comtet, D Delsart, N Bourgois, P Clavelou, F Rouhart, E Le Cadet, A Tirel, Y Mocquard, Y Jobic, F Le Ven, M-C Pouliquen, L Milandre, N Laksiri, A Fraisse, G Habib, V Chalvignac, F Thuny, F Targosz, G Runavot, P Chopat, P Sultan, S Richard, X Ducrocq, F Marcon, M C Selton-Suty, O Huttin, M Bruandet, R Tamazyan, Y Antakly, P Garçon, J Serfaty, N Hammoudi, E Donal, B Lelong, C Chabanne, F Viader, J Cogez, F Labombarda, E Saloux, F Buffon, M Baudet, D Logeart, M Bataille, F Godard, F Biausque, Y Lefetz, M Clément–Dupont, V Zegarac, T Schmitz, B Plicht, M Eissmann, A Mahabadi, M Obadia, N Iglesias Benyounes, F Macian, N Darodes, B Tanguy, D Mohty, F Vuillemet, R Onea, S Greciano, O Roth, J-P Neau, L Quillet, L Christiaens, D Saudeau, F Patat, O Singer, S Fichtlscherer, F Pico, C Charbonnel, I Durand-Zaleski, F Woimant, G Finet, F Mounier-Vehier, G Rodier, L Ernande, M Lièvre, Chantal Andrieux, Isabelle Sauret, Clémence Bruyère, Romain Chenu, Ludovic Trinquart, Khaled Alsaleh, Djennat Bousry, Sonia Branco, Maxime Brussieux, Cécile Gréaud, Zineb Kacher, Laurie Loret, Mahendran Niranjani, Audrey Olivier, Romain Pigeat, Karen Sahuc, Juliette Djadi-Prat
Abstract
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, randomized, 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) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization 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 randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3.
Results: A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization 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 randomization 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 ClinicalTrials.gov number, NCT00562289 .).
Source: PubMed