卵圆孔未闭封堵术治疗老年脑卒中患者：试验可行性的患者选择。

Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.

机构信息

From the Predictive Analytics and Comparative Effectiveness (PACE) Center (A.Y.W., J.N., B.K., D.K., D.M.K.), Institute for Clinical Research and Health Policy Studies (ICRHPS), Tufts Medical Center, Boston, MA; Department of Clinical Neurology (P.M.R., L.L., S.M., L.E.S.), Oxford University, London, United Kingdom; Comprehensive Stroke Center and Department of Neurology (J.L.S.), David Geffen School of Medicine, University of California, Los Angeles; Comprehensive Stroke Center (S.E.K.), Department of Neurology, University of Pennsylvania Medical Center, Philadelphia; Division of Cardiology (J.C.), Department of Medicine, University of Colorado Denver, Aurora; Université Paris Cité (J.-L.M.), Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266; GHU-Paris Psychiatrie et Neurosciences (J.-L.M.), Hôpital Sainte Anne; Département de Physiologie (G.D.), Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est Créteil (UPEC); Centre d'Investigations Cliniques (G.C.), Unité de Recherche Clinique, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, France; Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH; Division of Cardiovascular Medicine (H.C.H., B.L.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; Department of Population Health (P.J.), University of Oxford, United Kingdom; Department of Neurology (J.S.K.), Gangneung Asan Hospital, University of Ulsan College of Medicine; Department of Cardiology (P.H.L.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Neurology (H.P.M.), Bern University Hospital; Medical Faculty (B.M.), University of Bern, Switzerland; Cardiology Department (M.R.), Weill Cornell Medical Center, Cornell, NY; Division of Cardiology (R.W.S.), Department of Medicine, UTHealth/McGovern Medical School and The Memorial Hermann Heart and Vascular Institute, Houston, TX; Department of Cardiology (L.S.), Rigshospitalet, Copenhagen University Hospital, Denmark; Division of Cardiology (J.-K.S.), Asan Medical Center Heart Institute, University of Ulsan College of Medicine, Seoul, South Korea; BHF Cardiovascular Epidemiology Unit (E.D.A.), Department of Public Health and Primary Care, University of Cambridge; Victor Phillip Dahdaleh Heart and Lung Research Institute (E.D.A.), BHF Centre of Research Excellence, School of Clinical Medicine, Addenbrooke's Hospital; NIHR Blood and Transplant Research Unit in Donor Health and Behaviour (E.D.A.), all University of Cambridge; Health Data Research UK Cambridge (E.D.A.), Wellcome Genome Campus and University of Cambridge, Hinxton; University of Cambridge (E.D.A.), United Kingdom; Health Data Science Centre (E.D.A.), Human Technopole, Milan, Italy; Department of Medicine (M.D., S.H.), Columbia University, College of Physicians and Surgeons, New York, NY; Department of Neurology (M.S.V.E.), Vagelos College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY; Division of Neurology-Stroke Program (C.J.), Department of Medicine, University Health Network, Toronto Western Hospital, Ontario, Canada; Stroke Center (P.M.), Neurology Service, Lausanne University Hospital; Department of Neurology (M.-L.M., K.N.), University of Bern; Department of Neurology (M.-L.M.), Stadtspital Zürich; Department of Neurology and Stroke Centre (K.N.), Cantonal Hospital Aarau, Switzerland; Sapienza University of Rome (F.P.), Italy; Department of Neurology (J.S.), Hospital Universitari de Girona Dr Josep Trueta - IDIBGI, Spain; Department of Neurology and Stroke Center (C.W.), University Duisburg-Essen, Germany; Department of Public Health (D.K.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Neurology (D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA.

出版信息

Neurology. 2024 May 28;102(10):e209388. doi: 10.1212/WNL.0000000000209388. Epub 2024 May 3.

DOI:10.1212/WNL.0000000000209388

PMID:38701403

Abstract

BACKGROUND AND OBJECTIVES

Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT.

METHODS

Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the "RoPE-Ox" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT.

RESULTS

Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up.

DISCUSSION

Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.

摘要

背景和目的

卵圆孔未闭（PFO）封堵是否对有 PFO 和隐源性卒中的老年患者有益尚不清楚，因为随机对照试验（RCT）主要纳入了 60 岁以下的患者。我们的目的是估计 PFO 封堵在老年患者中的预期效果，以预测计划 RCT 所需的人数。

方法

有效性估计值来自主要的观察性研究（矛盾栓塞风险[RoPE]研究和牛津血管研究，统称为“RoPE-Ox”数据库）和所有 6 项主要 RCT（系统、协作、PFO 封堵评估[SCOPE]联盟）。为了估计卒中复发风险，在包含年龄的观察性数据库中计算了年龄大于 60 岁的患者的观察结果（n=549）。为了根据 RoPE 评分和高危 PFO 特征估计 PFO 封堵与药物治疗相比降低复发性卒中的发生率，我们在 SCOPE 数据库的 RCT 数据中开发了 Cox 比例风险回归模型（n=3740）。这些估计值用于计算未来 RCT 所需的样本量。

结果

使用 Kaplan-Meier 估计值，5 年卒中复发风险总体为 13.7%（95%CI 10.5-17.9%），高危 PFO 特征者为 14.9%（95%CI 10.2-21.6%）。总体上，PFO 封堵的事件发生率相对降低 12.9%，高危 PFO 特征者降低 48.8%。使用这些估计值，招募所有有隐源性卒中和 PFO 的老年患者需要比以前的 PFO 封堵试验更大的样本量，但选择性招募高危 PFO 特征患者需要 630 名患者（90%的效力）和 471 名患者（80%的效力），平均随访 5 年。