IJCS | Volume 33, Nº4, July and August 2020

312 Table 2 - Data concerning number of patients, mean age, dropouts and serious adverse events of patients enrolled in each study. For acronyms see text Number of patients Mean age (years) Dropouts (number of patients) Serious adverse events (%) Closure Control Closure Control Closure Control Closure Control CLOSURE 1 447 462 46.3 ± 9.6 45.7 ± 9.1 69 87 16.9 16.6 RESPECT 499 481 45.7 ± 9.7 46.2 ± 10.0 46 83 23.0 21.6 PC TRIAL 204 210 44.3 ± 10.2 44.6 ± 10.1 31 42 21.1 17.6 CLOSE 238 235 42.9 ± 10.1 43.8 ± 10.5 21 12 35.7 33.2 REDUCE 441 223 45.4 ± 9.3 44.8 ± 9.6 39 33 23.1 27.8 DEFENSE PFO 60 60 49 ± 15 54 ± 12 - - - - Table 3 - Data concerning stroke, transient ischemic attack (TIA) and atrial fibrillation (AF), in patients involved in trials comparing closure of patent foramen ovale versus medical therapy (total number of patients in brackets). For acronyms see text Stroke TIA AF Closure Control Closure Control Closure Control CLOSURE 1 12 (447) 13 (462) 13 (447) 17 (462) 23 (402) 3 (458) RESPECT 9 (499) 16 (481) 6 (499) 4 (481) 3 (499) 3 (481) PC TRIAL 1 (204) 5 (210) 5 (204) 7 (210) 6 (204) 2 (210) CLOSE 0 (238) 14 (235) 8 (238) 8 (235) 11 (238) 2 (235) REDUCE 6 (441) 12 (223) 21 (441) 8 (223) 29 (441) 1 (223) DEFENSE PFO 0 (60) 5 (60) 0 (60) 1 (60) 2 (60) 0 (60) Pereira et al. Patent foramen ovale in cryptogenic stroke Int J Cardiovasc Sci. 2020; 33(4):307-317 Original Article Data on risk difference and annualized risk difference concerning the three outcomes under evaluation are presented in supplementary file 2. Discussion Controversy has persisted after the first reports were published on whether PFO closure reduces the risk of recurrent stroke for patients with cryptogenic stroke and documented PFO, when compared with medical therapy. Since 2012, six randomized controlled trials were published with the aim of comparing these two forms of secondary prevention. 3,5,6,8-10 In the present updated meta-analysis, transcatheter PFO closure in cryptogenic strokes was shown to be superior to medical therapy in reducing recurrent stroke, although the risk of TIA was similar between the two groups. We also confirmed that patients who underwent transcatheter closure were more likely to develop transient atrial fibrillation as compared with the medical-therapy group. Our findings are in line with the results of recent meta-analyses, 12-19 However, the present study includes data of the RESPECT trial published in 2013, as opposed to recent meta-analyses, which selected the RESPECT long-term results, published in 2017, and therefore are not the primary results of a controlled trial, but rather a follow-up study. All six studies included young to middle-age patients with PFO documented on transesophageal echocardiography (TE) and cryptogenic stroke, usually in the six months prior to randomization. Three randomized controlled trials (RCTs) conducted earlier, which were published in 2012 and 2013, failed