Abstract
Introduction: Venous thromboembolism (VTE) in the form of deep venous thrombosis (DVT) or pulmonary embolism (PE) is a complication of malignancy. Several studies have demonstrated the superiority of dalteparin (Fragmin®), a low molecular weight heparin (LMWH), in comparison to oral vitamin K antagonists in preventing VTE recurrence in the setting of active cancer. LMWH is the preferred treatment of cancer associated thrombosis. However, the cost of LMWH can be prohibitive and the need for daily subcutaneous injections can decrease patients' quality of life. While rivaroxaban (Xarelto®), a Factor Xa inhibitor, has been approved for the treatment and secondary prevention of DVT and PE, there is limited data regarding its use in cancer patients. The objective of our study is to determine the efficacy and safety of rivaroxaban compared to dalteparin in cancer associated thrombosis.
Methods: This is a retrospective chart review of cancer patients greater than age 18 treated at H. Lee Moffitt Cancer Center between May 3, 2010 and June 30, 2015 on anticoagulation with rivaroxaban or dalteparin. Patients were excluded if the length of anticoagulant therapy was < 30 days, anticoagulant therapy was initiated > 6 months after VTE diagnosis, the indication for treatment was not DVT/PE, if patients had contraindications to either LMWH or rivaroxaban, or patients were not on treatment doses of therapy. Out of 459 patients identified, 226 patients (107 in the rivaroxaban group, and 119 in the dalteparin group) were eligible for analysis based on our exclusion criteria. Efficacy was determined by the incidence of recurrent VTE, such as recurrent DVT, new fatal or non-fatal PE within 30 days. The secondary endpoint of the study was to determine the safety of rivaroxaban compared to dalteparin in cancer patients for the treatment of VTE. Safety was determined by the incidence and severity of bleeding. Major bleeding was defined as clinically overt if it was associated with a fall in hemoglobin of 2 g/dL or more, required transfusions of ≥ 2 units of packed red blood cells, involved retroperitoneal, intracranial, or critical site bleeding, or if it contributed to death. Minor bleeding was defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact with a physician, interruption or discontinuation of anticoagulation treatment, or associated with any other discomfort such as pain or impairment of activities of daily life. Descriptive statistical analyses were utilized. Chi square analysis and t- test were performed to compare categorical and continuous variables. All data was analyzed using SPSS version 21.0 statistical software.
Results: Rivaroxaban had a similar rate of DVT and PE failure with 1 event versus 2 with dalteparin (p = 0.625). The rivaroxaban group had 0 major and 8 minor bleeds compared to 3 major and 8 minor bleeds in the dalteparin group with p values of 0.09 and 0.86 respectively. Comorbidities and risk factors for thrombosis were similar in both groups as summarized in Table 1.
Table. Rivaroxaban vs. Dalteparin: No Significant Differences in the Efficacy and Safety Profile in Cancer Associated Thrombosis RivaroxabanN = 107 DalteparinN =119 P value DVT Failure within 30 days 1 (0.93%) 2 (1.68%) 0.625 PE Failure within 30 days 1 (0.93%) 1 (0.84%) 0.94 Major Bleeding 0 (0 %) 3 (2.5%) 0.09 Minor Bleeding 8 (7.5%) 8 (6.7%) 0.864 Median Age (Yrs) 61 65 0.93 MaleFemale 58 (54.2%) 49 (45.8%) 60 (50.4%) 59 (49.6%) 0.596 Active Cancer 96 (86.5%) 111 (93.2%) 0.350 Surgery within 30 Days 14 (13.1%) 13 (10.9%) 0.684 Hypertension 58 (54.2%) 61 (51.3%) 0.69 Diabetes 14 (13.1%) 14 (11.8%) 0.84 Coronary Artery Disease 6 (5.61%) 11 (9.2%) 0.326 History of Previous DVT 12 (11.2%) 5 (4.2%) 0.074 BMI >30 39 (36.4%) 48 (40.3%) 0.585 Creatinine Clearance (Cr Cl) 30 - 50 Cr Cl 50 - 70 7 (6.5%) 100 (93.3%) 7 (5.9%) 112 (94.1%) 0.837
Conclusions: Our study evaluated the safety and efficacy of rivaroxaban compared to dalteparin in patients with predominantly active cancer treated at a large comprehensive cancer center and found rivaroxaban to be comparable to dalteparin in this cohort. There were no significant differences in regards to recurrent VTE or major/minor bleeding with patients on rivaroxaban or dalteparin in our cohort of patients. Large randomized trials evaluating the efficacy and safety of rivaroxaban in the oncology population are needed to further validate our findings.
Disclosures
No relevant conflicts of interest to declare.
How I Manage Cancer-Associated Thrombosis
