Device Closure of Patent Foramen Ovale Versus Medical Therapy in Cryptogenic Stroke: A Systematic Review and Meta-Analysis

Study Questions:

What is the role of device closure versus medical therapy in patients with cryptogenic stroke and patent foramen ovale (PFO)?


Several databases were searched from their inception to March 2013, which yielded three 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-effects model. A supplementary analysis pooled the results from only two trials (RESPECT [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. A fixed-effects model was used with the Mantel-Haenszel method with nonfixed zero-cell correction to pool data.


The meta-analysis yielded effect-estimate hazard ratios of 0.67 (95% confidence interval [CI], 0.44-1.00; I2 = 0%) in the intention-to-treat cohort, 0.62 (95% CI, 0.40-0.95; I2 = 0%) in the per protocol cohort, and 0.61 (95% CI, 0.40-0.95; I2 = 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, 0.29-1.01; I2 = 0%), 0.48 (95% CI, 0.24-0.94; I2 = 26%), and 0.42 (95% CI, 0.21-0.84; I2 = 26%) in the intention-to-treat, per-protocol, and as-treated populations, respectively.


The authors concluded that PFO closure is beneficial as compared to medical therapy in the prevention of recurrent neurological events.


This systematic review suggests that device closure may have a beneficial effect in preventing recurrent neurological events in patients with cryptogenic stroke and PFO. Furthermore, the safety of the device was comparable to medical therapy, with a low incidence of adverse events. However, it should be noted that so far, published randomized controlled studies have not shown superiority of PFO closure over medical therapy. Based on available evidence, it would be appropriate that individual patient characteristics, their clinical presentation, and structural assessment of the shunt be the subjects of a thorough discussion between the treating physicians (multidisciplinary team) and their patients concerning the risks, benefits, and alternatives of device closure. This will allow for patient-centered treatment and possible identification of the most appropriate individuals for percutaneous closure of PFO.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Congenital Heart Disease

Keywords: Stroke, Foramen Ovale

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