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

Objectives: 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).

Study design and setting: 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.

Results: 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.

Conclusion: 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.