Prophylactic Anticoagulation for COVID-19 Pneumonia: The Case for High Dose

A recent clinical trial conducted in France examined the effectiveness of different anticoagulation therapies for patients with hypoxemic COVID-19 pneumonia.¹

The study sought to determine whether high-dose prophylactic anticoagulation (HD-PA) or therapeutic anticoagulation (TA) reduced mortality or disease duration compared to standard-dose prophylactic anticoagulation (SD-PA).

Findings suggest that high-dose prophylactic anticoagulation may be the most effective anticoagulation therapy for patients with hypoxemic COVID-19 pneumonia, as it reduces the risk of de novo thrombosis without significantly increasing the risk of bleeding.

Therefore, the investigators led by Vincent Labbé, MD, Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire Tenon, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, stated this clinical trial supports the routine empirical use of HD-PA in patients with severe hypoxemic COVID-19 pneumonia.

High-dose Prophylactic Anticoagulation Shows Favorable Outcomes

In addition to assessing the therapies' efficacy in reducing disease duration or mortality, investigators examined whether therapeutic anticoagulation outperformed high-dose prophylactic anticoagulation.

While therapeutic anticoagulation showed similar probabilities of a favorable outcome compared with both therapies, it did not outperform treatment with high-dose prophylactic anticoagulation, which demonstrated significantly better net clinical outcome by decreasing the risk of de novo thrombosis.

Specifically, the 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).

The investigation also found HD-PA and TA use significantly reduced thrombosis compared with SD-PA, with an absolute difference of -14.7 (95% CI -6.2 to -23.2) for both treatments. The use of HD-PA significantly reduced net clinical outcome compared with SD-PA, with an absolute difference of -13.5 (95% CI -2.6 to -24.3).

Comparing Anticoagulation Therapies for COVID-19 Pneumonia

The ANTICOVID study was a randomized clinical open-label trial that included 339 patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram. Patients were recruited from 23 health centers in France from April-December 2021.

Of the patients randomized, 334 were included in the primary analysis—114 in the SD-PA group, 110 in the HD-PA group, and 110 in the TA group. At randomization, 90% of the patients were in the intensive care unit (ICU).

Patients were randomized 1:1:1 to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days. The main outcomes and measures were a hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. The main secondary outcome was net clinical outcome at day 28, which was a composite of thrombosis, major bleeding, and all-cause death.

"HD-PA use provided the best net benefit, driven by a 4-fold reduction in de novo thrombosis (mostly, pulmonary artery) compared with SD-PA use, with no increase in major bleeding; and TA use did not provide additional benefit compared with HD-PA use," investigators wrote.

References:

1. Labbé V, Contou D, Heming N, et al. Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia: The ANTICOVID Randomized Clinical Trial. JAMA Intern Med. Published online March 22, 2023. doi:10.1001/jamainternmed.2023.0456