A retrospective real-world major bleeding (MB) comparison of direct oral anticoagulants (DOAC) and low molecular weight heparin (LMWH) in genitourinary cancer-associated venous thromboembolism (GU-CAVTE) with reported randomized clinical trials (RTC).
Authors: Dashkevych Ulyana , Brucks Eric , Saboda Kathylynn , Chipollini Juan , Babiker Hani M. , McBride Ali , Recio Boiles Alejandro 
Published: March 2021

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Background: MB is a serious complication in patients with CAVTE receiving treatment with DOAC or LMWH. The most recent meta-analysis of the four major RCT showed that MB events rate were similar among the DOAC and LMWH group, however, it was noted that MB occurred at GU site 4.9 times more in DOAC than LMWH patients. While GUCA (e.g. bladder and testicular) are considered to be high-risk based on the Khorana Score, they were underrepresented among the RCT ( < 12%). We present a Real-World retrospective cohort study analyzing the MB rates in patients presenting with GU-CAVTE treated either by a DOAC or LMWH compared to those of the RTC. Methods: We performed a retrospective chart review of patients with a diagnosed GUCA and VTE who presented to The University of Arizona Cancer Center (UACC) and were subsequently placed on anticoagulant therapy with either a DOAC or LMWH from 11/2013-4/2020. MB outcome was defined as documented Hgb drop of ≥2 g/dL, ≥2 units of PRBC, MB in a critical site, or contributing to death. MB was extracted and compared from the SELECT D, ADAM VTE, and Caravaggio for DOAC and Hokusai for the LMWH control arm with the GUCA subgroup. Recurrent VTE was collected. In situations where there was insufficient data to categorize individuals, those individuals were excluded from the analysis. The proportion of MB reported in each study were compared using a binomial test. Results: Our review included 56 patients with similar baseline characteristics to the RCT, who were prescribed enoxaparin (n = 13), apixaban (n = 27) and rivaroxaban (n = 16). Our UACC data was compared to the RCT reported MB outcomes with rivaroxaban (12% vs 8%, [p = 0.63]), apixaban (11% vs 6%, [p = 0.40]), and LMWH (both 0 vs 1% [p = 0.67]). No statistical difference among DOAC selection [p = 0.90]. Our UACC rate of MB in patients with GUCA for both DOAC combined versus LWMH were 11.6% (5/43) and 0% [p = 0.1910], compared to the RCT GU subgroup was 5.7% (6/104) [p = 0.02] and 0.6% (1/175) [p = 1.0], respectively. Furthermore, our data found no statistical significance difference among the recurrent VTE rate among DOAC, LMWH, UACC Retrospective or RCT events. Conclusions: In agreement with the four major RCT, our study demonstrated that patients with high-risk GUCA and underlying VTE treated with a DOAC had a non-significant higher incidence of MB compared to those treated with LMWH. Further, our Real-World experience showed that GUCA DOAC had a significantly higher MB event rate compared to the RCT subgroup population. We acknowledge there are inherent biases in all retrospective studies and RCT. These data support the idea that DOAC should be further studied and used with caution in patients with a high risk of bleeding. We recommend LMWH being the safest anticoagulation modality for High-Risk Bleeding GU malignancy.