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Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia

A randomized trial of 334 patients with severe hypoxemic COVID-19 pneumonia supports the empirical use of high-dose prophylactic anticoagulation (HD-PA). “The results of the ANTICOVID RCT indicate that neither [high-dose prophylactic anticoagulation (HD-PA)] nor [therapeutic anticoagulation (TA)] use improved the primary hierarchical outcomes—death and time to clinical improvement—compared with SD-PA use among patients with hypoxemic COVID-19 pneumonia and with no initial macrovascular thrombosis,” the authors conclude. “However, HD-PA use compared with SD-PA use was associated with a better net clinical benefit that was driven by a significantly lower rate of thrombosis and with a low risk of major bleeding. There was no additional benefit of TA use compared with HD-PA use. The results of the main analysis were consistent with the findings in the subgroup of critically ill patients, which represented 90% of our study population.”

At 23 health centers in France from Apr. 14 to Dec. 13, 2021, investigators randomized 339 patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram. Participants randomly received SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days, with these effects on a hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28: “Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, −14.7 [95% CI −6.2 to −23.2] and −14.7 [95% CI −6.2 to −23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, −13.5; 95% CI −2.6 to −24.3).”

Editorial: “These findings align with prior observations made throughout the COVID-19 pandemic that patients infected with SARS-CoV-2 who are hypoxemic and require hospitalization have a heightened risk for venous thromboembolism, including catheter-associated thrombosis, and that increasing the intensity of anticoagulation reduces the risk,” editorialists write. “We have learned much since the first reports in early 2020 of an outbreak of a new pneumonic illness in Wuhan, China, caused by SARS-CoV-2. The ANTICOVID trial provides additional insights into the optimal dose of anticoagulant therapy for treating patients hospitalized with hypoxemic COVID-19 pneumonia: a higher dose of prophylactic LMWH (twice the standard dose) is necessary and sufficient to prevent thrombotic complications without increasing the rate of major bleeding. However, additional studies are needed to address the questions that remain unanswered.”

Source: JAMA Internal Medicine