• WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Claire L Vale, Peter J Godolphin, David J Fisher, HigginsJulian P TJPT, Alexandra McAleenan, Francesca Spiga, Tobias Tritschler, de Barros E SilvaPedro Gabriel MeloPGM, David D Berg, Jeffrey S Berger, Lindsay R Berry, Behnood Bikdeli, Marc Blondon, Erin A Bohula, Marco Cattaneo, Riccardo Colombo, Valeria Coluccio, Maria T DeSancho, Michael E Farkouh, Valentin Fuster, Massimo Girardis, Judith S Hochman, Thomas P Jensen, Vivekanand Jha, Peter Jüni, Ajay J Kirtane, Patrick Lawler, Grégoire Le Gal, Ramon Lecumberri, Steven R Lentz, Renato D Lopes, Elizabeth Lorenzi, Marco Marietta, Carlos Henrique Miranda, Nuccia Morici, Susan C Morpeth, David A Morrow, Zoe K McQuilten, Nuria Muñoz-Rivas, Matthew D Neal, Suman Pant, Sahil A Parikh, Usha Perepu, Parham Sadeghipour, Sanjum Sethi, Michelle Sholzberg, Alex C Spyropoulos, Gregg W Stone, Azita Hajhossein Talasaz, Steven Tong, James Totterdell, Balasubramanian Venkatesh, Maddalena Alessandra Wu, Ryan Zarychanski, Stephane Zuily, Julie Viry, Jamie Rylance, AdhikariNeill K JNKJ, Janet V Diaz, John C Marshall, SterneJonathan A CJAC, and Srinivas Murthy.
• Ann. Intern. Med. 2025 Jan 1; 178 (1): 596959-69.

BackgroundReported results of clinical trials assessing higher-dose anticoagulation in patients hospitalized for COVID-19 have been inconsistent.PurposeTo estimate the association of higher- versus lower-dose anticoagulation with clinical outcomes.Data SourcesRandomized trials were identified from the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov with no restriction by trial status or language.Study SelectionEligible randomized trials assigned patients hospitalized for COVID-19 to higher- versus lower-dose anticoagulation.Data Extraction20 eligible trials provided data in a prospectively agreed format. Two further studies were included based on published data. The primary outcome was all-cause mortality 28 days after randomization. Secondary outcomes were progression to invasive mechanical ventilation or death, thromboembolic events, and major bleeding.Data SynthesisTherapeutic- compared with prophylactic-dose anticoagulation with heparins reduced 28-day mortality (OR, 0.77 [95% CI, 0.64 to 0.93]; I 2 = 29%; 11 trials, 6297 patients, of whom 5456 required low or no oxygen at randomization). The ORs for 28-day mortality were 1.21 (CI, 0.93 to 1.58; I 2 = 0%) for therapeutic-dose compared with intermediate-dose anticoagulation (6 trials, 1803 patients, 843 receiving noninvasive ventilation at randomization) and 0.95 (CI, 0.76 to 1.19; I 2 = 0%; 10 trials, 3897 patients, 2935 receiving no or low oxygen at randomization) for intermediate- versus prophylactic-dose anticoagulation. Treatment effects appeared broadly consistent across predefined patient subgroups, although some analyses were limited in power. Higher- compared with lower-dose anticoagulation was associated with fewer thromboembolic events, but a greater risk for major bleeding.ConclusionTherapeutic-dose compared with prophylactic-dose anticoagulation reduced 28-day mortality. Mortality was similar for intermediate-dose compared with prophylactic-dose anticoagulation and higher for therapeutic-dose compared with intermediate-dose anticoagulation, although this comparison was not estimated precisely.Primary Funding SourceNo direct funding. (PROSPERO: CRD42020213461).

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