Comparative Effectiveness of Direct Oral Anticoagulants Versus Low Molecular Weight Heparins in Cancer Associated Thrombosis (CAT)

Introduction: Venous thromboembolism (VTE) is a fatal comorbidity found in cancer patients. Cancer patients are at an increased risk of developing VTE and bleeding. Low-molecular weight heparins (LMWHs) have been the therapy of choice for cancer associated thrombosis (CAT). Direct-oral anticoagulants (DOACs) are a relatively newer drug class used for the treatment of CAT and may be a reasonable choice of treatment due to their ease of administration and relatively lower cost. There is limited real-world data on the safety and effectiveness of DOACs in cancer patients. This study aimed to study the prevalence and predictors associated with the use of these drugs and also conducted a comparative safety and effectiveness assessment of DOACs versus LMWHs in cancer patients. Methods: This was a retrospective cohort study using SEER Medicare data from the years 2011-2019. Patients diagnosed with cancer (lung, pancreatic, breast, colorectal, prostate, or stomach) who were diagnosed with venous thromboembolism (VTE) and had a prescription of either a LMWH (dalteparin/enoxaparin) or a DOAC (rivaroxaban/edoxaban/ apixaban/dabigatran) were included in the cohort. Patients had to be age >=66 at the time of VTE diagnosis and continuously enrolled in Medicare parts A, B & D one year before the VTE diagnosis. An intention to treat approach was employed in which patients were categorized into either LMWH or the DOAC group depending on the first anticoagulant a patient was started on post CAT diagnosis. Multivariable logistic regression was employed to identify significant factors associated with the use of DOACs versus LMWHs. Patients were followed for 12 months and time to recurrent VTE and bleeding events between these two cohorts were compared using Cox Proportional Hazards Regression and Kaplan Meier Curves. Both the cohorts were balanced for their baseline differences using Inverse Probability of Treatment Weighting (IPTW) approach. Different sensitivity analyses were carried out to assess the robustness of the results. Results: The study cohort included 4892 LMWH and 5080 DOAC treated patients. Patients with more advanced (distant) cancer (OR=0.54, 95% CI=0.41-0.70) were significantly less likely to receive a DOAC as compared patients in the initial stages (In-Situ). Certain cancer types including breast (OR=1.93, 95% CI=1.65-2.25), colorectal (OR=1.50, 95% CI=1.18-1.90) and prostate (OR=2.12, 95% CI=1.77-2.52) were more likely than lung cancer patients to be prescribed DOACs. Patients were significantly more likely to be prescribed a DOAC in 2019 (OR=106.39, 95% CI= 42.19-268.28) and the more recent years as compared to 2011. Rate of recurrent VTE were found to be lower in DOAC patients in comparison to patients on LMWH (HR=0.66, 95% CI=0.54-0.81) in the intent to treat analysis as well as in the different sensitivity analyses. A significant reduction in the risk of major bleeding (HR=0.84, 95% CI=0.73-0.96) was found in the DOAC cohort in the intention to treat analysis, however when patients were censored at discontinuation/treatment switch and observation period was truncated to 12 months the two groups had similar bleeding rates. Conclusion: This study suggests that cancer patients on DOACs had significantly lower rates of recurrent VTE, however bleeding rates were found to be similar. Even in the absence of a consistent clinical guideline physicians have been prescribing DOACs to patients with CAT possibly due to the availability of safety data from clinical trials in the recent years. More research needs to be done on a larger population with more cancer types to assess its effectiveness in a larger cancer population