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01-09-2018 | Original Paper

Patent foramen ovale closure or medical therapy for cryptogenic ischemic stroke: an updated meta-analysis of randomized controlled trials

Authors: Volker Schulze, Yingfeng Lin, Athanasios Karathanos, Maximilian Brockmeyer, Tobias Zeus, Amin Polzin, Stefan Perings, Malte Kelm, Georg Wolff

Published in: Clinical Research in Cardiology | Issue 9/2018

Abstract

Background

Previous randomized controlled trials (RCT) failed to demonstrate benefits of patent foramen ovale (PFO) closure (PFO-C) over medical therapy (MT) for secondary prevention of cryptogenic ischemic stroke. Three recently published RCTs, however, turned out positive for PFO-C and warrant an updated meta-analysis.

Methods

Data from all available RCTs on PFO-C vs. MT for secondary prevention of cryptogenic ischemic stroke up until October 2017 were abstracted and analyzed in a comprehensive meta-analysis. Clinical efficacy outcomes were recurrent stroke, recurrent TIA, and their combination; safety outcomes were mortality, major bleeding, venous thromboembolism (VTE), and new-onset atrial fibrillation/flutter (NOAF).

Results

Five trials including a total of 3440 patients were included in the meta-analysis. PFO-C significantly reduced recurrent stroke [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.19–0.90; p = 0.03] and the combination of recurrent stroke + TIA (OR 0.53, CI 0.36–0.80; p = 0.002) compared to MT; recurrent TIA alone showed no differences (OR 0.77; CI 0.51–1.14; p = 0.19). NOAF was significantly more frequent after PFO-C (OR 5.75, CI 3.09–10.70; p < 0.00001). Mortality (OR 0.80, CI 0.39–1.67), major bleeding (OR 0.96, CI 0.48–1.92), and VTE (OR 2.45, CI 0.75–7.99) remained neutral. Trials with superior patient selection for PFO-C showed advantageous results compared to MT.

Conclusions

PFO-C after cryptogenic ischemic stroke is safe and effective to reduce the risk of recurrent stroke and recurrent stroke + TIA, albeit with an increased risk for NOAF.

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Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Statistics C, Stroke Statistics S (2017) Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 135(10):e146–e603. https://doi.org/10.1161/CIR.0000000000000485 CrossRefPubMedPubMedCentral

Bal S, Patel SK, Almekhlafi M, Modi J, Demchuk AM, Coutts SB (2012) High rate of magnetic resonance imaging stroke recurrence in cryptogenic transient ischemic attack and minor stroke patients. Stroke 43(12):3387–3388. https://doi.org/10.1161/STROKEAHA.112.671172 CrossRefPubMed

Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O’Donnell MJ, Sacco RL, Connolly SJ, Cryptogenic Stroke EIWG (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

Cohnheim J (1877) Vorlesungen über allgemeine Pathologie—ein Handbuch für Aerzte und Studirende. Erste Ausgabe, Berlin

Hagen PT, Scholz DG, Edwards WD (1984) Incidence and size of patent foramen ovale during the first ten decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc 59(1):17–20CrossRefPubMed

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

Lechat P, Mas JL, Lascault G, Loron P, Theard M, Klimczac M, Drobinski G, Thomas D, Grosgogeat Y (1988) Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 318(18):1148–1152. https://doi.org/10.1056/NEJM198805053181802 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

Mas JL, Arquizan C, Lamy C, Zuber M, Cabanes L, Derumeaux G, Coste J, Patent Foramen O, Atrial Septal Aneurysm Study G (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

10.

Serena J, Marti-Fabregas J, Santamarina E, Rodriguez JJ, Perez-Ayuso MJ, Masjuan J, Segura T, Gallego J, Davalos A, Codicia R-t-LSiCSS, Stroke Project of the Cerebrovascular Diseases Study Group SSoN (2008) Recurrent stroke and massive right-to-left shunt: results from the prospective Spanish multicenter (CODICIA) study. Stroke 39 (12):3131–3136. https://doi.org/10.1161/STROKEAHA.108.521427 CrossRefPubMed

11.

Furlan AJ, Reisman M, Massaro J, Mauri L, Adams H, Albers GW, Felberg R, Herrmann H, Kar S, Landzberg M, Raizner A, Wechsler L, Investigators CI (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

12.

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, Investigators PCT (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

13.

Carroll JD, Saver JL, Thaler DE, Smalling RW, Berry S, MacDonald LA, Marks DS, Tirschwell DL, Investigators R (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

14.

Kent DM, Dahabreh IJ, Ruthazer R, Furlan AJ, Reisman M, Carroll JD, Saver JL, Smalling RW, Juni P, Mattle HP, Meier B, Thaler DE (2016) Device closure of patent foramen ovale after stroke: pooled analysis of completed randomized trials. J Am Coll Cardiol 67(8):907–917. https://doi.org/10.1016/j.jacc.2015.12.023 CrossRefPubMedPubMedCentral

15.

Stortecky S, da Costa BR, Mattle HP, Carroll J, Hornung M, Sievert H, Trelle S, Windecker S, Meier B, Juni P (2015) Percutaneous closure of patent foramen ovale in patients with cryptogenic embolism: a network meta-analysis. Eur Heart J 36(2):120–128. https://doi.org/10.1093/eurheartj/ehu292 CrossRefPubMed

16.

Pandit A, Aryal MR, Pandit AA, Jalota L, Kantharajpur S, Hakim FA, Lee HR (2014) Amplatzer PFO occluder device may prevent recurrent stroke in patients with patent foramen ovale and cryptogenic stroke: a meta-analysis of randomised trials. Heart Lung Circ 23(4):303–308. https://doi.org/10.1016/j.hlc.2013.12.003 CrossRefPubMed

17.

Li J, Liu J, Liu M, Zhang S, Hao Z, Zhang J, Zhang C (2015) Closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and a history of cryptogenic stroke or transient ischemic attack. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD009938.pub2 CrossRefPubMedPubMedCentral

18.

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

19.

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, American Heart Association Stroke Council CoC, Stroke Nursing CoCC, Council on Peripheral Vascular D (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

20.

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, Gore RCSI. (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

21.

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, Investigators C (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

22.

Saver JL, Carroll JD, Thaler DE, Smalling RW, MacDonald LA, Marks DS, Tirschwell DL, Investigators R (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

23.

The Cochrane Collaboration (2011) Cochrane handbook for systematic reviews of interventions|Cochrane Community (beta). In: The Cochrane Collaboration [Internet]. http://community.cochrane.org/handbook. Accessed 3 Oct 2017

24.

Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700. https://doi.org/10.1136/bmj.b2700 CrossRefPubMedPubMedCentral

25.

Leonard T, Duffy JC (2002) A Bayesian fixed effects analysis of the Mantel–Haenszel model applied to meta-analysis. Stat Med 21(16):2295–2312. https://doi.org/10.1002/sim.1048 CrossRefPubMed

26.

Fleiss JL (1986) Analysis of data from multiclinic trials. Control Clin Trials 7(4):267–275CrossRefPubMed

27.

Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. https://doi.org/10.1136/bmj.327.7414.557 CrossRefPubMedPubMedCentral

28.

Seeger P, Gabrielsson A (1968) Applicability of the Cochran Q test and the F test for statistical analysis of dichotomous data for dependent samples. Psychol Bull 69(4):269–277. https://doi.org/10.1037/h0025667 CrossRefPubMed

29.

DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28(2):105–114. https://doi.org/10.1016/j.cct.2006.04.004 CrossRefPubMed

30.

DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188CrossRefPubMed

31.

DerSimonian R, Laird N (2015) Meta-analysis in clinical trials revisited. Contemp Clin Trials 45(Pt A):139–145. https://doi.org/10.1016/j.cct.2015.09.002 CrossRefPubMedPubMedCentral

32.

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, Investigators E, Coordinators (2014) Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med 370(26):2467–2477. https://doi.org/10.1056/NEJMoa1311376 CrossRefPubMed

33.

Saver JL (2016) Cryptogenic stroke. N Engl J Med 375(11):e26. https://doi.org/10.1056/NEJMc1609156 CrossRefPubMed

34.

Thaler DE, Wahl A (2012) Critique of closure or medical therapy for cryptogenic stroke with patent foramen ovale: the hole truth? Stroke 43(11):3147–3149. https://doi.org/10.1161/STROKEAHA.112.659599 CrossRefPubMed

35.

Krumsdorf U, Ostermayer S, Billinger K, Trepels T, Zadan E, Horvath K, Sievert H (2004) Incidence and clinical course of thrombus formation on atrial septal defect and patient foramen ovale closure devices in 1000 consecutive patients. J Am Coll Cardiol 43(2):302–309CrossRefPubMed

36.

Taaffe M, Fischer E, Baranowski A, Majunke N, Heinisch C, Leetz M, Hein R, Bayard Y, Buscheck F, Reschke M, Hoffmann I, Wunderlich N, Wilson N, Sievert H (2008) Comparison of three patent foramen ovale closure devices in a randomized trial (Amplatzer versus CardioSEAL-STARflex versus Helex occluder). Am J Cardiol 101(9):1353–1358. https://doi.org/10.1016/j.amjcard.2007.12.040 CrossRefPubMed

37.

Staubach S, Steinberg DH, Zimmermann W, Wawra N, Wilson N, Wunderlich N, Sievert H (2009) New onset atrial fibrillation after patent foramen ovale closure. Catheter Cardiovasc Interv 74(6):889–895. https://doi.org/10.1002/ccd.22172 CrossRefPubMed

38.

Luermans JG, Post MC, Plokker HW, Ten Berg JM, Suttorp MJ (2008) Complications and mid-term outcome after percutaneous patent foramen ovale closure in patients with cryptogenic stroke. Neth Heart J 16(10):332–336CrossRefPubMedPubMedCentral

39.

Bonvini RF, Sztajzel R, Dorsaz PA, Righini M, Bonvin C, Alibegovic J, Sigwart U, Camenzind E, Verin V, Sztajzel J (2010) Incidence of atrial fibrillation after percutaneous closure of patent foramen ovale and small atrial septal defects in patients presenting with cryptogenic stroke. Int J Stroke 5(1):4–9. https://doi.org/10.1111/j.1747-4949.2009.00336.x CrossRefPubMed

40.

Burow A, Schwerzmann M, Wallmann D, Tanner H, Sakata T, Windecker S, Meier B, Delacretaz E (2008) Atrial fibrillation following device closure of patent foramen ovale. Cardiology 111(1):47–50. https://doi.org/10.1159/000113427 CrossRefPubMed

41.

Jarral OA, Saso S, Vecht JA, Harling L, Rao C, Ahmed K, Gatzoulis MA, Malik IS, Athanasiou T (2011) Does patent foramen ovale closure have an anti-arrhythmic effect? A meta-analysis. Int J Cardiol 153(1):4–9. https://doi.org/10.1016/j.ijcard.2011.02.027 CrossRefPubMed

42.

De Rosa S, Sievert H, Sabatino J, Polimeni A, Sorrentino S, Indolfi C (2018) Percutaneous closure versus medical treatment in stroke patients with patent foramen ovale: a systematic review and meta-analysis. Ann Intern Med. https://doi.org/10.7326/M17-3033 PubMedCrossRef

43.

Mojadidi MK, Elgendy AY, Elgendy IY, Mahmoud AN, Elbadawi A, Eshtehardi P, Patel NK, Wayangankar S, Tobis JM, Meier B (2017) Transcatheter patent foramen ovale closure after cryptogenic stroke: an updated meta-analysis of randomized trials. JACC Cardiovasc Interv 10(21):2228–2230. https://doi.org/10.1016/j.jcin.2017.09.002 CrossRefPubMed

44.

Shah R, Nayyar M, Jovin IS, Rashid A, Bondy BR, Fan TM, Flaherty MP, Rao SV (2018) Device closure versus medical therapy alone for patent foramen ovale in patients with cryptogenic stroke: a systematic review and meta-analysis. Ann Intern Med. https://doi.org/10.7326/M17-2679 CrossRefPubMedPubMedCentral

Title: Patent foramen ovale closure or medical therapy for cryptogenic ischemic stroke: an updated meta-analysis of randomized controlled trials
Authors: Volker Schulze
Yingfeng Lin
Athanasios Karathanos
Maximilian Brockmeyer
Tobias Zeus
Amin Polzin
Stefan Perings
Malte Kelm
Georg Wolff
Publication date: 01-09-2018
Publisher: Springer Berlin Heidelberg
Published in: Clinical Research in Cardiology / Issue 9/2018
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI: https://doi.org/10.1007/s00392-018-1224-4

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Patent foramen ovale closure or medical therapy for cryptogenic ischemic stroke: an updated meta-analysis of randomized controlled trials

Abstract

Background

Methods

Results

Conclusions

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