Long-term treatment effects of inotersen on health-related quality of life in patients with hATTR amyloidosis with polyneuropathy: Analysis of the open-label extension of the NEURO-TTR trial.

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.

Real-world overall survival with abiraterone acetate versus enzalutamide in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

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.

Economic burden of recurrent hyperkalemia in patients with chronic kidney disease.

BACKGROUND: Hyperkalemia is a common complication of chronic kidney disease (CKD) and can become recurrent in half of cases. However, the incremental economic burden associated with recurrent hyperkalemia is unknown. OBJECTIVE: To evaluate all-cause health care resource utilization (HRU) and medical costs in patients with stage 3/4 CKD with recurrent hyperkalemia vs normokalaemia and vs nonrecurrent hyperkalemia. METHODS: Data were from Optum's de-identified Market Clarity Data (January 1, 2016, to August 1, 2022). This retrospective observational cohort study compared patients with stage 3/4 CKD with recurrent hyperkalemia (≥2 hyperkalemia events within 1 year [hyperkalemia event: hyperkalemia diagnosis or potassium [K+]>5 mmol/l]; index was the first hyperkalemia event) with an exact- and propensity score-matched cohort of patients with normokalemia (K+ ≥3.5 to ≤5 mmol/l; random K+ as index) and separately with a matched cohort of patients with nonrecurrent hyperkalemia (1 hyperkalemia event within 1 year; index was hyperkalemia event). Patient characteristics, medication use, HRU, and medical costs were compared between cohorts using standardized mean differences during the 12-month baseline period. All-cause HRU and medical costs during the 12-month follow-up were compared using Wilcoxon rank sum tests for continuous variables and McNemar tests for categorical variables. Substudies of recurrent hyperkalemia vs normokalemia were conducted for patients with Medicare coverage and renin-angiotensin-aldosterone system inhibitor (RAASi) use. RESULTS: The recurrent hyperkalemia vs normokalemia sample comprised 4,549 matched pairs (Medicare substudy: 3,151; RAASi substudy: 3,535) and the recurrent hyperkalemia vs nonrecurrent hyperkalemia sample comprised 1,599 matched pairs. Baseline characteristics, HRU, and medical costs of the cohorts were similar after matching. During follow-up, patients with recurrent hyperkalemia had a mean of 11.2 more health care encounters (0.5 more inpatient admissions, 0.3 more emergency department visits, and 7.2 more outpatient visits) than patients with normokalemia. Patients with recurrent hyperkalemia also had double the total annual medical costs vs normokalemia ($34,163 vs $15,175; P < 0.001), mainly driven by inpatient costs ($21,250 vs $7,392), which accounted for 62.2% and 48.7% of total costs, respectively. Results were similar in the RAASi and Medicare substudies. Recurrent hyperkalemia was associated with a mean 4.3 more all-cause health care encounters and $14,057 higher medical costs (both P < 0.001) than nonrecurrent hyperkalemia. CONCLUSIONS: Recurrent hyperkalemia in patients with stage 3/4 CKD was associated with higher all-cause HRU and medical costs compared with normokalemia (including in patients with Medicare coverage and RAASi use) and nonrecurrent hyperkalemia. Research is needed to understand if long-term treatment strategies aimed at preventing hyperkalemia recurrence may alleviate this economic burden.

Hyperkalemia and risk of chronic kidney disease progression: A propensity score matched analysis.

BACKGROUND: Hyperkalemia is a known complication of chronic kidney disease (CKD); however, it is not known whether hyperkalemia directly contributes to CKD progression and the risk of death. Clarifying the extent to which hyperkalemia is associated with CKD progression and mortality can inform clinical practice and guide future research. The objective of this study was to quantify the risks of CKD progression and mortality associated with hyperkalemia in patients with stages 3b/4 CKD. METHODS: This was a real-world, exact and propensity score-matched, observational cohort study using data (January 2016-December 2021) from Optum's deidentified Market Clarity Data, a large US integrated insurance claims/electronic medical record database. The study included matched adult patients with stages 3b/4 CKD with and without hyperkalemia, not regularly treated with an intestinal potassium (K+) binder. Measured outcomes were CKD progression and all-cause mortality. CKD progression was defined as diagnosis of CKD stage 4 (if stage 3b at index), CKD stage 5 or kidney failure, or receipt of dialysis or kidney transplantation. RESULTS: After matching, there were 6,619 patients in each of the hyperkalemia and non-hyperkalemia cohorts, with a mean (standard deviation) follow-up time of 2.12 (1.42) years. Use of any renin-angiotensin-aldosterone system inhibitors (RAASi) during baseline was common (75.9%) and most patients had CKD stage 3b (71.2%). Patients with hyperkalemia had a 1.60-fold (95% confidence interval [CI] 1.50, 1.71) higher risk of CKD progression and a 1.09-fold (1.02, 1.16) higher risk of all-cause mortality relative to patients without hyperkalemia. Relative risks of CKD progression associated with hyperkalemia were similar within the subset of patients receiving RAASi and across CKD stages, and when alternative definitions of CKD progression were used. CONCLUSIONS: Patients with CKD stages 3b/4 and hyperkalemia experienced significantly higher risks of CKD progression and all-cause mortality than propensity score-matched patients without hyperkalemia.

Frequency and economic burden of exacerbations in inhaled corticosteroid/long-acting beta-agonist-treated patients with asthma: A retrospective US claims study.

INTRODUCTION: Despite adherence to inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) therapy, many patients with asthma experience moderate exacerbations. Data on the impact of moderate exacerbations on the healthcare system are limited. This study assessed the frequency and economic burden of moderate exacerbations in patients receiving ICS/LABA. METHODS: Retrospective, longitudinal study analyzed data from Optum's de-identified Clinformatics® Data Mart Database recorded between October 1, 2015, and December 31, 2019. Eligibility criteria included patients ≥18 years of age with ≥1 ICS/LABA claim and ≥1 medical claim for asthma in the 12 months pre-index (first ICS/LABA claim). Primary objectives included describing moderate exacerbation frequency, and associated healthcare resource utilization (HRU) and costs. A secondary objective was assessing the relationship between moderate exacerbations and subsequent risk of severe exacerbations. Patients were stratified by moderate exacerbation frequency in the 12 months post index. Moderate exacerbations were identified using a newly developed algorithm. RESULTS: In the first 12 months post index 61.6% of patients experienced ≥1 moderate exacerbation. Mean number of asthma-related visits was 4.1 per person/year and median total asthma-related costs was $3544. HRU and costs increased with increasing exacerbation frequency. Outpatient and inpatient visits accounted for a similar proportion of these costs. Moderate exacerbations were associated with an increased rate and risk of future severe exacerbations (incidence rate ratio, 1.56; hazard ratio, 1.51 [both p < 0.001]). CONCLUSIONS: This study highlighted that a high proportion of patients continue to experience moderate exacerbations despite ICS/LABA therapy and subsequently experience increased economic burden and risk of future severe exacerbations.

Development and validation of a claims-based algorithm to identify moderate exacerbations in patients with asthma treated in the US.

INTRODUCTION: Definitions of moderate asthma exacerbation have been inconsistent, making their economic burden difficult to assess. An algorithm to accurately identify moderate exacerbations from claims data is needed. METHODS: A retrospective cohort study of Reliant Medical Group patients aged ≥18 years, with ≥1 prescription claim for inhaled corticosteroid/long-acting ß2-agonist, and ≥1 medical claim with a diagnosis code for asthma was conducted. The objective was to refine current algorithms to identify moderate exacerbations in claims data and assess the refined algorithm's performance. Positive and negative predictive values (PPV and NPV) were assessed via chart review of 150 moderate exacerbations events and 50 patients without exacerbations. Sensitivity analyses assessed alternative algorithms and compared healthcare resource utilization (HRU) between algorithm-identified patients (claims group) and those confirmed by chart review (confirmed group) to have experienced a moderate exacerbation. RESULTS: Algorithm-identified moderate exacerbations were: visit of ≤1 day with an asthma exacerbation diagnosis OR visit of ≤1 day with selected asthma diagnoses AND ≥1 respiratory pharmacy claim, excluding systemic corticosteroids, within 14 days after the first claim. The algorithm's PPV was 42%; the NPV was 78%. HRU was similar for both groups. CONCLUSION: This algorithm identified potential moderate exacerbations from claims data; however, the modest PPV underscores its limitations in identifying moderate exacerbations, although performance was partially due to identification of previously unidentified severe exacerbations. Application of this algorithm in future claims-based studies may help quantify the economic burden of moderate and severe exacerbations in asthma when an algorithm identifying severe exacerbations is applied first.

Burden of hyperphagia and obesity in Bardet-Biedl syndrome: a multicountry survey.

BACKGROUND: Signs and symptoms of Bardet-Biedl syndrome (BBS) occur during early childhood, progress over time, and place substantial, multifaceted burden on patients and their caregivers. Hyperphagia may be a contributing factor to early-onset obesity in BBS; however, there are limited insights into its impacts on patients and caregivers. We quantified disease burden as it relates to the physical and emotional impacts of hyperphagia in BBS. METHODS: The CAREgiver Burden in BBS (CARE-BBS) study was a multicountry, cross-sectional survey of adult caregivers of patients with BBS who have had hyperphagia and obesity. The survey consisted of questionnaires including Symptoms of Hyperphagia, Impacts of Hyperphagia, Impact of Weight on Quality of Life (IWQOL)-Kids Parent Proxy, and Patient-Reported Outcome Measurement Information System (PROMIS) v1.0-Global Health 7. In addition, clinical characteristics, medical history, and weight management questions were included. Outcomes were scored and summarized descriptively in aggregate and by country, age, and obesity severity according to weight class. RESULTS: There were 242 caregivers of patients with BBS who completed the survey. Caregivers observed hyperphagic behaviors throughout the day, with negotiating for food (90%) and waking up and asking or looking for food during the night (88%) being the most frequent. Hyperphagia had at least a moderate negative impact on most patients' mood/emotions (56%), sleep (54%), school (57%), leisure (62%), and familial relationships (51%). Hyperphagia affected concentration at school (78%), and symptoms of BBS contributed to patients missing ≥ 1 day of school a week (82%). Responses from the IWQOL-Kids Parent Proxy suggested obesity most greatly negatively affected physical comfort (mean [standard deviation (SD)], 41.7 [17.2]), body esteem (41.0 [17.8]), and social life (41.7 [18.0]). On the PROMIS questionnaire, mean (SD) global health score for pediatric patients with BBS and overweight or obesity (36.8 [10.6]) was lower than the general population (mean, 50). CONCLUSIONS: Evidence from this study suggests that hyperphagia and obesity may have broad negative impacts on the lives of patients with BBS, including physical health, emotional well-being, school performance, and personal relationships. Therapies that target hyperphagia may alleviate the extensive clinical and nonclinical impacts experienced by patients with BBS and their caregivers.

Caregiver burden in Bardet-Biedl syndrome: findings from the CARE-BBS study.

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.

Unintended Consequences of Increased Out-of-Pocket Costs During Medicare Coverage Gap on Anticoagulant Discontinuation and Stroke.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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]). CONCLUSION: 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.

Cost-Effectiveness Analysis of Pembrolizumab as an Adjuvant Treatment of Resected Stage IIB or IIC Melanoma in the United States.

INTRODUCTION: Pembrolizumab was approved in the US as adjuvant treatment of patients with stage IIB or IIC melanoma post-complete resection, based on prolonged recurrence-free survival vs. placebo in the Phase 3 KEYNOTE-716 trial. This study aimed to evaluate the cost-effectiveness of pembrolizumab vs. observation as adjuvant treatment of stage IIB or IIC melanoma from a US health sector perspective. METHODS: A Markov cohort model was constructed to simulate patient transitions among recurrence-free, locoregional recurrence, distant metastasis, and death. Transition probabilities from recurrence-free and locoregional recurrence were estimated via multistate parametric modeling based on patient-level data from an interim analysis (data cutoff date: 04-Jan-2022). Transition probabilities from distant metastasis were based on KEYNOTE-006 data and network meta-analysis. Costs were estimated in 2022 US dollars. Utilities were based on applying US value set to EQ-5D-5L data collected in trial and literature. RESULTS: Compared to observation, pembrolizumab increased total costs by $80,423 and provided gains of 1.17 quality-adjusted life years (QALYs) and 1.24 life years (LYs) over lifetime, resulting in incremental cost-effectiveness ratios of $68,736/QALY and $65,059/LY. The higher upfront costs of adjuvant treatment were largely offset by reductions in costs of subsequent treatment, downstream disease management, and terminal care, reflecting the lower risk of recurrence with pembrolizumab. Results were robust in one-way sensitivity and scenario analyses. At a $150,000/QALY threshold, pembrolizumab was cost-effective vs. observation in 73.9% of probabilistic simulations that considered parameter uncertainty. CONCLUSION: As an adjuvant treatment of stage IIB or IIC melanoma, pembrolizumab was estimated to reduce recurrence, extend patients' life and QALYs, and be cost-effective versus observation at a US willingness-to-pay threshold.

Real-world clinical burden among patients with and without heart failure worsening after cardiac resynchronization therapy.

OBJECTIVE: Cardiac resynchronization therapy (CRT) can improve cardiac function in patients with heart failure (HF); however, in some patients, HF worsens despite CRT. This study characterized the long-term clinical burden of patients with and without HF worsening (HFW) within 6 months post CRT implantation. METHODS: A claims database (2007-2018) was used to identify two cohorts of adults: those with HFW within 180 days post-CRT and those with no HFW (NHFW). The evaluated clinical outcomes were cardiovascular events/complications, HF-related interventions, hospice enrollment, and all-cause mortality. Inverse probability of treatment weighting (IPTW) was used to adjust for confounders; adjusted comparisons were assessed using weighted Cox proportional hazard ratios (HRs). RESULTS: Among the 12,753 adults analyzed (HFW: N = 4,785; NHFW: N = 7,968), the mean age was 72 years and the mean duration of follow-up was approximately 2 years. The clinical burden was greater for HFW than for NHFW in terms of all-cause mortality (19.7% vs. 12.1%) and occurrence of atrial fibrillation (57.4% vs. 51.2%). In the IPTW-adjusted Cox proportional hazard analyses, patients with HFW had a 54% higher average hazard of experiencing all-cause mortality compared to NHFW (adjusted average HR = 1.54, 95% confidence interval [CI]: 1.41-1.70; p < .001). Of the clinical events experienced by ≥5% of patients, the greatest differences in average hazard were for HF decompensation (adjusted average HR = 1.83, 95% CI: 1.60-2.09) and HF decompensation or death (HR = 1.63, 95%CI: 1.50-1.77). CONCLUSION: Patients with early HFW post-CRT experienced a significantly higher clinical burden than those without HFW. Vigilance for signs of worsening HF in the first 6 months post-CRT is warranted.

Food Marketing Practices of Major Online Grocery Retailers in the United States, 2019-2020.

BACKGROUND: Food marketing influences consumers' preferences for and selection of marketed products. Although a substantial body of research has described food-marketing practices in brick-and-mortar stores, no research has examined food marketing in online grocery retail despite its growing importance as a source of food-at-home purchases. OBJECTIVE: To develop and apply a coding instrument to describe food marketing and the nutritional quality of marketed products in online grocery stores. DESIGN: Quantitative content analysis and review of product Nutrition Facts labels and ingredients lists to calculate nutrient density and level of processing using the NOVA classification system. PARTICIPANTS/SETTING: Foods and beverages (n = 3,473) marketed in the top revenue-generating online grocery retailers and those participating in the US Department of Agriculture Supplemental Nutrition Assistance Program Online Purchasing Pilot (n = 21) in 2019-2020. MAIN OUTCOME MEASURES: Use of marketing mix strategies (ie, product, placement, promotion, and pricing) across retailers and nutritional quality of marketed products. Products were considered of poor nutritional quality in the case that they were ultraprocessed (NOVA category 4) and excessive in sodium, saturated fat, free sugars, and/or other sweeteners. Products were also classified into 13 mutually exclusive food groups. STATISTICAL TESTS PERFORMED: The proportion of retailers using each marketing strategy, proportion of products of poor nutritional quality, and proportion of products in each food group were calculated. RESULTS: Retailers commonly used product recommendations, search result ordering, branded website content, user-generated content, and social media engagement to market products online. Candy, sweets, and snacks made up the largest percentage of marketed products (17.3%), followed by fruit, vegetables, and legumes (16.7%). Most (62%) marketed products were of poor nutritional quality. Staple food categories such as fruits, vegetables, and grains were frequently marketed, particularly through price reductions and product recommendations. CONCLUSIONS: Online grocery retailers use a variety of customizable food marketing strategies on their websites. Although most marketed products are of poor nutritional quality, there is potential for marketing of staple food categories online that is not feasible in a brick-and-mortar store.

Real-World Economic Burden Among Patients With And Without Heart Failure Worsening After Cardiac Resynchronization Therapy.

INTRODUCTION: Although cardiac resynchronization therapy (CRT) has the potential to improve cardiac function in patients with heart failure (HF), a considerable portion of patients do not respond to therapy. This study assessed the economic burden among patients with and without HF worsening after receiving CRT in real-world practice. METHODS: In this retrospective claims-based study using Optum's de-identified Clinformatics® Data Mart Database (January 2007-December 2018), adults who received CRT were stratified into two cohorts based on whether they showed evidence of HF worsening within 180 days post-CRT implantation. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding, accounting for demographics (e.g., age, sex), the Quan-Charlson Comorbidity Index, other clinical characteristics, healthcare resource utilization (HRU), and healthcare costs during the 180 days pre-CRT (baseline period). Annualized all-cause and congestive HF-related HRU and healthcare costs from payer and patient perspectives were assessed from day 181 post-CRT (follow-up period), and compared between cohorts using incidence rate ratios (IRRs) and cost ratios (CRs). RESULTS: This study included 12,753 patients (n = 4785 with HF worsening; n = 7968 without). Mean age was 72 years and roughly two-thirds were male. Baseline characteristics were balanced between cohorts post-IPTW. During follow-up, patients with HF worsening had significantly greater annual all-cause inpatient [adjusted IRR (95% confidence interval) = 1.55 (1.44, 1.66), p < 0.001], outpatient [adjusted IRR = 1.46 (1.32, 1.61), p < 0.001], and emergency department [adjusted IRR = 1.31 (1.22, 1.41), p < 0.001] visits. Mean annual total per patient payer-paid amounts were significantly higher for patients with HF worsening versus without HF worsening [adjusted CR = 1.68 (1.56, 1.80), p < 0.001]. Annual patient-paid medical costs were also higher for patients with HF worsening [adjusted CR = 1.31 (1.25, 1.38), p < 0.001]. Results were similar for congestive HF-related HRU and costs. CONCLUSIONS: The incremental economic burden among patients with HF worsening following CRT is substantial. Efforts aimed at CRT optimization may help reduce this burden.