Dr Anna Marciniak, Dr Brian Clapp.
Patent foramen ovale (PFO) is a common finding, occurring in up to 25% of population.1 An association between PFO and stroke has consistently been seen in up to 50% of patients without an identifiable cause, so-called cryptogenic stroke (CS) and only in 20% with an identified cause.2 PFOs are also associated with other conditions including migraine with aura, obstructive sleep apnea, decompression sickness and other venoarterial embolic phenomena.
A large body of observational data point towards the benefit of device closure, however three randomised controlled trials have generally failed to send a conclusive answer. CLOSURE I, PC and RESPECT trials, looked at the comparison of percutaneous closure of PFO versus medical treatment for secondary stroke prevention.
The CLOSURE 1 trial included 909 patients (age 18–60 years) who suffered CS or TIA within 6-months prior to recruitment and were randomized to PFO closure with a STARFlex device (n=447) or best medical treatment (n=462) and followed up for 2 years.3 The device closure did not offer a greater benefit than medical therapy alone for stroke/TIA prevention. The PC trial studied 414 patients under the age of 60 years who had suffered a previous stroke, TIA or peripheral embolic event. A total of 204 patients were randomised to Amplatzer PFO Occluder and compared with medical treatment in 210 subjects.4 Over a mean follow-up duration of 4 years, the results all favored closure but did not reach statistical significance. Finally, the RESPECT trial enrolled 980 subjects (age 18–60 years) with PFO and CS within 270 days, randomized to medical therapy (n=481) with one or more antiplatelet (74.8%) or warfarin (25.2%) or PFO closure using the Amplatzer device (n=499).5 Due to a higher dropout rate among medical therapy patients, the treatment exposure between the 2 groups was unequal. Primary analysis of the intention to treat cohort was not statistically significant. However, the long-term results of the RESPECT trial were recently released and showed that PFO closure is superior to medical management in reducing recurrent cryptogenic ischemic stroke.
There were significant limitations of these trials associated with the study design, recruitment process, inclusion criteria and in device characteristics. All three studies missed their primary end points of reducing the rate of the recurrence of a stroke but trended towards superiority of the device closure with the long term RESPECT results favouring it. There is still a need for adequate powered study and we hope that ongoing new trials will clearly help to differentiate those patient for optimal medical therapy or device closure.
- Meissner I, Whisnant JP, Khandheria BK, et al. Prevalence of potential risk factors for stroke assessed by transesophageal echocardiography and carotid ultrasonography: the SPARC study. Mayo Clin Proc 1999;74:862–9.
- Handke M, Harloff A, Olschewski M, et al. Patent foramen ovale and cryptogenic stroke in older patients. N Engl J Med 2007;357:2262–8
- Furlan AJ, Reisman M, Massaro J, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012;366:991–9.
- Carroll JD, Saver JL, Thaler DE, et al . Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med 2013;368:1092–100.
- Meier B, Kalesan B, Mattle HP, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med 2013;368:1083–91