1. In this randomized controlled trial, the effects of thromboprophylaxis on clinical outcomes after coronavirus disease 2019 (COVID-19) hospitalization were inconclusive due to early termination of enrollment.

2. The incidence of death or thromboembolism was low in this cohort of patients discharged following COVID-19 hospitalization.

Evidence Rating Level: 3 (Average)

Study Rundown: Prior studies have shown that hospitalization is associated with an increased risk for venous thromboembolism (VTE) both during the hospitalization course and after discharge in patients hospitalized with COVID-19 infection. However, there is a gap in knowledge as to understanding whether a course of extended thromboprophylaxis beginning at the time of discharge from the hospital through 30 days would decrease the frequency of thromboembolism and death. Accordingly, this randomized controlled trial compared antithrombotic strategies in hospitalized COVID-19 patients following discharge. The study results were inconclusive as the trial was terminated early secondary to a lower-than-expected primary event rate and slow enrollment. However, arterial thromboembolism or all-cause mortality at 30 days showed estimates of efficacy ranging from a 56% reduction in risk for apixaban compared with placebo. These study’s findings were limited by the lowered risk for hospitalization and death due to COVID-19 vaccines, as well as reduced illness severity in the delta and omicron variant peaks. Nevertheless, these study’s findings are significant, as they demonstrate that thromboprophylaxis may result in a decrease in the incidence of death or thromboembolism in patients discharged after hospitalization with COVID-19.

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Relevant Reading: Seeing the Positive in Negative Studies

In-Depth [single-group multicenter study]: This was an adaptive, multistage prospective, randomized, double-blind, placebo-controlled trial designed to compare the effectiveness and safety of various antithrombotic strategies for patients discharged after hospitalization for COVID-19. Patients older than 18 years and hospitalized for 48 hours or longer with a SARS-CoV-2 infection (positive polymerase chain reaction, antigen, or point-of-care test results within two weeks of the hospital admission date) were eligible for the study. Patients who had an existing indication for either therapeutic or prophylactic dose anticoagulation at hospital discharge, those with a contraindication to antithrombotic therapy (for example, ischemic stroke, intracranial bleed, or neurosurgery within three months, known bleeding within the past 30 days, or known major surgery within 14 days), as well as those with an inherited or active acquired bleeding disorder, were excluded from the study. The primary outcome measured was the composite of all-cause mortality, venous thrombosis, and arterial thrombosis within 30 days of randomization. Outcomes in the primary analysis were assessed via an intention-to-treat comparison with log-binomial regression models. Based on the primary analysis, the incidence of the primary endpoint was 2.13% (95% Confidence Interval [CI],1.14 to 3.62) in the apixaban group and 2.31% (95% CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in two (0.4%) and one (0.2%), as well as clinically relevant nonmajor bleeding in three (0.6%) and six (1.1%) apixaban-treated and placebo-treated participants, respectively. However, enrollment and the study were terminated early after a lower-than-anticipated event rate and a declining rate of COVID-19 hospitalizations. In summary, these study’s results were imprecise and inconclusive due to early enrollment termination, but the incidence of death or thromboembolism was low in this cohort of patients with COVID-19 hospitalization.

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