The aim of this study was to evaluate the effectiveness of  PFO closure with MT vs MT alone for the reduction in recurrent stroke episodes amongst patients with cryptogenic stroke.

Cryptogenic stroke (CS) is a diagnosis of exclusion when no well-defined etiology for stroke is identified and constitutes upto 10-40% of all cerebrovascular events. Patent Foramen Ovale(PFO) has a prevalence of 25-30% in the general population but can be seen in 66% of patients with CS. Several meta-analyses comparing PFO closure with medical treatment(MT) and MT alone in preventing cryptogenic strokes have had inter-study variability.

Umbrella meta-analysis was performed using meta-analyses between January-2019 and August-2021 following PRISMA guidelines. English full-text studies comparing surgical PFO closure with MT vs MT as the management of CS were identified by using MeSH keywords. Data on interventions and outcome were extracted and relative risks (RR) were converted to log RR using RevMan 5.4. Random effects models with generic inverse variance were used to calculate RR along with its 95% confidence interval for reduction of recurrent stroke episodes. p<0.05 was considered significant. Heterogeneity (I2) was calculated and I2>50 considered higher.

Out of the 1591 studies screened, we found eight meta-analyses that evaluated the effect of interventions on  reduction of CS, recurrent stroke or TIA. Our umbrella meta-analysis showed that patients with PFO closure and MT had a 62% lower risk of recurrent strokes as compared to those managed with MT alone (pooled RR:0.38; 95%CI:0.30-0.48; p<0.00001) There was no heterogeneity (I2= 0%;p=0.53) and overall risk of bias was low on Newcastle-Ottawa Scale.

PFO closure in addition to MT reduces the risk of recurrence of strokes in patients with cryptogenic stroke. More studies are needed to evaluate effectiveness of early closure and specific risk profiles that would benefit from early intervention to mitigate the burden of strokes.