Through Thick and Thin: Is Anticoagulation Warranted in COVID-19 Infection?

Volume 9, Issue 1

During the early days of the COVID-19 pandemic, providers advocated for therapeutic anticoagulation (AC) for patients with severe infection due to concerns over thromboembolism. These concerns largely stemmed from the perceived risk of thrombosis that was derived from elevated levels of serum D-dimer. Since then, significant effort has gone into studying the benefit of anticoagulation for patients with COVID-19. In this week’s issue of Talking Therapeutics, we explore three recent studies evaluating this intriguing topic.

Point 1: No AC for Those in the Outpatient Setting

A trial published this week, conducted in the United States and involving 657 symptomatic outpatients with COVID-19, was stopped early because of an unanticipated low event rate. Randomized participants initiated trial treatment with aspirin (81 mg once daily), apixaban (2.5 mg twice daily), apixaban (5.0 mg twice daily), or placebo. The rates of an adjudicated composite outcome (all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause) after 45 days were 0.0%, 0.7%, 1.4%, and 0.0%, respectively. There were no significant differences between the active groups and the placebo group.

These data do not support the use of aspirin or apixaban in the outpatient setting to reduce the major adverse cardiovascular or pulmonary consequences associated with symptomatic but clinically stable SARS-CoV-2 infection.

Point 2: Maybe AC for Inpatients Who Are Not Critically Ill?

A paper published in the New England Journal of Medicine (NEJM) on August 4 involved patients who were hospitalized with COVID-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment). Patients were randomly assigned to receive regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis.

Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days, compared with usual-care thromboprophylaxis, was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03-1.58). The adjusted absolute between group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5-7.2).

These data suggest that in noncritically ill patients with COVID-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support, as compared with usual-care thromboprophylaxis.

Point 3: No AC for Critically Ill Patients

Another trial published in the NEJM on August 4 enrolled critically ill patients with severe COVID-19 who were randomly assigned to a regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care.

The trial was stopped when the prespecified criterion for futility was met. Data on the primary outcome were available for 1098 patients. The median value for organ support-free days was 1 (interquartile range, −1-16) among the patients assigned to therapeutic dose anticoagulation, and was 4 (interquartile range, −1-16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67-1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%).

These data suggest that in critically ill patients with COVID-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis.

Disclaimer: The views and opinions expressed are those of the author(s) and do not necessarily reflect the official policy or position of the Population Health Learning Network or HMP Global, their employees, and affiliates. Any content provided by our bloggers or authors are of their opinion and are not intended to malign any religion, ethnic group, club, association, organization, company, individual, or anyone or anything.