Table 1.
Randomized clinical trials of anticoagulant therapy in COVID-19 patients.
| Drugs | Dose/Patients | Interval§ (days) | Primary outcomes | Major bleeding& | |
|---|---|---|---|---|---|
| Outpatients | |||||
| Connors et al., 2021 (ACTIV-4B) | Apixaban | Control: 164 Prophylactic: 165 Therapeutic: 164 |
10 | AT did not reduce major thromboembolism or death | 0 vs. 0 vs. 0 |
| Ananworanich et al., 2021 | Rivaroxaban | Control: 222 Prophylactic: 222 |
<10 | AT did not reduce disease progression, but increase asymptomatic participants* | 0 vs. 0 |
| Gonzalez-Ochoa et al., 2021 | Sulodexide | Control: 119 Therapeutic: 124 |
<3 | Fewer patients with AT required hospitalization and supplemental oxygen* | 0 vs. 1 |
| Non-critically ill patients | |||||
| REMAP-CAP Investigators et al., 2021a | LMWH | Prophylactic: 1050 Therapeutic: 1181 |
<3 | Therapeutic AT increased the probability of survival or organ support-free days* | 0.9% vs. 1.9% |
| Sholzberg et al., 2021 (RAPID) | LMWH | Prophylactic: 237 Therapeutic: 228 |
1.5 | Mortality (vs. Prophylactic): OR: 0.22 (0.07–0.65)* |
1.7% vs. 0.9% |
| Spyropoulos et al., 2021 (HEP-COVID) | Enoxaparin | Prophylactic: 124 Therapeutic: 129 |
<3 | Therapeutic anticoagulation significantly reduced major thromboembolism and death* | 1.6% vs. 4.7% |
| Marcos-Jubilar et al., 2022 | Bemiparin | Prophylactic: 33 Therapeutic: 32 |
6 vs. 5& | Mortality (vs. Prophylactic): OR: 2.13 (0.18–24.76) |
0 vs. 0 |
| Lopes et al., 2021 (ACTION) | Rivaroxaban Enoxaparin¦ |
Prophylactic: 304 Therapeutic: 311 |
<3 | Mortality (vs. Prophylactic): RR: 1.49 (0.90–2.46) |
2% vs. 8%* |
| Severe patients | |||||
| INSPIRATION Investigators et al., 2021 | Enoxaparin | Prophylactic: 276 Intermediate: 286 |
4 | Mortality (vs. Prophylactic): HR: 1.06 (0.83–1.36) |
2.5% vs. 1.4% |
| Perepu et al., 2021 | Enoxaparin | Prophylactic: 86 Intermediate: 87 |
5 | Mortality (vs. Prophylactic): OR: 0.66 (0.30–1.45) |
2.3% vs. 2.3% |
| REMAP-CAP Investigators et al., 2021b | LMWH | Prophylactic: 567 Therapeutic: 536 |
<3 | Therapeutic AT did not increase probability of survival or organ support-free days | 2.3% vs. 3.8% |
| Lemos et al., 2020 (HESACOVID) | Enoxaparin | Prophylactic: 10 Therapeutic: 10 |
<4 | Therapeutic AT significantly increased PaO2/FiO2 ratio | 0 vs. 0 |
*
p < 0.05.
§
The median time from diagnosis to initiation of study treatment.
&
vs. Prophylactic/control.
¦
Clinically stable patients received therapeutic rivaroxaban and clinically unstable ones received therapeutic enoxaparin or unfractionated heparin.
AT, anticoagulation; LMWH, low molecular weight heparin; OR/HR, odds/hazard ratio; and RR, relative risk.