Comparative Efficacy of Direct Oral Anticoagulants and Low-Molecular-Weight Heparin in Cancer-Associated Thromboembolism: A Systematic Review and Meta-Analysis

Figure 1. PRISMA diagram illustrating the selection process for inclusion of studies in the meta-analysis The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram showcases the step-by-step procedure employed to identify and select studies for inclusion in the meta-analysis. Initially, 2500 articles were identified through a literature review. After removing duplicates and carefully evaluating titles and abstracts, 11 studies that met the inclusion criteria were chosen.

Figure 2. Representation of the Cochrane risk of bias assessment for randomized controlled trials The figure highlights the presence of trials with moderate-to-high quality, indicating a reliable and robust study design. Source: references [15-18,21-23,25].

Figure 3. Funnel plots of primary outcomes (A) Venous thromboembolism recurrence and (B) deep vein thrombosis. RR: risk ratio, SE: standard error.

Figure 4. Funnel plots of primary outcomes (A) pulmonary embolism and (B) major bleeding. RR: risk ratio, SE: standard error.

Figure 5. Funnel plots of primary outcomes: clinically relevant non-major bleeding RR: risk ratio, SE: standard error.

Figure 6. Forest plot of VTE recurrence The results of the comparative analysis, indicate a significant reduction in the risk of VTE recurrence associated with the use of DOACs compared to LMWH. The findings further revealed that regardless of whether dalteparin or enoxaparin was utilized as the control drug, DOACs consistently exhibited a lower risk of VTE recurrence. VTE: venous thromboembolism, DOACs: direct oral anticoagulants, LMWHs: low molecular weight heparins, RR: relative risk, CI: confidence interval, M-H: Mantel Hansel. Source: references [15-25].

Figure 7. Forest plot of incidence of DVT The figure illustrates the comparison between the use of DOACs and LMWH, revealing a significantly lower risk of DVT with DOACs. Notably when dalteparin was employed as the control arm, the reduced risk of DVT was particularly pronounced. DVT: deep vein thrombosis, DOACs: direct oral anticoagulants, LMWHs: low molecular weight heparins, RR: relative risk, CI: confidence interval, M-H: Mantel Hansel. Source: references [15,17,21,22,24,25].

Figure 8. Forest plot of the risk of PE This figure illustrates that the use of DOACs was associated with a non-significant decrease in the risk of PE. PE: pulmonary embolism, DOACs: direct oral anticoagulants, LMWHs: low molecular weight heparins, RR: relative risk, CI: confidence interval, M-H: Mantel Hansel. Source: references [15,18,21,22,24].

Figure 9. Forest plot of the risk of major bleeding The figure depicts that the use of DOACs was associated with a non-significant increase in the risk of major bleeding. However, subgroup analysis revealed that when enoxaparin was used as the control arm, treatment with DOACs was linked to a non-significant decrease in the risk of major bleeding. In contrast, when dalteparin was used as the control drug, the use of DOACs significantly increased the risk of major bleeding. DOACs: direct oral anticoagulants, LMWHs: low molecular weight heparins, RR: relative risk, CI: confidence interval, M-H: Mantel Hansel. Source: references [15,16,18-25].

Figure 10. Forest plot of the risk of CRNMB The figure illustrates the association between the use of DOACs for treatment and an increased risk of CRNMB compared to LMWHs. Subgroup analysis indicated that this increased risk remained consistent with DOACs, regardless of whether enoxaparin or dalteparin was used as the control drug. CRNMB: clinically relevant non-major bleeding, DOACs: direct oral anticoagulants, LMWHs: low molecular weight heparins, RR: relative risk, CI: confidence interval, M-H: Mantel Hansel. Source: references [15-19,21-23,25].