Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2019; 11(10): 866-876
Published online Oct 15, 2019. 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
Alejandro Recio-Boiles, Sumana Veeravelli, Jessica Vondrak, Hani M Babiker, Aaron J Scott, Rachna T Shroff, Hitendra Patel, Emad Elquza, Ali McBride
Alejandro Recio-Boiles, Hani M Babiker, Aaron J Scott, Rachna T Shroff, Emad Elquza, Department of Medicine, Hematology and Medical Oncology, University of Arizona Cancer Center, Tucson, AZ 85724, United States
Sumana Veeravelli, Jessica Vondrak, Department of Medicine, Internal Medicine Residency Program, University of Arizona, Tucson, AZ 85725, United States
Hitendra Patel, UC San Diego Health Moores Cancer Center, La Jolla, CA 92093, United States
Ali McBride, University of Arizona College of Pharmacy, Tucson, AZ 85725, United States
Author contributions: Recio-Boiles A, Patel H, Elquza E, and McBride A designed and drafted the study concept. Recio-Boiles A, Vondrak J, and Veeravelli S collected the data. Recio-Boiles A, Elquza E, and McBride A performed data analysis and interpretation. Recio-Boiles A, Babiker HM, Scott AJ, Shroff RT, Elquza E, and McBride A contributed to writing, revising and editing the manuscript. All authors helped to perform the research, revision of the manuscript and have approved the final version.
Institutional review board statement: This study has a statement on ethics approval by the Institutional Review Board of University of Arizona Cancer Center, which is a part of the University of Arizona The Human Subjects Protection Program.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Alejandro Recio-Boiles, MD, Assistant Professor of Medicine, Department of Medicine, Hematology and Medical Oncology, University of Arizona Cancer Center, 1515 N Campbell Ave, Tucson, AZ 85724, United States. areciomd@email.arizona.edu
Telephone: +1-520-6264703 Fax: +1-520-6268095
Received: February 26, 2019
Peer-review started: February 27, 2019
First decision: July 31, 2019
Revised: September 3, 2019
Accepted: September 12, 2019
Article in press: September 12, 2019
Published online: October 15, 2019
Processing time: 232 Days and 9 Hours
ARTICLE HIGHLIGHTS
Research background

Venous thromboembolism (VTE) is a common occurrence in cancer patients, specifically in those patients with advanced disease. The goal of anticoagulation therapy is to prevent VTE recurrence while mitigating the safety side effects of therapy, mainly major bleed (MB). Gastrointestinal (GI) cancers are associated with a high incidence of thromboembolic events and an even higher risk of bleeding events while on active chemotherapy. Recurrent VTE efficacy and MB safety complications due to secondary VTE prophylaxis remain a noticeable limitation in treating patients with cancer-associated VTE (CAVTE) with vitamin K antagonist and low molecular weight heparin (LMWH). Direct oral anticoagulants (DOACs), a newer set of agents with easier access and administration for CAVTE, have promising effectiveness outcomes although there is a safeness hesitance to utilize these agents in select subsets of high-risk cancer patients.

Research motivation

The current role of DOACs in cancer patients is still unfolding and current treatment guidelines recommend them as a preferred option. Since the advent of DOACs, our clinical practice has noticed an unusual safety profile often having to be addressed by changes in administration, holding of therapy, cessation of therapy or switching to another treatment regimen. We wanted to analyze the efficacy and safety outcome of our own institutional real-world experience with DOAC’s in the GI cancer setting.

Research objectives

The goal of our study was to evaluate our institutional outcomes of DOACs and LMWH in patients with active GICA-VTE at The University of Arizona Cancer Center based on safety and efficacy reported events.

Research methods

Subjects were extracted from a retrospective chart review of GI cancer patients treated at our comprehensive cancer center for incidental or symptomatic VTE with either DOACs or LMWH. Outcomes events, recurrent VTE and MB, were recorded from patients with an active GI malignancy and concurrent anticoagulation therapy at and beyond 6 mo.

Research results

Patients on apixaban (n = 29), rivaroxaban (n = 37) and LMWH (n = 40) met inclusion criteria. Recurrent VTE at 6 mo was noted in 7.5% (n = 3), 6.8% (n = 2) and 2.7% (n = 1) of patients on LMWH, apixaban and rivaroxaban, respectively (all P= NS). MB at 6 mo was 5% (n = 2) for LMWH, 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). Beyond six-months, MB rates were 21% and 10% for DOACs and LMWH (P = NS), respectively, while maintaining efficacy. Significant predictors of any 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).

Research conclusions

Rivaroxaban compared to apixaban and LMWH had a significantly higher risk of major bleeding on GICA-VTE patients with equivocal efficacy.

Research perspectives

Our study shows similar efficacy of LMWH as compared to apixaban and rivaroxaban. Nonetheless, the safety profiles of these new DOACs have to lead to the preferred use of apixaban, which had lower bleeding events in the high-risk GI cancer patient population.