This study aims to assess the risk of direct oral anticoagulant (DOAC) discontinuation among Medicare beneficiaries with non-valvular atrial fibrillation (NVAF) who reach the Medicare coverage gap stratified by low-income subsidy (LIS) status and the impact of DOAC discontinuation on rates of stroke and systemic embolism (SE) among beneficiaries with increased out-of-pocket (OOP) costs due to not receiving LIS. In this retrospective cohort study, Medicare claims data (2015–2020) were used to identify beneficiaries with NVAF who initiated rivaroxaban or apixaban and entered the coverage gap during ≥ 1 year. DOAC discontinuation rates during the coverage gap were stratified by receipt of Medicare Part D Low-Income Subsidy (LIS), a proxy for not experiencing increased OOP costs. Among non-LIS beneficiaries, incidence rates of stroke and SE during the subsequent 12 months were compared between beneficiaries who did and did not discontinue DOAC in the coverage gap. Among 303,695 beneficiaries, mean age was 77.3 years, and 28% received LIS. After adjusting for baseline differences, non-LIS beneficiaries (N = 218,838) had 78% higher risk of discontinuing DOAC during the coverage gap vs. LIS recipients (adjusted hazard ratio [aHR], 1.78; 95% CI [1.73, 1.82]). Among non-LIS beneficiaries, DOAC discontinuation during coverage gap (N = 91,397; 34%) was associated with 14% higher risk of experiencing stroke and SE during the subsequent 12 months (aHR, 1.14; 95% CI [1.08, 1.20]). Increased OOP costs during Medicare coverage gap were associated with higher risk of DOAC discontinuation, which in turn was associated with higher risk of stroke and SE among beneficiaries with NVAF.
Abstract Background There are no large head-to-head phase 3 clinical trials comparing overall survival (OS) for abiraterone and enzalutamide. This study used Medicare claims data to compare OS in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) who initiated abiraterone or enzalutamide. Methods This retrospective analysis of the Medicare database (2009–2020) included adult men with ≥1 claim for prostate cancer, metastatic diagnosis, and no prior chemotherapy or novel hormone therapy who initiated first-line (1L) abiraterone or enzalutamide in the index period (September 10, 2014 to May 31, 2017). Cox proportional-hazards models with inverse probability treatment-weighting (IPTW) were used to compare OS between abiraterone- and enzalutamide-treated patients, adjusting for baseline characteristics. Subgroup analyses by baseline characteristics were also conducted. Results Overall, 5506 patients who received 1L abiraterone ( n = 2911) or enzalutamide ( n = 2595) were included. Median follow-up was comparable in both cohorts (abiraterone, 19.1 months; enzalutamide, 20.3 months). IPTW-adjusted median OS (95% CI) was 20.6 months (19.7‒21.4) for abiraterone and 22.5 months (21.2‒23.8) for enzalutamide, with an IPTW-adjusted hazard ratio (95% CI) of 1.10 (1.04–1.16). Median OS was significantly shorter for abiraterone versus enzalutamide in patients ≥75 years old; White patients; patients with baseline diabetes, cardiovascular disease, both diabetes and cardiovascular disease, and renal disease; and across all socioeconomic strata. Conclusions In the Medicare chemotherapy-naïve mCRPC population, 1L abiraterone was associated with worse OS versus enzalutamide in the overall population and among subgroups with older age and comorbidities, supporting findings from previous real-world studies and demonstrating a disparity in outcomes.
Background This real‐world evidence study compared risks of cardiovascular events in hospital settings among patients with chronic kidney disease (CKD) with and without hyperkalemia. Methods and Results Adults with CKD stages 3b/4 with and without hyperkalemia were identified from Optum's deidentified Market Clarity Data (January 2016–August 2022). Patients with hyperkalemia were exact and propensity score matched to patients without hyperkalemia. The index date was the first CKD stage 3b/4 diagnosis with ≥1 hyperkalemia diagnosis and ≥1 serum potassium >5.0 mmol/L in the preceding 12 months (baseline) for patients with hyperkalemia and a randomly selected CKD stage 3b/4 diagnosis for controls. Cardiovascular composite end points included major adverse cardiovascular events plus (a composite end point of all‐cause mortality, myocardial infarction, stroke, or heart failure) and cardiac arrhythmias (a composite end point of new onset atrial fibrillation and other atrial and ventricular arrythmias), all in the hospital setting. We compared cardiovascular events between cohorts using cause‐specific Cox proportional hazards regression. The study included 5301 matched pairs in the analysis of major adverse cardiovascular events plus and 5564 in the analysis of arrhythmia. Cardiovascular events were more likely among patients with hyperkalemia relative to those without hyperkalemia, with the risk of major adverse cardiovascular events plus increased by 32% (23%–40%) and the risk of arrhythmia increased by 59% (44%–75%; both P <0.001). Conclusions Among patients with CKD stages 3b/4, patients with hyperkalemia experienced significantly higher risks of major adverse cardiovascular events and arrhythmia in hospital settings relative to patients without hyperkalemia.
Abstract Introduction/Aims Hereditary transthyretin‐mediated amyloidosis with polyneuropathy (hATTR‐PN) progressively affects patients' functionality and compromises health‐related quality of life (HRQL). The aim of this study was to quantify the projected long‐term treatment effects of inotersen vs placebo on HRQL measures. Methods The inotersen phase 2/3 randomized, double‐blind, placebo‐controlled trial NEURO‐TTR (NCT01737398, 65 weeks) and its subsequent open‐label extension (OLE; NCT02175004, 104 weeks) included 172 (112 inotersen and 60 placebo) patients. Placebo double‐blind period and overall inotersen‐inotersen (double‐blind/OLE) treatment period (170 weeks) data were used to extrapolate the long‐term placebo‐placebo effect using mixed‐effects models with repeated measures. Changes from baseline in the Norfolk Quality of Life‐Diabetic Neuropathy (QoL‐DN) and 36‐Item Short Form Health Survey version 2 (SF‐36v2) in hATTR‐PN were estimated. Differences in changes were compared between the inotersen‐inotersen and extrapolated placebo‐placebo arms. Results Inotersen‐inotersen patients maintained their HRQL with an observed change ranging from 10.3% improvement (Norfolk QoL‐DN item “Pain kept you awake at night”) to 11.6% deterioration (SF‐36v2 Activities of Daily Living subdomain). The extrapolated placebo‐placebo results suggest greater deterioration over time compared with inotersen‐inotersen treatment on Norfolk QoL‐DN total score (23.6; 95% confidence interval [CI], 8.9‐38.3; P < .01), Activities of Daily Living (4.6; 95% CI, 2.0‐7.3; P < .001), and “Pain kept you awake at night” (1.2; 95% CI, 0.4‐1.9; P < .01). Similarly, greater deterioration was expected for the SF‐36v2 Physical Component Summary (8.0; 95% CI, 3.2‐12.8, P < .01), Bodily Pain (7.8; 95% CI, 2.0‐13.5; P < .01), and Physical Functioning (10.6; 95% CI, 5.5‐15.6; P < .0001). Discussion Long‐term (>3 years) inotersen treatment was associated with slowing and, in some domains, halting of deterioration in key HRQL outcome measures, particularly physical functioning and pain.
Abstract Background Bardet-Biedl syndrome (BBS) is a rare, genetically heterogeneous obesity syndrome associated with hyperphagia. Given the early onset of BBS symptoms in childhood and multifaceted complications, this study aimed to quantify the caregiver burden associated with BBS. Methods A cross-sectional, multi-country survey of caregivers from the United States (US), United Kingdom (UK), Canada, and Germany was designed to quantify the extent of caregiver burden associated with obesity and hyperphagia symptoms (i.e., uncontrollable hunger) among patients with BBS. Results A total of 242 caregivers across the four countries met the inclusion criteria and completed the survey. The mean (standard deviation [SD]) age of the caregivers was 41.9 (6.7) years, and the mean (SD) age of individuals with BBS in their care was 12.0 (3.7) years. Hyperphagia contributed to a BBS diagnosis in 230 of 242 individuals (95.0%). On average, caregivers used eight different weight management approaches for those in their care and expressed a strong desire for more effective weight management methods. Based on the Impacts of Hyperphagia: Caregiver version , patients’ hyperphagia had a moderate-to-severe impact on caregiver mood (56.6%), sleep (46.6%), and relationships (48.0%). Caregivers reported experiencing a high level of personal strain (mean [SD], 17.1 [2.9]) and family impact (mean [SD] score, 26.0 [3.8]) due to BBS, as measured by the Revised Impact on Family Scale . Among caregivers in the workforce, there also was high impairment in total work productivity (mean [SD], 60.9% [21.4%]) due to caring for patients with BBS according to the Work Productivity and Activity Impairment . More than half (53%) of the caregivers reported spending over 5,000 out-of-pocket in local currency for medical expenses for the patient with BBS in their care. Conclusions Obesity and hyperphagia have negative impacts on the lives of caregivers of patients with BBS. The burden is demonstrated to be multifaceted, with various components that may interact with and confound each other, including intensive weight management efforts, productivity loses, impaired family dynamics and out-of-pocket medical expenses.
