Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial

Brazilian RCT (n=615) reported that in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes or reduce death, and increased bleeding vs prophylactic anticoagulation with heparin.

SPS commentary:

The primary efficacy outcome (time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30; analysed with the win ratio method) was similar between groups with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0.86 [95% CI 0.59–1.22], p=0.40).

The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (RR 3.64 [95% CI 1.61–8.27], p=0.0010).

The study researchers suggest that rivaroxaban, a direct, selective factor Xa inhibitor, does not share heparin's possible pleiotropic effects. Heparins, which inhibit multiple coagulation proteases, might have other anti-inflammatory and antiviral effects, some of which might be specific to COVID-19. This lack of anti-inflammatory effect of rivaroxaban may have been attenuated by the high use of corticosteroids. Furthermore,  patients hospitalised with COVID-19 might have abnormal absorption of oral anticoagulation, leading to erratic and variable effects, which could also contribute to different findings between the studies.

 

The researchers therefore suggest that routine use of rivaroxaban at a therapeutic dose does not provide clinical benefit to patients hospitalised with COVID-19 when compared with traditional thromboprophylaxis with heparin.

The Lancet