ABC | Volume 113, Nº1, July 2019

Statement Statement on Antiplatelet Agents and Anticoagulants in Cardiology – 2019 Arq Bras Cardiol. 2019; 113(1):111-134 Table 12 – Risk of Paradoxical Embolism (RoPE) score. The higher the RoPE score, the higher the causality between patent foramen ovale and stroke Characteristic Points No PH or SAH 1 No PH of diabetes 1 No PH of stroke/TIA 1 Non-smoker 1 Cortical infarct on imaging exam 1 Age (in years): 18 to 29 30 to 39 40 to 49 50 to 59 60 to 69 ≥ 70 5 4 3 2 1 0 PH: personal history; SAH: systemic arterial hypertension; TIA: transient ischemic attack. thrombus formed in the left atrium, antiplatelet therapy or anticoagulation are justified in the following situations: Primary prevention: no studies have evaluated primary prevention of embolic events in patients with PFO. Considering that the causal relation between PFO and systemic embolism is still uncertain, that the embolic event rate in patients with PFO alone is extremely low, and that the risks inherent in anticoagulant and antiplatelet therapy are not negligible, the use of antiplatelet agents or anticoagulation are not indicated as primary prevention of embolic events in patients with PFO. 146 Secondary prevention: the best therapeutic strategy after an embolic event in the presence of PFO continues to be the focus of debate and controversy due to the dubious correlation which exists between the 2 phenomena. In 2002, the PICSS substudy of the WARSS study 144 compared the use of warfarin to ASA (325 mg daily) in patients with stroke and PFO, in a subgroup of 265 patients with cryptogenic stroke. There were no statistically significant differences in the rate of recurrent embolic events between the warfarin and the ASA groups in this situation. Another study 147 randomized 47 patients after cryptogenic stroke to ASA (240 mg daily) or warfarin (with an INR goal of 2 to 3), and the authors did not observe any difference between the risk of ischemic stroke or TIA between the groups. A meta-analysis 148 with data from only 2 randomized studies did not identify differences in favor of warfarin in comparison with ASA in the presence of stroke. Another recent meta-analysis 149 compared the use of antiplatelet agents with oral anticoagulation in patients with cryptogenic stroke, using individual data of 2,385 patients from 12 observational studies, and they did not observe any differences in the rates of recurrent stroke between patients receiving oral anticoagulation or antiplatelet agents. In 2017, the results of the CLOSE study were published, which compared percutaneous PFO closure to medical therapy with antiplatelet therapy or anticoagulation. Statistical analysis was not conducted between the clinical treatment groups, as the study did not recruit the target of 900 patients and the event rate was lower than expected. When evaluating the data in absolute values, however, it is possible to observe an incidence of 3 cases in the anticoagulation group and 7 in the antiplatelet therapy group, with an estimated probability of stroke over 5 years of 1.5% and 3%, respectively. 45 Percutaneous or surgical PFO closure should also be considered in select cases; this discussion, however, lies beyond the scope of this paper. There is, thus, insufficient evidence for recommending the preferential use of oral anticoagulation over antiplatelet agents, given the low rate of recurrent embolic events in young patients with cryptogenic stroke. The use of antiplatelet agents, thus, seems to be adequate due to the accumulated risk of hemorrhagic complications in these patients in the event that they receive oral anticoagulation and to the efficacy of antiplatelet agents in reducing the risk of embolic events in the general population, which has already been proven (Table 13). It is worth highlighting that the studies on secondary prevention on which these guidelines are based 144,147,150 were not designed to demonstrate the superiority of oral anticoagulation over antiplatelet therapy, for which reason they are not statistically powered to provide evidence of any possible benefits of oral anticoagulation over antiplatelet therapy. Table 13 – Recommendations for the use of antiplatelet agents and anticoagulants in primary and secondary prevention of cryptogenic stroke in patients with patent foramen ovale Indications Grade of recommendation Level of evidence Patients who are not indicated for anticoagulation for other reasons should be started on antiplatelet therapy as secondary prevention I B Use of warfarin as a first choice following the first event IIb B After a recurrent event while using antiplatelet agents, the use of warfarin with an INR goal between 2 and 3 should be considered IIa C Use of Factor Xa inhibitors or thrombin inhibitors following the first event as an alternative to warfarin IIb C Use of antiplatelet agents or anticoagulants as primary prevention III C INR: international normalized ratio. 126