卵圆孔未闭封堵与卒中后抗凝或抗血小板治疗的比较
Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke.
机构信息
From the Department of Neurology, Sainte-Anne Hospital, INSERM 894, Département Hospitalo-Universitaire (DHU) NeuroVasc Sorbonne Paris-Cité (J.-L.M., G.T.), and the Department of Neurology, Saint-Joseph Hospital (M.Z.), Paris Descartes University, the Department of Neurology and Stroke Unit (C.G.) and the Department of Cardiology (J.-M.J.), Bichat Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), INSERM 1148, DHU FIRE (Fibrosis Inflammation and Remodeling in Cardiovascular, Renal, and Respiratory Diseases) Sorbonne Paris-Cité, the Department of Neurology, Saint-Antoine Hospital, AP-HP, Pierre et Marie Curie University (P.F.), the Department of Neurology, Lariboisière Hospital, DHU NeuroVasc Sorbonne Paris-Cité, Paris Diderot University (P.R.), and the Epidemiology and Clinical Research Unit, Georges Pompidou European Hospital, AP-HP, INSERM Centre d'Investigation Clinique 1418 (A.C.-N., G.C.), Paris, the Departments of Physiology (G.D.), Neurology (H.H.), and Cardiology (J.-L.D.-R.), Henri Mondor Hospital, AP-HP, University Paris Est Creteil, Creteil, the Departments of Neurology (B.G.) and Cardiology (P. Guérin), Centre Hospitalier Universitaire (CHU) Nantes, Nantes, the Department of Neurology, University Hospital, Rouen (E.M.), the Stroke Department (L.M.) and the Departments of Interventional Cardiology (R.R.) and Cardiovascular Investigations (M.B.), Pierre Wertheimer and Louis Pradel Hospitals, Lyon University, Lyon, the Department of Neurology, Gui de Chauliac Hospital, INSERM 894 (C.A.), and the Department of Interventional Cardiology, Clinique du Millénaire, INSERM 1191 (C.P.), Montpellier University, Montpellier, the Department of Neurology, Dijon Stroke Registry, EA 7460 (Y.B.), and the Department of Cardiology (J.-C.E.), University Hospital, Burgundy University, Dijon, the Departments of Neurology (F.V., T.M.) and Cardiology (N.M.), Jean Minjoz University Hospital, Franche-Comté University, Besançon, the Departments of Neurology (O.D.) and Cardiology (B.B.), Michallon Hospital, Grenoble Alpes University, Grenoble, the Department of Neurology and Stroke Unit (S.C.) and the Department of Cardiology (L.L.), University Hospital, Jules Verne Picardie University, Amiens, the Department of Neurology, Yves le Foll Hospital, Saint Brieuc (C.V.), the Department of Neurology and Stroke Unit (N.D.-P.) and the Department of Cardiology and Congenital Heart Disease (F.G.), Centre Hospitalier Régional Universitaire (CHRU) Lille, Lille Nord de France University, Lille, the Department of Neurology and Stroke Unit (I.S.) and the Department of Congenital Cardiac Diseases (J.-B.T.), CHU Bordeaux, Bordeaux University, Bordeaux, the Department of Neurology, University Hospital, INSERM 1059, Lyon University, Saint-Etienne (P. Garnier), the Departments of Neurology (A.F.) and Cardiology (J.-R.L.), University Hospital, Clermont-Ferrand, the Department of Neurology and Stroke Unit, Cavale Blanche Hospital, INSERM 1078, University of Western Brittany, Brest (S.T.), the Department of Neurology, La Timone Hospital, Aix-Marseille University, Marseille (E.R.-B.), the Department of Neurology, Saint-Jean Hospital, Perpignan (D.S.), the Department of Neurology and Stroke Unit, Central Hospital, Nancy (J.-C.L.), the Departments of Neurology (J.-F.P.) and Cardiology and Vascular Diseases (J.-M.S.), Pontchaillou Hospital, Rennes University, Rennes, the Department of Neurology, Caen University Hospital, Caen (M.A.), the Department of Neurology, Docteur Schaffner Hospital, Lens (C.L.) - all in France; the Stroke Center, Department of Neurology, Vaudois University Hospital, Lausanne University, Lausanne, Switzerland (P.M.); the Department of Cardiology, CHU Sart Tilman, Liege University, Liege, Belgium (L.P.); and the Department of Neurology, University Hospital, Duisburg-Essen University, Duisberg-Essen, Germany (C.W.).
出版信息
N Engl J Med. 2017 Sep 14;377(11):1011-1021. doi: 10.1056/NEJMoa1705915.
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 .).
背景
卵圆孔未闭（PFO）封堵术预防复发性卒中的试验结果尚无定论。我们研究了伴有提示卒中风险的心脏超声特征的隐源性卒中患者，他们是否可从 PFO 封堵或抗凝治疗中获益，与抗血小板治疗相比。
方法
在一项多中心、随机、开放标签试验中，我们按照 1:1:1 的比例，将年龄在 16 至 60 岁之间、近期归因于 PFO 的卒中患者（伴有房间隔瘤或大房间隔分流）随机分为经导管 PFO 封堵联合长期抗血小板治疗（PFO 封堵组）、单纯抗血小板治疗（单纯抗血小板组）或口服抗凝治疗（抗凝组）（随机分组 1）。对不能接受抗凝或 PFO 封堵的患者，随机分配至另一种非禁忌的治疗方法或抗血小板治疗（随机分组 2 和 3）。主要结局为卒中的发生。PFO 封堵联合抗血小板治疗与单纯抗血小板治疗的比较是在随机分组 1 和 2 的合并数据上进行的，而口服抗凝与单纯抗血小板治疗的比较是在随机分组 1 和 3 的合并数据上进行的。
结果
共有 663 例患者接受了随机分组，平均随访时间为 5.3±2.0 年。在随机分组 1 和 2 的分析中，PFO 封堵组的 238 例患者中无卒中发生，而单纯抗血小板组的 235 例患者中有 14 例发生卒中（风险比，0.03；95%置信区间，0 至 0.26；P<0.001）。PFO 封堵术的并发症发生在 14 例患者（5.9%）。与单纯抗血小板组相比，PFO 封堵组的心房颤动发生率更高（4.6%比 0.9%，P=0.02）。各组之间严重不良事件的发生率无显著差异（P=0.56）。在随机分组 1 和 3 的分析中，7 例患者接受抗血小板治疗，3 例患者接受口服抗凝治疗，其中各有 1 例发生卒中。
结论
在归因于 PFO 的近期隐源性卒中且伴有房间隔瘤或大房间隔分流的患者中，与单纯抗血小板治疗相比，PFO 封堵联合抗血小板治疗组的卒中复发率更低。PFO 封堵与心房颤动风险增加相关。（由法国卫生部资助；CLOSE ClinicalTrials.gov 编号，NCT00562289）。
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