IJCS | Volume 33, Nº4, July and August 2020

311 Cont. Table 1 - The main aspects of selected studies Total number of patients Inclusion criteria Device and additional therapy Medical therapy Follow-up duration (years) Primary outcomes Level of significance adopted REDUCE (2017) 664 1.18 to 59 y of age 2. PFO documented on TE 3.CS within the previous 180 days Helex Septal Occluder or Cardioform Septal Occluder + Antiplatelet therapy as in the medical therapy arm + clopidogrel at the time of the procedure and for 3 days 75-325 mg/day aspirin or 50- 100 mg/day Aspirin + 225-400 mg/day dipyridamole or 75 mg/day clopidogrel Mean: 3.2 Two coprimary end points of clinical ischemic stroke and new brain infarction 5% DEFENSE PFO (2018) 120 1. High-risk PFO - PFO with atrial septal aneurysm, hypermobility (phasic septal excursion into either atrium ≥ 10 mm), or PFO size (maximum separation of the septum primum from the secundum) ≥ 2 mm 2. CS within the previous 6 mo Amplatzer PFO Occluder + dual antiplatelet regimen (aspirin 100 mg/ day in combination with clopidogrel 75 mg/day) for at least 6 months; anticoagulation therapy allowed as alternative Aspirin or aspirin + clopidogrel or aspirin + cilostazol or warfarin Median: 2.8 Composite of stroke, vascular death, or major bleeding 5% A: closure group; B: medical therapy group; PFO: patent foramen ovale; TE: transesophageal echocardiography; CS: cryptogenic ischemic stroke; TIA: transient ischemic attack; PTE: peripheral thromboembolic event; D: days; Mo: month; Y: years; ER: extended-release; Aspirin: acetylsalicylic acid. For acronyms see text. Pereira et al. Patent foramen ovale in cryptogenic stroke Int J Cardiovasc Sci. 2020; 33(4):307-317 Original Article to medical therapy arm. The mean age was 46 years in both groups. Furthermore, dropouts were observed in each study and similar rate of serious adverse events were seen between the two treatment arms. Efficacy and safety endpoints are illustrated in Table 3. The clinical endpoints under evaluation in the present report were: stroke, transient ischemic attack and incidence of atrial fibrillation during the follow- up period. When compared to medical treatment only, PFO closure significantly reduced the rate of recurrent stroke (risk ratio, 0.37; 95% confidence interval [CI], 0.17 to 0.78; p = 0.01; I squared 51.12; Figure 2). However, PFO closure did not offer any significant benefit in the prevention of TIA (risk ratio, 0.96; 95% CI, 0.64 to 1.44; p = 0.85; I squared 0.00; Figure 3). Each study demonstrated a relatively low frequency of device and procedure-related complications. PFO closure increased the risk of atrial fibrillation (risk ratio with PFO closure, 4.64; 95% CI, 2.38 to 9.01; p < 0.01; I squared 3.84, Figure 4). Importantly, in most cases, AF was periprocedural.