NOVEMBER 13, 2017: 2227–3 0 2228 meta-analysis of the earlier 3 randomized trials, percutaneous PFO closure was superior to medical therapy for secondary prevention of cryptogenic stroke, especially in patients with a large shunt or atrial septal aneurysm (2). Recently, the extended follow-up results of the RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment) trial (3) and 2 new randomized trials were presented. We performed an updated meta-analysis to evaluate the efficacy and safety of transcatheter PFO closure versus medical therapy for cryptogenic stroke (PROSPERO [International prospective register of systematic reviews]# CRD42017067347). Electronic databases and scientific conferences were searched for clinical trials that randomized patients with cryptogenic stroke to percutaneous PFO closure versus medical therapy. Two authors (AYE and IYE) extracted data on patient characteristics and outcomes at the longest follow-up available. Primary efficacy outcome was recurrent stroke and primary safety endpoint was atrial fibrillation/flutter (AF). Random-effects risk ratios (RRs) were estimated using a DerSimonian and Laird method. Heterogeneity was calculated using the I2 test and publication bias using Egger’s test. Statistical analyses were conducted using STATA 14 (StataCorp, College Station, Texas). Five trials (n= 3,440; mean follow-up 4.0 years) were included. Compared with medical therapy, risk of recurrent stroke was lower with closure (2.0% vs. 4.5%; RR: 0.42; 95% confidence interval [CI]: 0.20 to 0.91; I2= 59%; p= 0.027). AF risk was higher with closure (4.0% vs. 0.7%; RR: 4.55; 95% CI: 2.16 to 9.60; I2= 25%, p< 0.01)(Figure 1). Risk of AF was not different with the Amplatzer PFO occluder (Abbott, Chicago, Illinois)(RR: 2.10; 95% CI: 0.80 to 5.56, I2= 0%; p= 0.13) but was significant with the STARFlex (NMT Medical, Boston Massachusetts)(RR: 7.92; 95% CI: 2.40 to 26.21; p< 0.01) and Gore (WL Gore & Associates, Flagstaff, Arizona)(RR: 14.66; 95% CI: 2.01 to 106.95; p< 0.01) devices. There was no publication bias for both primary outcomes (p= 0.11 and p= 0.14, respectively). This updated meta-analysis of 5 multicenter trials demonstrated that in patients with cryptogenic stroke and a PFO, transcatheter closure is superior to medical therapy for secondary prevention of stroke. All included trials suggested that closure is associated with a lower incidence of recurrent stroke except for the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients with a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent

Foramen Ovale) trial. The lack of efficacy observed in the CLOSURE I trial has often been attributed to suboptimal effective PFO closure in the device arm, with 14% demonstrating significant residual right-to-left shunting on a 6-month follow-up transesophageal echocardiography (4). The STAR-Flex device has been associated with more AF and thrombogenesis compared with other devices (5). A patient-level analysis of the CLOSURE I, PC (Percutaneous Closure of PFO Using the Amplatzer PFO Occluder with Medical Treatment in Patients with Cryptogenic Embolism), and RESPECT trials demonstrated that transcatheter PFO closure was superior to medical therapy (2), which was further confirmed in this meta-analysis. The enhanced efficacy in the CLOSE (Patent Foramen Ovale Closure or Anticoagulants versus Antiplatelet Therapy to Prevent Stroke Recurrence) and Gore-REDUCE (Gore Helex Septal Occluder/Gore Cardioform Septal Occluder and Antiplatelet Medical Management …