Closure of Patent Foramen Ovale and Cryptogenic Stroke: Unresolved Issues
- 463 Downloads
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.
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.
In patients with cryptogenic stroke aged < 60 years, PFO closure is superior to antiplatelet therapy in the prevention of recurrent stroke.
KeywordsCryptogenic stroke Patent foramen ovale Closure of PFO Antiplatelet treatment Anticoagulation Stroke prevention
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.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 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.•• 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
- 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.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
- 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.
- 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
- 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