Updated meta-analysis of randomized controlled trials on the safety and efficacy of different prophylactic anticoagulation dosing regimens in non-critically ill hospitalized patients with COVID-19.

We thank Prof. Čulić and colleagues for their interest in our meta-analysis on the safety and efficacy of different prophylactic anticoagulation dosing regimens in coronavirus disease 2019 (COVID-19) patients.1 Throughout the COVID-19 pandemic, the high rate of thromboembolic events among COVID-19 patients has been a topic of extensive and ongoing research.2,3 Several randomized controlled trials (RCTs) have tested different anticoagulation regimens for preventing thromboembolic events.1 However, the results of the RCTs have not been univocal, and the majority of these lack statistical power for individual hard endpoints such as death. For these reasons, we pooled the data on the safety and efficacy of prophylactic anticoagulation at escalated dose vs. standard dose in critically and non-critically ill hospitalized patients with COVID-19. This meta-analysis did not find any mortality benefit of an escalated dose over the standard dose of prophylactic anticoagulation. Moreover, there was a reduction of venous thromboembolism (VTE) counterbalanced by increased major bleeding in patients treated with escalated-dose prophylactic anticoagulation compared with those treated with a standard dose.1 As the evidence has constantly been evolving after the publication of our meta-analysis (14 September 2021), further RCTs have become available in the setting of non-critically ill hospitalized patients.4–6 The HEP-COVID trial, published on 7 October 2021, is the most relevant.4 We agree with the authors that in non-critically ill hospitalized patients, the data reported by the HEP-COVID and the ATTACC, ACTIV-4a, and REMAP-CAP trials may suggest improved outcomes with an escalated dose of prophylactic anticoagulation compared with the standard dose.4,7 Briefly, HEP-COVID showed a reduction of the primary endpoint (composite