Comparison of Enoxaparin and Unfractionated Heparin in Hospitalized Patients in Terms of Clinical and Cost Effectiveness
Thromboembolic disease represents one of the severe complications in hospitalized patients. Low molecular weight and unfractionated heparin are most commonly used during hospitalization as part of pharmacological thromboprophylaxis. An extensive study conducted in the United States evaluated the clinical and cost-effectiveness and safety of both therapy modalities in hospitalized patients at risk of thromboembolic disease.
Introduction
Thromboembolic disease manifesting as deep vein thrombosis and pulmonary embolism increases morbidity and mortality in hospitalized patients and also raises the cost of their treatment. Hospitalization for more severe illnesses, even non-surgical ones, is associated with a temporary increase in the risk of thromboembolic disease. It is estimated that 10–20% of these patients develop thromboembolic disease in the absence of thromboprophylaxis.
According to the recommendations of expert societies, routine thromboprophylaxis is suitable for individuals with an increased risk of thromboembolic disease. Low molecular weight heparin (LMWH) or unfractionated heparin is most commonly administered as thromboprophylaxis. Earlier studies have demonstrated higher clinical efficacy and lower treatment costs with enoxaparin (from the LMWH group) compared to unfractionated heparin, without increased risk of adverse effects. The extensive research cited below evaluated the efficacy and safety of both treatment modalities in current real-world clinical practice settings.
Methodology and Study Goals
The retrospective cohort study included patients ≥ 18 years old who were hospitalized for at least 6 days from January 2010 to August 2016. They were included based on evaluating several excluding criteria to limit the risk of bias. After discharge from the healthcare facility, they were followed for an additional 90 days to assess the potential need for rehospitalization.
The primary goal of the study was to determine the incidence of thromboembolic disease during hospitalization and rehospitalization. Secondary goals included overall mortality during hospitalization and mortality due to pulmonary embolism during hospitalization and rehospitalization. Economic parameters included the total cost of hospitalization and rehospitalization and the cost of pharmacological prophylaxis during hospitalization. Safety parameters evaluated the incidence of severe bleeding and heparin-induced thrombocytopenia.
Results
The study included a total of 376,858 patients, with 64% undergoing prophylaxis with enoxaparin (n = 242,474) and 36% with unfractionated heparin (n = 134,384). Among patients on enoxaparin, the incidence of thromboembolic disease during hospitalization was 0.47%, overall mortality during hospitalization was 3.58%, and mortality associated with pulmonary embolism was 0.03%; in the group with unfractionated heparin, it was 0.76%, 5.47%, and 0.08%, respectively. Multivariate regression analysis demonstrated a significant reduction in the risk of thromboembolic disease by 15% (odds ratio [OR] 0.85; p = 0.001), overall mortality during hospitalization by 9% (OR 0.91; p < 0.0001), and mortality associated with pulmonary embolism by 33% (OR 0.67; p = 0.015) in patients on enoxaparin compared to those on unfractionated heparin.
Rehospitalization for any reason was recorded in 105,836 (44%) patients on enoxaparin and 57,763 (43%) on unfractionated heparin. During rehospitalization, the incidence of thromboembolic disease in the enoxaparin group was 2.71%, overall mortality during hospitalization was 4.32%, and mortality associated with pulmonary embolism was 0.18%; in the unfractionated heparin group, it was 3.15%, 4.90%, and 0.15%, respectively. Rehospitalization demonstrated a significant reduction in the risk of thromboembolic disease by 10% (OR 0.90; p = 0.0022) in patients on enoxaparin compared to those on unfractionated heparin, but an 8% increase in the risk of mortality during hospitalization (OR 1.08; p = 0.008).
Severe bleeding was observed during hospitalization in 5,328 (2.2%) patients on enoxaparin and 6,281 (4.7%) on unfractionated heparin (p < 0.0001). In the case of rehospitalization, severe bleeding was recorded in 3,161 (3%) patients on enoxaparin and 2,374 (4.1%) patients on unfractionated heparin (p < 0.0001). Thus, in the enoxaparin group, there was a 41% lower risk of bleeding during the initial hospitalization (OR 0.59; 95% confidence interval [CI] 0.57–0.62) and a 19% lower risk during rehospitalization (OR 0.81; 95% CI 0.77–0.86).
Heparin-induced thrombocytopenia was observed in 105 (0.04%) patients on enoxaparin and 172 (0.1%) on unfractionated heparin (p < 0.0001). Similarly, this was also the case during rehospitalization (0.06% vs. 0.2%; p < 0.0001). Regarding economic parameters, patients on enoxaparin had significantly lower average total costs of hospitalization, even during rehospitalization. Higher adjusted average costs associated with pharmacoprophylaxis during hospitalization were observed in patients on enoxaparin.
Conclusion
In this study, enoxaparin administration was associated with a significantly lower risk of thromboembolic disease, overall mortality, and mortality associated with pulmonary embolism during hospitalization, as well as a lower average total cost of hospitalization compared to unfractionated heparin.
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Source: Veeranki S. P., Xiao Z., Levorsen A. et al. Real-world comparative effectiveness and cost comparison of thromboprophylactic use of enoxaparin versus unfractionated heparin in 376,858 medically ill hospitalized US patients. Am J Cardiovasc Drugs 2021; 21 (4): 443–452, doi: 10.1007/s40256-020-00456-4.
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