Effectiveness and Safety of Rivaroxaban and Low Molecular Weight Heparin in Cancer-Associated Venous Thromboembolism.

Background: Direct-acting oral anticoagulants (DOACs) are alternatives to low molecular weight heparin (LMWH) in most cancer-associated thrombosis (CAT) patients. Objectives: This study sought to compare the effectiveness and safety of rivaroxaban and LMWH for venous thromboembolism (VTE) treatment in patients with an active cancer type not associated with a high risk of DOAC bleeding. Methods: An analysis of electronic health records from January 2012 to December 2020 was performed. Patients were adults, had active cancer, experienced an index CAT event, and were treated with rivaroxaban or LMWH. Patients with cancers with an established high risk of bleeding on DOACs were excluded. Baseline covariates were balanced using propensity score-overlap weighting. HRs with 95% CIs were calculated. Results: We identified 3,708 CAT patients treated with rivaroxaban (29.5%) or LMWH (70.5%). The median (25th-75th percentiles) time on anticoagulation was 180 (69-365) and 96 (40-336) days for rivaroxaban and LMWH patients. At 3 months, rivaroxaban was associated with a 31% reduced risk of recurrent VTE vs LMWH (4.2% vs 6.1%; HR: 0.69; 95% CI: 0.51-0.92). No difference in bleeding-related hospitalizations or all-cause mortality was observed (HR: 0.79; 95% CI: 0.55-1.13 and HR: 1.07; 95% CI: 0.85-1.35, respectively). Rivaroxaban reduced the recurrent VTE risk (HR: 0.74; 95% CI: 0.57-0.97) but not bleeding-related hospitalizations or all-cause mortality at 6 months. At 12 months, no difference was observed between cohorts for any of the previously mentioned outcomes. Conclusions: Among active cancer patients experiencing VTE and not at high risk of bleeding on DOACs, rivaroxaban was associated with a reduced risk of recurrent VTE versus LMWHs at 3 and 6 months but not 12 months. (Observational Study in Cancer-Associated Thrombosis for Rivaroxaban-United States Cohort [OSCAR-US]; NCT04979780).

Cancer-Associated ThrOmboSIs - Patient-Reported OutcoMes With RivarOxaban (COSIMO) - Baseline characteristics and clinical outcomes.

BACKGROUND: Patients with cancer-associated thrombosis (CAT) have a high risk of recurrent venous thromboembolic events, which contribute to significant morbidity and mortality. Direct oral anticoagulants may provide a convenient treatment option for these patients. OBJECTIVES: To assess clinical characteristics and outcomes of patients with active cancer changing to rivaroxaban after ≥4 weeks of standard therapy for the treatment of venous thromboembolism (VTE) in clinical practice. This analysis focused on secondary outcomes of Cancer-associated thrOmboSIs - Patient-reported outcoMes with rivarOxaban (COSIMO). PATIENTS: COSIMO was a multinational, prospective, noninterventional, single-arm cohort study. Overall, 505 patients received at least one dose of rivaroxaban; 96.6% changing from low-molecular-weight heparin, 1.6% from a vitamin K antagonist, and 1.8% from fondaparinux. RESULTS: Most patients had solid tumors (n = 449; 88.9%) and approximately half of these patients had metastases. The qualifying venous thromboembolic event was deep vein thrombosis (DVT) in 45.3% of patients, pulmonary embolism (PE) in 37.2% of patients, DVT with PE in 9.7% of patients, and catheter-associated DVT in 7.5% of patients. Approximately 75.1% of patients received rivaroxaban for at least 3 months; 150 (29.7%) patients received concomitant chemotherapy during the study. VTE recurrence, major bleeding, nonmajor bleeding, and major adverse cardiovascular events occurred in 18 (3.6%), 18 (3.6%), 81 (16.0%), and 12 (2.4%) patients, respectively. CONCLUSIONS: In patients with CAT who changed to rivaroxaban treatment after ≥4 weeks of standard therapy, the observed incidence proportions of recurrent VTE and bleeding events were in keeping with the recognized effectiveness and safety profile of rivaroxaban for the treatment of CAT.

Anticoagulation Treatment in Cancer-Associated Venous Thromboembolism: Assessment of Patient Preferences Using a Discrete Choice Experiment (COSIMO Study).

INTRODUCTION: Clinical guidelines recommend anticoagulation therapy for the treatment of cancer-associated venous thromboembolism (VTE), but little is known about preferences. Therefore, the objective of this discrete choice experiment (DCE) was to elucidate patient preferences regarding anticoagulation convenience attributes. METHODS: Adult patients with cancer-associated VTE who switched to direct oral anticoagulants were included in a single-arm study (COSIMO). Patients were asked to decide between hypothetical treatment options based on a combination of the following attributes: route of administration (injection/tablet), frequency of intake (once/twice daily), need for regular controls of the international normalized ratio (INR) at least every 3 to 4 weeks (yes/no), interactions with food/alcohol (yes/no), and distance to treating physician (1 vs. 20 km) as an additional neutral attribute. DCE data were collected by structured telephone interviews and analyzed based on a conditional logit regression. RESULTS: Overall, 163 patients (mean age 63.7 years, 49.1% female) were included. They strongly preferred oral administration compared with self-injections (importance of this attribute for overall treatment decisions: 73.8%), and a treatment without dietary restrictions (11.8%). Even if these attributes were less important (7.2% and 6.5%, respectively), patients indicated a preference for a shorter distance to the treating physician and once-daily dosing compared with twice-daily intake. "Need for regular controls of INR at least every 3 to 4 weeks" showed no significant impact on the treatment decision (0.7%). CONCLUSION: This study showed that treatment-related decision making in cancer-associated VTE, assuming comparable effectiveness and safety of anticoagulant treatments, is predominantly driven by "route of administration," with patients strongly preferring oral administration.

Human SIRT1 associates with mitotic chromatin and contributes to chromosomal condensation.

SIRT1 is a NAD-dependent deacetylase that participates in cellular controls of gene expression, metabolism, genomic stability and anti-aging. Here we report that SIRT1 levels rise in prometaphase leading to SIRT1 global association with mitotic chromatin until telophase. Moreover, SIRT1 contributes to chromosomal condensation by mediating chromosomal loading of histone H1 and the condensin I complex. Consistently, SIRT1 knockdown led to improper condensation and overall aberrant mitosis. Our data highlight new role for SIRT1 in maintenance of chromosome stability in mitosis and suggests how diminished SIRT1 activity during aging and tumorigenesis may lead to aneuploidy and genomic instability.