Recio-Boiles Alejandro, Veeravelli Sumana, Vondrak Jessica, Babiker Hani M, Scott Aaron J, Shroff Rachna T, Patel Hitendra, Elquza Emad, McBride Ali
Department of Medicine, Hematology and Medical Oncology, University of Arizona Cancer Center, Tucson, AZ 85724, United States.
Department of Medicine, Internal Medicine Residency Program, University of Arizona, Tucson, AZ 85725, United States.
World J Gastrointest Oncol. 2019 Oct 15;11(10):866-876. doi: 10.4251/wjgo.v11.i10.866.
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.
To evaluate patient risk factors, effectiveness (VTE) and safety (MB) of DOACs and low molecular weight heparin (LMWH) in patients with active GICA-VTE.
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.
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% ( = 3), 6.8% ( = 2) and 2.7% ( = 1) of patients on enoxaparin, apixaban and rivaroxaban, respectively (all = NS). MB at 6 mo were 5% ( = 2) for enoxaparin, 6.8% ( = 2) for apixaban and 21.6% ( = 8) for rivaroxaban (overall = 0.048; LMWH = 0.0423; all other = 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).
Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.
与其他实体瘤相比，胃肠道癌（GICA）与静脉血栓栓塞（VTE）的发生率较高相关，此外，抗凝治疗期间复发性VTE和大出血（MB）并发症的发生率也有所增加。GICA-VTE仍然是一个具有挑战性的临床情况，对于直接口服抗凝剂（DOAC）的使用存在MB方面的担忧，尤其是在进行积极的癌症治疗时。
评估DOACs和低分子肝素（LMWH）在活动性GICA-VTE患者中的患者风险因素、有效性（VTE）和安全性（MB）。
对2013年11月至2017年2月在综合癌症中心接受DOACs和LMWH治疗且患有GICA以及有症状或偶然发生VTE的患者进行回顾性病历审查。纳入标准包括在任何阶段诊断出的活动性胃肠道癌或在VTE诊断前/后6个月接受治疗，且被处方使用DOACs或LMWH达6个月或更长时间。采用卡方检验进行总体比较，采用Fisher精确检验对复发性VTE和MB事件患者比例进行两两比较。比值比用于比较暴露于危险因素下发生结局的相对可能性。
共有144例患者接受了抗凝治疗，其中106例符合纳入标准，分别为阿哌沙班（27.3%）、利伐沙班（34.9%）和依诺肝素（37.7%），38例被排除。患者在GICA诊断时的中位年龄为66.5岁，在CAVTE事件时为67岁，男性占62%，白种人占80%，IV期患者占70%，胰腺癌患者占40.5%，Khorana评分（≥3分）的患者占30%，43.5%的患者正在接受积极化疗。64%的患者完成了抗凝治疗（范围为1至43个月）。接受依诺肝素、阿哌沙班和利伐沙班治疗的患者在6个月时复发性VTE的发生率分别为7.5%（n = 3）、6.8%（n = 2）和2.7%（n = 1）（均P =无统计学意义）。依诺肝素、阿哌沙班和利伐沙班在6个月时MB的发生率分别为5%（n = 2）、6.8%（n = 2）和21.6%（n = 8）（总体P = 0.048；LMWH组P = 0.0423；其他组均P =无统计学意义）。所有抗凝治疗的主要或次要结局的显著预测因素包括：积极的全身治疗（OR = 5.1，95%CI：1.3 - 19.3）、高Khorana评分[≥3分]（OR = 5.5，95%CI：1.7 - 17.1）、现吸烟者（OR = 6.7，95%CI：2.1 - 21.0）、胰腺癌（OR = 6.8，95%CI：1.9 - 23.2）和IV期疾病（OR = 9.9，95%CI：1.2 - 79.1）。
与阿哌沙班和依诺肝素相比，利伐沙班在GICA-VTE患者中导致MB的风险显著更高，而疗效相当。
