ACTIV-4, REMAP-CAP, and ATTACC multiplatform trials also studied therapeutic dose anticoagulation in patients with COVID-19 admitted to hospital wards, referred to as moderate state. Moderately ill patients were a priori stratified according to baseline D-dimer (high, low, or missing), with a high D-dimer defined as at least twice the local upper limit of normal at baseline. Otherwise, the study design was similar to that in critically ill patients, with the same primary endpoint of organ-free support days up to day 21. For the moderately ill population, on Jan 21, 2021, the data and safety monitoring board recommended to discontinue enrolling patients because the prespecified boundary for superiority—ie, more than 99% posterior probability on the primary outcome—had been reached. At that time, 1772 patients were randomly assigned, and unadjudicated preliminary data from 1398 patients with an evaluable primary outcome were available (unpublished; based on the ACTIV-4, REMAP-CAP, and ATTACC trials; table 1).49ATTACC, ACTIV-4a and REMAP-CAP
Results of Interim Analysis. As a post-hoc analysis, investigators estimated the need for organ support—eg, transitioning from the ward to ICU or receiving high flow nasal oxygen. Therapeutic anticoagulation decreased the need for organ support from approximately 25% to 18% in patients with a high D-dimer at baseline and from 19% to 13% in those with a low D-dimer at baseline.49ATTACC, ACTIV-4a and REMAP-CAP
Results of Interim Analysis. Full study results with adjudicated outcome data from all randomly assigned patients are eagerly awaited, but given the Bayesian approach of the trial, the overall conclusion will probably be similar to the results which are already available. The number needed-to-treat to prevent one patient from transitioning to organ support (including high nasal oxygen) would be approximately 14 patients in those with high D-dimer at baseline and 16 in those with low D-dimer at baseline, and the number needed to prevent one death would be approximately 50 patients.49ATTACC, ACTIV-4a and REMAP-CAP
Results of Interim Analysis. These results are promising, but they are not comprehensively communicated into the public domain or peer reviewed. The question arises whether guidelines and treatment protocols should be changed to include therapeutic anticoagulation in all patients admitted to the wards with COVID-19. On March 25, 2021, NICE adapted the COVID-19 rapid guidelines55National Institute for Health and Care Excellence
COVID-19 rapid guideline: managing COVID-19. to consider a therapeutic dose of low-molecular-weight heparin in patients with COVID-19 who are likely to be in hospital for at least 2 days, need supplemental oxygen, and have not yet received high-flow oxygen or other organ support. However, we are reluctant to change our clinical practice on the basis of preliminary data, and the generalisability of this study population to all patients should be judged first from the full paper to assess the risk–benefit balance. Once the paper is published after peer-review, this hesitation will potentially change into adoption in guidelines and practice during this fast-changing pandemic landscape, especially if results from ongoing studies addressing the effect of therapeutic anticoagulation in this population, such as the RAPID trial,56Sholzberg M Tang GH Negri E et al.Coagulopathy of hospitalised COVID-19: a pragmatic randomised controlled trial of therapeutic anticoagulation versus standard care as a rapid response to the COVID-19 pandemic (RAPID COVID COAG - RAPID trial): a structured summary of a study protocol for a randomised controlled trial. confirm these observed findings. Again, we expect that data on antiplatelet agents will become available in the near future, but to our knowledge, data from randomised controlled trials have not yet been published.