Table 3.

Summary of the effect of different anticoagulant treatment options during COVID-19 infection from large trials

Author	Trial	Journal	Design	Population	N	Intervention	Outcome	Main findings
Spyropoulos et al. [111]	The HEP-COVID randomized clinical trial	JAMA Intern Med, 2021	MCRCT	Non-ICU and ICU	253	Standard prophylactic- or intermediate-dose LMWH or UFH versus therapeutic-dose enoxaparin	VTE, ATE, death, major bleeding, at 30 days	Reduced VTE, ATE, and death in non-ICU treatment group No treatment effects in ICU population No differences in major bleeding between groups
Perepu et al. [112]		J Thromb Haemost, 2021	MCRCT	ICU and/or ISTH overt DIC score ≥3	176	Standard prophylactic-dose versus intermediate-dose enoxaparin	Death, VTE, ATE, major bleeding, at 30 days	No treatment effects were observed No differences in major bleeding between groups
Lopes et al. [113]	The ACTION randomized clinical trial	Lancet, 2021	MCRCT	Predominately hospitalized clinically stable	615	Standard prophylactic-dose enoxaparin or UFH versus therapeutic-dose rivaroxaban or enoxaparin or UFH	Time to death, duration of hospitalization, duration of supplemental oxygen, at 30 days	No treatment effects were observed Significantly increased number of bleeding complications in the treatment group
Sadeghipour et al. [114]	The INSPIRATION randomized clinical trial	JAMA, 2021	MCRCT	ICU	562	Standard prophylactic-dose versus intermediate-dose enoxaparin	VTE, ATE, ECMO, death, at 30 days	No treatment effects were observed No differences in major bleeding between groups
Sholzberg et al. [131]	The RAPID randomized clinical trial	BMJ, 2021	MCRCT	Moderately ill hospitalized	465	Standard prophylactic-dose versus therapeutic-dose heparin	Death, invasive or noninvasive mechanical ventilation, ICU admission, at 28 days	No treatment effects were observed No differences in major bleeding between groups
Lawler and colleagues [106]	The ATTACC, ACTIV-4a, and REMAP-CAP, multiplatform randomized clinical trial	N Engl J Med, 2021	MPRCT	Noncritically ill	2244	Standard prophylactic-dose versus therapeutic-dose heparin	Organ support-free days, death, at 21 days	Increased probability of survival to hospital discharge with reduced organ support in the treatment group Major bleeding occurred more frequently in the treatment group
Goligher and collegues [107]	The ATTACC, ACTIV-4a, and REMAP-CAP, multiplatform randomized clinical trial	NEJM, 2021	MPRCT	Critically ill	1098	Standard prophylactic-dose versus therapeutic-dose heparin	Organ support-free days, death, at 21 days	No differences in probability of survival to hospital discharge with reduced organ support in the treatment group Major bleeding occurred more frequently in the treatment group

MCRCT, multicenter randomized clinical trial; ICU, intensive care unit; LMWH, low molecular weight heparin; UFH, unfractionated heparin; VTE, venous thromboembolism; ATE, arterial thromboembolism; DIC, disseminated intravascular coagulation; ECMO, extracorporeal membrane oxygenation.