Anticoagulation does not improve outcomes in symptomatic outpatients with COVID-19 (ACTIV-4B)

Reference

Connors JM, Brooks MM, Sciurba FC, et al, for the ACTIV-4B Investigators. Effect of antithrombotic therapy on clinical outcomes in outpatients with clinically stable symptomatic COVID-19. The ACTIV-4B randomized clinical trial. JAMA 2021;326(17):1703-1712.

Synopsis

The balance of benefit versus harm of antithrombotic therapy for clinically stable outpatients with symptomatic COVID-19 remains uncertain. These investigators identified outpatient adults, aged 40 years to 80 years, with newly diagnosed symptomatic SARS-CoV-2 infection by positive PCR or antigen test. Study patients (N = 657) randomly received (concealed allocation assignment) aspirin (81 mg once daily) plus placebo, apixaban 2.5 mg twice daily, apixaban 5.0 mg twice daily, or placebo twice daily. The individuals who assessed outcomes remained masked to treatment group assignments. The trial was terminated early because of lower-than-anticipated event rates, resulting in a total of 558 patients who initiated trial treatment. Complete follow-up occurred for 99.6% of these 558 patients at 45 days or time of trial termination. Using intention-to-treat analysis of all randomized patients, no significant group differences occurred in the risk of the primary composite end point of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization. Overall excess bleeding events were increased in both the aspirin and apixaban groups compared with the placebo-only group, but no major bleeding events occurred in any group.