ABC | Volume 115, Nº2, August 2020

Statement Arq Bras Cardiol. 2020; 115(2):292-301 Position Statement on the Use of Antiplatelet Agents and Anticoagulants in Patients Infected with the New Coronavirus (COVID-19) – 2020 1. Introduction Thenewcoronavirus (SARS-CoV-2) pandemichas led todebate about the best treatment for the disease and its complications. Recent publications have shown that cardiovascular disease is among the main risk factors for disease progression, including high blood pressure and diabetes mellitus. 1-6 It has been demonstrated that patients infected with the new coronavirus (COVID-19) have distinct activation of prothrombotic mechanisms, including a greater likelihood of thrombotic events. Acute coronary syndrome (ACS) with or without ST-elevation can occur in patients with COVID-19, although the actual incidence is still uncertain. 7-10 Thus, several issues related to using antiplatelet agents and anticoagulants in patients with suspected or confirmed COVID-19 infection remain uncertain. The following recommendations are valid for themost diverse clinical situations, such as atrial fibrillation, acute coronary syndrome, chronic coronary artery disease, percutaneous coronary intervention, post- cardiac surgery, ischemic stroke, and venous thromboembolism, and should be applied on a case-by-case basis. 2. Pathophysiology 2.1. Mechanism of Cellular Entry The functional receptor and gateway of the SARS-CoV-2 virus is angiotensin-converting enzyme 2. This carboxypeptidase has the opposite effect of angiotensin-converting enzyme 1, i.e., it increases the degradation of angiotensin 2 and thus has a vasodilating effect. In addition to being present in lung parenchyma, angiotensin-converting enzyme 2 is also distributed throughout the cardiovascular system, kidneys and heart. It is known that angiotensin-converting enzyme 2 has a certain role in ventricular function. Severe left ventricular dysfunction occurred in animal models that reduced the expression of angiotensin-converting enzyme 2. Apparently, infection with the newcoronavirus can promote downregulation of these receptors, which could lead tomyocardial injury and lung injury. 1,2,11 Despite this possible association, an observational study of 8,910 patients infected with SARS-Cov-2 found no increase in mortality among patients using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. 12 Thus, these medications should not be discontinued in patients who used themprior to infection. 2.2. Myocardial Injury Several studies,mainlyChinese, have demonstrated the impact of myocardial injury on the progression and severity of COVID-19. Chinese data indicate the presence of myocardial injury in approximately 20 to 30% of hospitalized patients, as well as in 40%of those who died. There are data showing that elevations in somemarkers, such as troponin andD-dimer, are associatedwith worse prognosis, intensive care unit hospitalization, mechanical ventilation, and death. 2,13,14 Themechanismof myocardial injury is still not well established. In addition to the direct effect of the virus, there is myocardial stress induced by respiratory failure and hypoxemia, including supply and demand imbalances, as well as the indirect action of systemic inflammatory response on myocardial tissue and endothelial function. 14-19 Data on the effects of myocardial inflammation is also insufficient. It is not clear whether COVID-19-inducedmyocarditis produces heart failurewith reduced ejection fraction. There have been anatomopathological findings of lymphocytic myocarditis, even in patients with preserved ejection fraction and signs of ventricular hypertrophy. 14-19 2.3. Association with Acute Coronary Syndrome The increased risk of ACS in patients with COVID-19 can be explained by increased thrombotic activity, evidenced by the frequent elevation of D-dimer and thrombocytopenia. There is also an increase in coronary events in direct association with viral respiratory infection. Factors related to inflammatory activity (e.g., endothelial dysfunction, platelet activation, macrophage activation, liver dysfunction, tissue factor expression and cytokine release) can increase the risk of atherosclerotic plaque instability. More recent studies have also identified high levels of antiphospholipid antibodies in patients withCOVID-19, although it is not known whether this is related to disease severity. 5,7-10,15,20 At the beginning of the infection phase, platelet inhibition can reduce the formation of intravascular fibrin and thrombus. Thus, the use of pre- but not post-admission acetylsalicylic acid was found to be associated with a lower risk of respiratory failure and mortality in patients with community-acquired pneumonia. Despite the fact that all P2Y 12 inhibitors reduce platelet and leukocyte aggregates and platelet-derived proinflammatory cytokines, ticagrelor, which is orally administered, is unique in having an additional well-documented target of inhibition: equilibrative nucleoside transporter 1, which contributes to the inhibition of cellular adenosine uptake. Therefore, ticagrelor has more potent anti-inflammatory properties, although it has not been tested in COVID-19. 7 It should be pointed out that in view of the high incidence of myocardial injury due to the virus and the indirect effects of infection, non-ischemic disease must be considered in an Content 1. Introduction .................................................................................... 294 2. Pathophysiology ............................................................................ 294 2.1. Mechanism of cellular entry ............................................................ 294 2.2. Myocardial Injury ............................................................................ 294 2.3. Association with Acute Coronary Syndrome .................................... 294 2.4. Thromboembolic Mechanism .......................................................... 295 3. Drug Interactions and Cardiovascular Pro- /Antithrombotic Effects .................................................................................................. 295 3.1. Antiretrovirals ................................................................................. 295 3.2. Hydroxychloroquine and Chloroquine .............................................. 296 3.3. Corticosteroides .............................................................................. 296 3.4. Heparinas ....................................................................................... 296 3.5. Imunoglobulinas e Anticorpos Anti-IL6 ............................................ 296 4. Recommendations ........................................................................ 296 4.1. Anticoagulants ................................................................................ 296 4.2. Antiplatelet Agents ......................................................................... 297 4.3. Thrombolytics ................................................................................. 299 5. Final Considerations ..................................................................... 299 References .......................................................................................... 300 294