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01-02-2019 | Original Paper

Interventional closure vs. medical therapy of patent foramen ovale for secondary prevention of stroke: updated meta-analysis

Authors: Davor Vukadinović, Stephan H. Schirmer, Aleksandra Nikolovska Vukadinović, Christian Ukena, Bruno Scheller, Felix Mahfoud, Michael Böhm

Published in: Clinical Research in Cardiology | Issue 2/2019

Abstract

Background

We aimed to explore whether interventional closure of patent foramen ovale (PFO) results in reduction of composite outcome [stroke/transitory ischemic attack (TIA), death, and thrombolysis in myocardial infarction—TIMI bleeding], stroke and stroke/TIA compared to medical treatment in patients with cryptogenic stroke.

Methods and results

Searching the PUBMED and Cochrane library database, we performed meta-analysis from all randomized controlled studies that compared effects of interventional PFO closure with medical treatment on stroke prevention. 3560 patients from six randomized trials were included. Interventional PFO closure reduced composite outcome (RR of 0.47, 0.26–0.85, p = 0.01), stroke (RR of 0.38, 0.18–0.82, p = 0.01) and stroke/TIA (RR of 0.56, 0.43–0.74, p < 0.0001). Analysis had 70.5% power to detect observed reduction of RR for the primary outcome, 70.6% for stroke and 98.7% for stroke/TIA. Bleeding rates were comparable (RR of 0.91, 0.60–1.38, p = 0.66), while there was higher burden of new AF (RR of 5.54, 3–10.2, p < 0.0001) after interventional closure. Subgroup analysis revealed that patients with large shunts had substantial less recurrent strokes over patients with small shunts (p for interaction = 0.02). Use of Amplatzer PFO device was associated with substantial less AF (RR of 2.36, p = 0.06) compared with other devices (RR of 8.93, p < 0.0001) (p for interaction = 0.04), with comparable benefit for stroke prevention (p for interaction = 0.73).

Conclusions

Interventional closure of PFO resulted in significant reduction of stroke and stroke/TIA compared with antiplatelets/anticoagulants with comparable bleeding rates between the groups, whereas AF occurred more frequently in the intervention group. Patients with large shunts had more benefit from interventional closure.

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Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O’Donnell MJ, Sacco RL, Connolly SJ (2014) Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol 13(4):429–438. https://doi.org/10.1016/s1474-4422(13)70310-7 CrossRefPubMed

Alsheikh-Ali AA, Thaler DE, Kent DM (2009) Patent foramen ovale in cryptogenic stroke: incidental or pathogenic? Stroke 40(7):2349–2355. https://doi.org/10.1161/strokeaha.109.547828 CrossRefPubMedPubMedCentral

Handke M, Harloff A, Olschewski M, Hetzel A, Geibel A (2007) Patent foramen ovale and cryptogenic stroke in older patients. N Engl J Med 357(22):2262–2268. https://doi.org/10.1056/NEJMoa071422 CrossRefPubMed

Meier B, Kalesan B, Mattle HP, Khattab AA, Hildick-Smith D, Dudek D, Andersen G, Ibrahim R, Schuler G, Walton AS, Wahl A, Windecker S, Juni P (2013) Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med 368(12):1083–1091. https://doi.org/10.1056/NEJMoa1211716 CrossRefPubMed

Furlan AJ, Reisman M, Massaro J, Mauri L, Adams H, Albers GW, Felberg R, Herrmann H, Kar S, Landzberg M, Raizner A, Wechsler L (2012) Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 366(11):991–999. https://doi.org/10.1056/NEJMoa1009639 CrossRefPubMed

Carroll JD, Saver JL, Thaler DE, Smalling RW, Berry S, MacDonald LA, Marks DS, Tirschwell DL (2013) Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med 368(12):1092–1100. https://doi.org/10.1056/NEJMoa1301440 CrossRefPubMed

Saver JL, Carroll JD, Thaler DE, Smalling RW, MacDonald LA, Marks DS, Tirschwell DL (2017) Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med 377(11):1022–1032. https://doi.org/10.1056/NEJMoa1610057 CrossRefPubMed

Mas JL, Derumeaux G, Guillon B, Massardier E, Hosseini H, Mechtouff L, Arquizan C, Bejot Y, Vuillier F, Detante O, Guidoux C, Canaple S, Vaduva C, Dequatre-Ponchelle N, Sibon I, Garnier P, Ferrier A, Timsit S, Robinet-Borgomano E, Sablot D, Lacour JC, Zuber M, Favrole P, Pinel JF, Apoil M, Reiner P, Lefebvre C, Guerin P, Piot C, Rossi R, Dubois-Rande JL, Eicher JC, Meneveau N, Lusson JR, Bertrand B, Schleich JM, Godart F, Thambo JB, Leborgne L, Michel P, Pierard L, Turc G, Barthelet M, Charles-Nelson A, Weimar C, Moulin T, Juliard JM, Chatellier G (2017) Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med 377(11):1011–1021. https://doi.org/10.1056/NEJMoa1705915 CrossRefPubMed

Sondergaard L, Kasner SE, Rhodes JF, Andersen G, Iversen HK, Nielsen-Kudsk JE, Settergren M, Sjostrand C, Roine RO, Hildick-Smith D, Spence JD, Thomassen L (2017) Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med 377(11):1033–1042. https://doi.org/10.1056/NEJMoa1707404 CrossRefPubMed

10.

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 (2018) Cryptogenic stroke and high-risk patent foramen ovale: The DEFENSE-PFO Trial. J Am Coll Cardiol 71(20):2335–2342. https://doi.org/10.1016/j.jacc.2018.02.046 CrossRefPubMed

11.

Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269, W264CrossRefPubMed

12.

Rao G, Lopez-Jimenez F, Boyd J, D’Amico F, Durant NH, Hlatky MA, Howard G, Kirley K, Masi C, Powell-Wiley TM, Solomonides AE, West CP, Wessel J (2017) Methodological standards for meta-analyses and qualitative systematic reviews of cardiac prevention and treatment studies: a scientific statement from the American Heart Association. Circulation 136(10):e172–e194. https://doi.org/10.1161/cir.0000000000000523 CrossRefPubMed

13.

Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12CrossRefPubMed

14.

Olivo SA, Macedo LG, Gadotti IC, Fuentes J, Stanton T, Magee DJ (2008) Scales to assess the quality of randomized controlled trials: a systematic review. Phys Ther 88(2):156–175. https://doi.org/10.2522/ptj.20070147 CrossRefPubMed

15.

Altman DG, Bland JM (2003) Interaction revisited: the difference between two estimates. BMJ 326(7382):219CrossRefPubMedPubMedCentral

16.

Turner RM, Bird SM, Higgins JP (2013) The impact of study size on meta-analyses: examination of underpowered studies in Cochrane reviews. PloS One 8(3):e59202. https://doi.org/10.1371/journal.pone.0059202 CrossRefPubMedPubMedCentral

17.

Schulze V, Lin Y, Karathanos A, Brockmeyer M, Zeus T, Polzin A, Perings S, Kelm M, Wolff G (2018) Patent foramen ovale closure or medical therapy for cryptogenic ischemic stroke: an updated meta-analysis of randomized controlled trials. Clin Res Cardiol. https://doi.org/10.1007/s00392-018-1224-4 CrossRefPubMed

18.

Alushi B, Lauten A, Cassese S, Colleran R, Schupke S, Rai H, Schunkert H, Meier B, Landmesser U, Kastrati A (2018) Patent foramen ovale closure versus medical therapy for prevention of recurrent cryptogenic embolism: updated meta-analysis of randomized clinical trials. Clin Res Cardiol. https://doi.org/10.1007/s00392-018-1246-y CrossRefPubMed

19.

Kent DM, Ruthazer R, Weimar C, Mas JL, Serena J, Homma S, Di Angelantonio E, Di Tullio MR, Lutz JS, Elkind MS, Griffith J, Jaigobin C, Mattle HP, Michel P, Mono ML, Nedeltchev K, Papetti F, Thaler DE (2013) An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke. Neurology 81(7):619–625. https://doi.org/10.1212/WNL.0b013e3182a08d59 CrossRefPubMedPubMedCentral

20.

Sanna T, Diener HC, Passman RS, Di Lazzaro V, Bernstein RA, Morillo CA, Rymer MM, Thijs V, Rogers T, Beckers F, Lindborg K, Brachmann J (2014) Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 370(26):2478–2486. https://doi.org/10.1056/NEJMoa1313600 CrossRefPubMed

21.

Gladstone DJ, Spring M, Dorian P, Panzov V, Thorpe KE, Hall J, Vaid H, O’Donnell M, Laupacis A, Cote R, Sharma M, Blakely JA, Shuaib A, Hachinski V, Coutts SB, Sahlas DJ, Teal P, Yip S, Spence JD, Buck B, Verreault S, Casaubon LK, Penn A, Selchen D, Jin A, Howse D, Mehdiratta M, Boyle K, Aviv R, Kapral MK, Mamdani M (2014) Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med 370(26):2467–2477. https://doi.org/10.1056/NEJMoa1311376 CrossRefPubMed

22.

Overell JR, Bone I, Lees KR (2000) Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology 55(8):1172–1179CrossRefPubMed

23.

Mas JL, Arquizan C, Lamy C, Zuber M, Cabanes L, Derumeaux G, Coste J (2001) Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 345(24):1740–1746. https://doi.org/10.1056/NEJMoa011503 CrossRefPubMed

24.

Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP (2002) Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation 105(22):2625–2631CrossRefPubMed

25.

Hart RG, Sharma M, Mundl H, Shoamanesh A, Kasner SE, Berkowitz SD, Pare G, Kirsch B, Pogue J, Pater C (2016) Rivaroxaban for secondary stroke prevention in patients with embolic strokes of undetermined source: design of the NAVIGATE ESUS randomized trial. Eur Stroke J 1(3):146–154CrossRefPubMedPubMedCentral

26.

Baumgartner H, Bonhoeffer P, De Groot NM, de Haan F, Deanfield JE, Galie N, Gatzoulis MA, Gohlke-Baerwolf C, Kaemmerer H, Kilner P, Meijboom F, Mulder BJ, Oechslin E, Oliver JM, Serraf A, Szatmari A, Thaulow E, Vouhe PR, Walma E (2010) ESC Guidelines for the management of grown-up congenital heart disease (new version 2010). Eur Heart J 31(23):2915–2957. https://doi.org/10.1093/eurheartj/ehq249 CrossRefPubMed

27.

Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, Johnston SC, Kasner SE, Kittner SJ, Mitchell PH, Rich MW, Richardson D, Schwamm LH, Wilson JA (2014) Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45(7):2160–2236. https://doi.org/10.1161/str.0000000000000024 CrossRefPubMed

28.

Messe SR, Gronseth G, Kent DM, Kizer JR, Homma S, Rosterman L, Kasner SE (2016) Practice advisory: recurrent stroke with patent foramen ovale (update of practice parameter): report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology 87(8):815–821. https://doi.org/10.1212/wnl.0000000000002961 CrossRefPubMedPubMedCentral

Title: Interventional closure vs. medical therapy of patent foramen ovale for secondary prevention of stroke: updated meta-analysis
Authors: Davor Vukadinović
Stephan H. Schirmer
Aleksandra Nikolovska Vukadinović
Christian Ukena
Bruno Scheller
Felix Mahfoud
Michael Böhm
Publication date: 01-02-2019
Publisher: Springer Berlin Heidelberg
Published in: Clinical Research in Cardiology / Issue 2/2019
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI: https://doi.org/10.1007/s00392-018-1334-z

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Conclusions

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