Top

Published in:

01-09-2018 | Original Paper

Patent foramen ovale closure versus medical therapy for prevention of recurrent cryptogenic embolism: updated meta-analysis of randomized clinical trials

Authors: Brunilda Alushi, Alexander Lauten, Salvatore Cassese, Roisin Colleran, Stefanie Schüpke, Himanshu Rai, Heribert Schunkert, Bernhard Meier, Ulf Landmesser, Adnan Kastrati

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

Abstract

Background

We performed an updated meta-analysis of all randomized-controlled trials (RCTs) comparing patent foramen ovale (PFO) closure with medical therapy for prevention of recurrent ischemic stroke.

Methods and results

We searched Medline, EMBASE, and Cochrane databases, and proceedings of international meetings for RCTs of patients with cryptogenic stroke and PFO comparing percutaneous PFO closure versus medical therapy for prevention of recurrent ischemic stroke. The primary outcome was a composite ischemic/embolic endpoint comprising stroke, transient ischemic attack (TIA), peripheral embolism, and early death in the intention-to-treat population. Secondary outcomes were all-cause death, stroke, TIA, atrial fibrillation (AF), and major bleeding. Of 3440 enrolled patients across five RCTs, 1829 were allocated to PFO closure and 1611 to medical therapy. The follow-up ranged from 2 to 5.9 years. PFO closure reduced the risk of the composite outcome [HR 0.52, (0.36–0.77); p < 0.01], and stroke, [HR 0.39, (0.19–0.83); p < 0.01], and increased the risk of AF [OR 3.75, (2.44–5.78); p < 0.01] as compared to medical therapy. NNT for stroke was 37 and NNH for AF 49, indicating a net clinical benefit of PFO closure. The meta-analysis had 95% power to detect a 50% relative risk reduction (RRR) in the primary outcome and 89% power to detect a 70% RRR in ischemic stroke. The risk of all-cause death (HR 1.08, p = 0.90), TIA [HR 0.73, (0.49–1.09); p = 0.12], and major bleeding [OR 0.97, (0.44–2.17); p = 0.95] was comparable between the groups.

Conclusions

Among patients with cryptogenic stroke and PFO, percutaneous closure of PFO is superior to medical therapy in preventing recurrent ischemic/embolic events and stroke but is associated with an increased risk of AF.

Available only for authorised users

Sacco RL, Ellenberg JH, Mohr JP, Tatemichi TK, Hier DB, Price TR, Wolf PA (1989) Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol 25 (4):382–390. https://doi.org/10.1002/ana.410250410 CrossRefPubMed

Lee BI, Nam HS, Heo JH, Kim DI, Yonsei Stroke T (2001) Yonsei Stroke Registry. Analysis of 1,000 patients with acute cerebral infarctions. Cerebrovasc Dis 12 (3):145–151. https://doi.org/10.1159/000047697 CrossRefPubMed

Lechat P, Lascault G, Mas JL, Loron P, Klimczac K, Guggiari M, Drobinski G, Fraysse JB, Thomas D, Grosgogeat Y (1989) Prevalence of patent foramen ovale in young patients with ischemic cerebral complications. Arch Mal Coeur Vaiss 82 (6):847–852PubMed

Knebel F, Masuhr F, von Hausen W, Walde T, Dreger H, Raab V, Yuerek M, Baumann G, Borges AC (2009) Transesophageal echocardiography in patients with cryptogenic cerebral ischemia. Cardiovasc Ultrasound 7:15. https://doi.org/10.1186/1476-7120-7-15 CrossRefPubMedPubMedCentral

Wahl A, Juni P, Mono ML, Kalesan B, Praz F, Geister L, Raber L, Nedeltchev K, Mattle HP, Windecker S, Meier B (2012) Long-term propensity score-matched comparison of percutaneous closure of patent foramen ovale with medical treatment after paradoxical embolism. Circulation 125 (6):803–812. https://doi.org/10.1161/CIRCULATIONAHA.111.030494 CrossRefPubMed

Capodanno D, Milazzo G, Vitale L, Di Stefano D, Di Salvo M, Grasso C, Tamburino C (2014) Updating the evidence on patent foramen ovale closure versus medical therapy in patients with cryptogenic stroke: a systematic review and comprehensive meta-analysis of 2,303 patients from three randomised trials and 2,231 patients from 11 observational studies. EuroIntervention 9 (11):1342–1349. https://doi.org/10.4244/EIJV9I11A225 CrossRefPubMed

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

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

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

10.

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

11.

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

12.

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

13.

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

14.

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

15.

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

16.

Juni P, Witschi A, Bloch R, Egger M (1999) The hazards of scoring the quality of clinical trials for meta-analysis. JAMA 282 (11):1054–1060CrossRefPubMed

17.

Bradburn MJ, Deeks JJ, Berlin JA, Russell Localio A (2007) Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med 26 (1):53–77. https://doi.org/10.1002/sim.2528 CrossRefPubMed

18.

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

19.

Cates CJ (2002) Simpson’s paradox and calculation of number needed to treat from meta-analysis. BMC Med Res Methodol 2:1CrossRefPubMedPubMedCentral

20.

Smeeth L, Haines A, Ebrahim S (1999) Numbers needed to treat derived from meta-analyses–sometimes informative, usually misleading. BMJ 318 (7197):1548–1551CrossRefPubMedPubMedCentral

21.

Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6 (7):e1000100. https://doi.org/10.1371/journal.pmed.1000100 CrossRefPubMedPubMedCentral

22.

Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan I, Kelly-Hayes M, Kenton EJ, Marks M, Schwamm LH, Tomsick T, American Heart A, American Stroke Association Council on S, Council on Cardiovascular R, Intervention, American Academy of N (2006) Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke 37 (2):577–617. https://doi.org/10.1161/01.STR.0000199147.30016.74 CrossRefPubMed

23.

Goel SS, Tuzcu EM, Shishehbor MH, de Oliveira EI, Borek PP, Krasuski RA, Rodriguez LL, Kapadia SR (2009) Morphology of the patent foramen ovale in asymptomatic versus symptomatic (stroke or transient ischemic attack) patients. Am J Cardiol 103 (1):124–129. https://doi.org/10.1016/j.amjcard.2008.08.036 CrossRefPubMed

24.

Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP, Investigators PFOiCSS (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.

Mattioli AV, Aquilina M, Oldani A, Longhini C, Mattioli G (2001) Atrial septal aneurysm as a cardioembolic source in adult patients with stroke and normal carotid arteries. A multicentre study. Eur Heart J 22 (3):261–268. https://doi.org/10.1053/euhj.2001.2293 CrossRefPubMed

26.

Alushi B, Biasco L, Orzan F, Omede P, Sciuto F, Moretti C, Belli R, Defilippi G, Barisone G, Cerrato P, Gaita F (2014) Patent foramen ovale treatment strategy: an Italian large prospective study. J Cardiovasc Med (Hagerstown) 15 (10):761–768. https://doi.org/10.2459/JCM.0000000000000138 CrossRef

27.

Wessler BS, Thaler DE, Ruthazer R, Weimar C, Di Tullio MR, Elkind MS, Homma S, Lutz JS, Mas JL, Mattle HP, Meier B, Nedeltchev K, Papetti F, Di Angelantonio E, Reisman M, Serena J, Kent DM (2014) Transesophageal echocardiography in cryptogenic stroke and patent foramen ovale: analysis of putative high-risk features from the risk of paradoxical embolism database. Circ Cardiovasc Imaging 7 (1):125–131. https://doi.org/10.1161/CIRCIMAGING.113.000807 CrossRefPubMed

28.

Ahmad Y, Howard JP, Arnold A, Shin MS, Cook C, Petraco R, Demir O, Williams L, Iglesias JF, Sutaria N, Malik I, Davies J, Mayet J, Francis D, Sen S (2018) Patent foramen ovale closure vs. medical therapy for cryptogenic stroke: a meta-analysis of randomized controlled trials. Eur Heart J. https://doi.org/10.1093/eurheartj/ehy121 PubMedPubMedCentralCrossRef

29.

Ando T, Holmes AA, Pahuja M, Javed A, Briasoulis A, Telila T, Takagi H, Schreiber T, Afonso L, Grines CL, Bangalore S (2017) Meta-analysis comparing patent foramen ovale closure versus medical therapy to prevent recurrent cryptogenic stroke. Am J Cardiol. https://doi.org/10.1016/j.amjcard.2017.11.037 CrossRefPubMed

30.

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

31.

Ntaios G, Papavasileiou V, Sagris D, Makaritsis K, Vemmos K, Steiner T, Michel P (2018) Closure of patent foramen ovale versus medical therapy in patients with cryptogenic stroke or transient ischemic attack: updated systematic review and meta-analysis. Stroke. https://doi.org/10.1161/strokeaha.117.020030 CrossRefPubMed

Title: Patent foramen ovale closure versus medical therapy for prevention of recurrent cryptogenic embolism: updated meta-analysis of randomized clinical trials
Authors: Brunilda Alushi
Alexander Lauten
Salvatore Cassese
Roisin Colleran
Stefanie Schüpke
Himanshu Rai
Heribert Schunkert
Bernhard Meier
Ulf Landmesser
Adnan Kastrati
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/s00392-018-1246-y

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

At a glance: The STEP trials

Springer Medicine

Patent foramen ovale closure versus medical therapy for prevention of recurrent cryptogenic embolism: updated meta-analysis of randomized clinical trials

Abstract

Background

Methods and results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods and results

Conclusions

Please log in to get access to this content

Other articles of this Issue 9/2018

Inflammation and the risk of atrial high-rate episodes (AHREs) in patients with cardiac implantable electronic devices

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

Efficacy and safety of bivalirudin for percutaneous coronary intervention in acute coronary syndromes: a meta-analysis of randomized-controlled trials

Risk factors and outcome of postoperative delirium after transcatheter aortic valve replacement

Creation of a restrictive atrial communication in heart failure with preserved and mid-range ejection fraction: effective palliation of left atrial hypertension and pulmonary congestion

NOAC monotherapy in patients with concomitant indications for oral anticoagulation undergoing transcatheter aortic valve implantation

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page