Comparative safety of enoxaparin versus other low-molecular-weight heparins in cancer-associated venous thromboembolism: a real-world cohort study from RIETE

Background: Low-molecular-weight heparins (LMWHs) are widely used in the treatment of cancer-associated venous thromboembolism (VTE), yet their long-term safety profiles remain insufficiently compared in clinical practice. Objectives: The primary outcome was major bleeding over a 6-month follow-up. Secondary outcomes included VTE recurrence, non-major clinically relevant bleeding, and all-cause mortality. Methods: We analyzed 7287 patients with active cancer and acute VTE from the RIETE registry (2009-2022) who were treated with full-dose enoxaparin ( = 5628) or tinzaparin/dalteparin ( = 1659). Analyses were adjusted using multivariable Cox models, Fine-Gray competing risk models, frailty models clustered by center, and propensity score approaches. Conclusion: In this large, observational study, enoxaparin, particularly in twice-daily regimens, was associated with significantly increased risks of bleeding and mortality compared to tinzaparin/dalteparin. These findings may help refine LMWH selection and dosing strategies in patients with cancer-associated VTE and warrant further investigation in prospective studies.