Cardiopulmonary events were unaffected by antithrombotic therapy in symptomatic outpatients with COVID-19 but the trial was terminated early.
The level of cardiopulmonary events such as symptomatic deep vein thrombosis, pulmonary embolism, myocardial infarction and ischaemic stroke are not affected by the use of antithrombotic therapy. This was the conclusion of a randomised, double-blind, placebo-controlled trial among symptomatic outpatients infected with COVID-19 undertaken by a group from the Brigham and Women’s Hospital, Boston, Massachusetts, US. The risks of thromboembolic events in patients with covid-19 are high and associated with a greater risk of death. While there is some evidence indicating that the use of heparins among non-critically ill hospitalised patients with Covid-19 increases the probability of survival, there is a paucity of data on the use of antithrombotic therapy among symptomatic outpatients.
The ACTIV-4B COVID-19 Outpatient Thrombosis Prevention Trial was designed to explore whether patients infected with COVID-19 but who were not sufficiently unwell to require hospitalisation, could benefit from anti-platelet or anticoagulant (i.e., antithrombotic) therapy, as a means of slowing disease progression. Patients aged between 40 and 80 years of age with a PCR or antigen confirmed diagnosis of COVID-19 were eligible for inclusion in the study. All were randomised in a 1:1:1:1 fashion to aspirin 81 mg daily (and matching placebo), apixaban 2.5 mg twice daily, apixaban 5 mg twice daily or placebo twice daily for a period of 45 days. The primary outcome of interest was a composite of cardiopulmonary outcomes including symptomatic deep vein thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, ischaemic stroke, hospitalisation for cardiovascular or pulmonary events and all-cause mortality, for up to 45 days.
Findings
In total, 657 patients with a median age of 54 years (59.1% women) were randomised to one of the four arms and the median time from diagnosis to randomisation was 7 days and 3 days between randomisation and the start of therapy. During this period of time, some patients were hospitalised and complete follow-up were available for only 556 individuals. Unfortunately, the incidence of cardiopulmonary events was low, with only 5 events; 1 deep vein thrombosis in the aspirin group, 3 cardiopulmonary events (all hospitalisations), 2 in the apixaban 5 mg group, 1 in apixaban 2.5 mg group) and one hospitalisation in the placebo group. While the event rate was very low, the authors also noted that there were no major bleeding events reported during the trial and there were no deaths. However, there were 4 suspected non-major bleeds in the aspirin group with 6 and 4 in the low and high apixaban groups respectively.
The authors reported that the trial was terminated early due to the low event rate. They concluded that while among clinically stable symptomatic outpatients, treatment with aspirin or apixaban did not reduce the rate of clinical outcomes. However, the generalisability of this conclusion is limited because of the low incidence of primary events.
Citation
Connors JM et al. Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19. The ACTIV-4B Randomized Clinical Trial. JAMA 2021
