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

Abstract

IntroductionCardiovascular 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.MethodsTo 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.ResultsWhile 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].ConclusionLate 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.

O uso dos Anticoagulantes Orais de Ação Direta (DOACs) como terapia anticoagulante na COVID-19

“…Tromboprofilaxia com DOAC mostrou-se eficaz na redução de AVC e TEP após a alta hospitalar de 1002 pacientes internados pela COVID-19. A ocorrência de TEP e AVC foi 5,3 vezes maior no grupo controle composto por 440 doentes (sem tromboprofilaxia) após a alta, evidenciando vantagem do uso de DOACs para este fim no período de aproximadamente 393 dias de observação do estudo, DOACs reduziram TEP em 42% (p = 0,012) e AVC em 23% (p = 0,028) (MOTLOCH LJ, et al, 2022). Um estudo prospectivo avaliou dupla terapia com DOAC (dabigatrana e endoxabana) em 25 pacientes e outra dupla terapia com apixabana e rivaroxabana em 12 doentes, em um contexto de 39 pacientes os quais estavam internados com COVID-19 e com ocorrência de TEP.…”

A systematic review on post-discharge venous thromboembolism prophylaxis in patients with COVID-19

“…Likewise, most of the included studies in this systematic review agreed with post-discharge VTE thromboprophylaxis if the patient's risk assessment indicated a high-risk situation for VTE. In between, three good-quality cohort studies reported a significant association between post-discharge VTE risk reduction and extended thromboprophylaxis [ 22 , 30 , 36 ]. As in the study by Li et al, this risk reduction was stated to be 82%; although, in the Courtney et al study, the chance of bleeding increased significantly with post-discharge AC [ 22 , 30 ].…”

“…Three high-quality studies, including the MICHELLE trial, recommended rivaroxaban 10mg daily for 30–35 days. Alternatively, apixaban 2.5mg BID and dabigatran 110mg BID can be used as the choices of DOACs [ 11 , 25 , 36 ]. Also, ISTH, the anticoagulation forum, the VAS, and the health system anticoagulation task force guidelines favored rivaroxaban 10mg daily for 30–42 days [ 35 , 50 – 52 ].…”

Cardiovascular imaging in COVID-19: insights into features and complications

“…Moreover, elevated levels of cardiac injury biomarkers such as N-terminal pro-B-type natriuretic peptide (NT-proBNP), cTn, or D-dimer were associated with a worse prognosis in the course of SARS-CoV2 infection [21]. There are findings of elevated creatine kinase MB fraction (CK-MB) as well as IL-6 levels in COVID-19 patients with acute myocardial injury [22]. Similarly, elevated fibrinogen and D-dimer have been shown predictors of poor prognostic outcome in hospitalized patients with COVID-19 [23].…”