A recent study found that full-dose anticoagulant rivaroxaban in COVID patients increased bleeding, and was not in any way more beneficial than conventional prophylaxis.

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COVID-19 appears to have a prothrombotic condition, with a substantially greater thrombotic risk than other viral infections, according to evidence gathered over the previous year and a half. This has resulted in the administration of higher-than-standard dosages of thromboprophylaxis (rivaroxaban and other medications) in hospitalised patients, but no consensus exists about the optimal anticoagulation strategy. The ACTION study found that full dosage rivaroxaban administered as a therapeutic anticoagulant in hospitalised COVID-19 patients produces a significant increase in bleeding, outweighing any potential moderate decrease in thrombotic events compared to conventional prophylaxis.

Objective

The ACTION trial's objective was to compare therapeutic anticoagulation versus preventative anticoagulation in individuals hospitalised with COVID-19 infection. 615 COVID-infected individuals admitted to the hospital with increased D-dimer values were randomly assigned to therapeutic or preventive anticoagulation.

Anticoagulation therapy inclusions

1. In-hospital rivaroxaban 20 mg daily for stable patients (94 per cent of the cohort) and in-hospital enoxaparin 1 mg/kg twice daily for those who were judged unstable.
2. Rivaroxaban was maintained for 30 days following discharge, regardless of the length of hospitalisation.
3. Approximately three-quarters of patients required some form of oxygen assistance, and 83% received systemic corticosteroids.
4. Before randomisation, almost nine out of ten were receiving anticoagulation (mainly routine thromboprophylaxis).
5. Around a quarter (27%) of participants had a D-dimer level that was at least three times the upper limit of normal.

The major outcome measure was a hierarchical analysis of fatality, hospitalisation length, and oxygen usage duration over a 30-day period, as determined by the unmatched win ratio technique. In this research, full-dose anticoagulation prevailed in 34.8 per cent of comparisons, compared to 41.3 per cent in the control arm, resulting in a non-significant win ratio of 0.86. (95 per cent CI 0.59-1.22). That is, therapeutic anticoagulation had a tendency to perform poorly, as was shown for each component of the composite result.

Across subgroups, the findings were consistent. With full-dose anticoagulation, the risk of a secondary composite outcome of thromboembolic events (venous thromboembolism, MI, stroke, systemic embolism, and serious adverse events of the extremities) was non-significantly reduced (RR 0.75; 95 per cent CI 0.45-1.26), while the risk of all-cause mortality was non-significantly greater (RR 1.49; 95 per cent CI 0.90-2.46).

The therapeutic-dose group experienced an increase in ISTH major bleeding, ISTH clinically significant non-major bleeding, and any bleeding. Therapeutic anticoagulation was not shown to be preferable to preventative anticoagulation in individuals hospitalised with COVID-19 infection and increased D-dimer. Rivaroxaban did not enhance clinical results in stable patients while enoxaparin did not enhance clinical results in unstable patients; However, there was a significant rise in severe bleeding.

Using heparin

ACTION was noteworthy in that it evaluated the therapy in the therapeutic-dose arm predominantly with a direct oral anticoagulant and continued treatment for up to 30 days post-discharge. Heparin was employed in most earlier trials, including the multiplatform effort, and therapy was limited to the hospital environment. Experts commented, "The choice of drug might be crucial. Since heparin has been demonstrated to have anticoagulant, antiinflammatory, and perhaps direct antiviral properties, which an oral factor Xa inhibitor like rivaroxaban may not have. This demonstrates that regular anticoagulation with this oral drug for 30 days in COVID patients who are hospitalised should not be done, as has been done off-label by several sites in several countries."

Although the optimal strategy for anticoagulating COVID-19 patients hospitalised remains unknown, the ACTION results show that "Certainly, therapeutic dosage of DOACs should never be used. According to this study, prophylactic heparin should continue to be utilised."

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.