Treatment Patterns and Survival Outcomes Among Androgen Receptor Pathway Inhibitor-Experienced Patients With Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: There is limited real-world data regarding subsequent treatment utilization and clinical outcomes following initial androgen receptor pathway inhibitor (ARPI) exposure for the treatment of advanced prostate cancer. This study aimed to address this evidence gap. METHODS: Electronic health records during 01/01/2013-07/31/2022 from Flatiron Health were used to identify adults with mCRPC, who had prior exposure to ARPIs (irrespective of the setting) and ≥1 post-ARPI line of therapy (LOT) in the mCRPC setting (index therapy: the first eligible LOT in the mCRPC setting). Treatment patterns and survival outcomes following the initiation of index therapy were reported. RESULTS: Among 804 ARPI-experienced mCRPC patients, 459 patients (57.1%) received another ARPI as their index therapy and 192 (23.9%) received chemotherapy as their index therapy. In the overall population, median time on the index therapy and median time from index therapy to next therapy were 4.1 and 6.2 months, respectively. Median overall survival and radiographic progression-free survival from the initiation of index therapy were 15.1 and 7.0 months, respectively. CONCLUSIONS: In this real-world analysis, more than half of patients attempted at least 1 additional ARPI in the mCRPC setting, despite prior treatment with ARPIs. The short treatment duration and survival time highlight the unmet need for additional, effective therapies that may improve clinical outcomes in this population.

Long-Term Temporal Trends of Real-World Healthcare Costs Associated with Nivolumab Plus Ipilimumab and Pembrolizumab Plus Axitinib as First-Line Treatment for Advanced or Metastatic Renal Cell Carcinoma.

INTRODUCTION: Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) are first-line (1L) treatments for advanced or metastatic renal cell carcinoma (aRCC), although the long-term trends in their associated real-world healthcare costs are not well defined. We compared the real-world healthcare costs of patients with aRCC who received 1L NIVO + IPI or PEM + AXI over 24 months. METHODS: Adults with RCC and secondary malignancy who initiated 1L NIVO + IPI or PEM + AXI were identified in the Merative MarketScan Commercial and Medicare Supplemental Databases (01/01/2004 to 09/30/2021). All-cause and RCC-related healthcare costs (unadjusted and adjusted) were assessed per patient per month (PPPM) at 6-month intervals post-treatment initiation (index date) up to 24 months, and differences between the NIVO + IPI and PEM + AXI cohorts were compared. RESULTS: Of 325 patients with aRCC, 219 received NIVO + IPI and 106 received PEM + AXI as the 1L treatment. According to patients' follow-up length, the analyses for months 7-12 included 210 patients in the NIVO + IPI cohort and 103 in the PEM + AXI cohort; months 13-18 included 119 and 48 patients, respectively; and months 19-24 included 81 and 25 patients. PPPM unadjusted all-cause total costs were $46,348 for NIVO + IPI and $38,097 for PEM + AXI in months 1-6; $26,840 versus $27,983, respectively, in months 7-12; $22,899 versus $25,137 in months 13-18; and $22,279 versus $27,947 in months 19-24. PPPM unadjusted RCC-related costs were $44,059 for NIVO + IPI and $36,456 for PEM + AXI in months 1-6; $25,144 versus $26,692, respectively, in months 7-12; $21,645 versus $23,709 in months 13-18; and $20,486 versus $25,515 in months 19-24. PPPM costs declined more rapidly for patients receiving NIVO + IPI compared to those receiving PEM + AXI, resulting in significantly lower all-cause costs associated with NIVO + IPI during months 19-24 (difference - $10,914 [95% confidence interval - $21,436, - $1091]) and RCC-related costs during months 7-12 (- $4747 [(- $8929, - $512]) and 19-24 (- $10,261 [- $20,842, - $421]) after adjustment. Cost savings for NIVO + IPI versus PEM + AXI were driven by differences in drug costs which, after adjustment, were significantly lower in months 7-12 (difference - $5555 [all-cause], - $5689 [RCC-related]); 13-18 (- $7217 and - $6870, respectively); and 19-24 (- $16,682 and - $16,125). CONCLUSION: Although the real-world PPPM healthcare costs of 1L NIVO + IPI were higher compared with PEM + AXI in the first 6 months of treatment, the costs associated with NIVO + IPI rapidly declined thereafter, resulting in significantly lower costs vs. PEM + AXI from months 7 to 24.

Treatment Preferences Among Patients with Renal Cell Carcinoma: Results from a Discrete Choice Experiment.

Introduction: The treatment landscape for advanced/metastatic renal cell carcinoma (aRCC) has evolved quickly with the introduction of immunotherapies as a first-line treatment option. This study examined the preferences of patients with aRCC to better understand the characteristics of preferred treatments and the tradeoffs patients are willing to make when choosing treatment. Methods and Materials: An online, cross-sectional survey was conducted in the US from May to August 2022 with adult patients with aRCC. A discrete-choice experiment assessed treatment preferences for aRCC. Attributes were identified through literature review and qualitative interviews and included progression-free survival, survival time, objective response rate, duration of response, risk of serious side effects, quality of life (QoL), and treatment regimen. Results: Survey results from 299 patients with aRCC were analyzed. Patients had a mean age of 55.7 years, were primarily White (50.5%) and were evenly representative of males (49.8%) and females (48.8%). Improvements in all attributes influenced treatment choice. On average, increasing survival time from 10% to 55% was most important, followed by improvements in QoL (ie, from worsens a lot to improves) and improvements to treatment regimen convenience (ie, less frequent infusions). Risk of serious adverse events and increased progression-free time, objective response rate (ORR), and duration of response (DOR) were of lesser importance. Conclusion: In this study, patients highlighted that improving survival time was the most important and that QoL is also an important consideration. Discussions during treatment decision-making may benefit from broader conversations around treatment characteristics, including impacts on QoL and convenience of the regimen.

Treatment-free survival and partitioned survival analysis of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib: 5-year update of CheckMate 214.

BACKGROUND: Immunotherapy can be associated with prolonged disease control even after cessation of treatment without the need for further cancer-directed therapy. Treatment-related adverse events (TRAEs) can also persist after discontinuation of therapy. Treatment-free survival (TFS) with and without toxicity as a component of a partitioned survival model can characterize patient survival time, which is not captured by standard outcome measures. METHODS: Data from 1096 patients with advanced renal cell carcinoma treated with first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the CheckMate 214 trial were analyzed. TFS was defined as the area between two Kaplan-Meier curves for time from randomization to protocol therapy discontinuation and time from randomization to subsequent systemic therapy initiation or death, estimated as the difference in 60-month restricted mean times with confidence intervals (CIs) obtained using bootstrap sampling. Time on protocol therapy and TFS were further characterized as time with and without grade 2+ and 3+TRAEs. Survival functions were estimated in subgroups including International Metastatic Renal Cell Carcinoma Database Consortium risk groups using the Kaplan-Meier method. RESULTS: At 5 years from randomization, 48% of patients treated with NIVO+IPI and 37% of patients treated with SUN were alive. In the intent-to-treat population, 18% of the NIVO+IPI-treated and 5% of SUN-treated patients are surviving treatment-free. For favorable-risk patients, the 60-month mean TFS was 14.4 months for NIVO+IPI versus 5.5 months for SUN (difference 8.9 months (95% CI 4.9 to 12.8)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 5.0 and 2.1 months, respectively, and with grade 3+TRAEs was 1.2 and 0.3 months, respectively. For intermediate/poor-risk patients, the 60-month mean TFS was 10.1 months for NIVO+IPI versus 4.1 months for SUN (difference 6.1 months (95% CI 4.2 to 7.9)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 4.0 versus 2.0 months, respectively, and 0.6 versus 0.3 months with grade 3+TRAEs. CONCLUSIONS: Although overall survival was similar, favorable-risk patients treated with NIVO+IPI spent more time surviving treatment-free with and without toxicity versus SUN after 60 months of follow-up. Intermediate/poor-risk patients treated with NIVO+IPI had longer survival and longer TFS without toxicity versus SUN. TRIAL REGISTRATION NUMBER: NCT02231749.

Temporal trends in anticoagulation use and clinical outcomes among medicare beneficiaries with non-valvular atrial fibrillation.

PURPOSE: Oral anticoagulants effectively prevent stroke/systemic embolism among patients with non-valvular atrial fibrillation but remain under-prescribed. This study evaluated temporal trends in oral anticoagulant use, the incidence of stroke/systemic embolism and major bleeding, and economic outcomes among elderly patients with non-valvular atrial fibrillation and CHA2DS2-VASc scores ≥ 2. METHODS: Retrospective analyses were conducted on Medicare claims data from January 1, 2012 through December 31, 2017. Non-valvular atrial fibrillation patients aged ≥ 65 years with CHA2DS2-VASc scores ≥ 2 were stratified by calendar year (2013-2016) of care to create calendar-year cohorts. Patient characteristics were evaluated across all cohorts during the baseline period (12 months before diagnosis). Treatment patterns and clinical and economic outcomes were evaluated during the follow-up period (from diagnosis through 12 months). RESULTS: Baseline patient characteristics remained generally similar between 2013 and 2016. Although lack of oral anticoagulant prescriptions among eligible patients remained relatively high, utilization did increase progressively (53-58%). Among treated patients, there was a progressive decrease in warfarin use (79-52%) and a progressive increase in overall direct oral anticoagulant use (21-48%). There were progressive decreases in the incidence of stroke/systemic embolism 1.9-1.4 events per 100 person years) and major bleeding (4.6-3.3 events per 100 person years) as well as all-cause costs between 2013 and 2016. CONCLUSIONS: The proportions of patients with non-valvular atrial fibrillation who were not prescribed an oral anticoagulant decreased but remained high. We observed an increase in direct oral anticoagulant use that coincided with decreased incidence of clinical outcomes as well as decreasing total healthcare costs.

Effectiveness and Safety of Apixaban vs Warfarin in Patients with Venous Thromboembolism with Risk Factors for Bleeding or for Recurrences.

INTRODUCTION: Patients at increased risk of bleeding and recurrent VTE who develop venous thromboembolism (VTE) present challenges for clinical management. This study evaluated the effectiveness and safety of apixaban vs warfarin in patients with VTE who have risk factors for bleeding or recurrences. METHODS: Adult patients with VTE initiating apixaban or warfarin were identified from five claims databases. Stabilized inverse probability treatment weighting (IPTW) was used to balance characteristics between cohorts for the main analysis. Subgroup interaction analyses were conducted to evaluate treatment effects among patients with and without each of the conditions that increased the risk of bleeding (thrombocytopenia and history of bleed) or recurrent VTE (thrombophilia, chronic liver disease, and immune-mediated disorders). RESULTS: A total of 94,333 warfarin and 60,786 apixaban patients with VTE met selection criteria. After IPTW, all patient characteristics were balanced between cohorts. Apixaban (vs warfarin) patients were at lower risk of recurrent VTE (HR [95% confidence interval (CI) 0.72 [0.67-0.78]), major bleeding (MB) (HR [95% CI] 0.70 [0.64-0.76]), and clinically relevant non-major (CRNM) bleeding (HR [95% CI] 0.83 [0.80-0.86]). Subgroup analyses showed generally consistent findings with the overall analysis. For most subgroup analyses, there were no significant interactions between treatment and subgroup strata on VTE, MB and CRNM bleeding. CONCLUSION: Patients with prescription fills for apixaban had lower risk of recurrent VTE, MB, and CRNM bleeding compared with warfarin patients. Treatment effects of apixaban vs warfarin were generally consistent across subgroups of patients at increased risk of bleeding/recurrences.

Venous thromboembolism incidence and risk factors associated with immune checkpoint inhibitors among patients with advanced non-small cell lung cancer.

BACKGROUND: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in patients with lung cancer. Systemic therapies, such as chemotherapy (chemo), are associated with increased risk of VTE. Immune checkpoint inhibitors (ICIs) are a new standard of care for the treatment of lung cancer, but their association with VTE is not fully understood. We evaluated the incidence of VTE and risk factors for patients with advanced non-small cell lung cancer (aNSCLC) treated with first-line ICI-based, chemo-based, or ICI+chemo regimens. METHODS: This retrospective cohort study used HealthCore Integrated Research Environment - Oncology data, an integrated database of administrative claims, coupled with clinical data from a cancer-care quality program. Patients with first-line treatment of stage IV non-small cell lung cancer from July 2014 to August 2020 were grouped based on three treatment types: ICI-based, chemo-based, or ICI+chemo. Patients with VTE before initiation of systemic treatment were excluded. Newly diagnosed VTE events were identified via inpatient and outpatient diagnosis codes. Cox proportional hazards models were used to investigate the factors associated with VTE risk. RESULTS: Among 2299 eligible patients (ICI-based, n=605; chemo-based, n=1092; ICI+chemo, n=602) with a median follow-up of 9.1 months, the VTE incidence rates (95% CI) per 100 person-years were 17.8 (95% CI 16.0 to 19.5) overall, 13.5 (95% CI 10.6 to 16.5) for ICI-based, 18.0 (95% CI 15.5 to 20.5) for chemo-based, and 22.4 (95% CI 20.2 to 24.5) for ICI+chemo. The 6-month cumulative incidence of VTE was 8.1% for ICI-based, 10.9% for chemo-based, and 12.8% for ICI+chemo. Pulmonary embolism was most common, accounting for 63% of the VTE events. After controlling for baseline patient characteristics, the risk of VTE was 26% lower for ICI-based regimens than for chemo-based regimens (HR 0.74, p=0.03). There was no meaningful difference in the risk between ICI+chemo and chemo-based regimens (HR 1.12, p=0.36). Previous radiation and severe obesity (body mass index ≥40) were associated with VTE. CONCLUSIONS: VTE incidence rate per 100 person-years was common across regimens in patients with aNSCLC, but numerically lower for patients receiving ICI-based regimens compared with those receiving chemo-based and ICI+chemo regimens. VTE is a common complication of lung cancer, and there is a continued need for awareness of VTE as a comorbidity in this population.

Effectiveness and safety of apixaban vs warfarin among venous thromboembolism patients at high-risk of bleeding.

This study evaluated effectiveness and safety of apixaban versus warfarin among venous thromboembolism patients at high-risk of bleeding (defined as having at least one of the following bleeding risk factors: ≥75 years; used antiplatelet, NSAIDs, or corticosteroids; had prior gastrointestinal bleeding or gastrointestinal-related conditions; late stage chronic kidney disease). Adult venous thromboembolism patients initiating apixaban or warfarin with ≥1 bleeding risk factor were identified from Medicare and four commercial claims databases in the United States. To balance characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting was conducted. Cox proportional hazards models were used to estimate the risk of recurrent venous thromboembolism, major bleeding, and clinically relevant non-major bleeding. In total, 88,281 patients were identified. After inverse probability treatment weighting, the baseline patient characteristics were well-balanced between the two cohorts. Among venous thromboembolism patients at high-risk of bleeding, apixaban was associated with significantly lower risk of recurrent venous thromboembolism, major bleeding and clinically relevant non-major bleeding. No significant interactions were observed between treatment and number of risk factors on major bleeding and clinically relevant non-major bleeding or between treatment and type of bleeding risk factors on any of the outcomes. In conclusion, apixaban was associated with significantly lower risk of recurrent venous thromboembolism and bleeding among venous thromboembolism patients at high-risk of bleeding. Effects were generally consistent across subgroups of patients with different number or type of bleeding risk factors.

Risk of stroke/systemic embolism, major bleeding, and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran, or rivaroxaban compared with warfarin in the United States medicare population: updated analysis.

OBJECTIVE: To provide an updated comparison of the risk and cost of stroke/systemic embolism (SE) and major bleeding between direct oral anticoagulants (DOAC: apixaban, rivaroxaban, dabigatran) and warfarin among non-valvular atrial fibrillation (NVAF) patients. METHODS: Adults (≥65 years) initiating warfarin or DOACs between 1 January 2013 and 31 December 2014 were selected from the Medicare database and propensity scores matched 1:1 to balance baseline characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major bleeding-related medical costs in each matched cohort. RESULTS: Of the 264,479 eligible patients, 38,740 apixaban-warfarin pairs, 76,677 rivaroxaban-warfarin pairs, and 20,955 dabigatran-warfarin pairs were matched. Apixaban (Hazard Ratio [HR] = 0.46; 95% Confidence Interval [CI] 0.38-0.56) and rivaroxaban (HR = 0.71; 95% CI 0.63-0.80) were associated with a significantly lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.57; 95% CI 0.51-0.63) and dabigatran (HR = 0.80; 95% CI 0.70-0.90) were associated with a significantly lower risk of major bleeding; rivaroxaban (HR = 1.14; 95% CI 1.07-1.21) was associated with a significantly higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban and rivaroxaban had significantly lower stroke/SE-related medical costs; and apixaban and dabigatran had significantly lower major bleeding-related medical costs. CONCLUSIONS: This real-world analysis showed DOACs to be associated with a lower risk of stroke/SE and major bleeding, and lower medical costs compared to warfarin. Among them, only apixaban appears to be associated with a significantly lower risk of all three outcomes collectively: stroke/SE, major bleeding, and lower related medical costs compared to warfarin.

Impact of apixaban treatment discontinuation on the risk of hospitalization among patients with nonvalvular atrial fibrillation and COVID-19.

INTRODUCTION: This study evaluated the risk of hospitalization among nonvalvular atrial fibrillation (NVAF) patients with an outpatient COVID-19 diagnosis who discontinued vs continued apixaban treatment. METHODS: Adult patients with NVAF with an apixaban prescription prior to an outpatient COVID-19 diagnosis were identified from Optum Clinformatics claims database (1 April 2020-31 March 2021). Continuers were those who continued apixaban as of the index date (date of initial outpatient COVID-19 diagnosis) and discontinuers were those who had the last day of apixaban supply on or before index. Patients were followed from COVID-19 diagnosis to change of continuation/discontinuation status, switch, death, end of continuous coverage or study end, whichever occurred first. Inverse probability treatment weighting (IPTW) was performed to balance cohorts. Cox proportional hazard models were used to compare the risk of all-cause hospitalization and hospitalization for ischemic stroke (IS), venous thromboembolism (VTE), myocardial infarction (MI), bleeding and mortality. RESULTS: A total of 7869 apixaban patients with COVID-19 were included: 6676 continuers (84.8%) and 1193 discontinuers (15.2%). Compared with continuers, discontinuers had a higher risk of all-cause hospitalization (hazard ratio [HR]: 1.23; 95% confidence interval [CI]: 1.08-1.40), IS (HR: 2.00; 95% CI: 1.03-3.87), VTE (HR: 2.37; 95% CI: 1.06-5.27) and mortality (HR: 2.28; 95% CI: 1.85-2.80). There were no significant differences in the risk of MI (HR: 1.01; 95% CI: 0.54-1.90) or bleeding-related hospitalization (HR: 1.13; 95% CI: 0.73-1.76). CONCLUSION: NVAF patients with COVID-19 who discontinued apixaban had a higher risk of hospitalization and thrombotic events vs those who continued apixaban, with no significant difference in bleeding-related hospitalization.

Risk Levels and Adverse Clinical Outcomes Among Patients With Nonvalvular Atrial Fibrillation Receiving Oral Anticoagulants.

Importance: The CHA2DS2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or TIA, vascular disease, age 65 to 74 years, and sex category) is the standard for assessing risk of stroke and systemic embolism and includes age and thromboembolic history. To our knowledge, no studies have comprehensively evaluated safety and effectiveness outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants according to independent, categorical risk strata. Objective: To evaluate the incidence of key adverse outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants by CHA2DS2-VASc risk score range, thromboembolic event history, and age group. Design, Setting, and Participants: This cohort study was a retrospective claims data analysis using combined data sets from 5 large health claims databases. Eligible participants were adult patients with nonvalvular atrial fibrillation who initiated oral anticoagulants. Data were analyzed between January 2012 and June 2019. Exposure: Initiation of oral anticoagulants. Main Outcomes and Measures: We observed clinical outcomes (including stroke or systemic embolism, major bleeding, and a composite outcome) on treatment through study end, censoring for discontinuation of oral anticoagulants, death, and insurance disenrollment. The population was stratified by CHA2DS2-VASc risk score; history of stroke, systemic embolism, or transient ischemic attack; and age groups. We calculated time to event, incidence rates, and cumulative incidence for outcomes. Results: We identified 1 141 097 patients with nonvalvular atrial fibrillation; the mean (SD) age was 75.0 (10.5) years, 608 127 patients (53.3%) were men, and over 1 million were placed in the 2 highest risk categories (high risk 1, 327 766 participants; high risk 2, 688 449 participants). Deyo-Charlson Comorbidity Index scores ranged progressively alongside CHA2DS2-VASc risk score strata (mean [SD] scores: low risk, 0.4 [1.0]; high risk 2, 4.1 [2.9]). The crude incidence of stroke and systemic embolism generally progressed alongside risk score strata (low risk, 0.25 events per 100 person-years [95% CI, 0.18-0.34 events]; high risk 2, 3.43 events per 100 person-years [95% CI, 3.06-4.20 events]); patients at the second-highest risk strata with thromboembolic event history had higher stroke incidence vs patients at the highest risk score strata without event history (2.06 events per 100 person-years [95% CI, 2.00-3.12 events] vs 1.18 events per 100 person-years [95% CI, 1.14-1.30 events]). Major bleeding and composite incidence also increased progressively alongside risk score strata (major bleeding: low risk, 0.68 events per 100 person-years [95% CI, 0.56-0.82 events]; high risk 2, 6.29 events per 100 person-years [95% CI, 6.21-6.62 events]; composite incidence: 1.22 events per 100 person-years [95% CI, 1.06-1.41 events]; high risk 2, 10.67 events per 100 person-years [95% CI, 10.26-11.48 events]). The 12-month cumulative incidence proportions for stroke and systemic embolism, major bleeding, and composite outcomes progressed alongside risk score strata (stroke or systemic embolism, 0.30%-1.85%; major bleeding, 0.55%-5.55%; composite, 1.05%-8.23%). Age subgroup analysis followed similar trends. Conclusions and Relevance: The observed incidence of stroke or systemic embolism and major bleeding events generally conformed to an expected increasing incidence by risk score, adding insight into the importance of specific risk score range, thromboembolic event history, and age group strata. These results can help inform clinical decision-making, research, and policy.

Effectiveness and Safety of Apixaban versus Warfarin in Venous Thromboembolism Patients with Chronic Kidney Disease.

There has been limited evidence reported about the outcomes of oral anticoagulants among patients with venous thromboembolism (VTE) and chronic kidney disease (CKD), especially those with stage V/end-stage renal disease (ESRD). This retrospective cohort analysis of five U.S. claims databases evaluated the risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB) for apixaban versus warfarin among VTE patients diagnosed with CKD, including ESRD. Inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Hazard ratios (HRs) were calculated for recurrent VTE, MB, and CRNMB among patients with CKD who experienced an index VTE. An interaction analysis was conducted to evaluate treatment effects across different stages of CKD. A total of 29,790 VTE patients with CKD were selected for analyses, of whom 10,669 (35.8%) initiated apixaban and 19,121 (64.2%) initiated warfarin. Among IPTW-balanced patient cohorts, the apixaban group had significantly lower risk of recurrent VTE (HR: 0.78; 95% confidence interval [CI]: 0.66-0.92), MB (HR: 0.76; 95% CI: 0.65-0.88), and CRNMB (HR: 0.86; 95% CI: 0.80-0.93) than the warfarin group. When stratified by CKD stage (stage I/II: 8.2%; stage III: 49.4%; stage IV: 12.8%; stage V/ESRD: 12.0%; stage unspecified: 17.6%), no significant interaction was observed for effects of apixaban versus warfarin on recurrent VTE or MB. In summary, apixaban was associated with a significantly lower risk of recurrent VTE and MB than warfarin among VTE patients with CKD. CKD stages did not have significant impact on treatment effects for recurrent VTE and MB.

Effectiveness and Safety of Apixaban Versus Warfarin Among Older Patients with Venous Thromboembolism with Different Demographics and Socioeconomic Status.

INTRODUCTION: Impact of demographics and socioeconomic status (SES) on anticoagulant treatment outcomes among patients with venous thromboembolism (VTE) is not well understood. This study evaluated risks of recurrent VTE, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among older patients with VTE initiating apixaban or warfarin stratified by demographics and SES. METHODS: Adult patients (≥ 65 years) who initiated apixaban or warfarin after a VTE event were selected from the US CMS Medicare database (September 2014-December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Patients were stratified by age, gender, race, and SES. For each subgroup, Cox proportional hazard models were used to evaluate if there was a significant interaction (p < 0.10) between treatment and subgroup for recurrent VTE, MB, and CRNMB. RESULTS: In total, 22,135 apixaban and 45,840 warfarin patients with VTE were included. Post-IPTW, patient characteristics were balanced between treatment cohorts. In older patients, apixaban treatment was associated with significantly lower risks of recurrent VTE (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.52-0.79), MB (HR 0.65; 95% CI 0.57-0.75), and CRNMB (HR 0.79; 95% CI 0.75-0.85) versus warfarin. When stratified by demographics and SES, higher incidence rates of recurrent VTE, MB, and CRNMB were observed for black vs white patients and patients with lower vs higher SES. Comparison of apixaban with warfarin by different demographic and SES subgroups showed generally consistent results as the overall analysis. For most subgroups, no significant interaction was observed between treatment and subgroup strata for recurrent VTE, MB, and CRNMB. CONCLUSION: Among older patients with VTE initiating apixaban or warfarin, higher rates of recurrent VTE and bleeding were observed in black patients and patients with lower SES. Apixaban had a lower risk of recurrent VTE, MB, and CRNMB compared to warfarin. Analyses of demographic and SES subgroups showed consistent findings.

Use of Non-Vitamin K Antagonist Oral Anticoagulants Among Patients with Nonvalvular Atrial Fibrillation and Multimorbidity.

INTRODUCTION: Non-valvular atrial fibrillation (NVAF) is often accompanied by multiple comorbid conditions, which increase the associated risks and complexity of patient management. This study evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) among multimorbid patients with NVAF who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. METHODS: A retrospective study of patients with NVAF and high multimorbidity who initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013 to 30 September 2015 was conducted using five insurance claims databases. Multimorbidity was defined as six or more comorbid conditions, and 1:1 propensity score matching (PSM) was conducted between the NOAC-warfarin and NOAC-NOAC cohorts. Cox proportional hazard models were used to evaluate the hazard ratios of stroke/SE and MB. RESULTS: Of the NVAF population (n = 466,991), 33.4% (n = 155,959) had multimorbidity, including 36,921 apixaban, 10,248 dabigatran, 45,509 rivaroxaban, and 63,281 warfarin patients. Compared to warfarin, apixaban and rivaroxaban were associated with a lower risk of stroke/SE (hazard ratio [HR] 0.63, 95% CI 0.54-0.74; HR 0.70, 95% CI 0.64-0.77, respectively). Apixaban and dabigatran were associated with a lower risk of MB (HR 0.61, 95% CI 0.56-0.67; HR 0.75, 95% CI 0.66-0.86, respectively) and rivaroxaban was associated with a higher risk of MB (HR 1.06, 95% CI 1.01-1.12) compared to warfarin. CONCLUSIONS: Among patients with NVAF and six or more comorbid conditions, NOACs were associated with varying risk of stroke/SE and MB compared to warfarin and to each other. Rather than a "one drug fits all" approach, our results may be useful for appropriate OAC treatment for multimorbid patients.

Effectiveness and safety of apixaban, LMWH, and warfarin among high-risk subgroups of VTE patients with active cancer.

OBJECTIVE: This pooled claims database study evaluated the risk of recurrent Venous Thromboembolism (VTE) and major bleeding (MB) among patients with VTE and active cancer prescribed apixaban, low-molecular weight heparin (LMWH), or warfarin stratified by high-risk subgroups. METHODS: Patients diagnosed with VTE in the setting of active cancer who initiated apixaban, LMWH, or warfarin were identified using four US commercial claims databases from 01SEP2014 to the end of the study period (MarketScan: 01MAR2014-30JUNE2017; Optum and Humana: 01MAR2014-31DEC2017; PharMetrics: 01MAR2014-31MAR2018). Stabilized inverse probability treatment weighting (IPTW) was used to balance treatment cohorts. Cox proportional hazard models were used to evaluate the risk of recurrent VTE and MB for each subgroup stratification: VTE risk level based on cancer types, metastatic diagnosis, cancer treatment, chemotherapy, gastrointestinal cancer, and index VTE event type (PE vs. DVT). Statistical significance (p < .10) of the interaction between treatment effects and subgroups was evaluated. RESULTS: Eligible subjects included 3393 apixaban, 6108 LMWH, and 4585 warfarin patients. After IPTW, all patient characteristics were balanced. Analyses stratified by the VTE risk level, metastatic diagnosis, cancer treatment, chemotherapy, gastrointestinal cancer and index VTE event type showed generally consistent results according to the respective subgroup (most of the p values for interaction >0.10). Two significant interactions were observed between apixaban vs. LMWH and VTE risk level (interaction p = .051) and metastatic diagnosis (interaction p < .001) for recurrent VTE; one significant interactions were observed between apixaban vs. LMWH and cancer treatment for MB (interaction p = .074). Additionally, for warfarin vs. LMWH, two significant interactions were observed between treatment and VTE risk level (interaction p = .005) and metastatic diagnosis (interaction p = .002) for recurrent VTE. CONCLUSIONS: Across these high-risk subgroups of VTE cancer patients, treatment outcomes associated with apixaban were generally positive compared to LMWH and warfarin.

Burden of major gastrointestinal bleeding among oral anticoagulant-treated non-valvular atrial fibrillation patients.

BACKGROUND: Gastrointestinal (GI) bleeding is the most common type of major bleeding associated with oral anticoagulant (OAC) treatment. Patients with major bleeding are at an increased risk of a stroke if an OAC is not reinitiated. METHODS: Non-valvular atrial fibrillation (NVAF) patients initiating OACs were identified from the Centers for Medicare and Medicaid Services (CMS) Medicare data and four US commercial claims databases. Patients who had a major GI bleeding event (hospitalization with primary diagnosis of GI bleeding) while on an OAC were selected. A control cohort of patients without a major GI bleed during OAC treatment was matched to major GI bleeding patients using propensity scores. Stroke/systemic embolism (SE), major bleeding, and mortality (in the CMS population) were examined using Cox proportional hazards models with robust sandwich estimates. RESULTS: A total of 15,888 patients with major GI bleeding and 833,052 patients without major GI bleeding were included in the study. Within 90 days of the major GI bleed, 58% of patients discontinued the initial OAC treatment. Patients with a major GI bleed had a higher risk of stroke/SE [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.42-1.74], major bleeding (HR: 2.79, 95% CI: 2.64-2.95), and all-cause mortality (HR: 1.29, 95% CI: 1.23-1.36) than patients without a major GI bleed. CONCLUSION: Patients with a major GI bleed on OAC had a high rate of OAC discontinuation and significantly higher risk of stroke/SE, major bleeding, and mortality after hospital discharge than those without. Effective management strategies are needed for patients with risk factors for major GI bleeding.

Effectiveness and Safety of Apixaban vs. Warfarin in Venous Thromboembolism Patients with Obesity and Morbid Obesity.

This study integrated 5 United States healthcare claims databases to evaluate the risk of recurrent venous thromboembolism (VTE) and major bleeding (MB) among VTE patients who initiated apixaban vs. warfarin, stratified by obesity. Obese and morbidly obese patients were identified based on diagnosis codes. Stabilized inverse probability treatment weighting (IPTW) was conducted to balance observed patient characteristics between treatment cohorts. An interaction analysis was conducted to evaluate treatment effects of apixaban vs. warfarin according to obesity status. Cox proportional hazard models were used to evaluate the risk of recurrent VTE and MB among IPTW weighted obese and morbidly obese patients. A total of 112,024 non-obese patients and 43,095 obese patients were identified, of whom 19,751 were morbidly obese. When stratified by obesity status post-IPTW, no significant interactions were observed for effects of apixaban vs. warfarin on recurrent VTE or MB (interaction p > 0.10). Among IPTW obese and morbidly obese patients, apixaban was associated with a significantly lower risk of recurrent VTE (obese: 0.73 [0.64-0.84]; morbidly obese: 0.65 [0.53-0.80]) and MB (obese: 0.73 [0.62-0.85]; morbidly obese: 0.68 [0.54-0.86]) as compared with warfarin. In this large sample of obese and morbidly obese VTE patients, apixaban had a significantly lower risk of recurrent VTE and MB vs. warfarin.

Effectiveness and safety of oral anticoagulants among non-valvular atrial fibrillation patients with polypharmacy.

AIMS: Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and presents a potential issue for the effective management of NVAF. This study compared the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients with polypharmacy newly prescribed oral anticoagulants (OACs). METHODS AND RESULTS: A retrospective study of NVAF patients with polypharmacy who initiated OACs from 01 January 2013 to 30 September 2015 was conducted using US CMS Medicare and four commercial databases. Polypharmacy was defined as ≥6 concomitant medications on the index date. Propensity score matching was conducted to compare non-vitamin K antagonists OACs (NOACs) to warfarin as well as between NOACs. Cox proportional hazard models were used to evaluate the risk of stroke/SE and MB. A total of 188 893 patients with polypharmacy were included, with an average of 8 concomitant medications (interquartile range 6-9). Compared to warfarin, apixaban [hazard ratio (HR): 0.59, 95% confidence interval (CI): 0.52-0.68], and rivaroxaban (HR: 0.75, 95% CI: 0.69-0.83) were associated with a lower risk of stroke/SE. Apixaban (HR: 0.57, 95% CI: 0.54-0.61) and dabigatran (HR: 0.76, 95% CI: 0.66-0.88) were associated with a decreased risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of stroke/SE and MB. Dabigatran was associated with lower risk of MB compared with rivaroxaban. CONCLUSIONS: In this observational study of anticoagulated NVAF patients with polypharmacy, effectiveness and safety profiles are more favourable for NOACs vs. warfarin. Our observations are hypothesis generating and may help inform future clinical trials regarding appropriate OAC treatment selection in polypharmacy patients.

Safety and effectiveness of apixaban compared with warfarin among clinically-relevant subgroups of venous thromboembolism patients in the United States Medicare population.

BACKGROUND: The AMPLIFY trial found significantly lower major bleeding (MB) and similar recurrent venous thromboembolism (VTE) risks associated with apixaban vs warfarin among patients with VTE. OBJECTIVES: To compare MB, clinically-relevant non-major (CRNM) bleeding, and recurrent VTE risks among clinically-relevant subgroups of newly diagnosed elderly patients with VTE prescribed apixaban vs warfarin. METHODS: US Medicare patients prescribed apixaban or warfarin within 30 days post-VTE encounter were identified. Propensity score matching (PSM) was used to control for patient characteristics. Cox models were used to assess MB, CRNM bleeding, and recurrent VTE. Subgroup analyses were conducted for index VTE encounter type, index VTE diagnosis type, index VTE etiology, sex, and frailty. RESULTS: Post-PSM, 11,363 matched pairs of patients prescribed apixaban or warfarin were identified. Apixaban had lower MB (Hazard Ratio [HR]:0.76; 95% CI:0.64-0.91) and similar recurrent VTE risks (HR:1.04; 95% CI:0.75-1.43) vs warfarin. No significant interactions were observed between treatment and index VTE encounter type, index VTE diagnosis type, or sex for risk of MB, CRNM bleeding, or recurrent VTE. Significant interactions: frail patients prescribed apixaban had a 15% lower, while non-frail patients prescribed apixaban had 32% lower CRNM bleeding risk vs those prescribed warfarin. Patients with provoked VTE prescribed apixaban trended toward a higher, while those with unprovoked VTE trended toward a lower risk of recurrent VTE vs patients prescribed warfarin. CONCLUSIONS: Apixaban was associated with significantly lower risks of MB and CRNM bleeding, and similar risk of recurrent VTE as compared with warfarin across the overall population and most subgroups.

Effectiveness and Safety of Apixaban, Low-Molecular-Weight Heparin, and Warfarin among Venous Thromboembolism Patients with Active Cancer: A U.S. Claims Data Analysis.

BACKGROUND: This study primarily evaluates the risk of recurrent venous thromboembolism (VTE) and major bleeding (MB) among patients with VTE and active cancer prescribed apixaban, low-molecular-weight heparin (LMWH), or warfarin, with claims data. METHODS: Four U.S. commercial insurance claims databases were used to identify patients with VTE and active cancer who initiated apixaban, LMWH, or warfarin within 30 days following the first VTE event. Stabilized inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Cox proportional hazard models were used to evaluate risk of recurrent VTE and MB. RESULTS: All eligibility criteria were fulfilled by 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients. After IPTW, all patient characteristics were balanced. When the follow-up was censored at 6 months, apixaban patients had a lower risk of recurrent VTE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.47-0.81) and MB (HR: 0.63; 95% CI: 0.47-0.86) versus LMWH. Apixaban patients had a lower risk of recurrent VTE (HR: 0.68; 95% CI: 0.52-0.90) and similar risk of MB (HR: 0.73; 95% CI: 0.53-1.00) versus warfarin. Warfarin patients had a similar risk of recurrent VTE (HR: 0.91; 95% CI: 0.72-1.15) and MB (HR: 0.87; 95% CI: 0.68-1.12) versus LMWH. The trends were similar for the entire follow-up; however, apixaban patients had a lower risk of MB versus warfarin patients. CONCLUSION: Patients with VTE and active cancer who initiated apixaban had a lower risk of recurrent VTE and MB compared with LMWH patients. Apixaban patients also had a lower risk of recurrent VTE compared with warfarin patients.