Comparative Genitourinary Safety of In-class Sodium-Glucose Cotransporter-2 Inhibitors among Patients with Heart Failure with Preserved Ejection Fraction: A Cohort Study.

PURPOSE: The American Heart Association recommended sodium-glucose cotransporter-2 inhibitors (SGLT2i) for the management of heart failure with preserved ejection fraction (HFpEF). However, little is known about their real-world in-class comparative safety in patients with HFpEF. We aimed to assess the comparative safety of SGLT2i in the risk of urinary tract infection (UTI) or genital infection separately or as a composite outcome among patients with HFpEF. METHODS: This cohort study using MarketScan® Commercial and Medicare supplemental databases (2012-2020) included patients aged ≥ 18 years with a diagnosis of HFpEF who initiated SGLT2i therapy. Three pairwise comparison groups were established: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. After stabilized inverse probability treatment weighting, Cox proportional hazards regression was used to compare the risk of UTI or genital infection separately or as a composite outcome in each cohort. RESULTS: The risk of the composite outcome did not significantly differ between canagliflozin and dapagliflozin (adjusted hazard ratio [aHR] 0.64; 95% confidence interval [CI] 0.36-1.14) or between empagliflozin and canagliflozin (aHR 1.25; 95% CI 0.77-2.05). Similarly, there was no evidence of difference between dapagliflozin and empagliflozin in this risk (aHR 0.76; 95% CI 0.48-1.21). The results of analyses separately assessing UTI or genital infection were similar. CONCLUSIONS: There was no significant difference in the risk of UTI or genital infection among patients with HFpEF who initiated canagliflozin, dapagliflozin, or empagliflozin.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are used for the management of heart failure with preserved ejection fraction (HFpEF). It is important to assess their comparative risk of urinary tract infection (UTI) or genital infection among patients with HFpEF. We compared patients with HFpEF using SGLT2i in three pairwise groups: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. We found that there was no significant difference in the risk of genitourinary infections including UTI or genital infections among dapagliflozin, empagliflozin, and canagliflozin.

Comparative Safety of Long-Acting vs. Short-Acting Erythropoiesis-Stimulating Agents Among Patients Undergoing Hemodialysis.

Both short-acting (epoetin alfa or beta) and long-acting (darbepoetin alfa or PEG-epoetin) erythropoiesis-stimulating agents (ESAs) are commonly prescribed for patients with kidney failure undergoing maintenance hemodialysis. We compared the risks of major adverse cardiovascular events (MACE) and of all-cause mortality associated with receipt of short- vs. long-acting ESAs. This retrospective cohort analysis included Medicare hemodialysis beneficiaries aged ≥ 18 years in the United States Renal Data System from January 2015 to December 2017. We included adults who survived > 90 days after initiating hemodialysis and received either short- or long-acting ESAs. Outcomes were MACE (first occurrence of stroke, acute myocardial infarction, or cardiovascular-related mortality) and all-cause mortality. After stabilized inverse probability of treatment weighting, Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for each outcome. Of 68,607 patients (mean age: 65 years, 45% females), 33,658 (49%) received long-acting ESAs and 34,949 (51%) received short-acting ESAs. There was no difference in the risk of MACE associated with receipt of short- vs. long-acting ESAs (HR: 1.02 (95% CI: 0.98-1.08)). However, long-acting (vs. short-acting) ESA receipt was associated with a lower risk of all-cause mortality (HR: 0.91 (95% CI: 0.87-0.96)). Compared with short-acting ESAs, long-acting ESAs were associated with a lower risk of all-cause mortality, with no difference in the risk of MACE. Future studies with a longer follow-up are needed to confirm these findings.

Association between trajectories of adherence to endocrine therapy and risk of treated breast cancer recurrence among US nonmetastatic breast cancer survivors.

BACKGROUND: Endocrine therapy is the mainstay treatment for breast cancer (BC) to reduce BC recurrence risk. During the first year of endocrine therapy use, nearly 30% of BC survivors are nonadherent, which may increase BC recurrence risk. This study is to examine the association between endocrine therapy adherence trajectories and BC recurrence risk in nonmetastatic BC survivors. METHODS: This retrospective cohort study included Medicare beneficiaries in the United States (US) with incident nonmetastatic BC followed by endocrine therapy initiation in 2010-2019 US Surveillance, Epidemiology, and End Results linked Medicare data. We calculated monthly fill-based proportion of days covered in the first year of endocrine therapy. We applied group-based trajectory models to identify distinct endocrine therapy adherence patterns. After the end of the first-year endocrine therapy trajectory measurement period, we estimated the risk of time to first treated BC recurrence within 4 years using Cox proportional hazards models. RESULTS: We identified 5 trajectories of adherence to endocrine therapy in BC Stages 0-I subgroup (n = 28,042) and in Stages II-III subgroup (n = 7781). A trajectory of discontinuation before 6 months accounted for 7.0% in Stages 0-I and 5.8% in Stages II-III subgroups, and this trajectory was associated with an increased treated BC recurrence risk compared to nearly perfect adherence (Stages 0-I: adjusted hazard [aHR] = 1.84, 95% CI = 1.46-2.33; Stages II-III: aHR = 1.38, 95% CI = 1.07-1.77). CONCLUSIONS: Nearly 7% of BC survivors who discontinued before completing 6 months of treatment was associated with an increased treated BC recurrence risk compared to those with nearly perfect adherence among Medicare nonmetastatic BC survivors.

Comparative effectiveness of sacubitril/valsartan versus angiotensin receptor blockers in patients with heart failure with preserved ejection fraction: A real-world study.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Sacubitril/valsartan (SAC/VAL) or angiotensin receptor blockers (ARBs) are recommended therapy for heart failure with preserved ejection fraction (HFpEF), but little is known about their real-world comparative effectiveness among patients with HFpEF. The objective of this study was to determine the comparative effectiveness of SAC/VAL vs ARBs in preventing HF-related hospitalization or all-cause hospitalization among patients with HFpEF. METHODS: We conducted a cohort study using IBM MarketScan commercial and Medicare supplemental databases to identify patients aged 18 years or older with a diagnosis of HFpEF and initiation of SAC/VAL (2015-2020) or ARB (2009-2014) therapy. The index date was the date of the first SAC/VAL or ARB prescription fill. After propensity score (PS) matching with a ratio of 1 up to 3, Cox proportional hazards regression was used with robust variance estimators to compare the risks of HF-related hospitalization and all-cause hospitalization between the 2 therapies. Several subgroup and sensitivity analyses were conducted to check the robustness of the main analysis. RESULTS: After PS matching, 2,520 patients (846 receiving SAC/VAL and 1,674 receiving an ARB) were included in the final analyses. After controlling for covariates, there was no difference in the risk of HF-related hospitalization between SAC/VAL and ARB recipients (adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 0.99-1.77). There was also no difference in the risk of all-cause hospitalization between SAC/VAL and ARB recipients (aHR, 1.06; 95% CI, 0.91-1.24). CONCLUSION: Among individuals with private or Medicare Advantage insurance plans, there was no significant difference in the risk of HF-related hospitalization or all-cause hospitalization between adults with HFpEF who received SAC/VAL and those who received ARB therapy.

Elucidating the association between direct-acting antivirals and Parkinson's disease in patients with hepatitis C virus infection.

BACKGROUND: Some epidemiological studies have found an increased association between Parkinson's disease (PD) and chronic hepatitis C virus (HCV) infection. Although a few studies have also found a decreased risk of PD with interferon-α therapy, the effect of direct-acting antivirals (DAAs) on Parkinson's disease remains unclear. The current study seeks to assess and elucidate the association between DAAs and PD in patients newly diagnosed with chronic HCV infection. METHODS: We conducted a retrospective cohort study of patients ≥18 years diagnosed with HCV using MarketScan Commercial and Medicare Supplemental database (2012-2019). Follow-up started with the initiation of DAA (or randomly assigned date for the non-DAA group) and ended at occurrence of PD, disenrollment, or end of the study period. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals. RESULTS: We identified 48,356 patients diagnosed with HCV. The mean follow-up time of the cohort was 1.31 years. The incidence rate of PD was 53 per 100,000 person-years for the DAA group and 48 per 100,000 person-years for the non-DAA group. The adjusted HR was 1.24 (95% CI = 0.56-2.73). Results were consistent across sensitivity and subgroup analyses. CONCLUSION: This study did not find an association between DAAs and PD among patients with HCV infection.

Association between trajectories of prescription opioid use and risk of opioid use disorder and overdose among US nonmetastatic breast cancer survivors.

PURPOSE: To examine the association between prescription opioid use trajectories and risk of opioid use disorder (OUD) or overdose among nonmetastatic breast cancer survivors by treatment type. METHODS: This retrospective cohort study included female nonmetastatic breast cancer survivors with at least 1 opioid prescription fill in 2010-2019 Surveillance, Epidemiology and End Results linked Medicare data. Opioid mean daily morphine milligram equivalents (MME) calculated within 1.5 years after initiating active breast cancer therapy. Group-based trajectory models identified distinct opioid use trajectory patterns. Risk of time to first OUD/overdose event within 1 year after the trajectory period was calculated for distinct trajectory groups using Cox proportional hazards models. Analyses were stratified by treatment type. RESULTS: Four opioid use trajectories were identified for each treatment group. For 38,030 survivors with systemic endocrine therapy, 3 trajectories were associated with increased OUD/overdose risk compared with early discontinuation: minimal dose (< 5 MME; adjusted hazard ratio [aHR] = 1.73 [95% CI 1.43-2.09]), very low dose (5-25 MME; 2.67 [2.05-3.48]), and moderate dose (51-90 MME; 6.20 [4.69-8.19]). For 9477 survivors with adjuvant chemotherapy, low-dose opioid use was associated with higher OUD/overdose risk (aHR = 7.33 [95% CI 2.52-21.31]) compared with early discontinuation. For 3513 survivors with neoadjuvant chemotherapy, the differences in OUD/OD risks across the 4 trajectories were not significant. CONCLUSIONS: Among Medicare nonmetastatic breast cancer survivors receiving systemic endocrine therapy or adjuvant chemotherapy, compared with early discontinuation, low-dose or moderate-dose opioid use were associated with six- to sevenfold higher OUD/overdose risk. Breast cancer survivors at high-risk of OUD/overdose may benefit from targeted interventions (e.g., pain clinic referral).

Demographics, Trends, and Clinical Characteristics of HIV Pre-Exposure Prophylaxis Recipients and People Newly Diagnosed with HIV from Large Electronic Health Records in Florida.

Florida is one of the HIV epicenters with high incidence and marked sociodemographic disparities. We analyzed a decade of statewide electronic health record/claims data-OneFlorida+-to identify and characterize pre-exposure prophylaxis (PrEP) recipients and newly diagnosed HIV cases in Florida. Refined computable phenotype algorithms were applied and a total of 2186 PrEP recipients and 7305 new HIV diagnoses were identified between January 2013 and April 2021. We examined patients' sociodemographic characteristics, stratified by self-reported sex, along with both frequency-driven and expert-selected descriptions of clinical conditions documented within 12 months before the first PrEP use or HIV diagnosis. PrEP utilization rate increased in both sexes; higher rates were observed among males with sex differences widening in recent years. HIV incidence peaked in 2016 and then decreased with minimal sex differences observed. Clinical characteristics were similar between the PrEP and new HIV diagnosis cohorts, characterized by a low prevalence of sexually transmitted infections (STIs) and a high prevalence of mental health and substance use conditions. Study limitations include the overrepresentation of Medicaid recipients, with over 96% of female PrEP users on Medicaid, and the inclusion of those engaged in regular health care. Although PrEP uptake increased in Florida, and HIV incidence decreased, sex disparity among PrEP recipients remained. Screening efforts beyond individuals with documented prior STI and high-risk behavior, especially for females, including integration of mental health care with HIV counseling and testing, are crucial to further equalize PrEP access and improve HIV prevention programs.

Risk of Fractures With Concomitant Use of Calcium Channel Blockers and Selective Serotonin Reuptake Inhibitors.

BACKGROUND: Despite their frequent concurrent use, little is known about the concomitant use of calcium channel blockers (CCBs) and selective serotonin reuptake inhibitors (SSRIs) on fracture risk. We compared risk of fractures in patients concomitantly treated with CCBs and SSRIs versus CCB-only users. We compared risk of fractures among concomitant CCB-SSRI users initiating cytochrome P450 3A4 (CYP3A4)-inhibiting SSRIs versus non-CYP3A4 inhibiting SSRIs. METHODS: This retrospective cohort study used IBM MarketScan commercial claims and Medicare Supplemental database (2007-2019). We included adults diagnosed with hypertension and depression, newly initiating SSRIs while being treated with CCBs (ie, concomitant CCB-SSRI users) and those who did not (ie, CCB-only users). Primary outcome was the first occurrence of any fracture. We used stabilized inverse probability of treatment weighting (sIPTW) based on propensity scores to balance baseline risk between groups. Cox proportional hazard regression modeling was used to compare fracture risk. RESULTS: We identified 191 352 concomitant CCB-SSRI and 956 760 CCB-only users (mean age = 56 years, 50.1% males). After sIPTW, compared with CCB-only users, CCBs-SSRIs users had a higher risk of fractures (hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.22-1.66). No difference in the risk of fractures between concomitant users of CCB-CYP3A4-inhibiting SSRIs and those of CCB-non-CYP3A4 inhibiting SSRIs (HR: 1.10, 95% CI: 0.87-1.40) was observed. CONCLUSION AND RELEVANCE: Short-term concomitant CCB-SSRI use was associated with increased fracture risk. Concomitant CCBs and CYP3A4-inhibiting SSRIs compared with CCBs and non-CYP3A4 inhibiting SSRIs use was not associated with increased risk.

Trajectories of Pre-Exposure Prophylaxis (PrEP) Adherence Among Commercially Insured Individuals.

We used group-based trajectory models to identify four distinct trajectory patterns of adherence to pre-exposure prophylaxis (PrEP) among 20,696 users. Only 44.5% were consistently PrEP adherent, with younger age, being female, or having substance use disorder or depression associated with early discontinuation. Public health efforts are needed to improve PrEP adherence.

Trends in Recommended Screening and Monitoring Tests for Users of HIV Pre-Exposure Prophylaxis Before and During the COVID-19 Pandemic.

Introduction: To ensure the health and safety of persons taking pre-exposure prophylaxis to prevent HIV infection, the 2017 Centers for Disease Control and Prevention guidelines recommended initial and follow-up laboratory testing. We assessed the trends in adherence rates to recommended laboratory testing among pre-exposure prophylaxis users and identified factors associated with HIV testing among pre-exposure prophylaxis users from 2016 to 2020 and also examined rate changes during the COVID-19 pandemic in 2020. Methods: We conducted a retrospective cohort study assessing the rates and trends of recommended laboratory testing among commercially insured pre-exposure prophylaxis users from 2016 to 2020, using the MarketScan database. We examined the proportion of pre-exposure prophylaxis users adhering to the following initial and follow-up laboratory testing: (1) HIV, creatinine clearance, hepatitis B virus, hepatitis C virus, and sexually transmitted infections (chlamydia/gonorrhea and syphilis) within 7 days before pre-exposure prophylaxis initiation; (2) HIV 90 days after initiation; and (3) HIV, creatinine clearance, and sexually transmitted infections 180 days after pre-exposure prophylaxis initiation. We used general linear models to examine trends and multivariable logistic regression to identify predictors of ≥1 HIV test within 180 days after index pre-exposure prophylaxis. Results: We identified 19,581 new pre-exposure prophylaxis users. Most were male (96%) and aged 18-34 years (55%). Adherence rates to recommended testing increased from 2016 through 2019 (e.g., 9.0%-13.6% for all initial screening tests 7 days before initiation, 42.1%-44.6% for HIV testing 90 days after initiation, 33.8%-40.6% for all follow-up tests within 180 days after initiation), but all rates decreased during the COVID-19 pandemic (12.4%, 33.6%, and 31.6%, respectively). Younger age (aged 13-17 years: AOR=0.44, 95% CI=0.28, 0.71) and ages 18-34 years (AOR=0.80, 95% CI=0.74, 0.86) were associated with a significantly lower likelihood of getting an HIV test within 180 days after initiation than ages 35-44 years, and female sex (AOR=0.64, 95% CI=0.55, 0.74) were associated with a significantly lower likelihood than male sex. Pre-exposure prophylaxis users with a history of sexually transmitted infections had a higher likelihood (AOR=1.27, 95% CI=1.16, 1.40) of getting tested than those without. Conclusions: Initial screening and follow-up testing rates were lower than those recommended by the Centers for Disease Control and Prevention. Public health efforts are needed to ensure that patients have access to needed laboratory testing during pandemics or natural disasters and to educate patients and clinicians about the importance of screening and monitoring tests to ensure the safety and health of pre-exposure prophylaxis users.

Trajectories of adherence to extended treatment with direct oral anticoagulants and risks of recurrent venous thromboembolism and major bleeding.

BACKGROUND: Little is known about medication adherence patterns and their association with effectiveness and safety among patients with venous thromboembolism (VTE) receiving direct oral anticoagulant (DOAC) therapy beyond 3-6 months of initial treatment. OBJECTIVE: To examine the associations between adherence trajectories of extended treatment with DOAC and the risks of recurrent VTE and major bleeding among patients with VTE. METHODS: We conducted a retrospective cohort study of patients with incident VTE who completed 6 months of initial anticoagulant treatment and received either DOAC extended therapy or no extended therapy using MarketScan Commercial and Medicare Supplemental databases (2013-2019). We used group-based trajectory models to identify distinct adherence patterns during extended treatment. Using inverse probability treatment weighted Cox proportional hazards models, we examined the association between the adherence trajectories and the risks of recurrent VTE and major bleeding. RESULTS: Among 10,960 patients with extended treatment with DOACs (rivaroxaban, apixaban, dabigatran, edoxaban) and 5,133 patients with no extended treatment, we identified 4 distinct trajectories (consistently high, gradually declining, rapidly declining, and no extended treatment). Compared with the no extended treatment group, the groups with consistently high adherence (hazard ratio = 0.09, 95% CI = 0.05-0.17) and with gradually declining adherence (0.13, 0.03-0.53) showed decreased recurrent VTE risk without increased major bleeding risk (consistently high adherence 1.19, 0.71-1.99; gradually declining adherence 1.96, 0.81-4.70). There was no difference in the risk of recurrent VTE (0.34, 0.10-1.16) for the group with rapidly declining adherence, but this group was associated with increased major bleeding risk (2.65, 1.01-6.92). CONCLUSIONS: Our findings underscore the clinical importance of continuing and remaining adherent to extended DOAC treatment without increased major bleeding risk for patients with VTE. DISCLOSURES: This research was supported by the BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program. The funding source had no role in the design, collection, analysis, or interpretation of the data or the decision to submit the article for publication. Dr Lo-Ciganic reported receiving research funding from Merck Sharp & Dohme Corp. Dr Dietrich reported receiving honorarium for training and education from BMS/Pfizer. Dr DeRemer is a stockholder of Portola Pharmaceuticals and reported receiving personal fees for advisory board meeting from BMS. No other disclosures were reported.

Economic Burden of Sanfilippo Syndrome in the United States.

Introduction: Sanfilippo syndrome is a rare disease and fatal genetic disorder with no FDA-approved treatment in the United States (US), and no comprehensive assessment of economic disease burden is available. Objectives: To develop a model to estimate the economic burden associated with Sanfilippo syndrome in the US using direct costs, indirect costs and valued intangibles (disability-adjusted life years, or DALYs) from 2023 onward. Design and Setting: A multistage comorbidity model was generated based on Sanfilippo syndrome symptoms, and disability weights from the 2010 Global Burden of Disease Study. Attributable increase in caregiver mental health burden were estimated using data from the CDC National Comorbidity Survey and retrospective studies on caregiver burden. Direct costs were approximated from the 2019 EveryLife Foundation survey, and indirect costs were estimated from Federal income data. Monetary valuations were adjusted to USD 2023 and given a 3% discount rate from 2023 onward. Main Outcome Measures: Incidence of Sanfilippo syndrome was calculated for each year, and year-over-year DALYs due to patient years lived with disability (YLDs) and years life lost (YLLs) were calculated by comparing to the health-adjusted life expectancy (HALE) in the US. Direct and indirect costs were calculated for each simulated patient from onset of symptoms to death. Results: From 2023-2043, overall economic burden in the US attributable to Sanfilippo syndrome was estimated to be $2.04 billion USD present value (2023) with current standard of care. The burden to individual families exceeded $8 million present value from time of birth per child born with Sanfilippo syndrome. Conclusion: Sanfilippo syndrome is a rare lysosomal storage disease, however the severe burden associated with the disease for individual families demonstrates a considerable cumulative impact. Our model represents the first disease burden value estimate associated with Sanfilippo syndrome, and underscores the substantial morbidity and mortality burden of Sanfilippo syndrome.

Nationwide trends in hospitalization, medical costs, and mortality for asthma after introduction of biologics: A cross-sectional study in the United States.

BACKGROUND: Asthma is the most common inflammatory lung disease in the United States. Since 2015, biologic therapies have provided targeted treatment for patients with severe asthma. OBJECTIVE: To evaluate the trends for in-hospital outcomes of asthma before (2012-2014) and after (2016-2018) the introduction of biologic therapies for asthma. METHODS: We conducted a nationwide cross-sectional analysis of patients aged 2 years or older who were hospitalized for asthma between 2012 and 2018 using data from the Nationwide Readmissions Database. Outcomes included rates of asthma hospital admission and asthma-related 30-day readmission, hospital length of stay, hospital costs, and inpatient mortality. Generalized linear models assessed trends in rates of asthma admission and readmission, length of stay, costs, and mortality quarterly during 2012-2014 and 2016-2018. RESULTS: Among 691,537 asthma-related admissions, quarterly asthma admission rates significantly decreased (-0.90%, 95% CI = -1.46% to - 0.34%; P = 0.002) during 2016-2018, mainly among adults, but not during 2012-2014. Quarterly assessed readmission rates decreased by 2.40% (-2.85% to -1.96%; P < 0.0001) during 2012-2014 and by 2.12% (-2.74% to - 1.50%; P < 0.0001) during 2016-2018. Mean length of stay for asthma admissions decreased quarterly by 0.44% (-0.49% to - 0.38%; P < 0.0001) during 2012-2014 and by 0.27% (-0.34% to - 0.20%; P < 0.0001) during 2016-2018. Quarterly hospital costs for admissions were unchanged during 2012-2014 but increased by 0.28% (0.21% to 0.35%; P < 0.0001) during 2016-2018. There were no significant trends in inpatient mortality during 2012-2014 and 2016-2018. CONCLUSIONS: After the introduction of new biologics for severe asthma in 2015, asthma-related hospital admissions decreased significantly, whereas hospital costs increased. Asthma-related 30-day readmission rates and length of stay for asthma admissions continuously decreased, whereas inpatient mortality rates remained stable. DISCLOSURES: This work was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL136945. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The data that support the findings of this study are available from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project.

Cost-effectiveness analysis of monthly, 3-monthly, and 6-monthly long-acting injectable and oral paliperidone in adults with schizophrenia.

BACKGROUND: Paliperidone is among the most cost-effective antipsychotics in adults with schizophrenia, and it has different formulations, including oral paliperidone extended-release (ER) and long-acting injectable (LAI) paliperidone formulations administered every month (PP1M), 3 months (PP3M), or 6 months (PP6M). However, cost-effectiveness analyses comparing different paliperidone formulations were limited. OBJECTIVE: To compare the cost-effectiveness across different paliperidone formulations. METHODS: A Markov model was developed to simulate 1,000 adults aged 40 years with stable schizophrenia transitioning among stable disease-medication adherent, stable disease-medication nonadherent, relapse with hospitalization, relapse with ambulatory care, and death states every 3 months for 5 years. Drug costs were estimated using the prices listed in the Veterans Affairs Federal Supply Schedule, and costs for treating complications were estimated from published studies. All costs were estimated from the US health care system perspective and standardized to 2022 US dollars using the Consumer Price Index Inflation Calculator. Quality-adjusted life-years (QALYs) were estimated using relapse rates from randomized clinical trials and health-related quality of life scores from observational studies. The estimated future costs and QALYs were discounted at 3%. We reported incremental net monetary benefits between alternative formulations at the $50,000 willingness-to-pay (WTP) threshold with a positive value indicating cost-effectiveness. The impact of parameter uncertainty on study outcomes was assessed using 1-way deterministic and probabilistic sensitivity analyses. RESULTS: In adults with schizophrenia stabilized with paliperidone ER, switching to LAI formulations was associated with increased QALY (PP1M = 0.05, PP3M = 0.14, PP6M = 0.15) and increased cost (PP1M = 49,433, PP3M = 26,698, PP6M = 26,147), leading to a negative incremental net monetary benefit (PP1M = -$46,804, PP3M = -$19,508, PP6M = -$18,886) compared with continuing ER. Among LAI formulations, PP6M was cost-saving with the most QALYs gained (cost = $63,277, QALY = 3.731), followed by PP3M (cost = $63,828, QALY = 3.729) and PP1M (cost = $86,563, QALY = 3.638). At the $50,000 WTP threshold, the probabilities for PP1M, PP3M, and PP6M being cost-effective compared with paliperidone ER were 0.4%, 10.2%, and 9.8%, respectively. The probability of PP6M being cost-effective was 92.6% for the PP6M-PP1M pair and 55.2% for the PP6M-PP3M pair, and 91.1% of PP3M use was cost-effective in the PP3M-PP1M pair. The results were generally robust in the sensitivity analyses, even at the $190,000 WTP threshold. CONCLUSIONS: For patients with schizophrenia stabilized with paliperidone ER, switching to LAI formulations was not cost-effective, suggesting the high drug costs for LAI may not justify the improved quality of life within 5 years. Among LAI formulations, PP6M was cost-effective over PP1M and PP3M.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors among patients with heart failure with preserved ejection fraction.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended by the American Heart Association for management of heart failure with preserved ejection fraction (HFpEF), but little is known about their in-class comparative effectiveness in real-world settings. OBJECTIVES: To assess the in-class comparative effectiveness of SGLT2i for preventing HF-related and all-cause hospitalizations among patients with HFpEF. METHODS: Using MarketScan® Commercial and Medicare Supplemental research databases (2012-2020), this cohort study included adults with HFpEF treated with SGLT2i. Stabilized inverse probability treatment weighted Cox proportional hazards regression was used to compare HF-related and all-cause hospitalizations in three pairwise comparisons: dapagliflozin versus canagliflozin, empagliflozin versus canagliflozin, and dapagliflozin versus empagliflozin. Subgroup and sensitivity analyses were conducted to assess robustness of the main analysis. RESULTS: In total, 3629 SGLT2i users (881 dapagliflozin, 1120 canagliflozin, and 1628 empagliflozin) were included. Compared with canagliflozin, dapagliflozin was associated with decreased risk of HF-related hospitalization (adjusted hazard ratio [aHR], 0.75; 95% confidence interval [CI], 0.56-1.01) and all-cause hospitalization (aHR, 0.84; 95% CI 0.73-0.97). Compared with canagliflozin, empagliflozin was associated with 55% decreased risk of HF-related hospitalization (aHR, 0.45; 95% CI 0.34-0.59) and 18% decreased risk of all-cause hospitalization (aHR, 0.82; 95% CI 0.73-0.93). Compared with empagliflozin, dapagliflozin was associated with 50% increased risk of HF-related hospitalization (aHR, 1.50; 95% CI 1.09-2.07) and a statistically nonsignificant increase in the risk of all-cause hospitalization (aHR, 1.05; 95% CI 0.92-1.20). CONCLUSIONS: Compared with canagliflozin or dapagliflozin use, empagliflozin use was associated with decreased risk of HF-related and all-cause hospitalizations. Compared with canagliflozin, dapagliflozin was associated with a reduced risk of HF-related and all-cause hospitalizations.

Association between treatment of hepatitis C virus and risk of cardiovascular disease among insured patients with the virus in the United States.

PURPOSE: Hepatitis C virus (HCV) infection has been associated with increased risk of cardiovascular disease (CVD). It is unclear whether HCV treatment affects risk of CVD among patients infected with HCV. We assessed the incidence and risk of CVD among insured patients with HCV infection and evaluated if HCV treatment was associated with reduced CVD risk. METHODS: This retrospective cohort study used MarketScan Commercial and Medicare Supplement databases. Patients newly diagnosed with HCV (vs. patients without HCV) between January 2008 and August 2015 were categorized by treatment (none, insufficient, or minimum effective) based on receipt and duration of anti-HCV treatments. After propensity score matching, time-dependent Cox proportional hazards models were used to compare CVD risk between patients with HCV versus without and between patients with HCV by treatment type and duration. RESULTS: HCV was associated with 13% increased risk of developing CVD overall (adjusted hazard ratio [aHR] 95% CI 1.26-1.35) and with 13% (aHR 1.07-1,18), 9% (aHR 1.03-1.15), and 32% (aHR 1.24-1.40) significantly increased risks of developing coronary artery disease, cerebrovascular disease, and peripheral vascular disease, respectively. Among patients with HCV, compared with no treatment, receipt of minimum effective treatment was associated with 24% decreased risk of CVD, and receipt of insufficient treatment was associated with 14% decreased risk of CVD. CONCLUSIONS: Individuals chronically infected with HCV had a higher incidence of CVD. Among patients with HCV, receipt of antiviral treatment for HCV was associated with decreased risk of CVD.

Hepatitis C Cascade of Care in the Direct-Acting Antivirals Era: A Meta-Analysis.

INTRODUCTION: The hepatitis C virus (HCV) epidemic remains a public health problem worldwide. A systematic review and meta-analysis were conducted to provide evidence of outcomes attained across the HCV care cascade in the era of direct-acting antivirals. METHODS: Studies from North America, Europe, and Australia (January 2014 through March 2021) reporting on HCV care cascade outcomes (screening to cure) were included. When calculating the proportions of individuals completing each step, the numerator for Steps 1-8 was the number of individuals completing each step; the denominator was the number of individuals completing the previous step for Steps 1-3 and Step 3 for Steps 4-8. In 2022, random effects meta-analyses were conducted to estimate pooled proportions with 95% CIs. RESULTS: Sixty-five studies comprising 7,402,185 individuals were identified. Among individuals with positive HCV ribonucleic acid test results, 62% (95% CI=55%, 70%) attended their first care appointment, 41% (95% CI=37%, 45%) initiated treatment, 38% (95% CI=29%, 48%) completed treatment, and 29% (95% CI=25%, 33%) achieved cure. HCV screening rates were 43% (95% CI=22%, 66%) in prisons or jails and 20% (95% CI=11%, 31%) in emergency departments. Linkage to care rates were 62% (95% CI=46%, 75%) for homeless individuals and 26% (95% CI=22%, 31%) for individuals diagnosed in emergency departments. Cure rates were 51% (95% CI=30%, 73%) in individuals with substance use disorder and 17% (95% CI=17%, 17%) in homeless individuals. Cure rates were lowest in the U.S. DISCUSSION: Despite the availability of effective all-oral direct-acting antiviral therapies, persistent gaps remain across the HCV care cascade, especially among traditionally marginalized populations. Public health interventions targeting identified priority areas (e.g., emergency departments) may improve screening and healthcare retention of vulnerable populations with HCV infection (e.g., substance use disorder populations).

Oral fluoroquinolones and risk of aortic aneurysm or dissection: A nationwide population-based propensity score-matched cohort study.

STUDY OBJECTIVE: To investigate risk of aortic aneurysm or dissection in patients using oral fluoroquinolones compared to those using macrolides in real-world clinical practice among a large US general population. DESIGN: Retrospective cohort study design. DATA SOURCE: MarketScan commercial and Medicare supplemental databases. PATIENTS: Adults patients with at least one prescription fill for fluoroquinolone or macrolide antibiotics. INTERVENTION: Fluoroquinolone or macrolide antibiotics. MEASUREMENTS AND MAIN RESULTS: The primary outcome was estimated incidence of aortic aneurysm or dissection associated with the use of fluoroquinolones compared with macrolides during a 60-day follow-up period in a 1:1 propensity score-matched cohort. We identified 3,174,620 patients (1,587,310 in each group) after 1:1 propensity score matching. Crude incidence of aortic aneurysm or dissection was 1.9 cases per 1000 person-years among fluoroquinolone users and 1.2 cases per 1000 person-years among macrolide users. In multivariable Cox regression, compared with macrolides, the use of fluoroquinolones was associated with an increased risk of aortic aneurysm or dissection (aHR: 1.34; 95% CI: 1.17-1.54). The association was primarily driven by a high incidence of aortic aneurysm cases (95.8%). Results of sensitivity (e.g., fluoroquinolone exposure ranging from 7 to 14 days (aHR: 1.47; 95% CI: 1.26-1.71)) and subgroup analyses (e.g., ciprofloxacin (aHR: 1.26; 95% CI: 1.07-1.49) and levofloxacin (aHR: 1.44; 95% CI: 1.19-1.52)) remained consistent with main findings. CONCLUSIONS: Fluoroquinolone use was associated with a 34% increased risk of aortic aneurysm or dissection compared with macrolide use among a general US population.

Trajectories of adherence to extended treatment with warfarin and risks of recurrent venous thromboembolism and major bleeding.

Background: Little is published about warfarin therapy adherence patterns beyond 6 months of initial anticoagulant treatment and their association with effectiveness and safety for patients with venous thromboembolism (VTE). Objectives: To compare the risks of recurrent VTE and major bleeding during extended treatment between adherence patterns using MarketScan Commercial and Medicare Supplemental databases (2013-2019). Methods: In a retrospective cohort study, we included patients with incident VTE who completed an initial 6-month anticoagulant treatment and received either warfarin or no extended therapy. Group-based trajectory models were used to identify distinct extended treatment trajectories. Associations between the trajectories and risk of hospitalization due to recurrent VTE and major bleeding were assessed using inverse probability treatment-weighted Cox proportional hazards models. Results: Compared with no extended treatment, consistently high warfarin adherence was associated with a significantly decreased risk of hospitalization due to recurrent VTE (hazard ratio [HR] = 0.23; 95% CI, 0.12-0.45), but gradually (HR = 0.29; 95CI, 0.08-1.06) or rapidly declining (HR = 0.14; 95% CI, 0.02-1.24) adherence showed no association with the risk of hospitalization due to recurrent VTE. Compared with no extended treatment, warfarin extended therapy was associated with an increased risk of hospitalization due to major bleeding regardless of adherence patterns (consistently high: HR = 2.08; 95% CI, 1.18-3.64, gradually declining: HR = 2.10; 95% CI, 0.74-5.95, and rapidly declining: HR = 9.19; 95% CI, 4.38-19.29). However, compared with rapidly declining adherence, consistently high (HR = 0.23; 95% CI, 0.11-0.47) and gradually declining (HR = 0.23; 95% CI, 0.08-0.64) adherence were associated with decreased risk of hospitalization due to major bleeding. Conclusion: The findings indicated that consistently high adherence to extended warfarin treatment was associated with a decreased risk of hospitalization due to recurrent VTE but an increased risk of hospitalization due to major bleeding compared with no extended treatment.

Impact of Direct-acting Antivirals on Hepatocellular Carcinoma and Mortality Among Medicaid Beneficiaries With Hepatitis C.

OBJECTIVE: The effects of all-oral direct-acting antivirals (DAAs) on hepatocellular carcinoma (HCC) and liver-related and all-cause mortality were assessed among Medicaid beneficiaries with hepatitis C virus (HCV). SUBJECTS: This cohort study used 2013-2019 Arizona Medicaid data from beneficiaries with HCV aged 18-64 years. METHODS: Risks of HCC and liver-related and all-cause mortality were compared between patients with or without DAA treatment, stratified by liver disease severity, using inverse probability of treatment weighted multivariable Cox proportional hazards regression models. RESULTS: Of 29,289 patients, 13.3% received DAAs. Among patients with compensated cirrhosis (CC), DAA treatment was associated with a lower risk of HCC [adjusted hazard ratio (aHR), 0.57; 95% CI, 0.37-0.88] compared with untreated patients although this association was not statistically significant for patients without cirrhosis or with decompensated cirrhosis (DCC). Compared with untreated patients, DAA treatment was associated with decreased risk of liver-related mortality for patients without cirrhosis (aHR: 0.02; 95% CI: 0.004-0.11), with CC (aHR: 0.09; 95% CI: 0.06-0.13), or with DCC (aHR: 0.20; 95% CI: 0.14-0.27). Similarly, compared with untreated patients, DAA treatment was associated with lower all-cause mortality for patients without cirrhosis (aHR: 0.10; 95% CI: 0.08-0.14), with CC (aHR: 0.07; 95% CI: 0.05-0.10), or with DCC (aHR: 0.15; 95% CI: 0.11-0.20). CONCLUSIONS: Among Arizona Medicaid beneficiaries with HCV, DAA treatment was associated with decreased risk of HCC for patients with CC but not for patients without cirrhosis or with DCC. However, DAA treatment was associated with decreased risk of liver-related and all-cause mortality.