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Closure of Patent Foramen Ovale and Cryptogenic Stroke: Unresolved Issues

  • Hans-Christoph DienerEmail author
  • Christian Gerloff
  • David E. Thaler
  • Jochen Wöhrle
Stroke (H Diener, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Stroke

Abstract

Purpose of Review

This review summarises the results of randomised trials comparing closure of patent foramen ovale (PFO) with antithrombotic therapy in patients with cryptogenic stroke.

Recent Findings

Initially, three randomised trials failed to show superiority of PFO closure over antithrombotic therapy in patients with cryptogenic stroke. Three recently performed trials and the prolongation of an earlier trial provided evidence that PFO closure in patients with cryptogenic stroke and an age range of 18–60 years is superior to stroke prevention with antiplatelet therapy. PFO closure was not superior to anticoagulation. Anticoagulation, however, has a higher long-term bleeding risk. PFO closure could result in atrial fibrillation (AF) in a small number of patients. In most patients, AF was transient in duration. Optimal patient selection requires future research.

Summary

In patients with cryptogenic stroke aged < 60 years, PFO closure is superior to antiplatelet therapy in the prevention of recurrent stroke.

Keywords

Cryptogenic stroke Patent foramen ovale Closure of PFO Antiplatelet treatment Anticoagulation Stroke prevention 

Notes

Compliance with Ethical Standards

Conflict of Interest

Hans-Christoph Diener reports grants and personal fees from Boehringer Ingelheim, during the conduct of the study; personal fees from Abbott, personal fees from Allergan, grants and personal fees from AstraZeneca, personal fees from Bayer Vital, personal fees from Bristol-Myers Squibb, personal fees from Brainsgate, personal fees from CoAxia, personal fees from Corimmun, personal fees from Covidien, personal fees from Daichii Sankyo, personal fees from D-Pharm, personal fees from EV3, personal fees from Fresenius, grants and personal fees from GlaxoSmithKline, grants and personal fees from Janssen-Cilag, personal fees from Knoll, personal fees from Merck Sharp & Dohme, personal fees from Lilly, personal fees from Medtronic, personal fees from Mind-Frame, personal fees from Neurobiological Technologies, grants and personal fees from Novartis, personal fees from Novo Nordisk, personal fees from Paion, personal fees from Parke-Davis, personal fees from Pfizer, grants and personal fees from Sanofi Aventis, personal fees from Schering-Plough, personal fees from Servier, personal fees from Solvay, personal fees from St. Jude, personal fees from Thrombogenics, grants from Lundbeck, grants from Syngis, grants from Talecris, personal fees from Wyeth, grants from German Research Council (DFG), grants from German Ministry of Education and Research (BMBF), grants from European Union, grants from Bertelsmann Foundation, grants from Heinz-Nixdorf Foundation, grants from National Institutes of Health, outside the submitted work. David E Thaler reports personal fees from Abbott, outside the submitted work. Christian Gerloff reports grants from DFG GE 844/4-1, grants from EU Grant Agreement no. 278276, grants from RV Nord, personal fees from Amgen, personal fees and other from Bayer Vital, personal fees from BMS, personal fees from Boehringer Ingelheim, other from Sanofi Aventis, personal fees from TV3, personal fees from Danish Research Council, outside the submitted work. Jochen Wöhrle declares no potential conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Lechat P, Mas JL, Lascault G, Loron P, Theard M, Klimczac M, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med. 1988;318(18):1148–52.CrossRefGoogle Scholar
  2. 2.
    Katsanos AH, Spence JD, Bogiatzi C, Parissis J, Giannopoulos S, Frogoudaki A, et al. Recurrent stroke and patent foramen ovale: a systematic review and meta-analysis. Stroke. 2014;45(11):3352–9.CrossRefGoogle Scholar
  3. 3.
    Furlan AJ, Reisman M, Massaro J, Mauri L, Adams H, Albers GW, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med. 2012;366(11):991–9.CrossRefGoogle Scholar
  4. 4.
    Meier B, Kalesan B, Mattle HP, Khattab AA, Hildick-Smith D, Dudek D, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med. 2013;368(12):1083–91.CrossRefGoogle Scholar
  5. 5.
    Carroll JD, Saver JL, Thaler DE, Smalling RW, Berry S, MacDonald LA, et al. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med. 2013;368(12):1092–100.CrossRefGoogle Scholar
  6. 6.
    •• Mas JL, Derumeaux G, Guillon B, Massardier E, Hosseini H, Mechtouff L, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011–21 Large randomised trial comparing PFO closure, antiplatelet therapy and anticoagualtion in patients with cryptogenic stroke and PFO. Trial was industry independent. CrossRefGoogle Scholar
  7. 7.
    •• Saver JL, Carroll JD, Thaler DE, Smalling RW, MacDonald LA, Marks DS, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017;377(11):1022–32 Large randomised trial comparing PFO closure with antiplatlet therapy in patients with crypotgenic stroke. Trial had the longest observation time. CrossRefGoogle Scholar
  8. 8.
    Sondergaard L, Kasner SE, Rhodes JF, Andersen G, Iversen HK, Nielsen-Kudsk JE, et al. Patent foramen Ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377(11):1033–42.CrossRefGoogle Scholar
  9. 9.
    Lee PH, Song JK, Kim JS, Heo R, Lee S, Kim DH, et al. Cryptogenic stroke and high-risk patent foramen ovale: the DEFENSE-PFO trial. J Am Coll Cardiol. 2018;71(20):2335–42.CrossRefGoogle Scholar
  10. 10.
    Spencer FA, Lopes LC, Kennedy SA, Guyatt G. Systematic review of percutaneous closure versus medical therapy in patients with cryptogenic stroke and patent foramen ovale. BMJ Open. 2014;4(3):e004282.CrossRefGoogle Scholar
  11. 11.
    •• Kuijpers T, Spencer FA, Siemieniuk RAC, Vandvik PO, Otto CM, Lytvyn L, et al. Patent foramen ovale closure, antiplatelet therapy or anticoagulation therapy alone for management of cryptogenic stroke? A clinical practice guideline. BMJ. 2018;362:k2515 Practice guideline for PFO closure based on a meta-analysis of the randomised trials. CrossRefGoogle Scholar
  12. 12.
    Mir H, Siemieniuk RAC, Ge LC, Foroutan F, Fralick M, Syed T, et al. Patent foramen ovale closure, antiplatelet therapy or anticoagulation in patients with patent foramen ovale and cryptogenic stroke: a systematic review and network meta-analysis incorporating complementary external evidence. BMJ Open. 2018;8(7):e023761.CrossRefGoogle Scholar
  13. 13.
    Saver JL, Mattle HP, Thaler D. Patent foramen ovale closure versus medical therapy for cryptogenic ischemic stroke: a topical review. Stroke. 2018;49(6):1541–8.CrossRefGoogle Scholar
  14. 14.
    Pristipino C, Sievert H, D'Ascenzo F, Mas JL, Meier B, Scacciatella P, et al. European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. EuroIntervention. 2018.  https://doi.org/10.4244/EIJ-D-18-00622.
  15. 15.
    Ntaios G, Papavasileiou V, Sagris D, Makaritsis K, Vemmos K, Steiner T, et al. Closure of patent foramen ovale versus medical therapy in patients with cryptogenic stroke or transient ischemic attack: updated systematic review and meta-analysis. Stroke. 2018;49(2):412–8.CrossRefGoogle Scholar
  16. 16.
    Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O'Donnell MJ, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13(4):429–38.CrossRefGoogle Scholar
  17. 17.
    Mazzucco S, Li L, Binney L, Rothwell PM, Oxford vascular study phenotyped C. Prevalence of patent foramen ovale in cryptogenic transient ischaemic attack and non-disabling stroke at older ages: a population-based study, systematic review, and meta-analysis. Lancet Neurol. 2018;17(7):609–17.CrossRefGoogle Scholar
  18. 18.
    Kent DM, Ruthazer R, Weimar C, Mas JL, Serena J, Homma S, et al. An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke. Neurology. 2013;81(7):619–25.CrossRefGoogle Scholar
  19. 19.
    Prefasi D, Martinez-Sanchez P, Fuentes B, Diez-Tejedor E. The utility of the RoPE score in cryptogenic stroke patients </=50 years in predicting a stroke-related patent foramen ovale. Int J Stroke. 2016;11(1):NP7–8.CrossRefGoogle Scholar
  20. 20.
    Mas JL, Arquizan C, Lamy C, Zuber M, Cabanes L, Derumeaux G, et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med. 2001;345(24):1740–6.CrossRefGoogle Scholar
  21. 21.
    Ahmad Y, Howard JP, Arnold A, Shin MS, Cook C, Petraco R, et al. Patent foramen ovale closure vs. medical therapy for cryptogenic stroke: a meta-analysis of randomized controlled trials. Eur Heart J. 2018;39(18):1638–49.CrossRefGoogle Scholar
  22. 22.
    Lapergue B, Decroix JP, Evrard S, Wang A, Bendetowicz D, Offroy MA, et al. Diagnostic yield of venous thrombosis and pulmonary embolism by combined CT venography and pulmonary angiography in patients with cryptogenic stroke and patent foramen Ovale. Eur Neurol. 2015;74(1–2):69–72.CrossRefGoogle Scholar
  23. 23.
    Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315–52.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hans-Christoph Diener
    • 1
    Email author
  • Christian Gerloff
    • 2
  • David E. Thaler
    • 3
  • Jochen Wöhrle
    • 4
  1. 1.Senior Professor of Clinical NeurosciencesMedical Faculty of the University Duisburg-EssenEssenGermany
  2. 2.Department of NeurologyUniversity Medical Center Eppendorf (UKE)HamburgGermany
  3. 3.Department of NeurologyTufts Medical Center and Tufts University School of MedicineBostonUSA
  4. 4.Department of Internal Medicine II – CardiologyUniversity Ulm GermanyUlmGermany

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