Background:In nonvalvular atrial fibrillation (NVAF), rivaroxaban is used to prevent stroke and systemic embolism. Objective: To evaluate major bleeding (MB) in NVAF patients treated with rivaroxaban in a real-world clinical setting. Methods: From January 1, 2013, to March 31, 2014, US Department of Defense electronic health care records were queried to describe MB rates and demographics. Major bleeding was identified using a validated algorithm. Results: Of 27 467 patients receiving rivaroxaban, 496 MB events occurred in 478 patients, an incidence of 2.86 per 100 person-years (95% confidence interval: 2.61-3.13). The MB patients were older, mean (SD) age of 78.4 (7.7) vs 75.7 (9.7) years, compared with non-MB patients. Patients with MB had higher rates of hypertension (95.6% vs 75.8%), coronary artery disease (64.2% vs 36.7%), heart failure (48.5% vs 23.7%), and renal disease (38.7% vs 16.7%). Of MB patients, 63.2% were taking 20 mg, 32.2% 15 mg, and 4.6% 10 mg of rivaroxaban. Four percent of MB patients took warfarin within the prior 30 days. Major bleeding was most commonly gastrointestinal (88.5%) or intracranial (7.5%). Although 46.7% of MB patients received a transfusion, none had sufficient evidence of receiving any type of clotting factor. Fourteen died during their MB hospitalization, yielding a fatal bleeding incidence rate of 0.08 per 100 person-years (95% confidence interval: 0.05-0.14). Mean age at death was 82.4 years. Conclusions: In this large observational study, the MB rate was generally consistent with the registration trial results, and fatal bleeds were rare.

No abstract

BackgroundRecommended therapeutic options for the management of venous thromboembolism (VTE) in patients with cancer are burdensome, and compliance with guidelines is unknown.ObjectivesTo describe current treatment patterns and to evaluate patient persistence on various anticoagulants.Patients/MethodsMedical and pharmacy claims from the Humana Database were analyzed (01/2007‐12/2014). Newly diagnosed cancer patients treated with anticoagulants were categorized into one of the following cohorts: low–molecular‐weight heparin (LMWH), warfarin, and rivaroxaban. Discontinuation, switching, and persistence with the index therapy were analyzed.ResultsA total of 2941 newly diagnosed patients with cancer who developed VTE and received anticoagulation in outpatient settings were identified. Of these, 97% initiated anticoagulation with LMWH (n=735; 25%), warfarin (n=1403; 47.7%), or rivaroxaban (n=709; 24.1%). Median treatment durations for the LMWH, warfarin, and rivaroxaban cohorts were 3.3, 7.9, and 7.9 months, respectively; Kaplan‐Meier rates of persistence to the initial therapy were 37%, 61%, and 61% at 6 months. Warfarin and rivaroxaban users were significantly more likely to remain on initial therapy compared to LMWH (adjusted hazard ratios [HRs; 95% CI]: warfarin, 0.33 [0.28‐0.38]; rivaroxaban, 0.38 [0.32‐0.46]). The proportion of patients that switched from their initial treatment to another anticoagulation treatment was 22.9%, 7.9%, and 4.7% in the LMWH, warfarin, and rivaroxaban cohorts, respectively.ConclusionsThis real‐world analysis showed that, despite guideline recommendations, warfarin and rivaroxaban are at least as equally utilized as LMWH for the treatment of cancer‐associated thrombosis. LMWH was associated with significantly lower persistence, shorter duration of treatment, and more switching than warfarin and rivaroxaban.

Anticoagulation is used to treat venous thromboembolism (VTE) in cancer patients, but may be associated with an increased risk of bleeding. VTE recurrence and major bleeding were assessed in cancer patients treated for VTE with the most currently prescribed anticoagulants in clinical practice. Newly diagnosed cancer patients (first VTE 1/1/2013‐05/31/2015) who initiated rivaroxaban, low‐molecular‐weight heparin (LMWH), or warfarin were identified from Humana claims data and observed until end of eligibility or end of data availability. VTE recurrence was a hospitalization with a primary diagnosis of VTE ≥7 days after first VTE. Major bleeding events on treatment were identified using validated criteria. Cohorts were compared using Kaplan–Meier rates at 6 and 12 months and Cox proportional hazards models. Cohorts were adjusted for their differences at baseline. A total of 2428 patients (rivaroxaban: 707; LMWH: 660; warfarin: 1061) met inclusion criteria. Patient characteristics were well balanced after weighting. There was a trend for lower VTE recurrence rates in rivaroxaban users compared to LMWH users at 6 months (13.2% vs. 17.1%; P = .060) and significantly lower at 12 months (16.5% vs. 22.2%; P = .030) [HR: 0.72, 95% CI: (0.52‐0.95); P = .024]. VTE recurrence rates were also lower for rivaroxaban than warfarin users at 6 months (13.2% vs. 17.5%; P = .014) and 12 months (15.7% vs. 19.9%; P = .017) [HR: 0.74, 95% CI: (0.56‐0.96); P = .028]. Major bleeding rates were similar across cohorts. This real‐world analysis suggests cancer patients with VTE treated with rivaroxaban had significantly lower risk of recurrent VTE and similar risk of bleeding compared to those treated with LMWH or warfarin.

Introduction: Therapeutic options for the management of venous thromboembolism (VTE) in patients with cancer remain limited. Guidelines recommend anticoagulation with low molecular weight heparin (LMWH) monotherapy for ≥3-6 months, and possibly indefinitely, for patients with active cancer. However, drug cost and patient preference issues may lead to non-compliance with these recommendations. The objective of this study is to describe current treatment patterns and to evaluate patient persistence on various anticoagulants. Methods: Medical and pharmacy claims from the Humana Database were analyzed. To reflect recent treatment patterns, the study population was restricted to patients who had their first VTE between 1/1/2013 and 12/31/2014. Newly diagnosed cancer patients with a first VTE diagnosis (deep vein thrombosis [DVT] or pulmonary embolism [PE]) occurring after their first cancer diagnosis (a 30-day window before the cancer diagnosis was allowed), and with ≥1 dispensing of an anticoagulant agent within 30 days after their VTE diagnosis, were selected. Based on the first anticoagulant agent received, patients were classified into one of the following cohorts: LMWH, LMWH/warfarin, warfarin and rivaroxaban. Use of other anticoagulants including fondaparinux, heparin, apixaban, or dabigatran was low and could not be analyzed due to small sample size. The observation period spanned from the date of the first anticoagulant dispensing to the end of insurance eligibility or the end of data availability, whichever occurred earlier. Discontinuation of the index therapy was defined by a time gap without refill of the index anticoagulant for more than 60 days after the presumed exhaustion of the last known dispensing. For patients in the LMWH/warfarin group, the 2 medications were filled simultaneously as an index therapy, with the expectation that the patients were bridged to warfarin; therefore, their persistence was evaluated based on warfarin therapy. Persistence on therapy was assessed for 12 months using Kaplan-Meier rates, and unadjusted Cox proportional hazards models were used to compare the time to discontinuation between cohorts. Results: A total of 2,941 newly diagnosed patients with cancer who developed VTE and received anticoagulation in outpatient settings were identified. Of these, 97% received anticoagulation with either LMWH (n=735; 25%), LMWH/warfarin (n=550; 18.7%), warfarin (n=853; 29%), rivaroxaban (n=709; 24.1%). Mean age and gender were similar across treatment cohorts. Approximately 90% of the patients had diagnoses of solid tumors. Diagnoses for DVT, PE, and DVT/PE were 55%, 27%, and 18%, respectively, and were similar across cohorts. Treatments for cancers associated with very high VTE risk (stomach, pancreas, and brain) ranged from 15% in LMWH to 6% in rivaroxaban cohorts, while high VTE risk (lung, lymphoma, gynecologic, bladder, testicular, and renal) ranged from 39% in LMWH to 30% in warfarin and LMWH/warfarin cohorts. Around 75% (warfarin) to 58% (rivaroxaban) of the VTE cases were diagnosed in inpatient settings. The median treatment durations for LMWH, LMWH/warfarin, warfarin, and rivaroxaban users were 3.29, 7.76, 8.12, and 7.92 months, respectively. Kaplan-Meier rates of persistence to the initial therapy were 37%, 60%, 62%, and 61% at 6 months, and 21%, 37%, 34%, and 36% and at 12 months for the LMWH, LMWH/warfarin, warfarin and rivaroxaban cohorts, respectively (Figure 1). LMWH/warfarin, warfarin, and rivaroxaban users were significantly more likely to remain on their initial therapy compared to LMWH, with hazard ratios (HRs; 95% CI) of 0.38 (0.32-0.45), 0.40 (0.34-0.46), and 0.42 (0.36-0.50), respectively (all p-values <0.0001). The proportion of patients that switched from their initial treatment to another anticoagulation treatment was 22.9%, 8.9%, 7.3% and 4.7% in the LMWH, LMWH/warfarin, warfarin, and rivaroxaban cohorts, respectively. Conclusion: This real-world analysis showed that despite guidelines recommendations, warfarin and rivaroxaban are nearly equally utilized as LMWH for the treatment of cancer-associated thrombosis. LMWH was associated with significantly lower persistence and shorter duration of treatment than warfarin and rivaroxaban. More patients switched from LMWH to other anticoagulants compared to patients starting on warfarin or rivaroxaban treatments. Disclosures Khorana: sanofi: Consultancy, Honoraria; Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria. McCrae:Janssen Scientific Affairs: Membership on an entity's Board of Directors or advisory committees. Milentijevic:Janssen Scientific Affairs: Employment, Equity Ownership. Fortier:Janssen Scientific Affairs: Research Funding. Nelson:Johnson & Johnson: Equity Ownership; Janssen Scientific Affairs: Employment. Laliberté:Janssen Scientific Affairs: Research Funding. Crivera:Janssen Scientific Affairs, LLC: Employment, Equity Ownership. Lefebvre:Janssen Scientific Affairs: Research Funding. Yannicelli:Janssen Scientific Affairs: Employment, Equity Ownership. Schein:Janssen Scientific Affairs, LLC: Employment.