Table 2 Summary of evidence from major RCTs evaluating the use of empirical antithrombotic therapy in COVID-19

Inpatient, critically ill (severe illness)

Anticoagulation (heparin-based)

ACTIV-4a–ATTACC–

REMAP-CAP^a, 54

INSPIRATION¹⁶³

Critically ill patients with COVID-19 should receive pharmacological thromboprophylaxis with unfractionated or low molecular weight heparin

Multiple RCTs show no benefit from intermediate- or therapeutic-dose anticoagulation over standard prophylactic-dose thromboprophylaxis, and potential for harm with dose escalation owing to higher bleeding rates

Prophylactic dosing should be adjusted for weight and eGFR

Aspirin or P2Y12 inhibitor^b

RECOVERY⁶⁵

REMAP-CAP⁶⁷

No clear benefit, and higher rates of major bleeding with empirical use of antiplatelet agents in critically ill patients with COVID-19

Inpatient, not critically ill (moderate illness)

Heparin-based anticoagulation or rivaroxaban

REMAP-CAP–

ACTIV-4a–ATTACC⁵³

ACTION⁶¹; RAPID⁶⁰; HEP-COVID⁵⁹

Moderately ill patients with COVID-19 should receive at least pharmacological thromboprophylaxis

Empirical therapeutic-dose anticoagulation might benefit certain individuals with high thrombosis and low bleeding risk, but data are conflicting

Aspirin

RECOVERY⁶⁵

No clear benefit for empirical use of aspirin in moderately ill patients with COVID-19

Outpatient, no hospitalization

Apixaban

ACTIV-4B⁶⁶

No clear benefit for empirical use of apixaban in outpatients with COVID-19

Aspirin

ACTIV-4B⁶⁶

No clear benefit for empirical use of aspirin in outpatients with COVID-19

Outpatient, following hospital discharge

Anticoagulation (apixaban, rivaroxaban, or enoxaparin)

MICHELLE⁶³

Possible benefit for prophylactic-dose rivaroxaban post-discharge in certain patients hospitalized for COVID-19 who have high thrombosis and low bleeding risk