Use Of Rivaroxaban For Treatment Research Articles

Safe and Effective Use of Rivaroxaban for Treatment of Cancer Associated Venous Thromboembolic Disease

Introduction: Venous thromboembolism (VTE) is a common complication of cancer, associated with significant morbidity and mortality. Low-molecular weight heparin (LMWH), the most widely used anticoagulant in this setting, is expensive and burdensome. Rivaroxaban (Riva) was approved for treatment of VTE in 2012, but there is limited experience in cancer-associated thrombosis (CAT). In 2014, we established a Clinical Pathway (CP) to guide use of rivaroxaban (Riva) for CAT at Memorial Sloan Kettering Cancer Center. We were concerned that a direct oral anticoagulant (DOAC) would be more likely than LMWH to cause upper gastrointestinal (GI) bleeding in the presence of abnormal mucosa. DOACs have partial renal clearance and are active in the urine, in contrast to LMWH, and we also anticipated increased genitourinary (GU) tract bleeding in the presence of GU lesions. Therefore, the key to our CP has been to recommend against use of Riva or other DOAC in the setting of active (GI) or (GU) tract lesions. As the elderly are known to be at higher risk of bleeding from anticoagulation, the CP recommended reduced dose Riva in patients≥75 year old (yo), (10 mg bid X 3 wks., followed by 15 mg daily). Otherwise, we adhere to the standard FDA approved guidelines. We published a 200-patient cohort in 2016 demonstrating rates of recurrent VTE and bleeding that were at least as low as historical controls with LMWH.This past year, two randomized clinical trials were published comparing a DOAC with dalteparin (“Hokusai VTE Cancer” of edoxaban, Raskob G.E. et al, NEJM, 2017, and “Select-D” of Riva, Young A.M. et al, JCO 2018). Both studies showed a trend towards better efficacy with the DOAC, but with increased GI/GU bleeding. However, those studies did not exclude patients with known GI/GU lesions. We now report our expanded experience with Riva treatment of CAT, confirming the safety and efficacy of Riva treatment of CAT when guided by our CP.Methods: From 1/1/2014 through 10/31/2016, 2000 patients at MSKCC received Riva. 1072 had CAT, defined as a lower extremity DVT and/or PE in a patient with active cancer or receiving cancer therapy. (The other 928 patients did not have active cancer, or received Riva for other indication). All patients treated with Riva for CAT are included in this analysis, even in the presence of active GI/GU lesions. Recurrent VTE, major bleeding (MB), clinically relevant non-major bleeding (CRNMB) leading to discontinuation of Riva, and death were competing risk endpoints for the purpose of the analysis. We also evaluated the outcomes of the subgroup of patients ≥75 yo.Results: At 6 months, the cumulative incidence for the various endpoints estimated within a competing risks framework were; recurrent VTE (4.2%), MB (2.2%), CRNMB (5.5%). Overall, the 6-month incidence of death was 22.2%. In the elderly patients, the risks of recurrent VTE and bleeding were similar to the <75 yo patients. It should be noted that only approximately half (48%) the elderly patients received reduced-dose Riva, at the discretion of the treating physician, and the numbers were too small to allow for comparison of full-dose and reduced dose.Conclusions: In our expanded experience of Riva therapy for CAT, applying our CP, we continue to maintain low rates of recurrent VTE and bleeding. Allowing for differences in methodology between a cohort study and randomized clinical trials, the rate of recurrent VTE was as low as the DOAC arm in Hokusai VTE Cancer and Select-D studies. Further, by applying the exclusion criteria in our CP, and not treating patients with known GI/GU lesions, we achieved a low rate of bleeding compared with the DOAC treatment arms in the two recent randomized clinical trials. Those two trials demonstrated bleeding rates greater than LMWH, particularly GI/GU bleeds. We saw no increased rates of recurrent VTE or bleeding in the elderly, which is reassuring, but we cannot conclude if reduced dose is of benefit. These new expanded observations further support the validity of our CP.The key to anticoagulation choice for CAT is not which anticoagulant is “better,” but rather which anticoagulant to choose for a specific patient. In the absence of GI/GU contraindications, Riva provides effective and safe anticoagulation, at substantially lower cost and burden to the patient than LMWH. In contrast, we propose that LMWH is preferable in patients with GI/GU lesions. (We are now obtaining specific data for that subgroup). [Display omitted] DisclosuresSoff:Amgen: Research Funding; Janssen: Research Funding. Mantha:Heidell, Pittoni, Murphy & Bach, LLP: Consultancy; GLG: Consultancy; Janssen: Research Funding.

Rebleeding In Central Nervous System after Use of Rivaroxaban for Treatment of Deep Venous Thrombosis in a Patient with Cerebral Vasculitis

Rebleeding In Central Nervous System after Use of Rivaroxaban for Treatment of Deep Venous Thrombosis in a Patient with Cerebral Vasculitis

Reduced Emergency Room Utilization for Initiation of Anticoagulation with Rivaroxaban Treatment of Cancer-Associated Thrombosis

▪Venous thromboembolism (VTE) is a leading cause of mortality and morbidity in cancer patients, and management represents a major cost to the healthcare system. We have previously presented in a cohort of 200 patients with cancer-associated thrombosis, rivaroxaban provides an alternative to low molecular weight heparin (LMWH), with 4.4% recurrent VTE and 2.2% major bleeding at 6 months (Mantha et al, ASH Abstract, 2015). Other recent publications have provided similar support for use of rivaroxaban in treatment of cancer-associated thrombosis (Bott-Kitslaar et al, Am J Med. 2016, Prins et al, Lancet Haem, 2014). In our early experience with rivaroxaban, fewer patients were sent to the Emergency Room (ER) for initiation of rivaroxaban than LMWH. We now characterize the site and cost of initiation of anticoagulation for the full 200 rivaroxaban patient cohort and a similar cohort of patients treated with LMWH demonstrating significant changes in practice and cost savings.In an IRB approved initiative we track all patients with cancer-associated thrombosis at MSKCC. We characterized the site of initiation of anticoagulation of the first 200 cancer patients with a pulmonary embolism (PE) or lower extremity deep vein thrombosis DVT since January 2014, treated with rivaroxaban. A similar cohort from June through December 2013 was treated with enoxaparin. We excluded patients whose VTE developed as an inpatient. Anticoagulation starts were classified as an emergency room (ER) visit or a second return outpatient visit on the same day for patient education and insurance authorization, a single outpatient visit, or telephone communication. Respective billing codes were then used as part of an economic evaluation to estimate the cost of the additional healthcare resources utilized, and therefore the costs saved by reduction in ER visits or second medical office visits.In the first 6 months of rivaroxaban availability, there was no decrease in ER utilization, compared with LMWH use. After 6 months of rivaroxaban availability, there was a significant decrease in ER visits for VTE management (p=0.008), which resulted in a decrease from baseline of 71% to 34% after one year (p=0.0001). Also of note, after one year of rivaroxaban availability, 18% of newly diagnosed VTE were managed by a simple telephone call to the patient or family member, typically after a recent outpatient visit. Only 2 patients who were started on rivaroxaban had required an additional outpatient visit to our Hematology clinic for evaluation.Based on 2016 Medicare billing codes, we calculated the cost for the additional resources utilized, beyond a single outpatient visit. During the first 6 months of rivaroxaban use, the cost of additional resources per 100 outpatient VTE patients ($47,067) was not significantly different than during the LMWH era ($43,144). However, as practice patterns evolved, ER utilization declined and more patients were managed without additional healthcare resources, resulting in an approximately 50% reduction in costs, for a savings of approximately $20,000 per 100 anticoagulation initiations.Management of cancer-associated thrombosis with LMWH is painful to the patient and expensive to the healthcare system. Patient quality of life is improved by treatment with rivaroxaban versus LMWH, with no evidence of loss of safety or efficacy. In this analysis, we expand on our prior observation that demonstrated a marked reduction in ER visits or hematology consults for the purpose of anticoagulation initiation and also show a substantial cost savings, of approximately $20,000 per 100 VTE patients. These changes in practice developed over an 18-month period, presumably reflecting a learning curve as healthcare providers became more familiar and comfortable with rivaroxaban. Of course, some patients with a new cancer-associated thrombosis should be sent to an ER for evaluation, based on their hemodynamic state or co-morbidities. However, our findings suggest that a majority of patients with cancer-associated thrombosis do not require ER visits, improving patient quality of life and sparing healthcare resources. [Display omitted] DisclosuresSoff:Janssen Pharmaceuticals: Other: Summer Student Internship. Mantha:Janssen Scientific Affairs, LLC: Research Funding. Soff:Janssen Scientific Affairs, LLC: Consultancy, Research Funding.

PCV40 - Budget Impact Analysis of The use of Rivaroxaban in Treatment of Venous Thromboembolism in Spain

PCV40 - Budget Impact Analysis of The use of Rivaroxaban in Treatment of Venous Thromboembolism in Spain

Safe and effective use of rivaroxaban for treatment of cancer-associated venous thromboembolic disease: a prospective cohort study

Low-molecular weight heparin (LMWH) has been the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. Rivaroxaban was approved in 2012 for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), but no prior studies have been reported specifically evaluating the efficacy and safety of rivaroxaban for cancer-associated thrombosis (CAT). Under a Quality Assessment Initiative (QAI), we established a Clinical Pathway to guide rivaroxaban use for CAT and now report a validation analysis of our first 200 patients. A 200 patient cohort with CAT (PE or symptomatic, proximal DVT), whose full course of anticoagulation was with rivaroxaban, were accrued. In competing risk analysis, primary endpoints at 6 months included new or recurrent PE or symptomatic proximal lower extremity DVT, major bleeding, clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban, or death. In competing risk analysis, the 6 months cumulative incidence of new or recurrent VTE was 4.4 % (95 % CI = 1.4–7.4 %), major bleeding was 2.2 % (95 % CI = 0−4.2 %) and all-cause mortality 17.6 % (95 % CI = 11.7–23.0 %). In this cohort of 200 patients with active cancer and CAT the rates of new or recurrent VTE and major bleeding were comparable to the cancer subgroup analysis from the EINSTEIN studies. The results of our Clinical Pathway provide guidance on Rivaroxaban use for treatment of CAT, and suggest that safety and efficacy is preserved, compared with past-published experience with LMWH.

Safe and Effective Use of Rivaroxaban for Treatment of Cancer-Associated Venous Thromboembolic Disease: A Quality Improvement Initiative

▪Background: Low-molecular weight heparin (LMWH) has been the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. LMWH injections are painful and costly. Rivaroxaban, an oral direct factor Xa inhibitor, was FDA approved in 2012 for treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), but there has been a knowledge gap for its use in patients with cancer-associated thrombosis (CAT). Under a Quality Assurance Initiative (QAI), we established a Clinical Pathway to guide rivaroxaban use for CAT, and began to offer rivaroxaban as an alternative to enoxaparin, in January 2014, for patients who met appropriate clinical criteria. We are tracking all cancer patients with PE or symptomatic proximal DVT, whose full course of anticoagulation is with rivaroxaban (allowing up to 3 days of initial parenteral anticoagulation). We now report the characteristics of the first 200 patients, and an outcome analysis of our first 100 patients, who have been treated for at least 6 months or otherwise reached an endpoint.Materials and Methods: The Clinical Pathway guidelines will be available on request, pending publication. Patients were not treated with rivaroxaban if they had active gastrointestinal or genitourinary lesions, or had undergone gastric resection due to anticipated excess bleeding risk or reduced absorption. This excluded under 5% of patients. The Pathway provided dosing guidelines in the setting of thrombocytopenia, advanced age, transient renal, or hepatic dysfunction. Primary endpoints include new or recurrent PE, symptomatic proximal lower extremity DVT, major bleeding (ISTH definition), clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban, or death. Considering those outcomes as competing risks, the cumulative incidence of each event type was calculated using R 3.2.0 for Windows and package "Survival".Results: The characteristics of our first 200 patients are in Table 1. 70% of the patients had PE. Of the solid tumor patients, 65.6% had metastatic disease. The first 100 patients have completed at least 6 months of rivaroxaban anticoagulation or otherwise reached a primary endpoint. At 6 months, the cumulative incidence of death was 14.4% (95% CI=6.8-21.4%), new or recurrent VTE was 4.3% (95% CI=0.1-8.4%), major bleeding was 1.1% (95% CI=0-3.1%), and clinically relevant non-major bleeding leading to rivaroxaban discontinuation was 7.9% (95% CI=2.1-13.3%).Conclusions: In the analysis of the first 100 patients entered into our QAI program, the rates of major bleeding, and new or recurrent VTE compare favorably to two published studies of LMWH for treatment of cancer associated thrombosis. In the CLOT study (Lee et al, NEJM, 2003) and the Daltecan study (Francis et al, JTH, 2015), the 6-month rates of new or recurrent VTE were approximately 9%, and the rates of major bleeding were 6% and 9.5% respectively. Our final analysis awaits the completion of 6 months follow-up on 200 patients, to be completed in December 2015. But the rates of major bleeding and recurrent VTE at this point suggest safety and efficacy to be at least non-inferior to LMWH, with the advantage of reduced patient burden, and support the ongoing use of our Clinical Pathway.Our low rate of major bleeding likely is influenced by the exclusion of patients with active GI or GU lesions, who would be expected to have a high bleeding risk with an oral direct anticoagulant. However, we estimate this excluded less than 5% of cancer patients with VTE. Further, we anticipated reduced drug clearance in the elderly, and used a reduced dose for patients greater than 75 years of age. This appeared to be associated with no loss in efficacy, and helped maintain a low rate of major bleeding.A randomized trial is the optimal approach to establish non-inferiority or superiority of rivaroxaban to LMWH for cancer associated thrombosis. However, our QAI Clinical Pathway provides guidance and reassurance for rivaroxaban use until a randomized trial is conducted.TableBaseline Characteristics of PatientsCharacteristicNumber of IndividualsGenderMale82Female118Event TypePE, with or without DVT140Proximal, Symptomatic Lower extremity DVT60Cancer TypeSolid Tumor186Hematologic Malignancy14Cancer Stage (Of Solid Tumors)No Evidence of Disease (Post-Cancer Surgery)11 (5.9%)11 (0.5%)24 (2.2%)316 (8.6%)4122 (65.6%)Unknown32 (17.2%) [Display omitted] DisclosuresNo relevant conflicts of interest to declare.