Patent Foramen Ovale Closure and Medical Treatments for Secondary Stroke Prevention

Abstract

Background and Purpose Patients discovered to have a patent foramen ovale in the setting of a cryptogenic stroke may be treated with percutaneous closure, antiplatelet therapy, or anticoagulants. A recent randomized trial (CLOSURE I) did not detect any benefit of closure over medical treatment alone; the optimal medical therapy is also unknown. We synthesized the available evidence on secondary stroke prevention in patients with patent foramen ovale and cryptogenic stroke. Methods A MEDLINE search was performed for finding longitudinal studies investigating medical treatment or closure, meta-analysis of incidence rates (IR), and IR ratios of recurrent cerebrovascular events. Results Fifty-two single-arm studies and 7 comparative nonrandomized studies and the CLOSURE I trial were reviewed. The summary IR of recurrent stroke was 0.36 events (95% CI, 0.24–0.56) per 100 person-years with closure versus 2.53 events (95% CI, 1.91–3.35) per 100 person-years with medical therapy. In comparative observational studies, closure was superior to medical therapy (IR ratio=0.19; 95% CI, 0.07–0.54). The IR for the closure arm of the CLOSURE I trial was higher than the summary estimate from observational studies; there was no significant benefit of closure over medical treatment (P=0.002 comparing efficacy estimates between observational studies and the trial). Observational and randomized data (9 studies) comparing medical therapies were consistent and suggested that anticoagulants are superior to antiplatelets for preventing stroke recurrence (IR ratio=0.42; 95% CI, 0.18–0.98). Conclusions Although further randomized trial data are needed to precisely determine the effects of closure on stroke recurrence, the results of CLOSURE I challenge the credibility of a substantial body of observational evidence strongly favoring mechanical closure over medical therapy.

Efficiency of transcatheter patent foramen ovale closure in children after paradoxical embolism events

“…Data from observational studies conducted before 2012 strongly favour percutaneous PFO closure [9]. However, the results of three randomised control studies (RCT) do not confirm the superiority of invasive procedures compared to medical treatment, including antiplatelets or oral anticoagulants [3][4][5], and numerous meta-analyses of RCTs are also inconclusive [10][11][12].…”

Patent foramen ovale: Unanswered questions

“…If medical therapy is chosen, a recent meta-analysis by Kent et al showed no difference between use of oral anticoagulation (warfarin) and antiplatelet therapy (aspirin, clopidogrel, ticlopidine, or aspirin plus dipyridamole) [78]. Given the lack of an obvious difference, the need for monitoring and dose adjustment, and the higher risk of bleeding with warfarin, antiplatelet therapy may be preferred compared to oral anticoagulation [79]. However, more randomized controlled trials are needed in this regard.…”

Austerity: a failed experiment on the people of Europe

“…5,6 Regarding the subsequent approach to treatment of the PFO, the authors will be aware of the results of the CLOSURE I trial 3 and a subsequent systematic review of the available literature. 4 The CLOSURE I trial did not demonstrate any statistical benefit from PFO closure with a STARFlex device compared with medical treatment in patients aged 60 and under with transient ischaemic attack (TIA) or stroke. The trial did show that PFO closure with this device was associated with an increased incidence of atrial fibrillation, thereby replacing a debatable stroke risk factor with one for which there is no doubt.…”

“…However, the CLOSURE I trial has not been without its own criticism, including the long time to recruitment, the inadequate power to identify small differences between device closure and medical therapy, the high non-closure rates (15%) and the exclusion of 'high risk' patients or patients thought to represent the population seen in daily practice. [2][3][4] The study does, however, remind us that vascular complications and atrial fibrillation should always be discussed with patients being considered for PFO closure.…”