+Thrombotic events such as a deep vein thrombosis and pulmonary embolisms are common in patients hospitalized with COVID-19. Severely ill patients with COVID-19 often experience thrombosis despite receiving the recommended thromboprophylaxis of a standard dose of low-molecular-weight heparin (LMWH). There is limited and conflicting data about the efficacy of utilizing a therapeutic dose of anticoagulation in such patients. Therefore, this randomized-controlled trial aimed to test the hypothesis that a therapeutic dose would be beneficial for inpatients with COVID-19 demonstrating high-risk features or with critical illness. Eligible participants were hospitalized nonpregnant adults diagnosed with COVID-19 requiring supplemental oxygen and a plasma D-dimer level of greater than 4 times the upper limit of normal or a sepsis-induced coagulopathy score of 4 or greater. A total of 253 participants (mean [SD] age, 66.7 [14.0] years; 53.8% males [136]) were included in the analysis. 124 participants were assigned to receive a prophylactic dose of LMWH (control group) while 129 were assigned to receive a greater, therapeutic dose of LMWH (enoxaparin 1 mg/kg subcutaneously twice daily; intervention group). The primary outcome measured was incidence of thrombotic events (venous [VTE] or arterial thromboembolism [ATE]) or death from any cause within 30+2 days after randomization. It was found that a therapeutic dose of LMWH significantly reduced the incidence of thromboembolism compared to a prophylactic dose (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; p<0.001). There was no significant difference in death between the two groups. Secondary outcomes included the composite primary outcome within 14 days after admission, progression to acute respiratory distress syndrome, new-onset atrial fibrillation, acute kidney injury, nonfatal cardiac arrest, endotracheal intubation, extracorporeal membrane oxygenation, and rehospitalization within 30 ± 2 days. Therapeutic-dose LMWH was found to reduce the incidence thromboembolism 14 from hospitalization (36.3% vs 23.3%; RR, 0.64; 95% CI, 0.43-0.95; p =0.02). There were no statistically significant differences in the remaining secondary outcomes. Finally, the principal safety outcome was major bleeding based on International Society on Thrombosis and Haemostasis criteria within 30 ± 2 days after randomization. There were 8 (3.2%) major bleed events, 2 (1.6%) in the prophylactic-dose vs 6 (4.7%) in the therapeutic-dose groups (RR, 2.88; 95% CI, 0.59-14.02; P = .17), none of which were fatal. Overall, this was a well-designed trial that concluded therapeutic-dose LMWH would benefit hospitalized COVID-19 with elevated D-dimer levels by reducing thromboembolic events without increasing major bleeding. Thus, it provides support for changing current standard of care for such patients.
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