Comparison of rivaroxaban and low molecular weight heparin in the treatment of cancer-associated venous thromboembolism: a Swedish national population-based register study.

BACKGROUND: Treating cancer-associated venous thromboembolism (CAT) with anticoagulation prevents recurrent venous thromboembolism (rVTE), but increases bleeding risk. OBJECTIVES: To compare incidence of rVTE, major bleeding, and all-cause mortality for rivaroxaban versus low molecular weight heparin (LMWH) in patients with CAT. METHODS: We developed a cohort study using Swedish national registers 2013-2019. Patients with CAT (venous thromboembolism within 6 months of cancer diagnosis) were included. Those with other indications or with high bleeding risk cancers were excluded (according to guidelines). Follow-up was from index-CAT until outcome, death, emigration, or end of study. Incidence rates (IR) per 1000 person-years with 95% confidence interval (CI) and propensity score overlap-weighted hazard ratios (HRs) for rivaroxaban versus LMWH were estimated. RESULTS: We included 283 patients on rivaroxaban and 5181 on LMWH. The IR for rVTE was 68.7 (95% CI 40.0-109.9) for rivaroxaban, compared with 91.6 (95% CI 81.9-102.0) for LMWH, with adjusted HR 0.77 (95% CI 0.43-1.35). The IR for major bleeding was 23.5 (95% CI 8.6-51.1) for rivaroxaban versus 49.2 (95% CI 42.3-56.9) for LMWH, with adjusted HR 0.62 (95% CI 0.26-1.49). The IR for all-cause mortality was 146.8 (95% CI 103.9-201.5) for rivaroxaban and 565.6 (95% CI 541.8-590.2) for LMWH with adjusted HR 0.48 (95% CI 0.34-0.67). CONCLUSIONS: Rivaroxaban performed similarly to LMWH for patients with CAT for rVTE and major bleeding. An all-cause mortality benefit was observed for rivaroxaban which potentially may be attributed to residual confounding. TRIAL REGISTRATION NUMBER: NCT05150938 (Registered 9 December 2021).

Safety profile of rivaroxaban in first-time users treated for venous thromboembolism in four European countries.

BACKGROUND: The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and secondary prevention of venous thromboembolism in routine clinical practice. METHODS: Cohorts were created using electronic healthcare databases from the UK, the Netherlands, Germany and Sweden. Patients with a first prescription of rivaroxaban or vitamin K antagonist during the period from December 2011 (in the UK, January 2012) to December 2017 (in Germany, December 2016) for venous thromboembolism indication, with no record of atrial fibrillation or recent cancer history, were observed until the occurrence of each safety outcome (hospitalization for intracranial, gastrointestinal, urogenital or other bleeding), death or study end (December 2018; in Germany, December 2017). Crude incidence rates of each outcome per 100 person-years were computed. RESULTS: Overall, 44 737 rivaroxaban and 45 842 vitamin K antagonist patients were enrolled, mean age, 59.9-63.8 years. Incidence rates were similar between rivaroxaban and vitamin K antagonist users with some exceptions, including higher incidence rates for gastrointestinal bleeding in rivaroxaban users than in vitamin K antagonist users. Among rivaroxaban users, mortality and bleeding risk generally increased with age, renal impairment and diabetes. CONCLUSIONS: This study provides further data from routine clinical practice that broadly support safety profile of rivaroxaban for VTE indication and complement findings from previous randomized clinical trials.

Comparison of Clinical Outcomes in Patients with Active Cancer Receiving Rivaroxaban or Low-Molecular-Weight Heparin: The OSCAR-UK Study.

BACKGROUND: In most patients with cancer-associated venous thromboembolism (CT), essentially those not at high risk of bleeding, guidelines recommend treatment with direct oral anticoagulants as an alternative to low-molecular-weight heparins (LMWHs). Population-based studies comparing these therapies are scarce. OBJECTIVES: To compare the risk of venous thromboembolism (VTE) recurrences, significant bleeding, and all-cause mortality in patients with CT receiving rivaroxaban or LMWHs. PATIENTS/METHODS: Using UK Clinical Practice Research Datalink data from 2013 to 2020, we generated a cohort of patients with first CT treated initially with either rivaroxaban or LMWH. Patients were observed 12 months for VTE recurrences, significant bleeds (major bleeds or clinically relevant nonmajor bleeding requiring hospitalization), and all-cause mortality. Overlap weighted sub-distribution hazard ratios (SHRs) compared rivaroxaban with LMWH in an intention-to-treat analysis. RESULTS: The cohort consisted of 2,259 patients with first CT, 314 receiving rivaroxaban, and 1,945 LMWH, mean age 72.4 and 66.9 years, respectively. In the 12-month observational period, 184 person-years following rivaroxaban and 1,057 following LMWH, 10 and 66 incident recurrent VTE events, 20 and 102 significant bleeds, and 10 and 133 deaths were observed in rivaroxaban and LMWH users, respectively. The weighted SHR at 12 months for VTE recurrences in rivaroxaban compared with LMWH were 0.80 (0.37-1.73); for significant bleeds 1.01 (0.57-1.81); and for all-cause mortality 0.49 (0.23-1.06). CONCLUSION: Patients with CT, not at high risk of bleeding, treated with either rivaroxaban or LMWH have comparable effectiveness and safety outcomes. This supports the recommendation that rivaroxaban is a reasonable alternative to LMWH for the treatment of CT.

Rivaroxaban Versus Low-Molecular-Weight Heparins in a Broad Cohort of Patients With Cancer-Associated Venous Thromboembolism: An Analysis of the OSCAR-US Program.

Cancer-associated venous thromboembolism (CAT) guidelines recommend direct oral anticoagulants as alternatives to low-molecular-weight heparin (LMWH) in most patients. This study compared the effectiveness and safety of rivaroxaban versus LMWH for a broad CAT cohort. The cohort study used electronic health data from January 2012 to December 2020 to evaluate patients with active cancer experiencing acute venous thromboembolism (VTE) and treated with rivaroxaban or LMWH. Propensity score-overlap weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE, bleeding-related hospitalization, and all-cause mortality were calculated. In total, 4935 patients were identified (27.9% on rivaroxaban and 72.1% on LMWH). The cancer types included gastrointestinal (29.4%), genitourinary (26.2%), lung (24.0%), breast (19.7%), and hematologic (14.4%). Rivaroxaban was associated with a reduction in recurrent VTE versus LMWH among all patients with cancer (HR = 0.78; 95%CI = 0.61-0.99) at 3 months. No differences in bleeding-related hospitalization or all-cause mortality were observed. Directionally similar results to those at 3 months were observed at 6 months for all outcomes. In conclusion, we observed fewer recurrent VTE cases and no increase in bleeding-related hospitalizations with rivaroxaban versus LMWH at 3 months in this patient cohort with various cancer types.

Incidence of hospital-acquired acute kidney injury and trajectories of glomerular filtration rate in older adults.

BACKGROUND: In older adults, epidemiological data on incidence rates (IR) of hospital-acquired acute kidney injury (AKI) are scarce. Also, little is known about trajectories of kidney function before hospitalization with AKI. METHODS: We used data from biennial face-to-face study visits from the prospective Berlin Initiative Study (BIS) including community-dwelling participants aged 70+ with repeat estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C. Primary outcome was first incident of hospital-acquired AKI assessed through linked insurance claims data. In a nested case-control study, kidney function decline prior to hospitalization with and without AKI was investigated using eGFR trajectories estimated with mixed-effects models adjusted for traditional cardiovascular comorbidities. RESULTS: Out of 2020 study participants (52.9% women; mean age 80.4 years) without prior AKI, 383 developed a first incident AKI, 1518 were hospitalized without AKI, and 119 were never hospitalized during a median follow-up of 8.8 years. IR per 1000 person years for hospital-acquired AKI was 26.8 (95% confidence interval (CI): 24.1-29.6); higher for men than women (33.9 (29.5-38.7) vs. 21.2 (18.1-24.6)). IR (CI) were lowest for persons aged 70-75 (13.1; 10.0-16.8) and highest for ≥ 90 years (54.6; 40.0-72.9). eGFR trajectories declined more steeply in men and women with AKI compared to men and women without AKI years before hospitalization. These differences in eGFR trajectories remained after adjustment for traditional comorbidities. CONCLUSION: AKI is a frequent in-hospital complication in individuals aged 70 + showing a striking increase of IR with age. eGFR decline was steeper in elderly patients with AKI compared to elderly patients without AKI years prior to hospitalization emphasising the need for long-term kidney function monitoring pre-admission to improve risk stratification.

Rivaroxaban versus Apixaban for Treatment of Cancer-Associated Venous Thromboembolism in Patients at Lower Risk of Bleeding.

This retrospective study, utilizing U.S. electronic health record (EHR) data from January 2013 to December 2020, sought to assess whether rivaroxaban and apixaban had similar effectiveness and safety in the treatment of cancer-associated venous thromboembolism (VTE) in patients with a cancer type not associated with a high risk of bleeding. We included adults diagnosed with active cancer, excluding esophageal, gastric, unresected colorectal, bladder, noncerebral central nervous system cancers and leukemia, who experienced VTE and received a therapeutic VTE dose of rivaroxaban or apixaban on day 7 post-VTE, and were active in the EHR ≥12 months prior to the VTE. Primary outcome was the composite of recurrent VTE or any bleed resulting in hospitalization at 3 months. Secondary outcomes included recurrent VTE, any bleed resulting in hospitalization, any critical organ bleed, and composites of these outcomes at 3 and 6 months. Inverse probability of treatment-weighted Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 1,344 apixaban and 1,093 rivaroxaban patients. At 3 months, rivaroxaban was found to have similar hazard to apixaban for developing recurrent VTE or any bleed resulting in hospitalization (HR: 0.87; 95% CI: 0.60-1.27). No differences were observed between cohorts for this outcome at 6 months (HR: 1.00; 95% CI: 0.71-1.40) or for any other outcome at 3 or 6 months. In conclusion, patients receiving rivaroxaban or apixaban showed similar risks of the composite of recurrent VTE or any bleed resulting in hospitalization in patients with cancer-associated VTE. This study was registered at www.clinicaltrials.gov as #NCT05461807. Key Points Rivaroxaban and apixaban have similar effectiveness and safety for treatment of cancer-associated VTE through 6 months.Clinicians should therefore consider patient preference and adherence when choosing the optimal anticoagulant.

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).

Risk factors for major gastrointestinal bleeding in the general population in Finland.

BACKGROUND: Data on non-drug related risk-factors for gastrointestinal bleeding (GIB) in the general population are limited, especially for life-style factors, clinical measurements and laboratory parameters. AIM: To identify and investigate non-drug risk factors for major GIB in the general population of Finland. METHODS: We performed a retrospective cohort study using data from the FINRISK health examination surveys, which have been conducted every 5 years across Finland from 1987 to 2007. Participants were adults aged 25 years to 74 years, excluding those with a previous hospitalization for GIB. Follow-up from enrollment was performed through linkage to national electronic health registers and ended at an event of GIB that led to hospitalization/death, death due to any other cause, or after 10 years. Covariates included demographics, socioeconomic and lifestyle factors, clinical measurements, laboratory parameters and comorbidities. Variable selection was undertaken using Least Absolute Shrinkage and Selection Operator (LASSO) and factors associated with GIB were identified using Cox regression. RESULTS: Among 33,508 participants, 403 (1.2%) experienced GIB [256 men (63.5%); mean age, 56.0 years (standard deviation (SD) ± 12.1)] and 33105 who did not experience GIB [15768 men (47.6%); mean age, 46.8 (SD ± 13) years], within 10 years of follow-up. Factors associated with a significantly increased risk of GIB were baseline age [per 10-year increase; hazard ratio (HR) 1.62, 95% confidence interval (CI): 1.42-1.86], unemployment (HR: 1.70, 95%CI: 1.11-2.59), body mass index (BMI) (HR: 1.15, 95%CI: 1.01-1.32), gamma-glutamyl transferase (GGT) (HR: 1.05, 95%CI: 1.02-1.09), precursors of GIB (HR: 1.90, 95%CI: 1.37-2.63), cancer (HR: 1.47, 95%CI: 1.10-1.97), psychiatric disorders (HR: 1.32, 95%CI: 1.01-1.71), heart failure (HR: 1.46, 95%CI: 1.04-2.05), and liver disorders (HR: 3.20, 95%CI: 2.06-4.97). Factors associated with a significantly decreased risk of GIB were systolic blood pressure (SBP) (HR: 0.78, 95%CI: 0.64-0.96), 6-10 cups of coffee a day (HR: 0.67, 95%CI: 0.46-0.99), or > 10 cups (HR: 0.43, 95%CI: 0.23-0.81). CONCLUSION: Our study confirms established risk-factors for GIB and identifies potential risk-factors not previously reported such as unemployment, BMI, GGT, SBP and coffee consumption.

Risk of venous thromboembolism in men with prostate cancer compared with men in the general population: a nationwide population-based cohort study in Sweden.

OBJECTIVE: To estimate the additional risk of venous thromboembolism (VTE) in men with prostate cancer compared with men without prostate cancer in Sweden. DESIGN: Nationwide cohort study following 92 105 men with prostate cancer and 466 241 men without prostate cancer (comparison cohort) matched 5:1 by birth year and residential region. SETTING: The male general population of Sweden (using the Nationwide Prostate Cancer data Base Sweden). PRIMARY AND SECONDARY OUTCOME MEASURES: Crude incidence proportion ratios (IPRs) comparing the incidence of VTE in men with prostate cancer and men in the comparison cohort. Cox regression was used to calculate HRs for VTE adjusted for confounders. RESULTS: 2955 men with prostate cancer and 9774 men in the comparison cohort experienced a first VTE during a median of 4.5 years' follow-up. Deep vein thrombosis (DVT) accounted for 52% of VTE cases in both cohorts. Median time from start of follow-up to VTE was 2.5 years (IQR 0.9-4.7) in the prostate cancer cohort and 2.9 years (IQR 1.3-5.0) in the comparison cohort. Crude incidence rates of VTE per 1000 person-years were 6.54 (95% CI 6.31 to 6.78) in the prostate cancer cohort (n=2955 events) and 4.27 (95% CI 4.18 to 4.35) in the comparison cohort (n=9774 events). The IPR decreased from 2.53 (95% CI 2.26 to 2.83) at 6 months to 1.59 (95% CI 1.52 to 1.67) at 5 years' follow-up. Adjusted HRs were 1.48 (95% CI 1.39 to 1.57) for DVT and 1.47 (95% CI 1.39 to 1.56) for pulmonary embolism after adjustment for patient characteristics. CONCLUSIONS: Swedish men with prostate cancer had a mean 50% increased risk of VTE during the 5 years following their cancer diagnosis compared with matched men free of prostate cancer. Physicians should be mindful of this marked increase in VTE risk in men with prostate cancer to help ensure timely diagnosis.

Population-based study of long-term anticoagulation for treatment and secondary prophylaxis of venous thromboembolism in men with prostate cancer in Sweden.

BACKGROUND: Epidemiological data on anticoagulation for venous thromboembolism (VTE) in prostate cancer are sparse. We aimed to investigate associations between anticoagulation duration and risks of VTE recurrence after treatment cessation and major on-treatment bleeding in men with prostate cancer in Sweden. METHODS: Using nationwide prostate cancer registry and prescribing data, we followed 1413 men with VTE and an outpatient anticoagulant prescription following prostate cancer diagnosis. Men were followed to identify cases of recurrent VTE, and hospitalized major bleeding. We calculated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) to quantify the association between anticoagulation duration (reference ≤ 3 months) and recurrent VTE using Cox regression. We estimated 1-year cumulative incidences of major bleedings from anticoagulation initiation. RESULTS: The outpatient anticoagulation prescribed was parenteral (64%), direct oral anticoagulant (31%), and vitamin K antagonist (20%). Median duration of anticoagulation was 7 months. Adjusted HRs (95% CI) for off-treatment recurrent pulmonary embolism (PE) were 0.32 (0.09-1.15) for > 3-6 months' duration, 0.21 (0.06-0.69) for > 6-9 months and 0.16 (0.05-0.55) for > 9 months; corresponding HRs for deep vein thrombosis (DVT) were 0.67 (0.27-1.66), 0.80 (0.31-2.07), and 1.19 (0.47-3.02). One-year cumulative incidences of intracranial, gastrointestinal and urogenital bleeding were 0.9%, 1.7%, 3.0% during treatment, and 1.2%, 0.9%, 1.6% after treatment cessation. CONCLUSION: The greatest possible benefit in reducing recurrent VTE risk occurred with > 9 months anticoagulation for PE and > 3-6 months for DVT, but larger studies are needed to confirm this. Risks of major bleeding were low overall.

Renal decline in patients with non-valvular atrial fibrillation treated with rivaroxaban or warfarin: A population-based study from the United Kingdom.

BACKGROUND: Reports suggest that renal decline is greater among patients with non-valvular atrial fibrillation (NVAF) treated chronically with warfarin vs. some non-vitamin K antagonist oral anticoagulants. METHODS AND RESULTS: Using primary care electronic health records from the United Kingdom we followed adults with NVAF and who started rivaroxaban (20 mg/day, N = 5338) or warfarin (N = 6314), excluding those with estimated glomerular filtration rate (eGFR) <50 ml/min/1.73m2, end-stage renal disease (ESRD) or no eGFR or serum creatinine (SCr) values recorded in the previous year. Outcomes were: doubling SCr levels, ≥30% decline in eGFR and progression to ESRD. We calculated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome. Average eGFR slope was estimated using mixed model regression. After a mean follow-up 2.5 years, the number of incident cases of adverse renal events within the two cohorts was: doubling SCr (n = 322), ≥30% decline in eGFR (n = 1179), and progression to ESRD (n = 22). Adjusted HRs (95% CIs) for the renal outcomes among rivaroxaban vs. warfarin users were: doubling SCr, 0.63 (0.49-0.81); ≥30% decline in eGFR, 0.76 (0.67-0.86); ESRD, 0.77 (0.29-2.04). Similar results were observed among patients with diabetes or heart failure. Estimated mean decline in renal function over the study period was 2.03 ml/min/1.73 m2/year among warfarin users and 1.65 ml/min/1.73 m2/year among rivaroxaban users (p = 0.03). CONCLUSIONS: We found clear evidence that patients with NVAF, preserved renal function at baseline and treated with rivaroxaban had a markedly reduced risk and rate of renal decline compared with those treated with warfarin.

Overall survival and second primary malignancies in men with metastatic prostate cancer.

BACKGROUND: Among prostate cancer (PC) patients, over 90% of distant metastases occur in the bone. PC treatments may be associated with side effects, including second primary malignancies (SPM). There is limited information on the incidence of SPM among men with bone metastatic PC (mPC) and among men with bone metastatic castration-resistant PC (mCRPC). We estimated overall survival and the incidence of SPM in men with mPC and mCRPC. METHODS: In the Prostate Cancer data Base Sweden, the National Prostate Cancer Register was linked to other national health care registers, 15,953 men with mPC in 1999-2011 were identified. Further, 693 men with mCRPC were identified. Outcomes were evaluated using stratified incidence rates, Kaplan-Meier estimators and Cox models. RESULTS: The mean age among men with mPC was 73.9 years and in men with mCRPC 70.0 years. The median respective survivals were 1.5 (13,965 deaths) and 1.14 years (599 deaths), and average times since PC diagnosis 1.8 and 4.7 years. We observed 2,669 SPMs in men with mPC and 100 SPMs in men with mCRPC. The incidence rate of SPM per 1,000 person-years was 81.8 (78.8-85.0) for mPC and 115.6 (95.1-140.7) for mCRPC. High age, prior neoplasms, urinary tract infection, congestive heart failure, diabetes and renal disease were most strongly associated with increased mortality risk. Prior neoplasms and prior use of antineoplastic agents were most strongly associated with increased SPM risk. Several factors associated with increased mortality and SPM risks were more prevalent in the mCRPC cohort. CONCLUSIONS: Our results on mortality for men with mPC and mCRPC are in line with previous studies from the same time period. Investigation of factors associated with mortality and SPM in men with mPC and mCRPC can help to further understand these outcomes in the era prior to several new treatments have come available.

Cancer risk in association with Parkinson disease: a population-based study.

PURPOSE: Data from large population-based studies on the association between Parkinson disease (PD) and the risk of developing cancer are scarce. We compared the risk of developing incident cancer between patients with or without PD. METHODS: We conducted a population-based follow-up study and a nested case-control analysis using data from the UK-based General Practice Research Database. We included PD patients aged >or=40 years with a first PD diagnosis between 1994 and 2005, and a matched comparison group free of PD. We assessed cancer incidence rates and relative risk estimates (odds ratios [ORs] with 95% confidence intervals [CI]). RESULTS: The risk of developing cancer overall was lower in PD patients as compared to patients without PD (crude incidence rate ratio 0.77, 95% CI 0.64-0.92). In the nested case-control analysis (adj. OR for all cancers 0.72, 95% CI 0.59-0.87) the risk reduction was strongest for smoking-related cancers (adj. OR 0.47, 95% CI 0.31-0.72). The adjusted OR for hematological malignancies was 0.32 (95% CI 0.14-0.74). Due to small numbers, ORs for other cancer entities did not reach statistical significance. CONCLUSIONS: With the exception of melanoma, PD patients were less likely to develop cancer than individuals without PD in this large observational study.