Review of Anticoagulation in Patients With COVID-19: Key Points
- Farkouh ME, Stone GW, Lala A, et al.
- Anticoagulation in Patients With COVID-19: JACC Review Topic of the Week. J Am Coll Cardiol 2022;79:917-928.
The following are key points to remember from this review on anticoagulation in patients with coronavirus disease 2019 (COVID-19):
- COVID-19 has led to unprecedented morbidity and mortality with >200 million cases and 4 million deaths worldwide. Apart from acute respiratory distress syndrome, COVID-19 is associated with thromboembolic disease.
- Viral entry through the endothelium may cause inflammation and vascular injury. Mononuclear cell activation can also trigger cytokine release and cytokine storm. Collectively, these lead to a prothrombotic state for patients with COVID-19. Other mechanisms may also contribute, including complement activation and anti-phospholipid antibodies.
- COVID-19 coagulopathy is categorized by laboratory abnormalities including increased levels of fibrinogen and D-dimer, mild prolongation of prothrombin time or activated partial thromboplastin time, and mild thrombocytopenia. Patients admitted with COVID-19 who have elevated D-dimer or troponin levels are associated with worse outcomes, including mortality.
- The incidence of venous thromboembolism in patients hospitalized with COVID-19 was 17% in a meta-analysis of 49 studies. The rate was higher in patients with critical illness (27.9%) as compared to those who were not critically ill (7.1%).
- Clinicians and researchers have explored the role of antithrombotic therapy to prevent COVID-19–associated thromboembolism. This includes use of standard prophylactic-dose anticoagulation, intermediate-dose anticoagulation, and therapeutic-dose anticoagulation given for prophylactic purposes.
- Several large observational studies have suggested that prophylactic-dose enoxaparin was associated with lower rates of intubation and death. However, the role of higher-dose prophylactic anticoagulation in preventing poor outcomes is not clear from observational studies.
- Two large trials have explored the use of anticoagulation outside of the hospital setting for patients with COVID-19. The MICHELLE trial compared rivaroxaban 10 mg daily for 35 days after hospital discharge with placebo and found a 67% relative risk reduction in their primary outcome without an increased risk of bleeding. Conversely, the ACTIV-4B study compared apixaban versus placebo in ambulatory patients with mild COVID-19 but was ended early due to a very low rate of thromboembolic events that did not meaningfully differ between treatment arms.
- Several trials have compared intermediate- or treatment-dose anticoagulation with standard prophylactic-dose anticoagulation in hospitalized patients with COVID-19. The multiplatform trial included 2,219 patients hospitalized without critical illness and found an increase in the number of organ support-free days with treatment-dose anticoagulation. In a concurrent trial of 1,098 critically ill patients in the multi-platform trial, treatment-dose anticoagulation did not increase the number of organ support-free days as compared to standard prophylaxis.
- In the HEP-COVID trial of 257 patients hospitalized with COVID-19 who required oxygen support and other risk factors, therapeutic-dose enoxaparin led to lower rates of thromboembolism and death as compared to standard-dose thromboprophylaxis. Similarly, in the RAPID trial of 465 patients with moderately ill COVID-19 and elevated D-dimer, therapeutic-dose heparin led to numerically (but not statistically) lower rates of death, intensive care unit (ICU) admission, and mechanical ventilation as compared to standard prophylactic-dose heparin.
- The authors are conducting a large-scale, prospective, multicenter, open-label randomized clinical trial of patients hospitalized with COVID-19 who will be randomized to receive prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary effectiveness outcome will be a composite of all-cause mortality, requirement for intensive care, systemic thromboembolism, or ischemic stroke within 30 days.
Keywords: Anticoagulants, Brain Ischemia, COVID-19, Critical Illness, Cytokines, Endothelium, Enoxaparin, Fibrinogen, Fibrinolytic Agents, Intubation, Ischemic Stroke, Partial Thromboplastin Time, Prothrombin Time, Respiration, Artificial, Risk Factors, Rivaroxaban, Secondary Prevention, Stroke, Thrombocytopenia, Troponin, Vascular Diseases, Venous Thromboembolism
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