Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial.

BACKGROUND: There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF). METHODS: The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA2DS2-VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.5 mg twice daily for patients ≥80 years of age, weight ≤60 kg, or both) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant nonmajor bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1. RESULTS: From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event. CONCLUSIONS: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02942407.

Variation in resource utilization and mortality among patients with varying MR type and severity.

BACKGROUND: Limited data exists regarding the relationships between resource use and outcomes in patients with mitral regurgitation (MR). We examined resource utilization and outcomes across MR type and severity. METHODS: Using the Duke Echocardiography Laboratory Database, we identified patients with an index echo demonstrating moderate or severe MR (2000-2016) and examined 5-year cumulative rates of resources (ie, TTE, TEE, cardiac catheterization, cardiology/CTS referral, MV surgery/TEER, hospitalizations) by severity and type. We performed a multivariable landmark analysis of resource use during a 6 to 12 month period and 5-year mortality; and a multivariable analysis of the association between MR type and 5-year hospitalization costs. RESULTS: Among 4,511 patients with moderate or severe MR, 84.7% had moderate MR and 42.2% had secondary ischemic MR. The median age was 70 years-moderate, 66 years-severe. The mean 5-year cumulative resource utilization rate was 11.1 encounters/patients. Among patients with moderate or severe MR, there was significant variation in utilization of each resource by MR type (all P < .05). For severe MR, the performance of cardiac catheterization or MV surgery during the landmark period was associated with significantly lower mortality; for moderate MR, CTS referral during the landmark was associated with significantly lower mortality (P < .05). Patients with secondary ischemic and non-ischemic MR had significantly higher 5-year hospitalization costs compared with primary myxomatous MR (P < .05). CONCLUSIONS: Resource utilization and outcomes vary by MR type and severity. Utilization of resources, such as TTE, during guideline-recommended surveillance periods was not associated with a reduction in mortality while other care (catheterization or surgery) was associated with improved survival.

Impact of risk factor control on peripheral artery disease outcomes and health disparities.

BACKGROUND: Peripheral artery disease (PAD) is associated with modifiable atherosclerotic risk factors like hypertension, diabetes, hyperlipidemia, and smoking. However, the effect of risk factor control on outcomes and disparities in achieving control is less well understood. METHODS: All patients in an integrated, regional health system with PAD-related encounters, fee-for-service Medicare, and clinical risk factor control data were identified. Component risk factors were dichotomized into controlled and uncontrolled categories (control defined as low-density lipoprotein < 100 mg/dL, hemoglobin A1c < 7.0%, SBP < 140 mmHg, and current nonsmoker) and composite categories (none, 1, ⩾ 2 uncontrolled RFs) created. The primary outcome was major adverse vascular events (MAVE, a composite of all-cause mortality, myocardial infarction, stroke, and lower-extremity revascularization and amputation). RESULTS: The cohort included 781 patients with PAD, average age 72.5 ± 9.8 years, of whom 30.1% were Black, and 19.1% were Medicaid dual-enrolled. In this cohort, 260 (33.3%) had no uncontrolled risk factors and 200 (25.6%) had two or more uncontrolled risk factors. Patients with the poorest risk factor control were more likely to be Black (p < 0.001), Medicaid dual-enrolled (p < 0.001), and have chronic limb-threatening ischemia (p = 0.009). Significant differences in MAVE by degree of risk factor control were observed at 30 days (none uncontrolled: 5.8%, 1 uncontrolled: 11.5%, ⩾ 2 uncontrolled: 13.6%; p = 0.01) but not at 1 year (p = 0.08). risk factor control was not associated with outcomes at 1 year after adjustment for patient and PAD-specific characteristics. CONCLUSIONS: risk factor control is poor among patients with PAD. Significant disparities in achieving optimal risk factor control represent a potential target for reducing inequities in outcomes.

The Current Evidence for Lipid Management in Patients with Lower Extremity Peripheral Artery Disease: What Is the Therapeutic Target?

PURPOSE OF REVIEW: There is a lack of consistency among the ACC/AHA and ESC Guidelines on the treatment of patients with lower extremity PAD to a targeted LDL-c level. A review of the current guidelines, as well as the evidence that exists for use of various lipid-lower therapies in patients with PAD, is needed to guide clinical practice and to examine the current gaps in evidence that exist. RECENT FINDINGS: There is evidence that statins and PCSK9 inhibitors reduce the risks of major adverse cardiovascular and limb events in patients with PAD. Most statin and non-statin trials have examined the association of LLT use with clinical outcomes, and not the association between the degree of LDL-c lowering and the reduction in risk of clinical outcomes. As such, there is a lack of agreement between the American and European PAD Guidelines over whether to treat patients with PAD to a targeted LDL-c goal. Both statins and PCSK9 inhibitors have been shown to reduce the risk of major cardiovascular and limb events in patients with PAD. Further research is needed to determine if target driven LDL-c lowering is associated with improved outcomes in patients with PAD.

Ad hoc percutaneous coronary intervention in patients with stable coronary artery disease: A report from the National Cardiovascular Data Registry CathPCI Registry.

Percutaneous coronary intervention (PCI) may be performed in the same procedure as diagnostic coronary angiography (ad hoc PCI). This study aimed to evaluate current rates of ad hoc PCI use and associated risks of adverse outcomes in patients with stable coronary artery disease (CAD). METHODS: We identified 550,742 patients with stable CAD who underwent PCI in the National Cardiovascular Data Registry CathPCI Registry from 2009 to 2017. We compared in-hospital bleeding, acute kidney injury (AKI), and mortality between patients receiving ad hoc versus non-ad hoc PCI using logistic regression with inverse probability weighted propensity adjustment. RESULTS: Between 2009 and 2017, 82.9% of patients underwent ad hoc PCI. Patients who did not undergo ad hoc PCI had higher prevalence of peripheral vascular disease, heart failure, chronic kidney disease, and coronary artery bypass graft. Ad hoc PCI was associated with lower bleeding risk (adjusted odds ratio [aOR] 0.83, 95% CI 0.79-0.87) but no differences in risks of AKI (aOR 0.95, 95% CI 0.90-1.00) or mortality (aOR 1.09, 95% CI 0.97-1.23) compared with non-ad hoc PCI. Ad hoc PCI was associated with AKI risk in patients with glomerular filtration rate <30 mL/min (interaction P < .001), mortality risk in multivessel PCI (interaction P = .031), and risks of AKI and mortality in PCI of chronic total occlusions (interaction P = .045 and .002, respectively). CONCLUSIONS: Ad hoc PCI is extremely common among US patients with stable CAD and is associated with lower bleeding risk but no differences in risks of AKI or mortality compared with non-ad hoc PCI.

Same-day discharge among patients undergoing elective PCI: Insights from the VA CART Program.

BACKGROUND: Available data suggest that same-day discharge (SDD) after elective percutaneous coronary intervention (PCI) is safe in select patients. Yet, little is known about contemporary adoption rates, safety, and costs in a universal health care system like the Veterans Affairs Health System. METHODS: Using data from the Veterans Affairs Clinical Assessment Reporting and Tracking Program linked with Health Economics Resource Center data, patients undergoing elective PCI for stable angina between October 1, 2007 and Sepetember 30, 2016, were stratified by SDD versus overnight stay. We examined trends of SDD, and using 2:1 propensity matching, we assessed 30-day rates of readmission, mortality, and total costs at 30 days. RESULTS: Of 21,261 PCIs from 67 sites, 728 were SDDs (3.9% of overall cohort). The rate of SDD increased from 1.6% in 2008 to 9.7% in 2016 (P < .001). SDD patients had lower rates of atrial fibrillation, peripheral arterial disease, and prior coronary artery bypass grafting and were treated at higher-volume centers. Thirty-day readmission and mortality did not differ significantly between the groups (readmission: 6.7% SDD vs 5.6% for overnight stay, P = .24; mortality: 0% vs. 0.07%, P = .99). The mean (SD) 30-day cost accrued by patients undergoing SDD was $23,656 ($15,480) versus $25,878 ($17,480) for an overnight stay. The accumulated median cost savings for SDD was $1503 (95% CI $738-$2,250). CONCLUSIONS: Veterans Affairs Health System has increasingly adopted SDD for elective PCI procedures, and this is associated with cost savings without an increase in readmission or mortality. Greater adoption has the potential to reduce costs without increasing adverse outcomes.

Opportunities for enhancing the care of older patients with ST-elevation myocardial infarction presenting for primary percutaneous coronary intervention: Rationale and design of the SAFE-STEMI for Seniors trial.

Advanced age is directly related to worse outcomes following ST-elevation myocardial infarction (STEMI) and higher complication rates from antithrombotic therapies and primary percutaneous coronary intervention (PCI). Often excluded from clinical trials, seniors presenting with STEMI remain an understudied population despite contributing to 140,000 hospital admissions annually. The SAFE-STEMI for Seniors study is a prospective, multicenter, unblinded, randomized clinical trial designed to examine the efficacy and safety of instantaneous wave-free ratio-guided complete revascularization in multivessel disease, while also investigating other components of STEMI care for patients ≥60 years including the efficacy and safety of zotarolimus-eluting stents for primary PCI and transradial PCI with the Glidesheath Slender and TR band. The SAFE-STEMI trial represents North America's first and only prospective randomized investigational device exemption study to use a Coordinated Registry Network infrastructure with collaborative partnering across industry manufacturers, promoting both efficiency and reduced cost of evidence development for regulatory decisions related to both diagnostic and therapeutic technologies in a single study design. The study has been powered to evaluate 2 independent co-primary end points in a population of older patients with STEMI: (1) third-generation drug-eluting stents for primary PCI and (2) instantaneous wave-free ratio-guided complete revascularization versus infarct-related artery-only revascularization.

Hospital evaluation of health literacy and associated outcomes in patients after acute myocardial infarction.

BACKGROUND: Low health literacy is common in the United States and may affect outcomes after myocardial infarction (MI). How often hospitals screen for low health literacy is unknown. METHODS: We surveyed 122 hospitals in the TRANSLATE-ACS study and divided them into those that reported routinely (>75% of patients), selectively (1%-75%), or never (0%) screening MI patients for low health literacy prior to discharge. We performed logistic regression with random intercepts to compare 6-week and 6-month patient-reported medication adherence and multivariable Cox regression to compare 1-year major adverse cardiovascular events and all-cause readmission risks between hospital groups. RESULTS: Overall, 25 (20.5%), 47 (38.5%), and 50 (41.0%) hospitals reported routinely, selectively, or never screening patients for low health literacy, respectively. Patients discharged from hospitals that routinely screened were more likely to report 6-week medication adherence [routinely: adjusted odds ratio (OR) 1.26, 95% CI 1.01-1.57; selectively: adjusted OR 1.19, 95% CI 1.00-1.43, both referenced to those discharged from hospitals that never screened]. Compared with hospitals that never screened health literacy, 1-year major adverse cardiovascular events were similar for hospitals that reported routinely screening (adjusted HR 0.92, 95% CI 0.75-1.14) or selectively screening (adjusted HR 1.01, 95% CI 0.84-1.21). Hospitals that reported selectively screening health literacy were associated with a lower adjusted risk of 1-year all-cause readmission (adjusted HR 0.89, 95% CI 0.79-1.00, P=.041). CONCLUSION: Only a minority of US hospitals routinely screen MI patients for low health literacy. Hospital screening was associated with higher medication adherence and lower readmission risk. Further investigation is needed to understand how inpatient screening can be implemented to improve longitudinal post-MI care.

Discharge timing and outcomes after uncomplicated non-ST-segment elevation acute myocardial infarction.

BACKGROUND: Length of stay after non-ST-segment elevation myocardial infarction (NSTEMI) continues to decrease, but information to guide duration of hospitalization is limited. METHODS: We used landmark analyses, in which the landmark defined potential days of discharge, to estimate complication rates on the first day the patient would have been out of the hospital, and estimated associations between timing of discharge and 30-day and 1-year event-free survival after discharge among NSTEMI patients. RESULTS: Among 20,410 NSTEMI patients, median length of stay was 7 (4, 12) days; 3,209 (15.7%) experienced a cardiac complication on days 0 to 2 and 1,322 (6.5%) were discharged without complications during hospital days 0 to 2. At the start of day 3, 15,879 patients (77.8%) were still hospitalized without complications. Of these, 1,689 (10.6%) were discharged event-free on day 3. Adjusted event-free survival rates of death or myocardial infarction from day 4 to 30 days after among the 1,689 patients was 99.1% compared with 93.1% for the 14,190 who remained hospitalized at the end of day 3. For 1-year mortality, these rates were 98.1% and 96.4%, respectively. Among 13,334 patients hospitalized without complications at the start of day 4, 1,706 were discharged event-free that day. Adjusted survival rates among these patients, compared with those still hospitalized at the end of day 4, were 98.0% versus 93.7% for 30-day death or myocardial infarction and 97.8% versus 96.1% for 1-year mortality. CONCLUSIONS: Patients with NSTEMI who had no serious complications during the first 2 hospital days were at low risk of subsequent short- and intermediate-term death or ischemic events.

Accuracy and validation of an automated electronic algorithm to identify patients with atrial fibrillation at risk for stroke.

BACKGROUND: There is no universally accepted algorithm for identifying atrial fibrillation (AF) patients and stroke risk using electronic data for use in performance measures. METHODS: Patients with AF seen in clinic were identified based on International Classification of Diseases, Ninth Revision(ICD-9) codes. CHADS(2) and CHA(2)DS(s)-Vasc scores were derived from a broad, 10-year algorithm using IICD-9 codes dating back 10 years and a restrictive, 1-year algorithm that required a diagnosis within the past year. Accuracy of claims-based AF diagnoses and of each stroke risk classification algorithm were evaluated using chart reviews for 300 patients. These algorithms were applied to assess system-wide anticoagulation rates. RESULTS: Between 6/1/2011, and 5/31/2012, we identified 6,397 patients with AF. Chart reviews confirmed AF or atrial flutter in 95.7%. A 1-year algorithm using CHA(2)DS(2)-Vasc score ≥2 to identify patients at risk for stroke maximized positive predictive value (97.5% [negative predictive value 65.1%]). The PPV of the 10-year algorithm using CHADS(2) was 88.0%; 12% those identified as high-risk had CHADS(2) scores <2. Anticoagulation rates were identical using 1-year and 10-year algorithms for patients with CHADS(2) scores ≥2 (58.5% on anticoagulation) and CHA(2)DS(2)-Vasc scores ≥2 (56.0% on anticoagulation). CONCLUSIONS: Automated methods can be used to identify patients with prevalent AF indicated for anticoagulation but may have misclassification up to 12%, which limits the utility of relying on administrative data alone for quality assessment. Misclassification is minimized by requiring comorbidity diagnoses within the prior year and using a CHA(2)DS(2)-Vasc based algorithm. Despite differences in accuracy between algorithms, system-wide anticoagulation rates assessed were similar regardless of algorithm used.

Does This Patient With Chest Pain Have Acute Coronary Syndrome?: The Rational Clinical Examination Systematic Review.

IMPORTANCE: About 10% of patients with acute chest pain are ultimately diagnosed with acute coronary syndrome (ACS). Early, accurate estimation of the probability of ACS in these patients using the clinical examination could prevent many hospital admissions among low-risk patients and ensure that high-risk patients are promptly treated. OBJECTIVE: To review systematically the accuracy of the initial history, physical examination, electrocardiogram, and risk scores incorporating these elements with the first cardiac-specific troponin. STUDY SELECTION: MEDLINE and EMBASE were searched (January 1, 1995-July 31, 2015), along with reference lists from retrieved articles, to identify prospective studies of diagnostic test accuracy among patients admitted to the emergency department with symptoms suggesting ACS. DATA EXTRACTION AND SYNTHESIS: We identified 2992 unique articles; 58 met inclusion criteria. MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, and likelihood ratio (LR) of findings for the diagnosis of ACS. The reference standard for ACS was either a final hospital diagnosis of ACS or occurrence of a cardiovascular event within 6 weeks. RESULTS: The clinical findings and risk factors most suggestive of ACS were prior abnormal stress test (specificity, 96%; LR, 3.1 [95% CI, 2.0-4.7]), peripheral arterial disease (specificity, 97%; LR, 2.7 [95% CI, 1.5-4.8]), and pain radiation to both arms (specificity, 96%; LR, 2.6 [95% CI, 1.8-3.7]). The most useful electrocardiogram findings were ST-segment depression (specificity, 95%; LR, 5.3 [95% CI, 2.1-8.6]) and any evidence of ischemia (specificity, 91%; LR, 3.6 [95% CI,1.6-5.7]). Both the History, Electrocardiogram, Age, Risk Factors, Troponin (HEART) and Thrombolysis in Myocardial Infarction (TIMI) risk scores performed well in diagnosing ACS: LR, 13 (95% CI, 7.0-24) for the high-risk range of the HEART score (7-10) and LR, 6.8 (95% CI, 5.2-8.9) for the high-risk range of the TIMI score (5-7). The most useful for identifying patients less likely to have ACS were the low-risk range HEART score (0-3) (LR, 0.20 [95% CI, 0.13-0.30]), low-risk range TIMI score (0-1) (LR, 0.31 [95% CI, 0.23-0.43]), or low to intermediate risk designation by the Heart Foundation of Australia and Cardiac Society of Australia and New Zealand risk algorithm (LR, 0.24 [95% CI, 0.19-0.31]). CONCLUSIONS AND RELEVANCE: Among patients with suspected ACS presenting to emergency departments, the initial history, physical examination, and electrocardiogram alone did not confirm or exclude the diagnosis of ACS. Instead, the HEART or TIMI risk scores, which incorporate the first cardiac troponin, provided more diagnostic information.

Ventricular Arrhythmias After Primary Percutaneous Coronary Intervention for STEMI.

Importance: Currently, mortality risk for patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) with an uncomplicated postprocedure course is low. Less is known regarding the risk of in-hospital ventricular tachycardia (VT) and ventricular fibrillation (VF). Objective: To evaluate the risk of late VT and VF after primary PCI for STEMI. Design, Setting, and Participants: This cohort study included adults aged 18 years or older with STEMI treated with primary PCI between January 1, 2015, and December 31, 2018, identified in the US National Cardiovascular Data Registry Chest Pain-MI Registry. Data were analyzed from April to December 2020. Main Outcomes and Measures: Multivariable logistic regression was used to evaluate the risk of late VT (≥7 beat run of VT during STEMI hospitalization ≥1 day after PCI) or VF (any episode of VF≥1 day after PCI) associated with cardiac arrest and associations between late VT or VF and in-hospital mortality in the overall cohort and a cohort with uncomplicated STEMI without prior myocardial infarction or heart failure, systolic blood pressure less than 90 mm Hg, cardiogenic shock, cardiac arrest, reinfarction, or left ventricular ejection fraction (LVEF) less than 40%. Results: A total of 174 126 eligible patients with STEMI were treated with primary PCI at 814 sites in the study; 15 460 (8.9%) had VT or VF after primary PCI, and 4156 (2.4%) had late VT or VF. Among the eligible patients, 99 905 (57.4%) at 807 sites had uncomplicated STEMI. The median age for patients with late VT or VF overall was 63 years (IQR, 55-73 years), and 75.5% were men; the median age for patients with late VT or VF with uncomplicated STEMI was 60 years (IQR, 53-69 years), and 77.7% were men. The median length of stay was 3 days (IQR, 2-7 days) for the overall cohort with late VT or VF and 3 days (IQR, 2-4 days) for the cohort with uncomplicated STEMI with late VT or VF. The risk of late VT or VF was 2.4% (overall) and 1.7% (uncomplicated STEMI). Late VT or VF with cardiac arrest occurred in 674 patients overall (0.4%) and in 117 with uncomplicated STEMI (0.1%). LVEF was the most significant factor associated with late VT or VF with cardiac arrest (adjusted odds ratio [AOR] for every 5-unit decrease ≤40%: 1.67; 95% CI, 1.54-1.85). Late VT or VF events were associated with increased odds of in-hospital mortality in the overall cohort (AOR, 6.40; 95% CI, 5.63-7.29) and the cohort with uncomplicated STEMI (AOR, 8.74; 95% CI, 6.53-11.70). Conclusions and Relevance: In this study, a small proportion of patients with STEMI treated with primary PCI had late VT or VF. However, late VT or VF with cardiac arrest was rare, particularly in the cohort with uncomplicated STEMI. This information may be useful when determining the optimal timing for hospital discharge after STEMI.

Case Volumes and Outcomes Among Early-Career Interventional Cardiologists in the United States.

BACKGROUND: Little is known about the procedural characteristics, case volumes, and mortality rates for early- vs non-early-career interventional cardiologists in the United States. OBJECTIVES: This study examined operator-level data for patients who underwent percutaneous coronary intervention (PCI) between April 2018 and June 2022. METHODS: Data were collected from the National Cardiovascular Data Registry CathPCI Registry, American Board of Internal Medicine certification database, and National Plan and Provider Enumeration System database. Early-career operators were within 5 years of the end of training. Annual case volume, expected mortality and bleeding risk, and observed/predicted mortality and bleeding outcomes were evaluated. RESULTS: A total of 1,451 operators were early career; 1,011 changed their career status during the study; and 6,251 were non-early career. Overall, 514,540 patients were treated by early-career and 2,296,576 patients by non-early-career operators. The median annual case volume per operator was 59 (Q1-Q3: 31-97) for early-career and 57 (Q1-Q3: 28-100) for non-early-career operators. Early-career operators were more likely to treat patients presenting with ST-segment elevation myocardial infarction and urgent indications for PCI (both P < 0.001). The median predicted mortality risk was 2.0% (Q1-Q3: 1.5%-2.7%) for early-career and 1.8% (Q1-Q3: 1.2%-2.4%) for non-early-career operators. The median predicted bleeding risk was 4.9% (Q1-Q3: 4.2%-5.7%) for early-career and 4.4% (Q1-Q3: 3.7%-5.3%) for non-early-career operators. After adjustment, an increased risk of mortality (OR: 1.08; 95% CI: 1.05-1.17; P < 0.0001) and bleeding (OR: 1.08; 95% CI: 1.05-1.12; P < 0.0001) were associated with early-career status. CONCLUSIONS: Early-career operators are caring for patients with more acute presentations and higher predicted risk of mortality and bleeding compared with more experienced colleagues, with modestly worse outcomes. These data should inform institutional practices to support the development of early-career proceduralists.

Interleukin-6 and Cardiovascular Events in Healthy Adults: MESA.

Background: Elevated interleukin (IL)-6 levels have been linked to adverse outcomes in patients with and without baseline cardiovascular disease (CVD). Objectives: The purpose of this study was to examine the association between circulating IL-6 levels and CVD events without baseline CVD across racial and ethnic groups. Methods: We conducted an observational analysis utilizing the MESA (Multi-Ethnic Study of Atherosclerosis), a multicenter, prospective community-based study of CVD at baseline from four racial and ethnic groups. IL-6 levels were measured at the time of enrollment (visit 1) and were divided into 3 terciles. Patient baseline characteristics and outcomes, including all-cause mortality, CV mortality, heart failure, and non-CV mortality, were included. Cox proportional hazard regression models were used to assess associations between IL-6 levels and study outcomes with IL-6 tercile 1 as reference. Results: Of 6,622 individuals, over half were women (53%) with a median age of 62 (IQR: 53-70) years. Racial and ethnic composition was non-Hispanic White (39%) followed by African American (27%), Hispanic (22%), and Chinese American (12%). Compared to tercile 1, participants with IL-6 tercile 3 had a higher adjusted risk of and all-cause mortality (HR: 1.98 [95% CI: 1.67-2.36]), CV mortality (HR: 1.55 [95% CI: 1.05-2.30]), non-CV mortality (HR: 2.05 [95% CI: 1.65-2.56]), and heart failure (HR: 1.48 [95% CI: 0.99-2.19]). When tested as a continuous variable, higher levels of IL-6 were associated with an increased risk of all individual outcomes. Compared to non-Hispanic White participants, the unadjusted and adjusted risk of all outcomes across all races and ethnicities was similar across all IL-6 terciles. Conclusions: High levels of circulating IL-6 are associated with worse CV outcomes and increased all-cause mortality consistently across all racial and ethnic groups.

Contribution of Clinical Trial Event Data by Data Source: A Prespecified Analysis of the ADAPTABLE Randomized Clinical Trial.

Importance: Pragmatic randomized clinical trials (RCTs) often use multiple data sources to examine clinical events, but the relative contribution of data sources to clinical end-point rates is understudied. Objective: To assess the contribution of data sources (electronic health records [EHRs], public/private insurance claims, and/or participant-reported data) to clinical end points among ADAPTABLE participants who had available data. Design, Setting, and Participants: The ADAPTABLE study was an open-label, pragmatic RCT from April 2016 through June 2019 conducted in research networks within clinical practice. Participants had existing atherosclerotic cardiovascular disease and available data to analyze. The characteristics of patients by combinations of data source availability were compared to examine the contribution of each of the data sources to end-point ascertainment. Data for this prespecified analysis were examined from January 2022 to June 2023. Exposures: Randomized exposure to 81 mg or 325 mg of aspirin daily. Main Outcomes and Measures: Number of events for the primary end point (composite of death, hospitalization for myocardial infarction, and hospitalization for stroke) that were contributed by EHR or claims data and then number of events contributed by each additional data source. Results: Of 15 006 participants randomized with at least 1 other source of data available beyond participant-reported data, there were 8756 (58.3%) with participant-reported and EHR data; 4291 (28.6%) with participant-reported, EHR, and claims data; 1412 (9.4%) with EHR-only data; 262 (1.7%) with participant-reported and claims data; 202 (1.3%) with EHR and claims data; and 83 (0.6%) with claims-only data. Participants with EHR-only data were younger (median age, 63.7 years; IQR, 55.8-71.4) compared with the other groups (range, 65.6-71.9 years). Among participants with both EHR and claims data, with or without participant-reported data (n = 4493), for each outcome, most events (92%-100%) were identified in the EHR or in claims data. For all clinical end points, participant-reported data contributed less than 10% of events not otherwise available from claims or EHR data. Conclusions and Relevance: In this analysis of a pragmatic RCT, claims and EHR data provided the most clinical end-point data when compared with participant-reported events. These findings provide a framework for collecting end points in pragmatic clinical trials. Further work is needed to understand the data source combinations that most effectively provide clinical end-point data in RCTs.

High economic burden of caring for patients with suspected extraesophageal reflux.

OBJECTIVES: Extraesophageal symptoms are common manifestations of gastroesophageal reflux disease (GERD). Lack of a definitive diagnostic or treatment standards complicate management, which often leads to multiple specialty consultations, procedures, pharmaceuticals and diagnostic tests. The aim of this study was to determine the economic burden associated with extraesophageal reflux (EER). METHODS: Direct costs of evaluation were estimated for patients referred with symptoms attributed to EER between 2007 and 2011. Medicare payment for evaluation and management and pharmaceutical prices was used to calculate first year and overall costs of evaluating and treating extraesophageal symptoms attributed to reflux. RESULTS: Overall, 281 patients were studied (cough (50%), hoarseness (23%), globus/post-nasal drainage (15%), asthma (9%), and sore throat (3%)). Over a median (interquartile range) of 32 (16-46) months follow-up, patients had a mean (95% confidence interval) of 10.1 (9.4-10.9) consultations with specialists and underwent 6.4 (3-9) diagnostic procedures. Overall, the mean initial year direct cost was $5,438 per patient being evaluated for EER. Medical and non-medical components contributed $5,154 and $283. Of the overall cost, 52% were attributable to the use of proton pump inhibitors. During the initial year, direct costs were 5.6 times higher than those reported for typical GERD ($971). A total of 54% of patients reported improvement of symptoms. Overall cost per improved patient was $13,700. CONCLUSIONS: EER contributes substantially to health-care expenditures. In this cohort, the cost for initial year's evaluation and treatment of EER symptoms was quintuple that of typical GERD. Prescription costs and, in particular, proton pump inhibitors were the single greatest contributor to the cost of EER management.

Analysis of Oral Anticoagulant Dosing and Adherence to Therapy Among Patients With Nonvalvular Atrial Fibrillation.

Importance: Although reduced doses of direct oral anticoagulants (DOACs) are approved for patients with nonvalvular atrial fibrillation (NVAF) at high risk of bleeding, little is known about dosing accuracy, particularly in patients with renal dysfunction. Objective: To determine whether underdosing of DOACs is associated with longitudinal adherence to anticoagulation. Design, Setting, and Participants: This retrospective cohort analysis used data from the Symphony Health claims data set. This national medical and prescription data set comprises 280 million patients and 1.8 million prescribers in the US. Patients included had at least 2 claims for NVAF between January 2015 and December 2017. The dates of analysis for this article were from February 2021 to July 2022. Exposures: This study included patients with CHA2DS2-VASc scores of 2 or higher who were treated with a dose of DOACs who did and did not meet label-specified criteria for dose reduction. Main Outcomes and Measures: Logistic regression models examined factors associated with off-label dosing (ie, dosing not recommended by US Food and Drug Administration [FDA] labeling), the association of creatinine clearance with recommended DOAC dosing, and the association of DOAC underdosing and excess dosing with 1-year adherence. Results: Among the 86 919 patients included (median [IQR] age, 74 [67-80] years; 43 724 men [50.3%]; 82 389 White patients [94.8%]), 7335 (8.4%) received an appropriately reduced dose, and 10 964 (12.6%) received an underdose not consistent with FDA recommendations, meaning that 59.9% (10 964 of 18 299) of those who received a reduced dose received an inappropriate dose. Patients who received off-label doses of DOACs were older (median [IQR] age, 79 [73-85] vs 73 [66-79] years) and had higher CHA2DS2-VASc scores (median [IQR], 5 [4-6] vs 4 [3-6]) compared with patients who received appropriate doses (as recommended by FDA labeling). Renal dysfunction, age, heart failure, and the prescribing clinician being in a surgical specialty were associated with dosing not recommended by FDA labeling. Almost one-third of patients (9792 patients [31.9%]) with creatinine clearance less than 60 mL per minute taking DOACs were either underdosed or excess-dosed not consistent with FDA recommendations. For every 10-unit decrease in creatinine clearance, the odds of the patient receiving an appropriately dosed DOAC was lower by 21%. Treatment with underdosed DOACs was associated with a lower likelihood of adherence (adjusted odds ratio, 0.88; 95% CI, 0.83-0.94) and higher risk of anticoagulation discontinuation (adjusted odds ratio, 1.20; 95% CI, 1.13-1.28) by 1 year. Conclusions and Relevance: In this study of oral anticoagulant dosing, DOAC dosing that did not follow FDA label recommendations was observed in a substantial number of patients with NVAF, occurred more frequently in patients with worse renal function, and was associated with less-consistent long-term anticoagulation. These results suggest a need for efforts to improve the quality of DOAC use and dosing.