ABC | Volume 113, Nº1, July 2019

Statement Statement on Antiplatelet Agents and Anticoagulants in Cardiology – 2019 Arq Bras Cardiol. 2019; 113(1):111-134 2.4 in both treatments. No ischemic events were observed in the apixaban group, while 6 events occurred in the conventional treatment group (p = 0.016). Finally, edoxaban was evaluated during the pericardioversion period in 2,199 patients in the ENSURE-AF randomized prospective study, in comparison with enoxaparin and warfarin, with enoxaparin being suspended when INR > 2. There were no differences regarding the primary outcome composed of stroke, systemic embolism, myocardial infarction, or cardiovascular death (odds ratio 0.46; 95% CI 0.12 to 1.4) or in the safety outcome of bleeding (odds ratio 1.48; 95% CI 0.64 to 3.55) for a total period of 28 days of treatment, followed up for more than 30 days. 80 In specific situations, for instance, for patients who are highly symptomatic or patients with high bleeding risks, cardioversion may be performed earlier, without 3 weeks of anticoagulation, as long as there are no thrombi in the atria or atrial appendices evaluated by TEE. Subsequently, anticoagulation is maintained for at least 4 weeks. 71,102 If TEE indicates that thrombi are present, anticoagulation is maintained for 3 weeks, and, in the event that cardioversion is scheduled, TEE should be repeated before the procedure. If there are doubts regarding medical adherence, TEE is also indicated in order to rule out thrombus. 78,103 This strategy was first evaluated in a randomized manner by the ACUTE study, which compared TEE and the conventional strategy (anticoagulation for 3 weeks before cardioversion). Patients randomized to TEE received heparin if they were hospitalized or warfarin for 5 days before TEE if they were not hospitalized, and cardioversion was performed if there were no thrombi. If they had thrombi (12% of patients), cardioversion was postponed for 3 weeks, with anticoagulation maintained during this period. There were no differences between the TEE and conventional groups regarding the incidence of ischemic stroke (0.6% versus 0.3%, respectively, RR 1.95, 95% CI 0.36 to 10.60) or embolic events in general (0.8% versus 0.5%, respectively, RR 1.62, 95% CI 0.39 to 6.76) during the 8-week period following cardioversion. The majority of events in the TEE group occurred in patients whose AF recurred or who were outside of the therapeutic range at the moment of the event, whereas, in the patients who were receiving warfarin, the events occurred in sinus rhythm and within the therapeutic range. It is also interesting to note that fewer bleeding episodes were observed in the TEE-guided group (2.9% versus 5.5%; p = 0.03). In this group, time to cardioversion was also shorter (3.0 ± 5.6 days versus 30.6 ± 10.6 days; p < 0.001), and the success rate of AF reversal was higher in comparison with the conventional strategy (71% versus 65.2%; p = 0.03), although there was no difference in the percentage of patients who remained in sinus rhythm for 8 weeks. 104 In the event that AF lasts less than 48 hours, which is easily determined by inquiring about symptoms, and the patient is not at a high thromboembolism risk (valve disease, ventricular dysfunction, prosthesis, prior history of thromboembolism), the risk of thromboembolism is very low and cardioversion may be performed 105,106 without prior full anticoagulation. Maintaining anticoagulation for 4 weeks after the procedure is controversial and there are no studies comparing different heparins or heparins and new anticoagulants for patients with AF lasting less than 48 hours. In the event of AF lasting less than 48 hours in patients with moderate to high risks of thromboembolic events (CHA 2 DS 2 -VASc > 1), unfractionated or low-molecular weight heparin before cardioversion and long-term maintenance are recommended. 86 In cases of AF with hemodynamic instability, urgent cardioversion should always be performed, with a pre- procedure heparin bolus. 86 In relation to heparins, unfractionated heparin has given way to low-molecular weight heparins. Indications for using heparins are: (1) following chemical or electrical cardioversion in hospitalized patients, (2) in combination with oral anticoagulation during INR adjustment; (3) during provisory interruption of warfarin anticoagulation in order to perform diagnostic procedures or therapies with hemorrhage risks (a strategy commonly known as a “heparin bridge”). Although there are 3 types of low-molecular weight heparin (dalteparin, enoxaparin, and nadroparin), enoxaparin has been the most widely used in clinical practice. 107 The flowchart in Figure 2 summarizes recommendations in relation to pericardioversion anticoagulation in atrial fibrillation. 6. Anticoagulation and Antiplatelet Therapy in Patients with Patent Foramen Ovale 6.1. Introduction Patent foramen ovale (PFO) is the most common congenital heart disease of fetal origin. 108-110 It is present in 15% to 35% of the adult population (15% to 25% in studies whose diagnostic method was echocardiogram 111,112 and 15% to 35% in autopsies). 113-115 Several reports exist on the relation between PFO and diverse pathologies, with different strengths of association, including: platypnea-orthodeoxia syndrome, 116 decompression syndrome, 117,118 systemic and coronary embolism, 119,120 obstructive sleep apnea-hypopnea syndrome (OSAHS), 121 migraine with aura, 122-125 and stroke. 126 6.2. Relation between Patent Foramen Ovale and Cryptogenic Stroke The causal relation between PFO and cryptogenic stroke, caused by paradoxical embolism of the right-left shunt, is dubious and much debated within the literature. 112,127 Meta- analysis data 128 have established a possible causal relation between PFO and cryptogenic stroke in patients < age 55. Another study 129 evaluated the presence of PFO using TEE in stroke patients and identified a higher incidence of PFO in cryptogenic stroke patients in comparison with patients with stroke of known cause, both in patients < age 55 and in patients > age 55. A retrospective Brazilian study 130 also identified the presence of PFO as a risk factor for cryptogenic stroke, with an odds ratio of 3.3 in patients with PFO compared to patients without PFO. In prospective population studies, on the other hand, the presence of PFO has not been related to increased stroke risk, either in patients who have already 124