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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. 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. 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. 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. 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. • Elderly patients are at a high risk of venous thromboembolism (VTE) • We evaluated safety and effectiveness of apixaban vs warfarin in clinically-relevant subgroups • Apixaban had a lower risk of major bleeding (MB) and similar risk of recurrent VTE vs warfarin. • The subgroup results for MB and recurrent VTE were generally consistent with the primary analysis. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether greater intraocular pressure (IOP) variation between visits was associated with higher likelihood of glaucoma progression. Design: Cohort study. Methods: A five-year minimum of data (June 1, 1990 through January 22, 2002) was collected on 151 patients (302 eyes) from 12 United States specialty centers. A post hoc analysis of visual field (VF) progression, glaucoma medication, intraocular pressure (IOP), and other ocular data was conducted for two nonmutually exclusive cohorts based on retrospective data abstracted well after actual patient visits. Mean IOP and standard deviations (SD) were calculated before treatment (medication or surgery) or progression, whichever occurred first, and before progression regardless of treatment. IOP variables were assessed in a univariate fashion; Cox proportional hazards models evaluated glaucoma progression as an outcome measure and IOP SD as a main predictor, controlling for covariates. Results: In cohort 1 (55 patients; 84 eyes), mean age was 63 years (range, 37 to 85 years), 58% were female, and 19% of eyes underwent VF progression. In cohort 2 (129 patients; 251 eyes), mean age was 66 years (range, 19 to 88 years), 55% were female, and 27% of eyes underwent VF progression. Mean IOP was 16.5 mm Hg (IOP SD, 2.0 mm Hg), and 16.4 mm Hg (IOP SD, 2.7 mm Hg) in cohorts 1 and 2, respectively. Controlling for age, mean IOP, VF stage, and other covariates, each unit increase in IOP SD resulted in a 4.2 times and 5.5 times higher risk of glaucoma progression for cohort 1 (95% confidence interval [CI], 1.3 to 12.9) and cohort 2 (95% CI, 3.4 to 9.1), respectively. Conclusions: IOP variability is an important predictor of glaucoma progression; SD is a convenient measure of variability to assess glaucoma progression risk. [Copyright &y& Elsevier]

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. 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. 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. Across these high-risk subgroups of VTE cancer patients, treatment outcomes associated with apixaban were generally positive compared to LMWH and warfarin. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Bilirubin is an antioxidant that may suppress lipid oxidation. Elevated bilirubin is associated with decreased cardiovascular events in HIV-uninfected populations. We examined these associations in people living with HIV (PLWH). Methods: Potential myocardial infarctions (MIs) and strokes were centrally adjudicated. We examined MI types: type 1 MI (T1MI) from atherosclerotic plaque instability and type 2 MI (T2MI) in the setting of oxygen demand/supply mismatch such as sepsis. We used multivariable Cox regression analyses to determine associations between total bilirubin levels and outcomes adjusting for traditional and HIV-specific risk factors. To minimize confounding by hepatobiliary disease, we conducted analyses limited to bilirubin values <2.1 mg/dL; among those with fibrosis-4 values <3.25; and among everyone. We repeated analyses stratified by hepatitis C status and time-updated atazanavir use. Results: Among 25,816 PLWH, there were 392 T1MI and 356 T2MI during follow-up. Adjusted hazard ratios for the association of higher bilirubin levels with T1MI were not significant. Higher bilirubin levels were associated with T2MI. By contrast, among PLWH on atazanavir, higher bilirubin levels were associated with fewer T2MI (hazard ratio 0.56:0.33–1.00). Higher bilirubin levels among those on atazanavir were associated with fewer T1MI combined with ischemic stroke. Limitations: Analyses were conducted with total rather than unconjugated bilirubin. Conclusions: Among PLWH, higher bilirubin levels were associated with T2MI among some subgroups. However, among those on atazanavir, there was a protective association between bilirubin and T2MI. These findings demonstrate different associations between outcomes and elevated bilirubin due to diverse causes and the importance of distinguishing MI types. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are at least as efficacious and safe as warfarin among non-valvular atrial fibrillation (NVAF) patients; limited evidence is available regarding NVAF patients with heart failure (HF). US Medicare enrollees with NVAF and HF initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected. Propensity score matching and Cox models were used to estimate the risk of stroke/systemic embolism (SE), major bleeding (MB), and major adverse cardiac events (MACE) comparing DOACs versus warfarin and DOACs versus DOACs. We identified 10,570 apixaban-warfarin, 4,297 dabigatran-warfarin, 15,712 rivaroxaban-warfarin, 4,263 apixaban-dabigatran, 10,477 apixaban-rivaroxaban, and 4,297 dabigatran-rivaroxaban matched pairs. Compared to warfarin, apixaban had lower rates of stroke/SE (hazard ratio = 0.64, 95% confidence interval = 0.48–0.85), MB (hazard ratio = 0.66, 0.58–0.76), and MACE (hazard ratio = 0.73,0.67–0.79); dabigatran and rivaroxaban had lower rates of MACE (hazard ratio = 0.87,0.77–0.99; hazard ratio = 0.84, 0.79–0.89, respectively). Rivaroxaban had a lower stroke/SE rate (hazard ratio = 0.65, 0.52–0.81) and higher MB rate (hazard ratio = 1.18, 1.08–1.30) versus warfarin. Compared to dabigatran and rivaroxaban, apixaban had lower MB (hazard ratio = 0.71, 0.57–0.89; hazard ratio = 0.55, 0.49–0.63) and MACE rates (hazard ratio = 0.80, 0.69–0.93; hazard ratio = 0.86, 0.79–0.94), respectively. All DOACs had lower MACE rates versus warfarin; differences were observed in stroke/SE and MB. Our findings provide insights about OAC therapy among NVAF patients with HF. [ABSTRACT FROM AUTHOR]

The objective of the study was to examine whether disease duration independently predicts treatment response among biologic-naïve patients with rheumatoid arthritis (RA) initiating abatacept in clinical practice. Using the Corrona RA registry (February 2006-January 2015), biologic-naïve patients with RA initiating abatacept with 12-month (±3 months) follow-up and assessment of disease activity (Clinical Disease Activity Index [CDAI]) at initiation and at 12 months were identified. The primary outcome was mean change in CDAI (ΔCDAI) from baseline to 12 months. Secondary outcomes at 12 months included achievement of low disease activity (LDA; CDAI ≤10 in patients with moderate/high disease activity at initiation) and remission (CDAI ≤2.8 in patients with low, moderate or high disease activity at initiation). Linear and logistic regression analyses were performed to examine the relationship between disease duration and response to abatacept. There were 281 biologic-naïve patients with RA initiating abatacept (disease duration 0-2 years, n = 107; 3-5 years, n = 45; 6-10 years, n = 50; >10 years, n = 79). Increased disease duration was associated with older age ( p = 0.047), and the median number of prior conventional disease-modifying antirheumatic drugs used was lowest in the 0- to 2-year duration group ( p < 0.001). Mean ΔCDAI (SE) ranged from −10.22 (1.19) for 0-2 years to −4.63 (1.38) for >10 years. In adjusted analyses, shorter disease duration was significantly associated with greater mean ΔCDAI ( p = 0.015) and greater likelihood of achieving LDA ( p = 0.048). In biologic-naïve patients with RA initiating abatacept, earlier disease (shorter disease duration) was associated with greater ΔCDAI and likelihood of achieving LDA. [ABSTRACT FROM AUTHOR]

Introduction: Patients with human immunodeficiency virus (HIV) infection have an increased risk of cardiovascular disease (CVD). While viral suppression with antiretroviral therapy decreases CVD risk overall, several studies have suggested that certain antiretrovirals, particularly certain protease inhibitors, may be associated with an increased relative risk of CVD. In AIDS Clinical Trials Group 5260 s, ritonavir-boosted atazanavir (ATV) was associated with slower atherosclerosis progression compared to ritonavir-boosted darunavir and raltegravir, potentially due to hyperbilirubinemia. Although hyperbilirubinemia may lead to increased rates of treatment discontinuation, it may also contribute to a favorable cardiovascular (CV) profile for ATV. To fully elucidate the effect of ATV on CVD risk among HIV-infected patients, a systematic review of the literature was performed. Methods: A systematic search of the PubMed and Embase databases was conducted on August 26, 2015, using terms to identify papers that discuss ATV, HIV, and CVD. Articles were limited to English-language publications of randomized-controlled or observational studies investigating adult humans. The primary outcome was the incidence of CVD. Articles describing surrogate markers of CVD were also included. Results: Ten studies were included in this qualitative analysis: six reported CVD outcomes, two reported data on atherosclerosis as assessed by carotid intima-media thickness (cIMT), and two reported outcomes related to endothelial function. The studies reporting the incidence of myocardial infarction (MI) among HIV-infected patients showed that ATV (boosted and unboosted) was not associated with an increased risk of acute MI. Other CV endpoints were similarly unaffected by treatment with ATV. Compared with non-ATV-based regimens, ATV had beneficial effects on cIMT progression in the publications identified, with no apparent impact on endothelial function. Conclusions: This analysis showed that there was no increased risk or occurrence of adverse CV events among HIV-infected patients receiving ATV. Markers of atherosclerosis were improved, suggesting a possible antioxidant effect of ATV, and endothelial function was not affected. Funding: Bristol-Myers Squibb (article processing charges and medical writing support). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: MCO reports consultant fees from Aveo, Bristol Myers Squibb (BMS), Eisai, Exelixis, Merck, Pfizer; research funding from Aravive, Astellas Medivation, AstraZeneca/MedImmune, Aveo, BMS, Merck, Pfizer, Surface Oncology; speaker’s bureau fees from BMS. LR, SG, VdT are employees of BMS and have stock ownership in BMS. XY is a former employee of BMS at the time the study was conducted. KB, OW, MD, and GS are employees of Oracle Life Sciences, who were contracted by Bristol Myers Squibb to conduct this research. DSM is a former Cerner Enviza, an Oracle Company’s employee at the time the study was conducted. The authors report no other conflicts of interest in this work., (© 2024 Ornstein et al.)

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., (© 2024. The Author(s).)

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., Competing Interests: Competing interests: CMM reports no conflicts of interest. OAJ reports no conflicts of interest. TP reports consulting or advisory roles with Bristol Myers Squibb (BMS), AstraZeneca, Ipsen, Pfizer, Novartis, Seagen, Roche, Exelixis, MSD, Merck Serono, Astellas Pharma, Johnson & Johnson, Eisai, MashupMD, Merck, and Incyte; travel, accommodations, expenses from Pfizer, MSD, AstraZeneca, Roche, and Ipsen; honoraria from AstraZeneca, Eisai, Merck, Novartis, Pfizer, Roche, Astellas Pharma, BMS GmbH & Co. KG, Exelixis, Incyte, Ipsen, Seagen, Merck Serono, Johnson & Johnson/Janssen, and MashupMD; and research funding from AstraZeneca, Roche, BMS, Exelixis, Ipsen, MSD, Novartis, Pfizer, Seagen, Merck Serono, Astellas Pharma, Johnson & Johnson, and Eisai. RJM reports consulting or advisory roles with Eisai, Exelixis, Merck, Genentech/Roche, Incyte, Pfizer, AstraZeneca, EMD Serono, Calithera Biosciences, and AVEO; travel, accommodations, and expenses from BMS; and research funding to institution from Pfizer, BMS, Eisai, Novartis, Genentech/Roche, Exelixis, Merck, and AVEO. NMT reports stock and other ownership interests with Amgen, Arcturus, Arcus Biosciences, BioCryst Pharmaceuticals, Corvus Pharmaceuticals, Johnson & Johnson/Janssen, Merck, Surface Oncology, Vanguard Health Care ETF, Xencor, First Trust Amex Biotech (FBT), Nuvation Bio, Revolution Medicines, and Spdr S&P Pharmaceuticals ETF; honoraria from BMS, Exelixis, Eisai Medical Research, Neoleukin Therapeutics, Merck Sharp & Dohme, Intellisphere, Oncorena, AstraZeneca/Merck, and Nektar Therapeutics; consulting or advisory roles with Oncorena, Merck Sharp & Dohme, BMS Foundation, and Nektar; and research funding to institution from Exelixis, BMS, Nektar, Arrowhead Pharmaceuticals, Novartis, and Calithera Biosciences. C-HL reports research funding to institution from BMS, Calithera, Eisai, Eli Lilly, Exelixis, Merck, and Pfizer; consulting or advisory roles with Amgen, BMS, Exelixis, Eisai, Merck, Pfizer, and EMD Serono; and honoraria from AiCME, Intellisphere, and Research to Practice. YT reports consulting or advisory roles with Eisai, MSD, Ono Pharmaceutical, and Taiho Pharmaceutical; honoraria from Astellas Pharma, BMS Japan, Chugai Pharma, Ono Pharmaceutical, Takeda, Merck, Pfizer, and MSD; and research funding to institution from Astellas Pharma, AstraZeneca, Chugai Pharma, Eisai, MSD, Ono Pharmaceutical, Pfizer, and Takeda. MHV reports consulting or advisory roles with Novartis, GSK, Exelixis, Merck, Corvus, Calithera, and AVEO; travel, accommodations, and expenses from Takeda, Novartis; research funding with BMS and Roche/Genentech. ERP reports consulting or advisory roles with Seattle Genetics/Astellas, AstraZeneca, AVEO, BMS/Medarex, Calithera Biosciences, EMD Serono, Exelixis, IMV, Janssen, MEI Pharma, Merck, Signatera, Pfizer, and Regeneron; and research funding to institution from BMS, Merck Sharp & Dohme, Astellas, and Genentech/Roche. TKC reports institutional and/or personal, paid and/or unpaid support for research, advisory boards, consultancy, and/or honoraria past 5 years, ongoing or not, from: Alkermes, Arcus Bio, AstraZeneca, Aravive, AVEO, Bayer, BMS, Calithera, Circle Pharma, Deciphera Pharmaceuticals, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Gilead, HiberCell, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Neomorph, Nuscan/PrecedeBio, Novartis, Oncohost, Pfizer, Roche, Sanofi/Aventis, Scholar Rock, Surface Oncology, Takeda, Tempest, Up-To-Date, CME events (Peerview, OncLive, MJH, CCO and others), outside the submitted work. Institutional patents filed on molecular alterations and immunotherapy response/toxicity, and ctDNA. Equity: Tempest, Pionyr, Osel, Precede Bio, CureResponse, InnDura Therapeutics, Primium. Committees: NCCN, GU Steering Committee, ASCO (BOD 6-2024-, ESMO, ACCRU, KidneyCan. Medical writing and editorial assistance support may have been funded by Communications companies in part. No speaker’s bureau. Mentored several non-US citizens on research projects with potential funding (in part) from non-US sources/Foreign Components. The institution (Dana-Farber Cancer Institute) may have received additional independent funding of drug companies or/and royalties potentially involved in research around the subject matter. TKC is supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942-16) and Program 5P30CA006516-56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan Mass Challenge, Hinda and Arthur Marcus Fund and Loker Pinard Funds for Kidney Cancer Research at DFCI. BIR reports consulting or advisory roles with Pfizer, Merck, BMS, AVEO, Surface Oncology, Corvus Pharmaceuticals, Aravive, Arrowhead Pharmaceuticals, Eisai, Genentech, Alkermes, NiKang Therapeutics, EUSA Pharma, Athenex, Debiopharm Group, and HiberCell; leadership roles with MJH Life Sciences and MashupMD; travel, accommodations, and expenses from Pfizer, BMS, and Merck; stock and other ownership interests with PTC Therapeutics; and research funding to institution from Pfizer, Roche/ Genentech, BMS, Merck, AstraZeneca/MedImmune, Incyte, Arrowhead Pharmaceuticals, Seagen, Surface Oncology, Dragonfly Therapeutics, Aravive, Exelixis, AVEO, Arcus Biosciences, HiberCell, Stata, ADC Therapeutics, Dracen, Janssen, Adela, Pionyr, VasGene Therapeutics, Gilead Sciences, Point Therapeutics, and Daiichi Sankyo/UCB Japan. HJH reports consulting or advisory roles with BMS, Pfizer, Exelixis, Bayer, Novartis, Merck, ARMO BioSciences, Corvus Pharmaceuticals, Surface Oncology, and Lilly; travel, accommodations, and expenses from BMS, Merck, Pfizer, Lilly, and Novartis; honoraria from BMS; and research funding to institution from BMS, Merck, Aravive, and Surface Oncology. BE reports consulting or advisory roles with Pfizer, BMS, Ipsen, AVEO, and Oncorena; travel, accommodations, and expenses from BMS, Ipsen, and MSD; honoraria from Pfizer, BMS, Ipsen, and Oncorena; and research funding to institution from BMS. LA reports consulting or advisory roles to institution with Astellas, BMS, Eisai, Ipsen, Janssen, MSD, Novartis, Pfizer, and Roche; non-financial interests with Pfizer, BMS, Ipsen, Roche, Exelixis, AVEO, AstraZeneca, MSD, ASCO, Kidney Foundation, and ESMO. LR reports employment with BMS and stock and other ownership interests with BMS. MBA reports consulting or advisory roles with Genentech, Novartis, BMS, Merck, Exelixis, Eisai, Agenus, Werewolf Pharma, Surface Oncology, Pyxis, Fathom Biotechnology, AVEO, Cota Healthcare, Idera, Ellipses Pharma, AstraZeneca, PACT Pharma, Pfizer, Scholar Rock, Asher Biotherapeutics, Takeda, Sanofi, Simcha Therapeutics, GlaxoSmithKline, Oncorena, and Pliant; stock and other ownership interests with Werewolf Pharma and Pyxis; and research funding to institution from BMS and Merck. MMR reports consulting or advisory roles (institution) with Ipsen and Debiopharm; personal fees from BMS and Tolmar Pharmaceuticals; grants from Novartis, Pfizer, Ipsen, TerSera, Merck, Ferring, Pierre Fabre, Roche, AstraZeneca, Bayer, and BMS. DFM reports consulting or advisory roles with BMS, Merck, Genentech/Roche, Pfizer, Exelixis, Novartis, Array BioPharma, Peloton Therapeutics, EMD Serono, Jounce Therapeutics, Alkermes, Lilly, Eisai, Calithera Biosciences, Iovance Biotherapeutics, Werewolf Therapeutics, Synthekine, AVEO, Sanofi, and Xilio Therapeutics; other relationship with Beth Israel Deaconess Medical Center; research funding to institution from BMS, Merck, Genentech, Novartis, and Alkermes; and uncompensated relationships with X4 Pharma and AVEO., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 CHA 2 DS 2 -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 CHA 2 DS 2 -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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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., Competing Interests: Competing interests: AAK reports funding to conduct the study of current manuscript from Bristol Myers Squibb (BMS); consulting fees from Janssen, Bayer, BMS, Pfizer, Sanofi, and Anthos; honoraria from WebMD CME; travel support from Bayer, Pfizer, Sanofi, and Anthos; and an unpaid leadership role as chair from MASAB of NBCA. NH and KG received funding (institutional) to conduct the study of the current manuscript from BMS. KG was an employee of HealthCore when the paper was written. JB reports stock ownership in Anthem. JP, LR, RP, NH, and TCB are employed by and have stock ownership in BMS., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., Competing Interests: A.T.C. received research support from Pfizer and Bristol Myers Squibb Company. J.S. and R.D. are employed by SIMR, LLC—a paid consultant to Pfizer and Bristol Myers Squibb Company, in connection with the development of the manuscript. T.L., P.H., B.E., and X.L. are employees of Pfizer, a study sponsor. A.D.D. and L.R. are employees of Bristol Myers Squibb Company, a study sponsor. H.Y. has no financial relationships or other potential conflicts of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

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., (© 2021. The Author(s).)

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., (Published on behalf of the European Society of Cardiology. © The Author(s) 2020.)

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.

In the phase 3 trial Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy, apixaban was noninferior to enoxaparin, overlapped and followed by warfarin, in the treatment of venous thromboembolism (VTE) with significantly less bleeding; in a real-world evaluation, risks for bleeding and recurrent VTE were lower with apixaban vs warfarin plus parenteral anticoagulant (PAC) bridge therapy. The present study extends this research by comparing outcomes over time and within selected subgroups. A retrospective observational cohort design and 4 US private health care claims databases were used. Study population included patients who initiated outpatient treatment with apixaban or warfarin (plus PAC bridge therapy) for VTE. Major bleeding, clinically relevant nonmajor (CRNM) bleeding, and recurrent VTE were compared during the 180-day follow-up period, at selected follow-up time points (days 21, 90, 180), and within subgroups (pulmonary embolism [PE] with or without deep vein thrombosis [DVT], DVT only, provoked VTE, unprovoked VTE) using multivariable shared frailty models. Study population consisted of 20 561 apixaban patients and 35 080 warfarin patients; baseline characteristics were comparable. Overall, at selected follow-up time points, and within the aforementioned subgroups, adjusted risks were lower among apixaban vs warfarin patients: major bleeding, by 27% to 39%, CRNM bleeding, by 17% to 28%, and recurrent VTE, by 25% to 39% (all P ≤ .01). In this real-world study of VTE patients, risks of bleeding and recurrent VTE were lower among apixaban (vs warfarin) patients during the 180-day follow-up period, at selected follow-up time points, and within subgroups defined by index VTE episode., (© 2020 by The American Society of Hematology.)

Atrial fibrillation (AF) prevalence increases with age; > 80% of US adults with AF are aged ≥ 65 years. Compare the risk of stroke/systemic embolism (SE), major bleeding (MB), net clinical outcome (NCO), and major adverse cardiac events (MACE) among elderly non-valvular AF (NVAF) Medicare patients prescribed direct oral anticoagulants (DOACs) VS warfarin. NVAF patients aged ≥ 65 years who initiated DOACs (apixaban, dabigatran, and rivaroxaban) or warfarin were selected from 01JAN2013-31DEC2015 in CMS Medicare data. Propensity score matching was used to balance DOAC and warfarin cohorts. Cox proportional hazards models estimated the risk of stroke/SE, MB, NCO, and MACE. 37,525 apixaban-warfarin, 18,131 dabigatran-warfarin, and 55,359 rivaroxaban-warfarin pairs were included. Compared to warfarin, apixaban (HR: 0.69; 95% CI 0.59-0.81) and rivaroxaban (HR: 0.82; 95% CI 0.73-0.91) had lower risk of stroke/SE, and dabigatran (HR: 0.88; 95% CI 0.72-1.07) had similar risk of stroke/SE. Apixaban (MB: HR: 0.61; 95% CI 0.57-0.67; NCO: HR: 0.64; 95% CI 0.60-0.69) and dabigatran (MB: HR: 0.79; 95% CI 0.71-0.89; NCO: HR: 0.84; 95% CI 0.76-0.93) had lower risk of MB and NCO, and rivaroxaban had higher risk of MB (HR: 1.08; 95% CI 1.02-1.14) and similar risk of NCO (HR: 1.04; 95% CI 0.99-1.09). Compared to warfarin, apixaban had a lower risk for stroke/SE, MB, and NCO; dabigatran had a lower risk of MB and NCO; and rivaroxaban had a lower risk of stroke/SE but higher risk of MB. All DOACs had lower risk of MACE compared to warfarin.

Introduction: Continuous usage of direct oral anticoagulants (DOACs) among nonvalvular atrial fibrillation (NVAF) patients is essential to maintain stroke prevention. We examined switching and discontinuation rates for the three most frequently initiated DOACs in NVAF patients in the USA., Methods: Patients who initiated apixaban, rivaroxaban, or dabigatran (index event/date) were identified from the Pharmetrics Plus claims database (Jan 1, 2013-Sep 30, 2016, includes patients with commercial and Medicare coverage) and grouped into cohorts by index DOAC. Patients were required to have a diagnosis of NVAF and continuous health plan enrollment for 12 months prior to the index date (baseline period) and at least 3 months during the follow-up period. Drug switching rates to any other DOAC or warfarin and index DOAC discontinuation rate were evaluated separately with descriptive statistics, Kaplan-Meier analysis, and multivariable Cox regression analysis., Results: Of the NVAF study population (n = 41,864), 37% initiated apixaban (n = 15,352; mean age 62 years), 51% initiated rivaroxaban (n = 21,250; mean age 61 years), and 13% initiated dabigatran (n = 5262; mean age 61 years). During the follow-up period, the unadjusted drug switching rates of patients treated with apixaban, rivaroxaban, and dabigatran were 3.6%, 6.3%, and 11.1%, respectively (p < 0.001 across the three cohorts); while the index DOAC discontinuation rates were 52.8%, 60.3%, and 62.9%, respectively (p < 0.001). After we controlled for differences in patient characteristics, patients treated with rivaroxaban (HR 1.8; 95% CI 1.6-2.0; p < 0.001) and dabigatran (HR 3.4; 95% CI 3.0-3.8, p < 0.001) had a significantly greater likelihood for drug switching than patients treated with apixaban. Also, both rivaroxaban (HR 1.1; 95% CI 1.1-1.2, p < 0.001) and dabigatran (HR 1.3; 95% CI 1.2-1.3, p < 0.001) treated patients were more likely to discontinue treatment., Conclusion: In the real-world setting, patients with NVAF newly treated with apixaban were less likely to switch or discontinue treatment compared to patients treated with rivaroxaban or dabigatran., Funding: Pfizer and Bristol-Myers Squibb.

The Universal Myocardial infarction (MI) definition divides MIs into different types. Type 1 MIs (T1MI) result spontaneously from atherosclerotic plaque instability. Type 2 MIs (T2MI) are due to secondary causes of myocardial oxygen demand/supply mismatch such as occurs with sepsis. T2MI are much more common among those with HIV than in the general population. T1MI and T2MI have different mechanisms, risk factors, and potential treatments suggesting that they should be distinguished to achieve a better scientific understanding of MIs in HIV. We sought to determine whether MI type could be accurately predicted by patient characteristics without adjudication in HIV-infected individuals. We developed a statistical model to predict T2MI versus T1MI using adjudicated events from six sites utilizing demographic characteristics, traditional cardiovascular, and HIV-related risk factors. Validation was assessed in a seventh site via mean calibration, and discrimination level was assessed by the area under the curve (AUC). Of 812 MIs, 388 were T2MI. HIV-related factors including hepatitis C infection were predictive of T2MI, whereas traditional cardiovascular risk factors including total cholesterol predicted T1MI. The score predicted 69 T2MI in the validation sample resulting in poor calibration, given that 90 T2MIs were observed. The development sample AUC was 0.75 versus 0.65 in the validation sample, suggesting relatively poor discrimination. The level of discrimination to predict MI type based on patient characteristics is insufficient for individual level prediction. Adjudication is required to distinguish MI types, which is necessary to advance understanding of this important outcome among HIV populations.

Background: Tenofovir disoproxil fumarate (TDF) has been associated with renal complications. The third agent in TDF-containing antiretroviral regimens may modify that risk. We compared renal adverse outcomes among treatment-naive HIV-infected patients initiating TDF-containing regimens including efavirenz (EFV) or other agents., Setting: This population-based historical cohort study used national Veterans Health Administration (VHA) clinical and administrative data sets to identify treatment-naive HIV-infected veterans initiating antiretroviral therapy with TDF/emtricitabine (FTC) + EFV, rilpivirine (RPV), elvitegravir/cobicistat (EVG/c), or ritonavir (RTV)-boosted protease inhibitors (PIs) from 2003 to 2015., Methods: Unadjusted incidence rates (IRs) for each regimen and covariate-adjusted hazard ratios [ using Cox proportional hazards models and inverse probability of treatment weighting] for between-regimen comparisons were calculated for renal outcomes including confirmed proteinuria, defined as 2 consecutive protein-to-creatinine ratios >150 mg/g or albumin-to-creatinine ratios >30 mg/g occurring ≥90 days apart; chronic kidney disease (CKD), defined as 2 consecutive estimated glomerular filtration rate measurements <60 mL·min·1.73 m occurring ≥90 days apart; and kidney dialysis., Results: Of 33,048 HIV-positive veterans, 4172 received EFV + TDF/FTC, 234 EVG/c/TDF/FTC, 173 RPV/TDF/FTC, and 2651 RTV-boosted PIs + TDF/FTC. Confirmed proteinuria and CKD IRs were numerically lower with EFV + TDF/FTC versus non-EFV + TDF/FTC (dialysis IRs were rare and comparable). After inverse probability of treatment weighting adjustment, EFV + TDF/FTC was associated with lower CKD risk versus non-EFV + TDF/FTC (hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72), EVG/c/TDF/FTC (0.75; 0.59 to 0.95), RPV/TDF/FTC (0.20; 0.17 to 0.24), and RTV-boosted PIs + TDF/FTC (0.62; 0.53 to 0.72)., Conclusions: EFV + TDF/FTC was associated with significantly lower risk of CKD versus other TDF-containing regimens in the Veterans Health Administration.

Objective: Patients with HIV infection have an increased risk of cardiovascular disease compared with uninfected individuals. Antiretroviral therapy with atazanavir (ATV) delays progression of atherosclerosis markers; whether this reduces cardiovascular disease event risk compared with other antiretroviral regimens is currently unknown., Design: Population-based, noninterventional, historical cohort study conducted from 1 July 2003 through 31 December 2015., Setting: Veterans Health Administration hospitals and clinics throughout the United States., Participants: Treatment-naive patients with HIV infection (N = 9500)., Antiretroviral Exposures: Initiating antiretroviral regimens containing ATV, other protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTIs), or integrase strand transfer inhibitors (INSTIs)., Main Outcome/effect Size Measures: Incidence rates of myocardial infarction (MI), stroke, and all-cause mortality within each regimen. ATV versus other protease inhibitor, NNRTI, or INSTI covariate-adjusted hazard ratios by using Cox proportional hazards models and inverse probability of treatment weighting., Results: Incidence rates for MI, stroke, and all-cause mortality with ATV-containing regimens (5.2, 10.4, and 16.0 per 1000 patient-years, respectively) were lower than with regimens containing other protease inhibitors (10.2, 21.9, and 23.3 per 1000 patient-years), NNRTIs (7.5, 15.9, and 17.5 per 1000 patient-years), or INSTIs (13.0, 33.1, and 21.5 per 1000 patient-years). After inverse probability of treatment weighting, adjusted hazard ratios (95% confidence intervals) for MI, stroke, and all-cause mortality with ATV-containing regimens versus all non-ATV-containing regimens were 0.59 (0.41-0.84), 0.64 (0.50-0.81), and 0.90 (0.73-1.11), respectively., Conclusion: Among treatment-naive HIV-infected patients in the Veterans Health Administration initiating ATV-containing regimens, risk of both MI and stroke were significantly lower than in those initiating regimens containing other protease inhibitors, NNRTIs, or INSTIs.

Objective: Determine the prevalence and costs of rheumatoid arthritis (RA) during three consecutive years: 2004, 2005, and 2006., Methods: Medical Expenditure Panel Survey was used for persons with RA. Regressions estimate health care costs and income loss. Absenteeism and age-adjusted workforce participation compared means and rates., Results: The prevalence of RA was 0.40% in 2004, 0.44% in 2005, and 0.43% in 2006. Health care cost associated with RA was $4422, $2902, and $1882 (all P < 0.01) in 2004, 2005, and 2006, respectively. Rheumatoid arthritis sufferers were employed, 36.8%, 39.5%, and 44% compared with 70.5%, 69.8%, and 71%. Individuals with RA also missed more days of work, 4.86 in 2004 (P = 0.04), 1.70 in 2005 (P = 0.22), and 2.99 in 2006 (P = 0.04). Rheumatoid arthritis reduced income by $2404 (P = 0.03), $2207 (P < 0.001), and $1212 (P = 0.002)., Conclusions: Costs of RA are considerable.

Background: Decompensated cirrhosis is a serious clinical complication of chronic hepatitis B (CHB) that places a large economic burden on the US health care system. Although entecavir has been shown to improve health outcomes in a cost-effective manner in mixed populations of CHB patients, the cost-effectiveness of entecavir has not been evaluated in CHB patients with decompensated cirrhosis., Methods: This study assessed the cost-effectiveness of entecavir versus adefovir, from a US payer perspective, in CHB patients with decompensated cirrhosis, using a health-state transition Markov model with four health states: hepatocellular carcinoma (HCC), HCC-free survival, post-liver transplant, and death. The model considered a hypothetical patient population similar to that included in a randomized controlled trial in the target population (ETV-048): predominantly male (74%), Asian (54%), mean age 52 years, hepatic decompensation (Child-Pugh score ≥ seven), hepatitis B e antigen-positive or -negative, treatment-naïve or lamivudine-experienced, and no liver transplant history. Clinical inputs were based on cumulative safety results for ETV-048 and published literature. Costs were obtained from published literature. Costs and outcomes were discounted at 3% per annum., Results: For 1000 patients over a 3-year time horizon, predicted overall survival and HCC-free survival were longer with entecavir than with adefovir (2.35 versus 2.30 years and 2.11 versus 2.03 years, respectively). Predicted total health care costs were $889 lower with entecavir than with adefovir ($91,878 versus $92,768). For incremental cost/life-year gained and incremental cost/HCC-free-year gained, entecavir was less costly and more effective than adefovir. Sensitivity analyses found the results to be robust to plausible variations in health-state costs and discount rate., Conclusion: This analysis suggests that entecavir improves survival outcomes in a cost-saving manner compared with adefovir in CHB patients with hepatic decompensation.