Author + information
- Received September 4, 2019
- Revision received February 18, 2020
- Accepted February 28, 2020
- Published online May 4, 2020.
- Guillaume Turc, MD, PhDa,
- Jong-Young Lee, MDb,
- Eric Brochet, MDc,
- Jong S. Kim, MD, PhDd,
- Jae-Kwan Song, MD, PhDe,∗∗∗ (, )@club_neurovasc,
- Jean-Louis Mas, MDa,∗∗ (, )
- on behalf of the CLOSE and DEFENSE-PFO Trial Investigators
- aDepartment of Neurology, GHU Paris Psychiatrie et Neurosciences, Université de Paris, INSERM U1266, and FHU Neurovasc, Paris, France
- bDivision of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
- cDepartment of Cardiology, Hôpital Bichat, AP-HP, Université Paris-Diderot, and INSERM U 1148, Paris, France
- dDepartment of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
- eDivision of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Background In patients with patent foramen ovale (PFO)–associated stroke, the presence of large shunt or atrial septal aneurysm (ASA) has been suggested to convey a high risk of stroke recurrence.
Objectives The purpose of this study was to assess the respective influence of PFO size and ASA status on stroke recurrence under medical therapy in patients with recent PFO-associated stroke without alternative cause.
Methods The authors pooled individual patient data from 2 prospective observational studies and the medical arms of 2 randomized trials, in which shunt size and ASA status was assessed by independent reading of echocardiographic images. Associations between PFO anatomical features and recurrent ischemic stroke were assessed by mixed effects Cox models.
Results Of 898 patients (mean age 45.3 years), 178 (19.8%) had ASA with large PFO, 71 (7.9%) ASA with nonlarge PFO, 397 (44.2%) large PFO without ASA, and 252 (28.1%) nonlarge PFO without ASA. Over a median follow-up of 3.8 years (interquartile range: 2.6 to 5.5 years), 47 (5.2%) patients experienced a recurrent stroke. There was a heterogeneity across studies for the association between PFO size and stroke recurrence (pinteraction = 0.01). In a model accounting for age, hypertension, antithrombotic therapy, and PFO anatomy, ASA was independently associated with recurrent stroke (adjusted hazard ratio: 3.27; 95% confidence interval: 1.82 to 5.86; p < 0.0001), whereas large PFO was not (average adjusted hazard ratio across studies: 1.43; 95% confidence interval: 0.50 to 4.03; p = 0.50).
Conclusions In patients with PFO-associated stroke, ASA is a more important predictor of recurrent stroke than shunt size. These results can help to better identify those patients with a high risk of stroke recurrence under medical therapy who may derive the most benefit from PFO closure. (Patent Foramen Ovale Closure or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence [CLOSE]; NCT00562289) (Device Closure versus Medical Therapy in Patients with Cryptogenic Stroke and High-Risk Patent Foramen Ovale [DEFENSE-PFO]; NCT01550588)
↵∗ Drs. Song and Mas have contributed equally to this work.
The CLOSE trial was funded by the French Ministry of Health. The DEFENSE-PFO trial was funded by a research grant from the Cardiovascular Research Foundation, Seoul, South Korea. Dr. Brochet is a proctor for and has received lecture fees from Abbott. Dr. Mas has participated in Advisory Boards and received lectures fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received September 4, 2019.
- Revision received February 18, 2020.
- Accepted February 28, 2020.
- 2020 American College of Cardiology Foundation
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