Thromboprophylaxis with standard-dose vs. flexible-dose heparin for hospitalized COVID-19 patients: a target trial emulation

• Published in: Journal of clinical epidemiology Vol. 151; pp. 96 - 103
• Main Authors: Martínez-Alés, Gonzalo, Domingo-Relloso, Arce, Quintana-Díaz, Manuel, Fernández-Capitán, Carmen, Hernán, Miguel A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2022; Elsevier Limited
• Subjects: Abnormalities; Adult; Anticoagulants; Anticoagulants - adverse effects; Clinical practice guidelines; Comorbidity; Coronaviruses; COVID-19; COVID-19 drug treatment; COVID-19 Testing; Electronic health records; Epidemiological methods; Epidemiology; Health risks; Heparin; Heparin - adverse effects; Heparin, Low-Molecular-Weight - therapeutic use; Hospitalization; Hospitals; Humans; Intensive care; Laboratories; Low–molecular weight heparin; Lymphocytes; Medical prognosis; Molecular weight; Mortality; Mortality risk; Original; Pneumonia; Proteins; Risk; Statistical analysis; Strategy; Target trial emulation; Thrombocytopenia; Thromboembolism; Thrombosis; Thrombosis - drug therapy; Thrombosis - prevention & control; Venous Thromboembolism - drug therapy; COVID-19; Low–molecular weight heparin; Anticoagulants; COVID-19 drug treatment; Epidemiological methods; Target trial emulation
• ISSN: 0895-4356; 1878-5921
• DOI: 10.1016/j.jclinepi.2022.08.006

To compare mortality of hospitalized COVID-19 patients under two low–molecular weight heparin (LMWH) thromboprophylaxis strategies: standard dose and variable dose (standard dose increased to intermediate dose in the presence of laboratory abnormalities indicating an increased thrombosis risk). Target trial emulation using observational data from 2,613 adults admitted with a COVID-19 diagnosis in Madrid, Spain between March 16 and April 15, 2020. A total of 1,284 patients were eligible. Among 503 patients without increased baseline thrombotic risk, 28-day mortality risk (95% confidence interval [CI]) was 9.0% (6.6, 11.7) under the standard dose strategy and 5.6% (3.3, 8.3) under the variable dose strategy; risk difference 3.4% (95% CI: −0.24, 6.9); mortality hazard ratio 1.61 (95% CI: 0.97, 2.89). Among 781 patients with increased baseline thrombotic risk, the 28-day mortality risk was 25.8% (22.7, 29.0) under the standard dose strategy and 18.1% (9.3, 28.9) under the intermediate dose strategy; risk difference 7.7% (95% CI: −3.5, 17.2); mortality hazard ratio 1.45 (95% CI: 0.81, 3.17). Major bleeding and LMWH-induced coagulopathy were rare under all strategies. Escalating anticoagulation intensity after signs of thrombosis risk may increase the survival of hospitalized COVID-19 patients. However, effect estimates were imprecise and additional studies are warranted. •Clinical guidelines recommend thromboprophylaxis with standard-dose low–molecular weight heparin (LMWH) for hospitalized COVID-19 patients.•Whether LMWH dose should be escalated to an intermediate nontherapeutic dose in presence of increased thrombosis risk remains under debate.•Using electronic health records, we estimated a lower mortality risk under a strategy that increased standard-dose LMWH to intermediate dose in the presence of increased thrombosis risk than under standard-dose anticoagulation.•Escalating the intensity of anticoagulation after signs of thrombosis risk may increase the survival of COVID-19 hospitalized patients.