Percutaneous patent foramen ovale closure for cryptogenic stroke: learning from clinical trial and error

Each year, over 690,000 people suffer from ischemic stroke in the United States. Of these, 25–30% are cryptogenic where the etiology cannot be determined (1). In the late 1980s, observational studies suggested a higher prevalence of patent foramen ovale (PFO) (40–50% versus 10–15%; P<0.001) in young people aged <40–55 years with cryptogenic stroke (2,3). Contrary to subsequent non-randomized studies (4), the first three randomized clinical trials (CLOSURE I, PC and RESPECT) failed to demonstrate superiority of percutaneous PFO closure over medical therapy for secondary prevention of stroke in a primary analysis (5-7).