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

Abstract

ObjectivesTo 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). Study Design and SettingTarget 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. ResultsA 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. ConclusionEscalating 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.