ABC | Volume 113, Nº1, July 2019

Statement Statement on Antiplatelet Agents and Anticoagulants in Cardiology – 2019 Arq Bras Cardiol. 2019; 113(1):111-134 and PLATO), the discontinuation of dual antiplatelet therapy may be considered in patients with increased bleeding risks as early as 6 months after treatment initiation. 42 The PEGASUS study evaluated patients who had had infarction 1 to 3 years prior to randomization. They studied the standard dose of ticagrelor (90 mg every 12 hours), a lower dose of ticagrelor (60 mg every 12 hours) and placebo. All patients received ASA and were followed for a median of 33 months. There was a significant reduction in the rates of infarction, cardiovascular death, and stroke, at the expense of an increase in events related to bleeding. The 60-mg dose of ticagrelor, however, demonstrated lower rates of bleeding in comparison with the 90-mg dose. 43 In following with this, the recommendation of these guidelines is to administer dual antiplatelet therapy for at least 12 months to patients undergoing PCI after ACS, which may be modified to a minimum duration of 6 months in the event of increased risks of bleeding. In the same manner as in stable coronary disease, more prolonged use (> 12 months) is not routinely indicated and may be considered in accordance with patients’ clinical and anatomical profiles. When opting for this more prolonged treatment, a 60-mg dose of ticagrelor every 12 hours may be considered in combination with ASA (Table 7). 4. Reversal of New Anticoagulants 4.1. Introduction At the same time that NOAC have been considered noninferior to vitamin K antagonists for ischemic stroke prevention in patients with AF and deep venous thrombosis treatment, they are related to lower risks of major bleeding, particularly hemorrhagic stroke. 44 Furthermore, notwithstanding the current unavailability of antidotes for all NOAC, major bleeding episodes caused by these drugs do not seem to lead to worse clinical outcomes when compared to bleeding episodes in patients receiving vitamin K antagonists whose anticoagulant effects may be rapidly reversed. 45 With the increased use of NOAC in clinical practice, the management of hemorrhagic events and the need to reverse anticoagulant effects in order to perform urgent procedures in patients receiving these medications have become common in emergency units. Table 7 – Recommendations on duration of dual antiplatelet therapy following percutaneous coronary intervention in acute coronary syndrome Indications Grade of recommendation Level of evidence In patients with ACS undergoing PCI, regardless of stent type, dual antiplatelet therapy should be maintained for a minimum period of 12 months I A In patients with ACS undergoing PCI with increased risks of bleeding, it is possible to consider maintaining dual antiplatelet therapy for a minimum period of 6 months IIa B In patients with ACS undergoing PCI with a drug-eluting stent who tolerate the routine dual antiplatelet therapy duration without bleeding episodes and who have low bleeding risks and high atherothrombotic risks (DAPT score ≥ 2 and PRECISE-DAPT < 25), it is possible to maintain antiplatelet therapy for > 12 months and ≤ 30 months IIb A ACS: acute coronary syndrome; PCI: percutaneous coronary intervention. In addition to general measures (Table 8), the utilization of antidotes, alternative therapies (e.g., prothrombin complex concentrates, factor VIIa, tranexamic acid) and the action of specialized teams (e.g., hematologists, endoscopists, neurologists, neurosurgeons, general surgeons, vascular surgeons, etc.) should be part of institutional protocols for reversing anticoagulation in the event of major bleeding episodes or urgent surgical procedures in patients receiving NOAC. 46 4.2. Antidotes Three antidotes are in diverse developmental phases (Table 10). To date, only the monoclonal antibody idarucizumab has been approved for commercial use as an antidote for dabigratan. Andexanet alfa, an antidote for factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), has yet to be approved for commercial use in Brazil. Finally, ciraparantag, which is still in the early stages of development, is potentially capable of neutralizing the effects of both direct thrombin inhibitors and factor Xa inhibitors (Tables 9 and 10). Potential indications for the use of antidotes for NOAC include: • A life-threatening bleeding episode (e.g. hemorrhagic stroke) or uncontrollable bleeding; • Persistent bleeding, notwithstanding hemostatic measures; • Risk of recurrent bleeding due to NOAC overdose or expected metabolism delay (e.g., renal insufficiency); • Bleeding in non-compressible locations or in vital organs (e.g., retroperitoneal, pericardial, or intraocular bleeding or intramuscular bleeding with compartment syndrome); Table 8 – General measures for controlling major bleeding events in patients receiving NOAC Mechanical compression when possible Determining last dose of NOAC Exams (renal and hepatic function, hemogram, complete coagulogram, and factor anti-Xa) Volume expansion and red cell concentrate, when necessary Activated charcoal if NOAC was taken < 2 hours prior NOAC: new oral anticoagulant. 120