Evaluation of the safety and effectiveness of direct oral anticoagulants and low molecular weight heparin in gastrointestinal cancer-associated venous thromboembolism

Alejandro Recio-Boiles; Sumana Veeravelli; Jessica Vondrak; Hani M Babiker; Aaron J Scott; Rachna T Shroff; Hitendra Patel; Emad Elquza; Ali McBride

doi:10.4251/wjgo.v11.i10.866

Evaluation of the safety and effectiveness of direct oral anticoagulants and low molecular weight heparin in gastrointestinal cancer-associated venous thromboembolism

World J Gastrointest Oncol. 2019 Oct 15;11(10):866-876. doi: 10.4251/wjgo.v11.i10.866.

Authors

Alejandro Recio-Boiles¹, Sumana Veeravelli², Jessica Vondrak², Hani M Babiker³, Aaron J Scott³, Rachna T Shroff³, Hitendra Patel⁴, Emad Elquza³, Ali McBride⁵

Affiliations

¹ Department of Medicine, Hematology and Medical Oncology, University of Arizona Cancer Center, Tucson, AZ 85724, United States. areciomd@email.arizona.edu.
² Department of Medicine, Internal Medicine Residency Program, University of Arizona, Tucson, AZ 85725, United States.
³ Department of Medicine, Hematology and Medical Oncology, University of Arizona Cancer Center, Tucson, AZ 85724, United States.
⁴ UC San Diego Health Moores Cancer Center, La Jolla, CA 92093, United States.
⁵ University of Arizona College of Pharmacy, Tucson, AZ 85725, United States.

Abstract

Background: Gastrointestinal cancer (GICA) is associated with a higher incidence of venous thromboembolism (VTE) compared to other solid tumors, moreover, recurrent VTE and major bleeding (MB) complications during anticoagulation treatment have an associated increase rate. GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants (DOAC), especially with active cancer therapies.

Aim: To evaluate patient risk factors, effectiveness (VTE) and safety (MB) of DOACs and low molecular weight heparin (LMWH) in patients with active GICA-VTE.

Methods: A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed. Inclusion criteria included active GI cancer diagnosed at any stage or treatment +/- 6 mo of VTE diagnosis, whom were prescribed 6 mo or more of DOACs or LMWH. The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events. Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor.

Results: A total of 144 patients were prescribed anticoagulation, in which 106 fulfilled inclusion criteria apixaban (27.3%), rivaroxaban (34.9%) and enoxaparin (37.7%), and 38 were excluded. Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event, with 62% males, 80% Caucasian, 70% stage IV, pancreatic cancer (40.5%), 30% Khorana Score (≥ 3 points), and 43.5% on active chemotherapy. Sixty-four percent of patients completed anticoagulation therapy (range 1 to 43 mo). Recurrent VTE at 6 mo was noted in 7.5% (n = 3), 6.8% (n = 2) and 2.7% (n = 1) of patients on enoxaparin, apixaban and rivaroxaban, respectively (all P = NS). MB at 6 mo were 5% (n = 2) for enoxaparin, 6.8% (n = 2) for apixaban and 21.6% (n = 8) for rivaroxaban (overall P = 0.048; vs LMWH P = 0.0423; all other P = NS). Significant predictors of a primary or secondary outcome for all anticoagulation therapies included: Active systemic treatment (OR = 5.1, 95%CI: 1.3-19.3), high Khorana Score [≥ 3 points] (OR = 5.5, 95%CI: 1.7-17.1), active smoker (OR = 6.7, 95%CI: 2.1-21.0), pancreatic cancer (OR = 6.8, 95%CI: 1.9-23.2), and stage IV disease (OR = 9.9, 95%CI: 1.2-79.1).

Conclusion: Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.

Keywords: Cancer associated thrombosis; Clinical risk; Direct oral anticoagulants; Gastrointestinal cancer; Low molecular weight heparin; Venous thromboembolism.