Background:

In critically ill patients, thromboprophylaxis is vital for preventing venous thromboembolism. Unfractionated heparin (UH) and enoxaparin (EP) can differ in the prognostic outcomes of the patients. This meta-analysis aims to compare the efficacy and safety of UH versus EP in terms of mortality, incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), overall Venous Thromboembolism (VTE), and post-treatment bleeding.

Methods:

We conducted a systematic review and meta-analysis following PRISMA guidelines. A comprehensive literature search was performed across PubMed, Embase, and Cochrane Library databases up to July 2024 for studies comparing outcomes between unfractionated heparin and enoxaparin. The analysis included 13 studies including 5 retrospective cohort studies, 1 prospective cohort study, and 7 randomized clinical trials. Inclusion criteria were adults (≥18 years old) and studies published in English, randomized controlled trials (RCTs), cohort studies, case-control studies, and cross-sectional studies. Exclusion criteria included patients (<18 years old), patients on warfarin therapy, hospital stays of ≤2 days, studies not involving UFH or LMWH for VTE prophylaxis, and non-original studies. The quality assessment was conducted independently by two reviewers using the New-castle Ottawa scale and Cochrane RoB2. The outcomes included bleeding complications, mortality, VTE, PE, and DVT. A random-effects meta-analysis assessed odds ratio (ORs) and 95% confidence intervals to compare all the outcomes between these two groups.

Results:

Out of the 13 included studies, 65331 participants were included with a female predominance of 51.68%. The mean age of the population is 65.16 (12.85) years. The total number of patients on UFH is 29858 and the total number of patients on enoxaparin is 36180. Our meta-analysis yielded the following results: There was comparable mortality between UH and EP [OR =1.19, 95% CI: 0.91 - 1.55, p = 0.20]. Similar incidence rates were reported for Deep Vein Thrombosis (DVT) [OR = 1.81, 95% CI: 0.87 - 3.78, p = 0.11] and Pulmonary Embolism (PE) [OR = 1.62, 95% CI: 0.62 - 4.21, p = 0.32], suggesting no significant difference between the two groups. There were comparable incidence rates for venous thromboembolism (VTE) [OR = 2.19, 95% CI: 0.88 - 5.45, p = 0.09], between UH and EP. Post-treatment bleeding had an OR of 1.08 [95% CI: 0.82 - 1.44, p = 0.58], showing no significant difference in post-treatment bleeding between the two treatments. However, sensitivity analysis by one study removal method showed increased odds of DVT [OR = 1.24, 95% CI, 1.03 - 1.49, p = 0.02] and VTE [OR = 1.30, 95% CI: 1.08 - 1.56, p = 0.01] rates for UH.

Conclusion:

Our meta-analysis showed no statistically significant differences between unfractionated heparin and enoxaparin for mortality, DVT, PE, VTE, and post-treatment bleeding. Although sensitivity analysis with one-study removal shows higher rates of DVT and VTE for UH, the results showed that one study should be carefully interpreted, considering one study as a confounder. Clinicians should consider these findings with caution and evaluate patient-specific factors when choosing between UH and EP for thromboprophylaxis in critically ill patients.

Disclosures

No relevant conflicts of interest to declare.

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2024
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