Analysis of North Carolina Medicaid Claims Data to Simulate a Pediatric Accountable Care Organization.

Importance: Despite momentum for pediatric value-based payment models, little is known about tailoring design elements to account for the unique needs and utilization patterns of children and young adults. Objective: To simulate attribution to a hypothetical pediatric accountable care organization (ACO) and describe baseline demographic characteristics, expenditures, and utilization patterns over the subsequent year. Design, Setting, and Participants: This retrospective cohort study used Medicaid claims data for children and young adults aged 1 to 20 years enrolled in North Carolina Medicaid at any time during 2017. Children and young adults receiving at least 50% of their primary care at a large academic medical center (AMC) in 2017 were attributed to the ACO. Data were analyzed from April 2020 to March 2021. Main Outcomes and Measures: Primary outcomes were total cost of care and care utilization during the 2018 performance year. Results: Among 930 266 children and young adults (377 233 children [40.6%] aged 6-12 years; 470 612 [50.6%] female) enrolled in Medicare in North Carolina in 2017, 27 290 children and young adults were attributed to the ACO. A total of 12 306 Black non-Hispanic children and young adults (45.1%), 6308 Hispanic or Latinx children and young adults (23.1%), and 6531 White non-Hispanic children and young adults (23.9%) were included. Most attributed individuals (23 133 individuals [84.7%]) had at least 1 claim in the performance year. The median (IQR) total cost of care in 2018 was $347 ($107-$1123); 272 individuals (1.0%) accounted for nearly half of total costs. Compared with children and young adults in the lowest-cost quartile, those in the highest-cost quartile were more likely to have complex medical conditions (399 individuals [6.9%] vs 3442 individuals [59.5%]) and to live farther from the AMC (median [IQR distance, 6.0 [4.6-20.3] miles vs 13.9 [4.6-30.9] miles). Total cost of care was accrued in home (43%), outpatient specialty (19%), inpatient (14%) and primary (8%) care. More than half of attributed children and young adults received care outside of the ACO; the median (IQR) cost for leaked care was $349 ($130-$1326). The costliest leaked encounters included inpatient, ancillary, and home health care, while the most frequently leaked encounters included behavioral health, emergency, and primary care. Conclusions and Relevance: This cohort study found that while most children attributed to the hypothetical Medicaid pediatric ACO lived locally with few health care encounters, a small group of children with medical complexity traveled long distances for care and used frequent and costly home-based and outpatient specialty care. Leaked care was substantial for all attributed children, with the cost of leaked care being higher than the total cost of care. These pediatric-specific clinical and utilization profiles have implications for future pediatric ACO design choices related to attribution, accounting for children with high costs, and strategies to address leaked care.

Dosing Variation at Initiation of Adalimumab and Etanercept and Clinical Outcomes in Juvenile Idiopathic Arthritis: A Childhood Arthritis and Rheumatology Research Alliance Registry Study.

OBJECTIVE: To determine the dose-response relationship of tumor necrosis factor (TNF) inhibition in the treatment of juvenile idiopathic arthritis (JIA). METHODS: Participants of the Childhood Arthritis and Rheumatology Research Alliance Registry were eligible for inclusion in the analyses if they started TNF inhibition treatment for JIA. The primary treatment response was determined 3 to 7 months after the start of treatment, based on the JIA American College of Rheumatology Pediatric criteria for improvement, clinical Juvenile Arthritis Disease Activity Score, and persistence of treatment after 6 months. Subsequently, pooled logistic regression models were performed to include long-term follow-up data. The models were adjusted for risk factors associated with poor treatment response. Dosing was expressed by body weight, body surface area, ideal body weight, fat free mass, and lean body mass. RESULTS: Participants treated with adalimumab (n = 328) and etanercept (n = 437) were included in the analyses (median dose 0.82 mg/kg body weight [interquartile range (IQR) 0.66-1.04] and 0.83 mg/kg body weight [IQR 0.75-0.95], respectively). The majority of analyses did not show a relationship between dose and outcome. Where associations were found, results were conflicting. Alternative dosing characteristics based on ideal body weight, fat free mass, and lean body mass did not result in stronger or more consistent associations. CONCLUSION: This study was not able to confirm our hypothesis that increased dosing of TNF inhibitors results in improved treatment outcomes. Although adjustment was performed for risk factors of impaired treatment response, residual confounding by indication likely explains the negative associations found in this study.

Trajectories of disease activity in patients with JIA in the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: To describe 2-year trajectories of the clinical Juvenile Arthritis Disease Activity Score, 10 joints (cJADAS10) and associated baseline characteristics in patients with JIA. METHODS: JIA patients in the Childhood Arthritis and Rheumatology Research Alliance Registry enrolled within 3 months of diagnosis from 15 June 2015 to 6 December 2017 with at least two cJADAS10 scores and 24 months of follow-up were included. Latent growth curve models of cJADAS10 were analysed; a combination of Bayesian information criterion, posterior probabilities and clinical judgement was used to select model of best fit. RESULTS: Five trajectories were identified among the 746 included patients: High, Rapidly Decreasing (HRD) (n = 199, 26.7%); High, Slowly Decreasing (HSD) (n = 154, 20.6%); High, Increasing (HI) (n = 39, 5.2%); Moderate, Persistent (MP) (n = 218, 29.2%); and Moderate, Decreasing (MD) (n = 136, 18.2%). Most patients spent a significant portion of time at moderate to high disease activity levels. At baseline, HSD patients were more likely to be older, have a lower physician global assessment, normal inflammatory markers, longer time to first biologic, and have taken systemic steroids compared with HRD. Those with a HI trajectory were more likely to be ANA negative, have a longer time to first biologic, and less likely to be taking a conventional synthetic DMARD compared with HRD. MP patients were more likely to be older with lower household income, longer time to diagnosis, and markers of higher disease activity than those with a MD trajectory. CONCLUSIONS: Five trajectories of JIA disease activity, and associated baseline variables, were identified.

Disease Recapture Rates After Medication Discontinuation and Flare in Juvenile Idiopathic Arthritis: An Observational Study Within the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: Children with well-controlled juvenile idiopathic arthritis (JIA) frequently experience flares after medication discontinuation, but the outcomes of these flares have not been well described. The objective of this study was to characterize the rates and predictors of disease recapture among children with JIA who restarted medication to treat disease flare. METHODS: Children with JIA who discontinued conventional synthetic or biologic disease-modifying antirheumatic drugs for well-controlled disease but subsequently experienced a flare and restarted medication were identified from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. The primary outcome was inactive disease (ID) (physician global assessment <1 and active joint count = 0) 6 months after flare. RESULTS: A total of 333 patients had complete data for ID at 6 months after flare. The recapture rate for the cohort was 55%, ranging from 47% (persistent oligoarthritis) to 69% (systemic arthritis) (P = 0.4). Approximately 67% of children achieved ID by 12 months. In the multivariable model, history and reinitiation of biologic drugs were associated with increased odds of successful recapture (odds ratio [OR] 4.79 [95% confidence interval (95% CI) 1.22-18.78] and OR 2.74 [95% CI 1.62-4.63], respectively). Number of joints with limited range of motion was associated with decreased odds (OR 0.83 per 1 joint increase [95% CI 0.72-0.95]). CONCLUSION: Approximately half of JIA flares post-discontinuation were recaptured within 6 months, but rates of recapture varied across JIA categories. These findings inform shared decision-making for patients, families, and clinicians regarding the risks and benefits of medication discontinuation. Better understanding of biologic predictors of successful recapture in JIA are needed.

Residual stroke risk despite oral anticoagulation in patients with atrial fibrillation.

Background: Oral anticoagulation (OAC) reduces the risk of thromboembolic events in patients with atrial fibrillation (AF); however, thromboembolism (TE) still can occur despite OAC. Factors associated with residual risk for stroke, systemic embolism, or transient ischemic attack events despite OAC have not been well described. Objective: The purpose of this study was to evaluate the residual risk of thromboembolic events in patients with AF despite OAC. Methods: A total of 18,955 patients were analyzed in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF I and II) using multivariable Cox proportional hazard modeling. Mean age was 72 ± 10.7, and 42% were women. There were 451 outcome events. Results: The risk of TE despite OAC increased with CHA2DS2-VASc score: 0.76 (95% confidence interval [CI] 0.63-0.92) events per 100 patient-years for CHA2DS2-VASc score <4 vs 2.01 (95% CI 1.81-2.24) events per 100-patient years for CHA2DS2-VASc score >4. Factors associated with increased risk were previous stroke or transient ischemic attack (hazard ratio [HR] 2.87; 95% CI 2.30-3.59; P <.001), female sex (HR 1.52; 95% CI 1.24-1.86; P <.001), hypertension (HR 1.50; 95% CI 1.09-2.06; P = .01), and permanent AF (HR 1.47; 95% CI 1.12-1.94; P = .001). When transient ischemic attack was excluded, the results were similar, but permanent AF was no longer significantly associated with thromboembolic events. Conclusion: Patients with AF have a residual risk of TE with increasing CHA2DS2-VASc score despite OAC. Key risk markers include previous stroke/transient ischemic attack, female sex, hypertension, and permanent AF.

Effectiveness and Safety of High-Dose Biologics in Juvenile Idiopathic Arthritis in the Childhood Arthritis and Rheumatology Research Alliance.

OBJECTIVE: To describe high-dose biologic use when treating juvenile idiopathic arthritis (JIA). METHODS: Patients with JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry and treated with a biologic after enrollment were eligible. We described the frequency of high-dose biologic use and characteristics of patients receiving high-dose biologics. We used regression modeling to compare 6-month outcomes (using disease activity measures) between those who increased their biologic from standard to high dose (high-dose group) to those who initiated and remained on standard dosing (no-change group), and to those who switched biologic agents (biologic-switch group). We also compared serious adverse events (SAEs) between groups. RESULTS: A total of 5,352 patients with JIA were treated with biologics following enrollment; 1,080 (20%) had ever received a high-dose biologic. There were no significant differences in outcomes between the high-dose group and the biologic-switch group; both improved disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score 10 (-3.53 and -3.95, respectively; P = 0.68). Although the SAE rates in the high-dose group and the biologic-switch group were numerically higher than the no-change group, the event rates were similar, and neither rate was significantly higher than in the no-change group (unadjusted incident rate ratio 2.5 [95% confidence interval (95% CI) 0.7-8.5] and 1.8 [95% CI 0.7-4.6], respectively). CONCLUSION: Dosing escalation appears to be a reasonable choice to improve disease control, but large, prospective, randomized studies evaluating specific biologic agents are needed.

Bimodal distribution of atrial fibrillation burden in 3 distinct cohorts: What is 'paroxysmal' atrial fibrillation?

BACKGROUND: Burden of atrial fibrillation (AF), as a continuous measure, is an emerging alternative classification often assumed to increase linearly with progression of disease. Yet there are no descriptions of AF burden distributions across populations. METHODS: We examined patterns of AF burden (% time in AF) across 3 different cohorts: outpatients with AF undergoing Holter monitoring in a national registry (ORBIT-AF II), routine outpatients undergoing Holter monitoring in a tertiary healthcare system (UHealth), and patients >= 65 years with cardiac implantable electronic devices (Merlin.netTM linked to Medicare). RESULTS: We included 2,058 ORBIT-AF II patients, 4,537 UHealth patients, and 39,710 from Merlin.net. Mean age ranged from 56 to 77 years, sex ranged from 40% to 61% male, and mean CHA2DS2-VASc scores ranged from 2.2 to 4.9. Across all cohorts, AF burden demonstrated skewed frequency towards the extremes, with the vast majority of patients having either very low or very high AF burden. This bimodal distribution was consistent across cohorts, across clinically-documented AF types (paroxysmal v persistent), patients with or without a known AF diagnosis, and among patients with different types of cardiac implantable electronic devices. CONCLUSIONS: Across 3 broad, diverse cohorts with continuous monitoring, distribution of AF burden was consistently skewed towards the extremes without an even, linear distribution or progression. As AF burden is increasingly recognized as a descriptor and potential risk-stratifier, these findings have important implications for future research and patient care.

Comparing health care use and costs among new Medicaid enrollees before and during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVE: To characterize health care use and costs among new Medicaid enrollees before and during the COVID pandemic. Results can help Medicaid non-expansion states understand health care use and costs of new enrollees in a period of enrollment growth. RESEARCH DESIGN: Retrospective cross-sectional analysis of North Carolina Medicaid claims data (January 1, 2018 - August 31, 2020). We used modified Poisson and ordinary least squares regression analysis to estimate health care use and costs as a function of personal characteristics and enrollment during COVID. Using data on existing enrollees before and during COVID, we projected the extent to which changes in outcomes among new enrollees during COVID were pandemic-related. SUBJECTS: 340,782 new enrollees pre-COVID (January 2018 - December 2019) and 56,428 new enrollees during COVID (March 2020 - June 2020). MEASURES: We observed new enrollees for 60-days after enrollment to identify emergency department (ED) visits, nonemergent ED visits, primary care visits, potentially-avoidable hospitalizations, dental visits, and health care costs. RESULTS: New Medicaid enrollees during COVID were less likely to have an ED visit (-46 % [95 % CI: -48 %, -43 %]), nonemergent ED visit (-52 % [95 % CI: -56 %, -48 %]), potentially-avoidable hospitalization (-52 % [95 % CI: -60 %, -43 %]), primary care visit (-34 % [95 % CI: -36 %, -33 %]), or dental visit (-36 % [95 % CI: -41 %, -30 %]). They were also less likely to incur any health care costs (-29 % [95 % CI: -30 %, -28 %]), and their total costs were 8 % lower [95 % CI: -12 %, -4 %]. Depending on the outcome, COVID explained between 34 % and 100 % of these reductions. CONCLUSIONS: New Medicaid enrollees during COVID used significantly less care than new enrollees pre-COVID. Most of the reduction stems from pandemic-related changes in supply and demand, but the profile of new enrollees before versus during COVID also differed.

Children with Heterozygous Familial Hypercholesterolemia in the United States: Data from the Cascade Screening for Awareness and Detection-FH Registry.

OBJECTIVE: To describe enrollment characteristics of youth in the Cascade Screening for Awareness and Detection of FH Registry. STUDY DESIGN: This is a cross-sectional analysis of 493 participants aged <18 years with heterozygous familial hypercholesterolemia recruited from US lipid clinics (n = 20) between April 1, 2014, and January 12, 2018. At enrollment, some were new patients and some were already in care. Clinical characteristics are described, including lipid levels and lipid-lowering treatments. RESULTS: Mean age at diagnosis was 9.4 (4.0) years; 47% female, 68% white and 12% Hispanic. Average (SD) highest Low-density lipoprotein cholesterol (LDL-C) was 238 (61) mg/dL before treatment. Lipid-lowering therapy was used by 64% of participants; 56% were treated with statin. LDL-C declined 84 mg/dL (33%) among those treated with lipid-lowering therapy; statins produced the greatest decline, 100 mg/dL (39% reduction). At enrollment, 39% had reached an LDL-C goal, either <130 mg/dL or ≥50% decrease from pre-treatment; 20% of those on lipid-lowering therapy reached both goals. CONCLUSIONS: Among youth enrolled in the Cascade Screening for Awareness and Detection of FH Registry, diagnosis occurred relatively late, only 77% of children eligible for lipid-lowering therapy were receiving treatment, and only 39% of those treated met their LDL-C goal. Opportunities exist for earlier diagnosis, broader use of lipid-lowering therapy, and greater reduction of LDL-C levels.

Children And The Opioid Epidemic: Age-Stratified Exposures And Harms.

Using North Carolina Medicaid 2016-18 claims data, we found that approximately one in ten adolescents (10.8 percent) filled at least one opioid prescription per year. Dentists, advanced practice providers, and surgeons were common prescribers of opioids to children. In addition, half of children who experienced opioid-related adverse events had filled opioid prescriptions in the prior six months.

Provision and Utilization of Team- and Community-Based Operative Care for Patients With Cleft Lip/Palate in North Carolina.

OBJECTIVE: To characterize operative care for cleft lip and/or palate (CL/P) based on location (ie, from American Cleft Palate Craniofacial Association [ACPA]-approved multidisciplinary teams or from community providers). DESIGN: Cross-sectional analysis of Healthcare Cost and Utilization Project State Inpatient Database and State Ambulatory Surgery & Services Database databases for North Carolina from 2012 to 2015. SETTING/PATIENTS AND MAIN OUTCOME MEASURES: Clinical encounters for children with CL/P undergoing operative procedures were identified, classified by location as "Team" versus "Community," and characterized by demographic, geographic, clinical, and procedural factors. A secondary evaluation reviewed concordance of team and community practices with an ACPA guideline related to coordination of care. RESULTS: Three teams and 39 community providers performed a total of 3010 cleft-related procedures across 2070 encounters. Teams performed 69.7% of total volume and performed the majority of cleft procedures, including cleft lip repair, palate repair, alveolar bone grafting, and correction of velopharyngeal insufficiency. Community locations principally offered myringotomy and rhinoplasty. Team care was associated with higher guideline concordance. CONCLUSIONS: American Cleft Palate Craniofacial Association -approved team-based care accounts for the majority of cleft-related care in North Carolina; however, a substantial volume of cleft-related procedures was provided by community providers, with 3 providers accounting for the vast majority of community cases.

Patterns of amiodarone use and outcomes in clinical practice for atrial fibrillation.

BACKGROUND: Amiodarone is the most effective antiarrhythmic drug (AAD) for atrial fibrillation (AF), but it has a high incidence of adverse effects. METHODS: Using the ORBIT AF registry, patients with AF on amiodarone at enrollment, prescribed amiodarone during follow-up, or never on amiodarone were analyzed for the proportion treated with a guideline-based indication for amiodarone, the variability in amiodarone use across sites, and the outcomes (mortality, hospitalization, and stroke) among patients treated with amiodarone. Hierarchical logistic regression modeling with site-specific random intercepts compared rates of amiodarone use across 170 sites. A logistic regression model for propensity to receive amiodarone created a propensity-matched cohort. Cox proportional hazards modeling, stratified by matched pairs evaluated the association between amiodarone and outcomes. RESULTS: Among 6,987 AF patients, 867 (12%) were on amiodarone at baseline and 451 (6%) started on incident amiodarone during the 3-year follow-up. Use of amiodarone varied among sites from 3% in the lowest tertile to 21% in the highest (p<0.0001). Among those treated, 32% had documented contraindications to other AADs or had failed another AAD in the past. Mortality, cardiovascular hospitalization, and stroke were similar among matched patients on and not on amiodarone at baseline, while incident amiodarone use in matched patients was associated with higher all-cause mortality (adjusted HR 2.06, 95% CI 1.35-3.16). CONCLUSIONS: Use of amiodarone among AF patients in community practice is highly variable. More than 2 out of 3 patients treated with amiodarone appeared to be eligible for a different AAD.

Guideline-directed therapies for comorbidities and clinical outcomes among individuals with atrial fibrillation.

BACKGROUND: Comorbidities are common in patients with atrial fibrillation (AF) and affect prognosis, yet are often undertreated. However, contemporary rates of use of guideline-directed therapies (GDT) for non-AF comorbidities and their association with outcomes are not well described. METHODS: We used the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF) to test the association between GDT for non-AF comorbidities and major adverse cardiac or neurovascular events (MACNE; cardiovascular death, myocardial infarction, stroke/thromboembolism, or new-onset heart failure), all-cause mortality, new-onset heart failure, and AF progression. Adjustment was performed using Cox proportional hazards models and logistic regression. RESULTS: Only 6,782 (33%) of the 20,434 patients eligible for 1 or more GDT for non-AF comorbidities received all indicated therapies. Use of all comorbidity-specific GDT was highest for patients with hyperlipidemia (75.6%) and lowest for those with diabetes mellitus (43.1%). Use of "all eligible" GDT was associated with a nonsignificant trend toward lower rates of MACNE (HR 0.90 [0.79-1.02]) and all-cause mortality (HR 0.90 [0.80-1.01]). Use of GDT for heart failure was associated with a lower risk of all-cause mortality (HR 0.77 [0.67-0.89]), and treatment of obstructive sleep apnea was associated with a lower risk of AF progression (OR 0.75 [0.62-0.90]). CONCLUSIONS: In AF patients, there is underuse of GDT for non-AF comorbidities. The association between GDT use and outcomes was strongest in heart failure and obstructive sleep apnea patients where use of GDT was associated with lower mortality and less AF progression.

Outcomes and Anticoagulation Use After Catheter Ablation for Atrial Fibrillation.

BACKGROUND: Studies evaluating the effects of atrial fibrillation (AF) catheter ablation versus antiarrhythmic therapy on outcomes have shown mixed results. In addition, guidelines recommend continuing oral anticoagulation (OAC) after ablation for those at risk of stroke, but real-world data are lacking. METHODS: We evaluated outcomes including death, myocardial infarction, stroke or systemic embolism, intracranial bleeding, major bleeding, and hospitalization in patients undergoing AF ablation compared with a propensity score matched cohort of patients treated with anti-arrhythmic medications only in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation registries. Cox proportional hazards regression was performed to evaluate the association between AF ablation and outcomes. We then evaluated patterns of treatment with OAC among AF ablation patients. RESULTS: Among 21 595 patients, 1190 (6%) underwent de novo AF ablation. Our propensity score-matched cohort included 1087 patients who underwent AF ablation matched 1:1 with 1087 patients treated with antiarrhythmic medications only. There were no significant differences in the risk of all-cause and cardiovascular death, and most other major adverse cardiovascular and neurological events. AF catheter ablation was associated with an increased risk of all-cause hospitalization during follow-up (hazard ratio, 1.24 [95% CI, 1.05-1.46]), particularly in the first 3 months (the standard blanking period) after the procedure. Among those who underwent AF ablation with a CHA2DS2 VASc score ≥2 for men and ≥3 for women, 23% had OAC discontinued after ablation. Among those who discontinued OAC, the median time to discontinuation was 6.2 months. CONCLUSIONS: In this large US national registry, we found no difference in adjusted rates of cardiovascular or all-cause death between patients treated with AF catheter ablation and antiarrhythmic medications only. Notably, discontinuation of OAC after ablation remains relatively common despite guideline recommendations for continued stroke prevention therapy in patients at risk of stroke.

Comparison of echocardiographic measurements to invasive measurements of diastolic function in infants with single ventricle physiology: a report from the Pediatric Heart Network Infant Single Ventricle Trial.

BACKGROUND: While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis. METHODS: Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman's test. RESULTS: Median age at echocardiogram was 4.6 (range 2.5-7.4) months. Median ventricular end-diastolic pressure was 7 (range 3-19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range -35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = -0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure. CONCLUSION: In this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.

Longitudinal low density lipoprotein cholesterol goal achievement and cardiovascular outcomes among adult patients with familial hypercholesterolemia: The CASCADE FH registry.

BACKGROUND AND AIMS: There are limited data from the US on outcomes of patients in specialty care for familial hypercholesterolemia (FH). METHODS: CASCADE FH Registry data were analyzed to assess longitudinal changes in medication usage, in low density lipoprotein cholesterol (LDL-C) levels, and the rate of major adverse cardiovascular events (MACE (myocardial infarction, coronary revascularization, stroke or transient ischemic attack) in adults with FH followed in US specialty clinics. RESULTS: The cohort consisted of 1900 individuals (61% women, 87% Caucasian), with mean age of 56 ±â€¯15 years, 37% prevalence of ASCVD at enrollment, mean pretreatment LDL-C 249 ±â€¯68 mg/dl, mean enrollment LDL-C 145 mg/dl and 93% taking lipid lowering therapy. Over follow up of 20 ±â€¯11 months, lipid lowering therapy use increased (mean decrease in LDL-C of 32 mg/dl (p < 0.001)). Only 48% of participants achieved LDL-C < 100 mg/dl and 22% achieved LDL-C < 70 mg/dl; ASCVD at enrollment was associated with greater likelihood of goal achievement. MACE event rates were almost 6 times higher among patients with prior ASCVD compared to those without (4.6 vs 0.8/100 patient years). Also associated with incident MACE were markers of FH severity and conventional ASCVD risk factors. CONCLUSIONS: With care in FH specialized clinics, LDL-C decreased, but LDL-C persisted >100 mg/dl in 52% of patients. High ASCVD event rates suggest that adults with FH warrant designation as having an ASCVD risk equivalent. Earlier and more aggressive therapy of FH is needed to prevent ASCVD events.

The patient journey with proprotein convertase subtilisin/kexin type 9 inhibitors in community practice.

BACKGROUND: Trials have demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective as an adjunct to statin therapy, but access and cost issues have limited their use in community practice. OBJECTIVE: The aim of the study was to better understand patients' experiences when trying to obtain, fill, and use PCSK9 inhibitor therapy in community practice. METHODS: We conducted a patient survey to evaluate patient experiences with PCSK9 inhibitors including medication initiation, indication for treatment, insurance approval status, medication persistence, and reason for discontinuation. The survey was emailed to 4740 adults who used a patient access support program. RESULTS: Overall, 1327 of 4740 adults completed the survey (28.0% response rate). Of those, 75.0% were aged >60 years, 52.8% were male, and 92.4% were White. At the time of PCSK9 inhibitor prescription, 70.2% were not on a statin (with 84.4% of those not on a statin reporting statin intolerance). Overall, 74.6% of patients found the drug approval process to be "somewhat" or "very" burdensome. Among n = 1216 patients who initiated treatment, 33.7% discontinued by the time of the survey, with 50.0% taking the drug for 1 to 6 months. Patient out-of-pocket costs were the leading reported reason for discontinuation. CONCLUSIONS: Most PCSK9 inhibitor users in community practice were not on a statin, presumably because of statin intolerance. The drug approval process and costs continue to be strong reasons for lower initiation of PCSK9 agents, as well as higher discontinuation rates.

Treatment of atrial fibrillation with concomitant coronary or peripheral artery disease: Results from the outcomes registry for better informed treatment of atrial fibrillation II.

BACKGROUND: Treatment patterns and outcomes of individuals with vascular disease who have new-onset atrial fibrillation (AF) are not well characterized. METHODS: Among patients with new-onset AF, we analyzed treatment and outcomes in those with or without vascular disease in the ORBIT-AF II registry. Vascular disease was defined as coronary disease with or without myocardial infarction (MI) or revascularization, or peripheral artery disease. The primary outcomes included major adverse cardiovascular or neurological events (MACNE) and major bleeding. Cox proportional hazard models were used to adjust the difference in patient characteristics. RESULTS: Overall 1920 of 6203 (31.0%) of new-onset AF had vascular disease. In patients with vascular disease, 62.2% of those were treated with direct oral anticoagulants (DOACs) and 23.4% with warfarin. Dual therapy and triple therapy were used in 36.9% and 4.9%, respectively. Vascular disease patients had increased risk of MACNE (adjusted hazard ratio [aHR] 1.83 [95%CIs 1.32-2.55]), but not major bleeding (aHR 1.24 [0.95-1.63]). Among patients with vascular disease, relative to those on warfarin, those treated with DOACs had similar risk for MACNE (aHR 1.20 [0.77-1.87]) but lower risks for bleeding, although it did not reach statistical significance (aHR 0.70 [0.43-1.15]). Concomitant antiplatelet therapy was associated with higher bleeding (aHR 2.27 [1.38-3.73]) with no apparent reduction in MACNE (aHR 1.50 [1.00-2.25]). CONCLUSIONS: Most patients with AF and vascular disease were managed with oral anticoagulation. About half of them were also treated with concomitant antiplatelet therapy, which was associated with increased risk of bleeding, without evidence of improved cardiovascular outcomes.

Comparison of Patient-Reported Care Satisfaction, Quality of Warfarin Therapy, and Outcomes of Atrial Fibrillation: Findings From the ORBIT - AF Registry.

Background Patient satisfaction with therapy is an important metric of care quality and has been associated with greater medication persistence. We evaluated the association of patient satisfaction with warfarin therapy to other metrics of anticoagulation care quality and clinical outcomes among patients with atrial fibrillation ( AF ). Methods and Results Using data from the ORBIT - AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, patients were identified with AF who were taking warfarin and had completed an Anti-Clot Treatment Scale ( ACTS ) questionnaire, a validated metric of patient-reported burden and benefit of oral anticoagulation. Multivariate regressions were used to determine association of ACTS burden and benefit scores with time in therapeutic international normalized ratio range ( TTR ; both ≥75% and ≥60%), warfarin discontinuation, and clinical outcomes (death, stroke, major bleed, and all-cause hospitalization). Among 1514 patients with AF on warfarin therapy (75±10 years; 42% women; CHA 2 DS 2- VAS c 3.9±1.7), those most burdened with warfarin therapy were younger and more likely to be women, have paroxysmal AF , and to be treated with antiarrhythmic drugs. After adjustment for covariates, ACTS burden scores were independent of TTR ( TTR ≥75%: odds ratio, 1.01 [95% CI , 0.99-1.03]; TTR ≥60%: odds ratio, 1.01 [95% CI , 0.98-1.05]), warfarin discontinuation (odds ratio, 0.99; 95% CI , 0.97-1.01), or clinical outcomes. ACTS benefit scores were also not associated with TTR , warfarin discontinuation, or clinical outcomes. Conclusions In a large registry of patients with AF taking warfarin, ACTS scores provided independent information beyond other traditional metrics of oral anticoagulation care quality and identified patient groups at high risk for dissatisfaction with warfarin therapy.

Early therapeutic persistence on dabigatran versus warfarin therapy in patients with atrial fibrillation: results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry.

Anticoagulation is highly effective for the prevention of stroke in patients with atrial fibrillation (AF) but it is dependent on patients continuing therapy. While studies have demonstrated suboptimal therapeutic persistence on warfarin, few have studied persistence rates with non vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran. We examined rates of continued use of dabigatran versus warfarin over 1 year among AF patients in the ORBIT-AF registry between June 29, 2010 and August 09, 2011. Multivariable logistic regression analysis was used to identify characteristics associated with 1-year persistent use of dabigatran therapy or warfarin. At baseline, 6.4 and 93.6% of 7150 AF patients were on dabigatran and warfarin, respectively. At 12 months, dabigatran-treated patients were less likely to have continued their therapy than warfarin-treated patients [Adjusted persistence rates: 66% (95% CI 60-72) vs. 82% (95% CI 80-84), p < .0001]. Predictors of dabigatran persistence included: CHA2DS2-VASc risk scores ≥ 2 OR 5.69, (95% CI 1.50-21.6) and BMI greater than 25 mg/m2 but less than 38 kg/m2 1.05 (1.01-1.09). Predictors of persistence on warfarin included: African American race (vs. White) 1.53 (1.07-2.19), Hispanic ethnicity (vs. White) 1.66 (1.06-2.60), paroxysmal and persistent AF (vs. new-onset) 1.68 (1.21-2.33) and 1.91 (1.35-2.69) respectively, LVH 1.40 (1.08-1.81), and CHA2DS2-VASc risk scores ≥ 2 1.94 (1.18-3.19). While 1-year persistence rates for dabigatran were lower than warfarin, persistence rates for both agents were not ideal. Future studies evaluating contemporary persistence are needed in order to assist in better targeting interventions aimed to improve anticoagulation persistence.