Variable Dose Thromboprophylaxis May Increase Survival in Patients With COVID-19

Patients hospitalized with COVID-19 at increased risk for thrombosis who received variable dose thromboprophylaxis had a decreased risk of mortality.

A variable dose thromboprophylaxis strategy may increase survival rates among patients hospitalized with COVID-19 at increased risk for thrombosis, according to study findings published in the Journal of Clinical Epidemiology.

In an observational study, researchers compared the effects of standard vs variable dose strategies of low-molecular-weight heparin (LMWH) on the risk of 28-day mortality in patients hospitalized with COVID-19 infection. Patients in both the standard and variable dose groups initially received subcutaneous enoxaparin (4000 IU) once daily, but those in the variable dose group had their dose increased (6000 IU) if baseline laboratory results showed an increased thrombotic risk.

Among patients with (n=781) and without (n=503) an increased thrombotic risk at baseline, the median age was 70 (IQR, 59-81) and 61 (IQR, 51-76) years, 60.2% and 47.1% were men, 52.5% and 6.2% had hematologic disease, and the median Charlson comorbidity index score was 3 (IQR, 2-5) and 2 (IQR, 1-4), respectively. In addition, baseline D-dimer concentrations were 1088.5 (IQR, 609.5-2159.5) and 540.0 (IQR, 368.0-802.0) ng/mL among patients with vs without an increased thrombotic risk at baseline, respectively.

For patients without an increased baseline thrombotic risk, the risk of 28-day mortality was 9.0% (95% CI, 6.6-11.7) and 5.6% (95% CI, 3.3-8.3) among those who received standard vs variable LMWH, respectively (hazard ratio [HR], 1.58; 95% CI, 0.93-2.88). The risk of 28-day mortality among patients with an increased baseline thrombotic risk was 25.8% (95% CI, 22.7-22.9) and 18.1% (95% CI, 9.3-28.9) among those who received standard vs variable LMHW, respectively (HR, 1.45; 95% CI, 0.81-3.17).

[O]ur results suggest that escalating the intensity of anticoagulation after detection of laboratory markers of thrombosis risk increases survival among non-critical COVID-19 hospitalized patients.

Adverse events among patients without an increased baseline thrombotic risk included 1 episode of major active bleeding, as well as 5 and 2 episodes of nonclinically and clinically significant coagulopathy, respectively. For patients with an increased baseline thrombotic risk, the number of episodes of major active bleeding (3 vs 0), clinically significant coagulopathy (11 vs 1), and nonclinically significant coagulopathy (25 vs 3) was increased among those who received standard vs variable LMWH, respectively.

The HR of 28-day mortality associated with standard vs variable LMWH was 1.25 (95% CI, 0.56-3.07) among patients with an increased baseline thrombotic risk after the analysis was restricted to only those with severe COVID-19 pneumonia.

Limitations include the observational design, potential residual confounding, and the exclusion of mortality events that may have occurred following hospital discharge.

“[O]ur results suggest that escalating the intensity of anticoagulation after detection of laboratory markers of thrombosis risk increases survival among non-critical COVID-19 hospitalized patients,” the researchers concluded.

References:

Martínez-Alés G, Domingo-Relloso A, Quintana-Díaz M, Fernández-Capitán C, Hernán MA, [email protected] Group. Thromboprophylaxis with standard-dose vs. flexible-dose heparin for hospitalized COVID-19 patients: a target trial emulation. J Clin Epidemiol. 2022;151:96-103. doi:10.1016/j.jclinepi.2022.08.006