Therapeutic anticoagulation in non-critically ill patients – definitive

In non-critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increases the probability of survival to hospital discharge with reduced use of organ support.

Thrombo-inflammation may contribute to morbidity and mortality in Covid-19. We
hypothesized that therapeutic-dose anticoagulation may improve outcomes in non-critically ill
patients hospitalized for Covid-19.

In an open-label adaptive multiplatform randomized controlled trial, non-critically ill patients
hospitalized for Covid-19, defined by the absence of critical care-level organ support at
enrollment, were randomized to a pragmatic strategy of therapeutic-dose anticoagulation with
heparin or usual care pharmacological thromboprophylaxis. The primary outcome combined
survival to hospital discharge and days free of organ support through 21 days, which was
evaluated with Bayesian statistical models according to baseline D-dimer.

The trial was stopped when prespecified criteria for superiority were met for therapeutic-dose
anticoagulation in groups defined by high (≥2-fold elevated) and low (<2-fold elevated) Ddimer.

Among 2219 participants in the final analysis, the probability that therapeutic
anticoagulation increased organ support-free days compared to thromboprophylaxis was 99.0%
(adjusted odds ratio 1.29, 95% credible interval 1.04 to 1.61). The adjusted absolute increase in
survival to hospital discharge without organ support with therapeutic-dose anticoagulation was
4.6% (95% credible interval 0.7 to 8.1). In the primary adaptive stopping groups, the final
probabilities of superiority for therapeutic anticoagulation were 97.3% in the high D-dimer
group and 92.9% in the low D-dimer group. Major bleeding occurred in 1.9% and 0.9% of
participants randomized to therapeutic anticoagulation and thromboprophylaxis, respectively