Patent foramen ovale not necessarily associated with stroke recurrence

Clinical Question

What is the risk of recurrent stroke in patients with cryptogenic stroke and patent foramen ovale who are treated medically?

Bottom Line

Among patients with cryptogenic stroke who are treated medically, the rate of recurrent stroke is similar between patients with patent foramen ovale and those without. Based on these results, it is unclear if surgical closure will prevent stroke recurrence. (LOE = 2a-)


Almekhlafi MA, Wilton SB, Rabi DM, Ghali WA, Lorenzetti DL, Hill MD. Recurrent cerebral ischemia in medically treated patent foramen ovale: a meta-analysis. Neurology 2009;73(2):89-97.  [PMID:19439720]

Study Design

Meta-analysis (randomized controlled trials)




Various (meta-analysis)


Up to 25% of strokes have no identifiable cause (cryptogenic stroke) and up to 50% of strokes in young patients have no cause. Patent foramen ovale (PFO) is often found in these patients, but we don't know whether PFO is a cause or an innocent bystander. The authors of this study searched multiple sources to identify observational studies of patients with cryptogenic stroke and PFO. Two authors independently assessed study eligibility (99.7% agreement) and extracted data. In addition to outcome data, they also extracted several factors related to methodologic quality. Ultimately, they included 15 studies with 2548 patients. Only 1 study randomized patients with PFO to receive either aspirin or warfarin; 1 study required all patients to take aspirin. In the remainder of studies, whether the patient was treated was left to the discretion of their physician. In those studies, between one fourth and two thirds of patients received antiplatelet agents and between one third and two thirds received warfarin (very few were untreated). Four of the studies, with nearly 1100 patients, also included a group of patients without PFO. In these studies, the risk of subsequent transient ischemic attack (TIA) or recurrent stroke was similar between the 2 groups. The pooled rate of recurrent TIA or recurrent stroke was 4 per 100 person-years (95% CI, 3.0 - 5.1) and the pooled recurrent stroke rate was 1.6 per 100 person-years (95% CI, 1.1 - 2.1). In another meta-analysis of case-control studies, it has been estimated that approximately one third of the PFOs discovered in patients with cryptogenic stroke are likely to be incidental (Stroke 2009; 40:2349-2355).