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      Early antithrombotic post-discharge therapy using prophylactic DOAC or dipyridamole improves long-term survival and cardiovascular outcomes in hospitalized COVID-19 survivors

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          Abstract

          Introduction

          Cardiovascular events are common in COVID-19. While the use of anticoagulation during hospitalization has been established in current guidelines, recommendations regarding antithrombotic therapy in the post-discharge period are conflicting.

          Methods

          To investigate this issue, we conducted a retrospective follow-up (393 ± 87 days) of 1,746 consecutive patients, hospitalized with and surviving COVID-19 pneumonia at a single tertiary medical center between April and December 2020. Survivors received either 30-day post-discharge antithrombotic treatment regime using prophylactic direct oral anticoagulation (DOAC; n = 1,002) or dipyridamole ( n = 304), or, no post-discharge antithrombotic treatment (Ctrl; n = 440). All-cause mortality, as well as cardiovascular mortality (CVM) and further cardiovascular outcomes (CVO) resulting in hospitalization due to pulmonary embolism (PE), myocardial infarction (MI) and stroke were investigated during the follow-up period.

          Results

          While no major bleeding events occured during follow-up in the treatment groups, Ctrl showed a high but evenly distributed rate all-cause mortality. All-cause mortality (CVM) was attenuated by prophylactic DOAC (0.6%, P < 0.001) and dipyridamole (0.7%, P < 0.001). This effect was also evident for both therapies after propensity score analyses using weighted binary logistic regression [DOAC: B = −3.33 (0.60), P < 0.001 and dipyridamole: B = −3.04 (0.76), P < 0.001]. While both treatment groups displayed a reduced rate of CVM [DOAC: B = −2.69 (0.74), P < 0.001 and dipyridamole: B = −17.95 (0.37), P < 0.001], the effect in the DOAC group was driven by reduction of both PE [ B−3.12 (1.42), P = 0.012] and stroke [ B = −3.08 (1.23), P = 0.028]. Dipyridamole significantly reduced rates of PE alone [ B = −17.05 (1.01), P < 0.001].

          Conclusion

          Late cardiovascular events and all-cause mortality were high in the year following hospitalization for COVID-19. Application of prophylactic DOAC or dipyridamole in the early post-discharge period improved mid- and long-term CVO and all-cause mortality in COVID-19 survivors.

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          Most cited references38

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          COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up

          Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, we review the current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexisting thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.
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            COVID-19 and its implications for thrombosis and anticoagulation

            Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC). The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness. The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur. The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations. Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested. COVID-19–associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC. Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated. Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported. If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed.
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              2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC).

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                Author and article information

                Contributors
                Journal
                Front Cardiovasc Med
                Front Cardiovasc Med
                Front. Cardiovasc. Med.
                Frontiers in Cardiovascular Medicine
                Frontiers Media S.A.
                2297-055X
                29 July 2022
                2022
                29 July 2022
                : 9
                : 916156
                Affiliations
                [1] 1Clinic II for Internal Medicine, University Hospital Salzburg, Paracelsus Medical University , Salzburg, Austria
                [2] 2Department of Internal Medicine, Cardiology, Nephrology and Intensive Care Medicine, Hospital Wiener Neustadt , Wiener Neustadt, Austria
                [3] 3Department of Internal Medicine I, Bashkir State Medical University , Ufa, Russia
                [4] 4Scientific Laboratory for the Study of Socio-Economic Problems of the Regions Bashkir State University , Ufa, Russia
                [5] 5Department of Internal Diseases II, Bashkir State Medical University , Ufa, Russia
                [6] 6Lomonosov Moscow State University Medical Center , Moscow, Russia
                [7] 7Department of Urology, Bashkir State Medical University , Ufa, Russia
                [8] 8Department of Pharmacy at The Second Affiliated Hospital, and Department of Pharmacology (The Key Laboratory of Cardiovascular Medicine Research, Ministry of Education) at College of Pharmacy, Harbin Medical University , Harbin, China
                [9] 9Department of Cardiology I, Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Munster , Munster, Germany
                Author notes

                Edited by: Zahra Raisi-Estabragh, Queen Mary University of London, United Kingdom

                Reviewed by: Mario Enrico Canonico, University of Naples Federico II, Italy; Christopher Barrett, Massachusetts Institute of Technology, United States

                *Correspondence: Lukas J. Motloch l.motloch@ 123456salk.at

                This article was submitted to General Cardiovascular Medicine, a section of the journal Frontiers in Cardiovascular Medicine

                †These authors have contributed equally to this work

                Article
                10.3389/fcvm.2022.916156
                9372296
                35966512
                5d6c5bb9-592f-4b73-a643-850f5467b6c0
                Copyright © 2022 Motloch, Jirak, Mirna, Fiedler, Davtyan, Lakman, Gareeva, Tyurin, Gumerov, Matskeplishvili, Pavlov, Cai, Kopp, Topf, Hoppe, Pistulli and Zagidullin.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 April 2022
                : 11 July 2022
                Page count
                Figures: 8, Tables: 3, Equations: 0, References: 41, Pages: 0, Words: 7018
                Funding
                Funded by: Russian Science Foundation, doi 10.13039/501100006769;
                Categories
                Cardiovascular Medicine
                Original Research

                covid-19,long covid-19,direct anticoagulation,dipyridamole,cardiovascular disease in covid-19

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