Device closure of patent foramen ovale versus medical therapy in cryptogenic stroke: a systematic review and meta-analysis

JACC Cardiovasc Interv. 2013 Dec;6(12):1316-23. doi: 10.1016/j.jcin.2013.08.001. Epub 2013 Oct 16.


Objectives: This study sought to perform a meta-analysis of randomized controlled trials comparing device closure with medical therapy in the prevention of recurrent neurological events in patients with cryptogenic stroke and patent foramen ovale.

Background: The optimal strategy for secondary prevention of cryptogenic stroke with a patent foramen ovale is unclear.

Methods: Several databases were searched from their inception to March 2013, which yielded 3 eligible studies. The results were pooled as per the different patient populations defined in the studies:-intention-to-treat, per-protocol, and as-treated cohorts. A generic inverse method was used based on time-to-event outcomes in a fixed-effect model. A supplementary analysis pooled the results from only 2 trials (RESPECT [Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment] and PC Trial [Randomized Clinical Trial Comparing the Efficacy of Percutaneous Closure of Patent Foramen Ovale (PFO) With Medical Treatment in Patients With Cryptogenic Embolism]) as a similar device was used in them.

Results: Our meta-analysis yielded effect-estimate hazard ratios of 0.67 (95% confidence interval [CI]: 0.44 to 1.00, I(2) = 0%) in the intention-to-treat cohort, 0.62 (95% CI: 0.40 to 0.95). I(2) = 0%) in the per-protocol cohort, and 0.61 (95% CI: 0.40 to 0.95, I(2) = 38%) in the as-treated cohort, showing beneficial effects of device closure. The results became more robust with pooled results from RESPECT and the PC Trial: The effect-estimate hazard ratios being 0.54 (95% CI: 0.29 to 1.01, I(2) = 0%), 0.48 (95% CI: 0.24 to 0.94, I(2) = 26%), and 0.42 (95% CI: 0.21 to 0.84, I(2) = 26%) in the intention-to-treat, per-protocol, and as-treated populations, respectively.

Conclusions: Our meta-analysis suggests that PFO closure is beneficial as compared to medical therapy in the prevention of recurrent neurological events. This meta-analysis helps to further strengthen the role of device closure in cryptogenic stroke.

Keywords: CI; HR; OR; PFO; TIA; confidence interval; cryptogenic stroke; device closure; hazard ratio; odds ratio; patent foramen ovale; recurrent stroke; transcatheter closure; transient ischemic attack.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anticoagulants / therapeutic use*
  • Cardiac Catheterization / instrumentation*
  • Chi-Square Distribution
  • Foramen Ovale, Patent / complications
  • Foramen Ovale, Patent / diagnosis
  • Foramen Ovale, Patent / therapy*
  • Humans
  • Intention to Treat Analysis
  • Odds Ratio
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Secondary Prevention / instrumentation*
  • Secondary Prevention / methods
  • Septal Occluder Device*
  • Stroke / diagnosis
  • Stroke / etiology
  • Stroke / prevention & control*
  • Treatment Outcome


  • Anticoagulants