Table 2.

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

Disease severity	Therapy	RCT	Summary of current evidence and recommendations
Inpatient, critically ill (severe illness)	Anticoagulation (heparin-based)	ACTIV-4a–ATTACC– REMAP-CAPa, 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 inhibitorb	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

eGFR, estimated glomerular filtration rate; RCT, randomized controlled trial. ^aATTACC–ACTIV-4a–REMAP-CAP was a multiplatform trial of anticoagulation in hospitalized patients with COVID-19. ^bClopidogrel, prasugrel or ticagrelor.