Patent Foramen Ovale Closure for Stroke Prevention

February 1, 2016

Optimal therapy for people with a history of patent foramen ovale and cryptogenic stroke has not been defined. We review several recent studies.

One of the major risk factors for stroke is a previous stroke. Knowing the cause of the first stroke is key, as this helps prevent the next one. However, in 25%-40% of cases – roughly 200,000 cases each year – the cause of the first stroke cannot be determined. Patent foramen ovale (PFO) is one of the known causes of cryptogenic stroke, as it allows thrombi from deep veins to travel to the brain (paradoxical embolism). While 15%-25% of adults have PFO, it is particularly common in young adults who had cryptogenic stroke. Recent studies explore treatment options in this patient population.

In people with PFO and cryptogenic stroke, optimal therapy has not been defined. AHA guidelines recommend evaluation of patients with PFO and a history of cryptogenic stroke or transient ischemic attack (TIA) for lower extremity/pelvic vein thrombosis. If deep vein thrombosis is present, PFO closure should be considered. Guidelines of the American College of Chest Physicians support this recommendation and also recommend a vitamin K antagonist for 3 months. Anticoagulant therapy is also indicated in these patients.

A Cochrane review and meta-analysis published in September 2015 revealed no difference in prevention of recurrent stroke between transcatheter device closure (using Amplatzer PFO Occluder or another device) and medical therapy.1 An additional analysis of two studies that used Amplatzer PFO Occluder revealed a possible advantage of the device over medical therapy; however, the difference between the groups had never reached statistical significance. Overall risk for all-cause mortality and adverse events were similar between the groups, but the use of device undesirably increased the risk of atrial fibrillation (which is itself a risk factor for cryptogenic stroke). The evidence included in the review is current to July 2014.

Shortly after the publication of the review, the results of extended follow-up of the RESPECT trial were reported.2 The study investigators found PFO closure with the Amplatzer PFO Occluder device to be superior to medical therapy in reducing the risk of a second stroke. In the device group, recurrent larger infarcts were less frequent, superficial and other infarcts were less common, and overall infarct size was smaller. This could be expected since larger and superficial infarcts are associated with paradoxical embolism. Patients who received the device had a 70% reduction in the relative risk of recurrent cryptogenic stroke compared to patients on medical therapy. These patients had a prior cryptogenic stroke, but not TIA, and were relatively young, 18-60 years of age.

PFO closure is supported by research evidence, but is it cost-effective? It is more likely to be cost effective in a younger population, according to a study by Pickett et al.3 Authors used a commonly accepted cost-effectiveness threshold of <$50,000/quality-adjusted life-year gained to evaluate cost-effectiveness at several time points. At 2.6 years, PFO closure was cost-effective but more costly than medical therapy. At 30.2 years (95% confidence interval, 28.2-36.2 years), the cost of medical therapy exceeded the cost of PFO closure. Hence, the procedure may be worth its high cost in younger individuals who will spend less on medications and have a lower risk of cryptogenic stroke over the course of 32 years.

The list of possible causes of cryptogenic stroke is not limited PFO; atrial fibrillation, atherosclerotic disease of the aortic arch, and inherited thrombophilias represent other possible causes. While antiplatelet therapy combined with risk factor modification is currently the standard of secondary stroke prevention, new management strategies will emerge from continued research and interdisciplinary dialogue.



1. Li J, et al. Closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and a history of cryptogenic stroke or transient ischemic attack. Cochrane Database Syst Rev. 2015;12.

2. RESPECT Confirms Long-term Safety, Efficacy of PFO Closure for Recurrent Stroke. TCTMD Website Accessed 15 Jan 2016.

3. Pickett CA, et al. Cost effectiveness of percutaneous closure versus medical therapy for cryptogenic stroke in patients with a patent foramen ovale. Am J Cardiol. 2014;114(10):1584-1589.