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Abstract Existing natural language processing (NLP) methods to convert free-text clinical notes into structured data often require problem-specific annotations and model training. This study aims to evaluate ChatGPT’s capacity to extract information from free-text medical notes efficiently and comprehensively. We developed a large language model (LLM)-based workflow, utilizing systems engineering methodology and spiral “prompt engineering” process, leveraging OpenAI’s API for batch querying ChatGPT. We evaluated the effectiveness of this method using a dataset of more than 1000 lung cancer pathology reports and a dataset of 191 pediatric osteosarcoma pathology reports, comparing the ChatGPT-3.5 (gpt-3.5-turbo-16k) outputs with expert-curated structured data. ChatGPT-3.5 demonstrated the ability to extract pathological classifications with an overall accuracy of 89%, in lung cancer dataset, outperforming the performance of two traditional NLP methods. The performance is influenced by the design of the instructive prompt. Our case analysis shows that most misclassifications were due to the lack of highly specialized pathology terminology, and erroneous interpretation of TNM staging rules. Reproducibility shows the relatively stable performance of ChatGPT-3.5 over time. In pediatric osteosarcoma dataset, ChatGPT-3.5 accurately classified both grades and margin status with accuracy of 98.6% and 100% respectively. Our study shows the feasibility of using ChatGPT to process large volumes of clinical notes for structured information extraction without requiring extensive task-specific human annotation and model training. The results underscore the potential role of LLMs in transforming unstructured healthcare data into structured formats, thereby supporting research and aiding clinical decision-making.

Objective: Aspirin has been used for primary prevention of atherosclerotic cardiovascular disease (ASCVD) for decades, but this indication has become controversial with recent trial data. The 2022 US Preventive Services Task Force (USPSTF) provided a recommendation to consider aspirin use for primary prevention in adults 40–59 years with a 10-year ASCVD risk ≥10 % and not at increased risk of bleeding, yet population estimates for the impact of this recommendation are unknown. The objective of this study is to determine the prevalence and demographics of the US population who meet eligibility criteria for aspirin under the new 2022 USPSTF guidelines. Methods: This is a serial cross-sectional study using data from the 2011-March 2020 National Health and Nutrition Examination Survey (NHANES) database. Individuals aged 40–59 years without a self-reported history of ASCVD were included. 10-year estimated ASCVD risk ≥10 % as calculated by the Pooled Cohort Equations (PCE) and increased bleeding risk determined using variables adapted from USPSTF guidelines were further applied as inclusion and exclusion criteria, respectively. The weighted frequencies of US adults aged 40–59 years qualifying for primary prevention aspirin, subgrouped by gender, age, and race/ethnicity, were calculated. Results: Among 72,840,734 US individuals aged 40–59 years, 7.2 million (10 %) are eligible for consideration of primary prevention aspirin by PCE criteria. Of these, approximately 30 % would be potentially excluded based on increased bleeding risks, resulting in a net eligible cohort of 5 million. This represents 7 % of US adults aged 40–59 years and only 2.6 % of adults ≥18 years. Men, age 50–59 years, and Black race have higher proportions meeting aspirin use eligibility. Conclusions: The overall prevalence of US individuals who qualify for aspirin for primary prevention under the 2022 USPSTF guidelines is modest, with larger proportional eligibility among men, older age, and Black individuals.

Background Dietary supplement use is prevalent in the general US population, but little is known regarding the driving reasons for their use among those with atherosclerotic cardiovascular disease (ASCVD). Methods and Results Data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to March 2020 were used to identify adults with ASCVD. Supplement use was assessed by interviewers using label review, and surveys captured self‐reported reasons for use. Demographic, clinical, medication, and laboratory characteristics were compared between supplement users and nonusers. Among individuals with ASCVD in the National Health and Nutrition Examination Survey (n=965; mean age, 65 years; 56.1% men; 73.7% White individuals), 73.1% reported taking ≥1 dietary supplements, most commonly multivitamins (35.4%), vitamin D (30.8%), and fish oil (19.8%). Of those taking supplements, 47.3% report taking them under the advisement of a health professional. Nearly one fifth (17.9%) reported taking at least 1 supplement for “heart health,” most commonly fish oil (11.1%), followed by CoQ10 (4.2%) and resveratrol (1.5%). Supplement users were older (68 versus 62 years; P=0.003), included more women (45.8% versus 37.7%; P=0.17), were less likely to smoke (11.0% versus 36.4%; P

Objective: National guidelines recommend statin therapy for patients with type 2 diabetes. We assessed the extent of moderate- to high-intensity statin therapy utilization in community practice. Methods: We evaluated lipid-lowering therapy (LLT) and low-density lipoprotein cholesterol (LDL-C) levels at baseline and 1-year follow-up in patients aged 40–75 years with type 2 diabetes but without atherosclerotic cardiovascular disease (ASCVD), across 90 health systems in the United States participating in an electronic health record–derived dataset, Cerner Real-World Data. Multivariable logistic regression was used to evaluate factors associated with utilization of moderate- to high-intensity statin. Results: We identified 241,232 patients with type 2 diabetes (58.1 % on moderate- to high-intensity statin, 7.0 % on low-intensity statin, and 34.9 % on no statin). Predictors of moderate- to high-intensity statin therapy included retinopathy (adjusted odds ratio [aOR], 1.26; 95 % confidence interval [CI], 1.15–1.38), hypertension (aOR, 1.52; 95 % CI, 1.43–1.61), and stage 3 chronic kidney disease (aOR, 1.14; 95 % CI, 1.07–1.21). Women (aOR, 0.85; 95 % CI, 0.82–0.87), and those with rheumatoid arthritis (aOR, 0.79; 95 % CI, 0.71–0.87), psoriasis (aOR, 0.85; 95 % CI, 0.75–0.96), and hepatitis C (aOR, 0.40; 95 % CI, 0.39–0.46), had reduced odds of moderate- to high-intensity statin treatment. Utilization of ezetimibe was rare (2.0 %). LDL-C control was suboptimal at baseline (37.0 % and 27.9 % had LDL-C ≥100 mg/dL and

Abstract Background Estimating cardiovascular (CV) event accrual is important for outcome trial planning. Limited data exist describing event accrual patterns in patients with type 2 diabetes (T2D). We compared apparent CV event accrual patterns with true event rates in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Methods Centrally adjudicated event dates and accrual rates for a 4-point major adverse CV event composite (MACE-4; includes CV death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina hospitalization), MACE-4 components, all-cause mortality (ACM), and heart failure hospitalization were compiled. We used three graphical methods (Weibull probability plot, plot of negative log of the Kaplan–Meier survival distribution estimate, and the Epanechnikov kernel-smoothed estimate of the hazard rate) to examine hazard rate morphology over time for the 7 outcomes. Results Plots for all outcomes showed real-time constant event hazard rates for the duration of the follow-up, confirmed by Weibull shape parameters. The Weibull shape parameters for ACM (1.14, 95% CI 1.08–1.21) and CV death (1.08, 95% CI 1.01–1.16) were not sufficiently > 1 as to require non-constant hazard rate models to accurately depict the data. The time lag between event occurrence and event adjudication being completed, the adjudication gap, improved over the course of the trial. Conclusions In TECOS, the nonfatal event hazard rates were constant over time. Small increases over time in the hazard rate for fatal events would not require complex modelling to predict event accrual, providing confidence in traditional modelling methods for predicting CV outcome trial event rates in this population. The adjudication gap provides a useful metric to monitor within-trial event accrual patterns. Clinical trial registration Clinicaltrials.gov NCT00790205.

Metabolic mechanisms underlying the heterogeneity of major adverse cardiovascular (CV) event (MACE) risk in individuals with type 2 diabetes mellitus (T2D) remain unclear. We hypothesized that circulating metabolites reflecting mitochondrial dysfunction predict incident MACE in T2D. Targeted mass-spectrometry profiling of 60 metabolites was performed on baseline plasma samples from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS; discovery cohort) and Exenatide Study of Cardiovascular Event Lowering (EXSCEL; validation cohort) biomarker substudy cohorts. A principal components analysis metabolite factor comprising medium-chain acylcarnitines (MCACs) was associated with MACE in TECOS and validated in EXSCEL, with higher levels associated with higher MACE risk. Meta-analysis showed that long-chain acylcarnitines (LCACs) and dicarboxylacylcarnitines were also associated with MACE. Metabolites remained associated with MACE in multivariate models and favorably changed with exenatide therapy. A third cohort (Cardiac Catheterization Genetics [CATHGEN]) with T2D was assessed to determine whether these metabolites improved discriminative capability of multivariate models for MACE. Nine metabolites (MCACs and LCACs and 1 dicarboxylacylcarnitine) were associated with time to MACE in the CATHGEN cohort. Addition of these metabolites to clinical models minimally improved the discriminative capability for MACE but did significantly down reclassify risk. Thus, metabolites reporting on dysregulated mitochondrial fatty acid oxidation are present in higher levels in individuals with T2D who experience subsequent MACE. These biomarkers may improve CV risk prediction models, be therapy responsive, and highlight emerging risk mechanisms.

Abstract There is increasing evidence that HFpEF is a heterogeneous clinical entity and distinct molecular pathways may contribute to pathophysiology. Leveraging unbiased proteomics to identify novel biomarkers, this study seeks to understand the underlying molecular mechanisms of HFpEF. The discovery cohort consisted of HFpEF cases and non-HF controls from the CATHGEN study (N = 176); the validation cohort consisted of participants from the TECOS trial of patients with diabetes (N = 109). Proteins associated with HFpEF were included in a LASSO model to create a discriminative multi-protein model and assessed in the validation cohort. Survival models and meta-analysis were used to test the association of proteins with incident clinical outcomes, including HF hospitalization, mortality and HFpEF hospitalization in CATHGEN, TECOS and the Jackson Heart Study. In the derivation set, 190 proteins were associated with HFpEF in univariate analysis, of which 65 remained significant in the multivariate model. Twenty (30.8%) of these proteins validated in TECOS, including LCN2, U-PAR, IL-1ra, KIM1, CSTB and Gal-9 (OR 1.93–2.77, p

Abstract Background Among individuals with atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes mellitus (T2DM) is common and confers increased risk for morbidity and mortality. Differentiating risk is key to optimize efficiency of treatment selection. Our objective was to develop and validate a model to predict risk of major adverse cardiovascular events (MACE) comprising the first event of cardiovascular death, myocardial infarction (MI), or stroke for individuals with both T2DM and ASCVD. Methods Using data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), we used Cox proportional hazards models to predict MACE among participants with T2DM and ASCVD. All baseline covariates collected in the trial were considered for inclusion, although some were excluded immediately because of large missingness or collinearity. A full model was developed using stepwise selection in each of 25 imputed datasets, and comprised candidate variables selected in 20 of the 25 datasets. A parsimonious model with a maximum of 10 degrees of freedom was created using Cox models with least absolute shrinkage and selection operator (LASSO), where the adjusted R-square was used as criterion for selection. The model was then externally validated among a cohort of participants with similar criteria in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial. Discrimination of both models was assessed using Harrell’s C-index and model calibration by the Greenwood-Nam-D’Agostino statistic based on 4-year event rates. Results Overall, 1491 (10.2%) of 14,671 participants in TECOS and 130 (9.3%) in the ACCORD validation cohort (n = 1404) had MACE over 3 years’ median follow-up. The final model included 9 characteristics (prior stroke, age, chronic kidney disease, prior MI, sex, heart failure, insulin use, atrial fibrillation, and microvascular complications). The model had moderate discrimination in both the internal and external validation samples (C-index = 0.65 and 0.61, respectively). The model was well calibrated across the risk spectrum—from a cumulative MACE rate of 6% at 4 years in the lowest risk quintile to 26% in the highest risk quintile. Conclusion Among patients with T2DM and prevalent ASCVD, this 9-factor risk model can quantify the risk of future ASCVD complications and inform decision making for treatments and intensity.

Background Premature discontinuation of P2Y12 inhibitor therapy has been associated with adverse cardiac events, which might be preventable by improving medication persistence. Current risk models have limited ability to predict patients at risk of P2Y12 inhibitor nonpersistence. Methods and Results ARTEMIS (Affordability and Real‐World Antiplatelet Treatment Effectiveness after Myocardial Infarction Study) was a randomized, controlled trial testing the impact of a copayment assistance intervention on P2Y12 inhibitor persistence and outcomes. Among 6212 patients post myocardial infarction with a planned 1‐year course of P2Y12 inhibitor therapy, nonpersistence was defined as a gap in P2Y12 inhibitor filled >30 days by pharmacy fill data. We developed a predictive model for 1‐year P2Y12 inhibitor nonpersistence among patients randomized to usual care. P2Y12 inhibitor nonpersistence rates were 23.8% (95% CI, 22.7%–24.8%) at 30 days and 47.9% (46.6%–49.1%) at 1 year; the majority of these patients had in‐hospital percutaneous coronary intervention. Patients who received the copayment assistance intervention had nonpersistence rates of 22.0% (20.7%–23.3%) at 30 days and 45.3% (43.8%–46.9%) at 1 year. A 53‐variable multivariable model predicting 1‐year persistence had a C‐index of 0.63 (optimism‐corrected C‐index 0.58). Model discrimination did not improve with inclusion of patient‐reported perceptions about disease, medication‐taking beliefs, and prior medication‐filling behavior in addition to demographic and medical history data (C‐index 0.62). Conclusions Despite addition of patient‐reported variables, models predicting persistence with P2Y12 inhibitor therapy performed poorly, thereby suggesting the need for continued patient and clinician education on the importance of P2Y12 inhibitor therapy after acute myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02406677.

Objective: Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease, yet little is known about Lp(a) testing patterns in real-world practice. The objective of this analysis was to determine how Lp(a) testing is used in clinical practice in comparison with low density lipoprotein cholesterol (LDL-C) testing alone, and to determine whether elevated Lp(a) level is associated with subsequent initiation of lipid-lowering therapy (LLT) and incident cardiovascular (CV) events. Methods: This is an observational cohort study, based on lab tests administered between Jan 1, 2015 and Dec 31, 2019. We used electronic health record (EHR) data from 11 United States health systems participating in the National Patient-Centered Clinical Research Network (PCORnet). We created two cohorts for comparison: 1) the Lp(a) cohort, of adults with an Lp(a) test and 2) the LDL-C cohort, of 4:1 date- and site-matched adults with an LDL-C test, but no Lp(a) test. The primary exposure was the presence of an Lp(a) or LDL-C test result. In the Lp(a) cohort, we used logistic regression to assess the relationship between Lp(a) results in mass units (< 50, 50-100, and > 100mg/dL) and molar units ( 250nmol/L) and initiation of LLT within 3 months. We used multivariable adjusted Cox proportional hazards regression to evaluate these Lp(a) levels and time to composite CV hospitalization, including hospitalization for myocardial infarction, revascularization and ischemic stroke. Results: Overall, 20,551 patients had Lp(a) test results and 2,584,773 patients had LDL-C test results (82,204 included in the matched LDL-C cohort). Compared with the LDL-C cohort, the Lp(a) cohort more frequently had prevalent ASCVD (24.3% vs. 8.5%) and multiple prior CV events (8.6% vs. 2.6%). Elevated Lp(a) was associated with greater odds of subsequent LLT initiation. Elevated Lp(a) reported in mass units was also associated with subsequent composite CV hospitalization [aHR (95% CI): Lp(a) 50-100mg/dL 1.25 (1.02-1.53), p 100mg/dL 1.23 (1.08-1.40), p

Background Among patients with nonvalvular atrial fibrillation (AF) and an elevated stroke risk, guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention. Changes in DOAC use over the past decade have not been well described. Methods and Results We evaluated trends in use of DOACs and warfarin from 2011 to 2020 among adults with AF and a CHA2DS2‐VASc score ≥2 based on electronic health record data from 88 health systems in the United States contributing to Cerner Real World Data. The use of DOACs and warfarin was described over time, by age, sex, race, and ethnicity, and at the health‐system level. We identified 436 864 patients with AF at risk for stroke (median age, 78 years; 52.1% men). From 2011 to 2020, overall anticoagulation rates increased from 56.3% to 64.7%, as DOAC use increased steadily (from 4.7% to 47.9%), while warfarin use declined (from 52.4% to 17.7%). DOAC uptake was similar across age, sex, and race and ethnicity groups but varied by health system. In 2020, the median health‐system‐level proportion of patients with AF on a DOAC was 49% (interquartile range, 40%–54%). Conclusions Over the past decade, anticoagulation rates for patients with AF have increased modestly as DOACs largely replaced warfarin, though significant gaps remain: One in 3 high‐risk patients with AF is not on any anticoagulant. While DOAC adoption was generally consistent across major demographic groups, use between health systems remained highly variable, suggesting that provider and system factors influence DOAC uptake use more than patient‐level factors.

Background Persistence to P2Y12 inhibitors after myocardial infarction (MI) remains low. Out‐of‐pocket cost is cited as a factor affecting medication compliance. We examined whether a copayment intervention affected 1‐year persistence to P2Y12 inhibitors and clinical outcomes. Methods and Results In an analysis of ARTEMIS (Affordability and Real‐World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study), patients with MI discharged on a P2Y12 inhibitor were stratified by baseline out‐of‐pocket medication burden: low ($0–$49 per month), intermediate ($50–$149 per month), and high (≥$150 per month). The impact of the voucher intervention on 1‐year P2Y12 inhibitor persistence was examined using a logistic regression model with generalized estimating equations. We assessed the rates of major adverse cardiovascular events among the groups using a Kaplan–Meier estimator. Among 7351 MI‐treated patients at 282 hospitals, 54.2% patients were in the low copay group, 32.0% in the middle copay group, and 13.8% in the high copay group. Patients in higher copay groups were more likely to have a history of prior MI, heart failure, and diabetes compared with the low copay group (all P

Abstract Introduction Texas Health Resources (THR), a large, nonprofit health care system based in the Dallas‐Fort Worth area, has collaborated with the University of Texas Southwestern Medical Center (UTSW) to develop and operate a unique, integrated approach for Learning Health System (LHS) workforce development. This training model centers on academic health system faculty members conducting later‐stage translational research within a partnering regional care delivery organization. Methods The THR Clinical Scholars Program engages early career UTSW faculty members to conduct studies that are likely to have an impact on care delivery at the health system level. Interested candidates submit formal applications to the program. A joint committee comprised of senior research faculty from UTSW and THR clinical leadership reviews proposals with a focus on the shared LHS needs of both institutions—developing high quality research output that can be applied to enhance care delivery. A key prioritization criterion for funding is the degree to which the research addresses a question relevant to THR as a high‐volume network with multiple channels for consumers to access care. The program emphasis is on supporting embedded research initiatives using health system data to generate knowledge that will improve the quality and efficiency of care for the patient populations served by the participant organizations. Results We discuss specific strategic and tactical components of the THR Clinical Scholars Program including an overview of the academic affiliation agreement between the collaborating organizations, criteria for successful program applications, data sharing, and funding. We also share project summaries from selected clinical scholars as examples of the LHS research done in the program to date. Conclusion This experience report provides an implementation framework for other academic health systems interested in adopting similar LHS workforce training models with community partners.

Background The WATCH‐DM (weight [body mass index], age, hypertension, creatinine, high‐density lipoprotein cholesterol, diabetes control [fasting plasma glucose], ECG QRS duration, myocardial infarction, and coronary artery bypass grafting) and TRS‐HFDM (Thrombolysis in Myocardial Infarction [TIMI] risk score for heart failure in diabetes) risk scores were developed to predict risk of heart failure (HF) among individuals with type 2 diabetes. WATCH‐DM was developed to predict incident HF, whereas TRS‐HFDM predicts HF hospitalization among patients with and without a prior HF history. We evaluated the model performance of both scores to predict incident HF events among patients with type 2 diabetes and no history of HF hospitalization across different cohorts and clinical settings with varying baseline risk. Methods and Results Incident HF risk was estimated by the integer‐based WATCH‐DM and TRS‐HFDM scores in participants with type 2 diabetes free of baseline HF from 2 randomized clinical trials (TECOS [Trial Evaluating Cardiovascular Outcomes With Sitagliptin], N=12 028; and Look AHEAD [Look Action for Health in Diabetes] trial, N=4867). The integer‐based WATCH‐DM score was also validated in electronic health record data from a single large health care system (N=7475). Model discrimination was assessed by the Harrell concordance index and calibration by the Greenwood‐Nam‐D’Agostino statistic. HF incidence rate was 7.5, 3.9, and 4.1 per 1000 person‐years in the TECOS, Look AHEAD trial, and electronic health record cohorts, respectively. Integer‐based WATCH‐DM and TRS‐HFDM scores had similar discrimination and calibration for predicting 5‐year HF risk in the Look AHEAD trial cohort (concordance indexes=0.70; Greenwood‐Nam‐D’Agostino P>0.30 for both). Both scores had lower discrimination and underpredicted HF risk in the TECOS cohort (concordance indexes=0.65 and 0.66, respectively; Greenwood‐Nam‐D’Agostino P

Background The COVID‐19 pandemic resulted in a rapid implementation of telemedicine into clinical practice. This study examined whether early outpatient follow‐up via telemedicine is as effective as in‐person visits for reducing 30‐day readmissions in patients with heart failure. Methods and Results Using electronic health records from a large health system, we included patients with heart failure living in North Carolina (N=6918) who were hospitalized between March 16, 2020 and March 14, 2021. All‐cause readmission within 30 days after discharge was examined using weighted logistic regression models. Overall, 7.6% (N=526) of patients received early telemedicine follow‐up, 38.8% (N=2681) received early in‐person follow‐up, and 53.6% (N=3711) did not receive follow‐up within 14 days of discharge. Compared with patients without early follow‐up, those who received early follow‐up were younger, were more likely to be Medicare beneficiaries, had more comorbidities, and were less likely to live in an disadvantaged neighborhood. Relative to in‐person visits, those with telemedicine follow‐up were of similar age, sex, and race but with generally fewer comorbidities. Overall, the 30‐day readmission rate (19.0%) varied among patients who received telemedicine visits (15.0%), in‐person visits (14.0%), or no follow‐up (23.1%). After covariate adjustment, patients who received either telemedicine (odds ratio [OR], 0.55; 95% CI, 0.44–0.72) or in‐person (OR, 0.52; 95% CI, 0.45–0.60) visits were similarly less likely to be readmitted within 30 days compared with patients with no follow‐up. Conclusions During the COVID‐19 pandemic, the use of telemedicine visits for early follow‐up increased rapidly. Patients with heart failure who received outpatient follow‐up either via telemedicine or in‐person had better outcomes than those who received no follow‐up.

Abstract The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.

Abstract Objective: To describe insulin use and postoperative glucose control in patients undergoing coronary artery bypass graft (CABG) surgery. Methods: We examined 2,390 patients with and without diabetes enrolled in the Contemporary Analysis of Perioperative Cardiovascular Surgical Care (CAPS-Care) Study who underwent CABG surgery (01/2004 - 06/2005) to describe postoperative insulin use, variation in insulin use across different hospitals, and associated in-hospital complications and clinical outcomes. Logistic regression was used to assess the adjusted relationship between insulin use and clinical outcomes. Results: Overall, insulin was used in 82% (n=1,959) of patients, including 95% (n=1,203) with diabetes (n=1,258) and 67% (n=756) without diabetes (n=1,132). Continuous insulin was used in 35.5% of patients in the operating room and in 56% in the intensive care unit. Continuous insulin use varied significantly among centers from 8-100% in patients with diabetes. When compared with all patients not receiving insulin, insulin use in patients without diabetes was associated with a higher rate of death or major complication (adjusted odds ratio [OR]=1.54; 95% confidence interval [CI] 1.15-2.04; P=0.003). In patients with diabetes, insulin use was not associated with a higher risk of adverse outcomes (adjusted OR=1.01; 95% CI 0.52-1.98; P=0.98). Conclusion: The postoperative use of insulin is high among CABG patients in the United States of America. Insulin use in patients without diabetes was associated with worse clinical outcomes compared to patients (both with and without diabetes) who did not receive insulin. Further investigation is needed to determine the optimal use of postoperative insulin after CABG.

Data on patterns of weight change among adults with overweight or obesity are minimal. We aimed to examine patterns of weight change and associated hospitalizations in a large health system, and to develop a model to predict 2-year significant weight gain.Data from the Duke University Health System was abstracted from 1/1/13 to 12/31/16 on patients with BMI ≥ 25 kg/m2 in 2014. A regression model was developed to predict patients that would increase their weight by 10% within 2 years. We estimated the association between weight change category and all-cause hospitalization using Cox proportional hazards models.Of the 37,253 patients in our cohort, 59% had stable weight over 2 years, while 24% gained ≥ 5% weight and 17% lost ≥ 5% weight. Our predictive model had reasonable discriminatory capacity to predict which individuals would gain ≥ 10% weight over 2 years (AUC 0.73). Compared with stable weight, the risk of hospitalization was increased by 37% for individuals with > 10% weight loss [adj. HR (95% CI): 1.37 (1.25,1.5)], by 30% for those with > 10% weight gain [adj. HR (95% CI): 1.3 (1.19,1.42)], by 18% for those with 5–10% weight loss [adj. HR (95% CI): 1.18 (1.09,1.28)], and by 10% for those with 5–10% weight gain [adj. HR (95% CI): 1.1 (1.02,1.19)].In this examination of a large health system, significant weight gain or loss of > 10% was associated with increased all-cause hospitalization over 2 years compared with stable weight. This analysis adds to the increasing observational evidence that weight stability may be a key health driver.

Background Patients with symptomatic severe aortic stenosis (ssAS) have a high mortality risk and compromised quality of life. Surgical/transcatheter aortic valve replacement (AVR) is a Class I recommendation, but it is unclear if this recommendation is uniformly applied. We determined the impact of managing cardiologists on the likelihood of ssAS treatment. Methods and Results Using natural language processing of Optum electronic health records, we identified 26 438 patients with newly diagnosed ssAS (2011–2016). Multilevel, multivariable Fine‐Gray competing risk models clustered by cardiologists were used to determine the impact of cardiologists on the likelihood of 1‐year AVR treatment. Within 1 year of diagnosis, 35.6% of patients with ssAS received an AVR; however, rates varied widely among managing cardiologists (0%, lowest quartile; 100%, highest quartile [median, 29.6%; 25th–75th percentiles, 13.3%–47.0%]). The odds of receiving AVR varied >2‐fold depending on the cardiologist (median odds ratio for AVR, 2.25; 95% CI, 2.14–2.36). Compared with patients with ssAS of cardiologists with the highest treatment rates, those treated by cardiologists with the lowest AVR rates experienced significantly higher 1‐year mortality (lowest quartile, adjusted hazard ratio, 1.22, 95% CI, 1.13–1.33). Conclusions Overall AVR rates for ssAS were low, highlighting a potential challenge for ssAS management in the United States. Cardiologist AVR use varied substantially; patients treated by cardiologists with lower AVR rates had higher mortality rates than those treated by cardiologists with higher AVR rates.

Abstract Background To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Methods TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses. Results During TECOS, 616 participants had ≥ 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81–1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83–1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83–1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes. Conclusions In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration clinicaltrials.gov no. NCT00790205

Objective: To identify the prevalence, treatment, and low-density lipoprotein cholesterol (LDL-C) control of individuals with LDL-C ≥190 ​mg/dL in contemporary clinical practice. Methods: We included adults (age ≥18 years) with LDL-C ≥190 ​mg/dL, at least one LDL-C level drawn from 255 health systems participating in Cerner HealthFacts database (2000–2017, n ​= ​4,623,851), and a detailed examination within Duke University Health System (DUHS, 2015–2017, n ​= ​267,710). Factors associated with LDL-C control were evaluated using multivariable logistic regression modeling. Results: The cross-sectional prevalence of LDL-C ≥190 ​mg/dL was 3.0% in Cerner (n ​= ​139,539/4,623,851) and 2.9% at DUHS (n ​= ​7728/267,710); among these, rates of repeat LDL-C measurement within 13 months were low: 27.9% (n ​= ​38,960) in Cerner, 54.5% (n ​= ​4211) at DUHS. Of patients with follow-up LDL-C levels, 23.6% in Cerner had a 50% of greater reduction in LDL-C, 18.3% achieved an LDL-C

Background With the availability of new lipid‐lowering therapy options, there is a need to compare the expected clinical benefit of different treatment strategies in different patient populations and over various time frames. We aimed to develop a time‐dependent model from published randomized controlled trials summarizing the relationship between low‐density lipoprotein cholesterol lowering and cardiovascular risk reduction and to apply the model to investigate the effect of treatment scenarios over time. Methods and Results A cardiovascular treatment benefit model was specified with parameters as time since treatment initiation, magnitude of low‐density lipoprotein cholesterol reduction, and additional patient characteristics. The model was estimated from randomized controlled trial data from 22 trials for statins and nonstatins. In 15 trials, the new time‐dependent model had better predictions than cholesterol treatment trialists’ estimations for a composite of coronary heart disease death, nonfatal myocardial infarction, and ischemic stroke. In explored scenarios, absolute risk reduction ≥2% with intensive treatment with high‐intensity statin, ezetimibe, and high‐dose proprotein convertase subtilisin/kexin type 9 inhibitor compared with high‐ or moderate‐intensity statin alone were achieved in higher‐risk populations with 2 to 5 years of treatment, and lower‐risk populations with 9 to 11 years of treatment. Conclusions The time‐dependent model accurately predicted treatment benefit seen from randomized controlled trials with a given lipid‐lowering therapy by incorporating patient profile, timing, duration, and treatment type. The model can facilitate decision making and scenario analyses with a given lipid‐lowering therapy strategy in various patient populations and time frames by providing an improved assessment of treatment benefit over time.

Background Aortic valve replacement (AVR) is a life‐saving treatment for patients with symptomatic severe aortic valve stenosis. We sought to determine whether transcatheter AVR has resulted in a more equitable treatment rate by race in the United States. Methods and Results A total of 32 853 patients with symptomatic severe aortic valve stenosis were retrospectively identified via Optum’s deidentified electronic health records database (2007–2017). AVR rates in non‐Hispanic Black and White patients were assessed in the year after diagnosis. Multivariate Fine‐Gray hazards models were used to evaluate the likelihood of AVR by race, with adjustment for patient factors and the managing cardiologist. Time‐trend and 1‐year symptomatic severe aortic valve stenosis survival analyses were also performed. From 2011 to 2016, the rate of AVR increased from 20.1% to 37.1%. Overall, Black individuals were less likely than Whites to receive AVR (22.9% versus 31.0%; unadjusted hazard ratio [HR], 0.70; 95% CI, 0.62–0.79; fully adjusted HR, 0.76; 95% CI, 0.67–0.85). Yet, during 2015 to 2016, AVR racial differences were attenuated (29.5% versus 35.2%; adjusted HR, 0.86; 95% CI, 0.74–1.02) because of greater uptake of transcatheter AVR in Blacks than Whites (53.4% of AVRs versus 47.3%; P=0.128). Untreated patients had significantly higher 1‐year mortality than those treated (adjusted HR, 0.57; 95% CI, 0.53–0.61), which was consistent by race (interaction P value=0.52). Conclusions Although transcatheter AVR has increased the use of AVR in the United States, treatment rates remain low. Black patients with symptomatic severe aortic valve stenosis were less likely than White patients to receive AVR, yet these differences have recently narrowed.

Background Hospitals commonly provide a short‐term supply of free P2Y12 inhibitors at discharge after myocardial infarction, but it is unclear if these programs improve medication persistence and outcomes. The ARTEMIS (Affordability and Real‐World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) trial randomized hospitals to usual care versus waived P2Y12 inhibitor copayment costs for 1‐year post‐myocardial infarction. Whether the impact of this intervention differed between hospitals with and without pre‐existing medication assistance programs is unknown. Methods and Results In this post hoc analysis of the ARTEMIS trial, we examined the associations of pre‐study free medication programs and the randomized copayment voucher intervention with P2Y12 inhibitor persistence (measured by pharmacy fills and patient report) and major adverse cardiovascular events using logistic regression models including a propensity score. Among 262 hospitals, 129 (49%) offered pre‐study free medication assistance. One‐year P2Y12 inhibitor persistence and major adverse cardiovascular events risks were similar between patients treated at hospitals with and without free medication programs (adjusted odds ratio 0.93, 95% CI, 0.82–1.05 and hazard ratio 0.92, 95% CI, 0.80–1.07, respectively). The randomized copayment voucher intervention improved persistence, assessed by pharmacy fills, in both hospitals with (53.6% versus 44.0%, adjusted odds ratio 1.45, 95% CI, 1.20–1.75) and without (59.0% versus 48.3%, adjusted odds ratio 1.46, 95% CI, 1.25–1.70) free medication programs (Pinteraction=0.71). Differences in patient‐reported persistence were not significant after adjustment. Conclusions While hospitals commonly report the ability to provide free short‐term P2Y12 inhibitors, we did not find association of this with medication persistence or major adverse cardiovascular events among patients with insurance coverage for prescription medication enrolled in the ARTEMIS trial. An intervention that provided copayment assistance vouchers for 1 year was successful in improving medication persistence in hospitals with and without pre‐existing short‐term medication programs. Registration URL: https://www.clini​caltr​ials.gov/. Unique identifier: NCT02406677.

Background Hospitals in the United States vary in their use of intensive care units (ICUs) for hemodynamically stable patients with non–ST‐segment–elevation myocardial infarction (NSTEMI). The association between ICU use and long‐term outcomes after NSTEMI is unknown. Methods and Results Using data from the National Cardiovascular Data Registry linked to Medicare claims, we identified 65 256 NSTEMI patients aged ≥ 65 years without cardiogenic shock or cardiac arrest on presentation between 2011 and 2014. We compared 1‐year medication non‐adherence, cardiovascular readmission, and mortality across hospitals by ICU use using multivariable regression models. Among 520 hospitals, 154 (29.6%) were high ICU users (>70% of stable NSTEMI patients admitted to ICU), 270 (51.9%) were intermediate (30%–70%), and 196 (37.7%) were low (

Background Limited data exist to guide treatment for patients with heart failure with preserved ejection fraction and atrial fibrillation, including the important decision regarding rate versus rhythm control. Methods and Results We analyzed the Get With The Guidelines—Heart Failure (GWTG‐HF) registry linked to Medicare claims data from 2008 to 2014 to describe current treatments for rate versus rhythm control and subsequent outcomes in patients with heart failure with preserved ejection fraction and atrial fibrillation using inverse probability weighted analysis. Rhythm control was defined as use of an antiarrhythmic medication, cardioversion, or AF ablation or surgery. Rate control was defined as use of any combination of β‐blocker, calcium channel blocker, and digoxin without evidence of rhythm control. Among 15 682 fee‐for‐service Medicare patients, at the time of discharge, 1857 were treated with rhythm control and 13 825 with rate control, with minimal differences in baseline characteristics between groups. There was higher all‐cause death at 1 year in the rate control compared with the rhythm control group (37.5% and 30.8%, respectively, P

Background Current treatment guidelines strongly recommend statin therapy for secondary prevention. However, it remains unclear whether patients’ perceptions of cardiovascular risk, beliefs on cholesterol, or the intensity of prescribed statin therapy differs for patients with coronary artery disease (CAD) versus cerebrovascular disease (CeVD) versus both CAD and CeVD (CAD&CeVD). Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry collected data on statin use, intensity, and core laboratory low‐density lipoprotein cholesterol levels for 3232 secondary prevention patients treated at 133 US clinics. Among individuals with CeVD only (n=403), CAD only (n=2202), and CeVD&CAD (n=627), no significant differences were observed in patient‐perceived cardiovascular disease risk, beliefs on cholesterol lowering, or perceived effectiveness and safety of statin therapy. However, patients with CeVD only were less likely to receive any statin therapy (76.2% versus 86.2%; adjusted odds ratio 0.64, 95% CI 0.45–0.91), or guideline‐recommended statin intensity (34.6% versus 50.4%; adjusted odds ratio 0.60, 95% CI 0.45–0.81) than those with CAD only. Individuals with CeVD only were also less likely to achieve low‐density lipoprotein cholesterol

Background When patients require readmission after a recent myocardial infarction (MI), returning to the discharging (index) hospital may be associated with better outcomes as a result of greater continuity in care. However, little evidence exists to answer this frequent patient question. Methods and Results Among Medicare patients aged ≥65 years discharged home alive post‐MI from 491 US hospitals in the ACTION (Acute Coronary Treatment Intervention Outcomes Network) Registry, we compared reason for readmission, duration of rehospitalization, and 30‐day mortality between patients readmitted to the index versus nonindex hospital within 30 days of index MI discharge. Among 53 471 MI patients, 7715 (14%) were readmitted within 30 days, and most readmitted patients (73%) returned to the discharging hospital. Reason for readmission was not significantly associated with location of readmission. In multivariable modeling, the strongest factors associated with readmission to a nonindex hospital were distance from the discharging hospital, transfer‐in during the index MI hospitalization, and frequency of nonindex hospital admissions in the year preceding to the index MI. Duration of rehospitalization did not differ significantly between patients readmitted to the index versus nonindex hospital (median, 4 versus 3 days; P=0.17). Mortality risk was also not significantly different between patients readmitted to the index versus nonindex hospital overall (7.4 versus 7.7%; adjusted odds ratio, 0.89; 95% CI, 0.73–1.10) and when stratified by reason for readmission (P for interaction=0.61). Conclusions Post‐MI readmissions did not differ in reason for readmission, duration of rehospitalization, or associated mortality when compared between patients who returned to the discharging hospital and those who sought care elsewhere.

Background Intravenous recombinant tissue‐type plasminogen activator (rtPA) remains the only medical therapy to improve outcomes for acute ischemic stroke (AIS), but the safety of rtPA in AIS patients with a history of recent myocardial infarction (MI) remains controversial. Methods and Results We sought to determine whether the presence of recent MI would alter the risk of mortality and rtPA‐related complications. Multivariate logistic regression models were used to compare in‐hospital outcomes between rtPA‐treated AIS patients with recent MI within 3 months and those with no history of MI from the Get With The Guidelines‐Stroke hospitals between February 2009 and December 2015. Among 40 396 AIS patients aged ≥65 years treated with rtPA, 241 (0.6%) had recent MI, of which 19.5% were ST‐segment–elevation myocardial infarction. Patients with recent MI had more severe stroke than those without (median National Institutes of Health Stroke Scale [interquartile range]: 13.0 [7.0–20.0] versus 11.0 [6.0–18.0]). Recent MI was associated with an increased risk of mortality compared with no history of MI (17.4% versus 9.0%; adjusted odds ratio 1.60 [95% CI, 1.10–2.33]; P=0.014), but no statistically significant differences in rtPA‐related complications (13.5% versus 9.4%; adjusted odds ratio 1.28 [0.88–1.86]; P=0.19). Recent ST‐segment–elevation myocardial infarction was associated with higher risk of death and rtPA‐related complications, but non–ST‐segment–elevation myocardial infarction was not. Conclusions Among older AIS patients treated with rtPA, recent MI was associated with an increased risk of in‐hospital mortality. Further investigations are necessary to determine whether the benefit of rtPA outweighs its risk among AIS patients with recent MI.

Background Although recommended in the guidelines, the safety of chronic P2Y12 inhibitor therapy in patients with chronic kidney disease (CKD) after an acute myocardial infarction (MI) is not well studied. Methods and Results The TRANSLATE‐ACS (Treatment with ADP Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study included 11 108 MI patients treated with percutaneous coronary intervention and discharged alive on a P2Y12 inhibitor from 233 US hospitals. We compared rates of GUSTO (Global Use of Strategies to Open Occluded Arteries) severe/moderate bleeding and premature discontinuation of P2Y12 inhibitor by 1 year after MI among patients with varying CKD severity. The majority of MI patients treated with percutaneous coronary intervention had CKD: 42% had stage 2 (mild), 27% had stage 3 (moderate), and 4% had stage ≥4 (severe/end stage). Higher potency P2Y12 inhibitors (prasugrel or ticagrelor) were prescribed at discharge in 39%, 35%, 23%, and 15% (P

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; CHA2DS2‐VASc 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.

Background Hospitalization for acute myocardial infarction (MI) in the United States is both common and expensive, but those features alone provide little insight into cost‐saving opportunities. Methods and Results To understand the cost drivers during hospitalization for acute MI and in the following year, we prospectively studied 11 969 patients with acute MI undergoing percutaneous coronary intervention at 233 US hospitals (2010–2013) from the TRANSLATE‐ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) registry. Baseline costs were collected in a random subset (n=4619 patients, 54% ST‐segment–elevation MI [STEMI]), while follow‐up costs out to 1 year were collected for all patients. The mean index length of stay was 3.1 days (for both STEMI and non‐STEMI) and mean intensive care unit length of stay was 1.2 days (1.4 days for STEMI and 1.0 days for non‐STEMI). Index hospital costs averaged $18 931 ($19 327 for STEMI, $18 465 for non‐STEMI), with 45% catheterization laboratory–related and 20% attributable to postprocedure hospital stay. Patient factors, including severity of illness and extent of coronary disease, and hospital characteristics, including for profit status and geographic region, identified significant variations in cost. Intensive care was used for 53% of non‐STEMI and increased costs by $3282. Postdischarge 1‐year costs averaged $8037, and 48% of patients were rehospitalized (half within 2 months and 57% with a cardiovascular diagnosis). Conclusions While much of the cost of patients with acute MI treated with percutaneous coronary intervention is probably not modifiable by the care team, cost reductions are still possible through quality‐preserving practice efficiencies, such as need‐based use rather than routine use of intensive care unit for patients with stable non‐STEMI. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00097591.

Background Many adults eligible for statin therapy for cardiovascular disease prevention are untreated. Our objective was to investigate patient‐reported reasons for statin underutilization, including noninitiation, refusal, and discontinuation. Methods and Results This study included the 5693 adults recommended for statin therapy in the PALM (Patient and Provider Assessment of Lipid Management) registry. Patient surveys evaluated statin experience, reasons for declining or discontinuing statins, and beliefs about statins and cardiovascular disease risk. Overall, 1511 of 5693 adults (26.5%) were not on treatment. Of those not on a statin, 894 (59.2%) reported never being offered a statin, 153 (10.1%) declined a statin, and 464 (30.7%) had discontinued therapy. Women (relative risk: 1.22), black adults (relative risk: 1.48), and those without insurance (relative risk: 1.38) were most likely to report never being offered a statin. Fear of side effects and perceived side effects were the most common reasons cited for declining or discontinuing a statin. Compared with statin users, those who declined or discontinued statins were less likely to believe statins are safe (70.4% of current users vs. 36.9% of those who declined and 37.4% of those who discontinued) or effective (86.3%, 67.4%, and 69.1%, respectively). Willingness to take a statin was high; 67.7% of those never offered and 59.7% of patients who discontinued a statin would consider initiating or retrying a statin. Conclusions More than half of patients eligible for statin therapy but not on treatment reported never being offered one by their doctor. Concern about side effects was the leading reason for statin refusal or discontinuation. Many patients were willing to reconsider statin therapy if offered.

Background In older adults undergoing cardiac surgery, prediction of downstream risk is critical. Our objective was to determine the association of 5‐m gait speed with 1‐year mortality and repeat hospitalization following cardiac surgery. Methods and Results In this prospective cohort of patients undergoing cardiac surgery at centers participating in the Society of Thoracic Surgeons Database with gait speed recorded, we examined all‐cause mortality using a landmark analysis at 0 to 30, 30 to 365, and >365 days, as well as repeat hospitalization. The cohort consisted of 8287 patients (median age, 74 years; 32% females). At 1 year, survival was 90% in the slow (1.00 m/s) gait speed tertiles, and risk of hospitalization was 45%, 33%, and 27%, respectively (both P

Background Adherence to evidence‐based guidelines is an important quality indicator; yet, there is lack of assessment of adherence to performance measures in acute ischemic stroke for most world regions. Methods and Results We analyzed 19 604 patients with acute ischemic stroke in the China National Stroke Registry and 194 876 patients in the Get With The Guidelines––Stroke registry in the United States from June 2012 to January 2013. Compared with their US counterparts, Chinese patients were younger, had a lower prevalence of comorbidities, and had similar median, lower mean, and less variability in National Institutes of Health Stroke Scale (median 4 [25th percentile–75th percentile, 2–7], mean 5.4±5.6 versus median 4 [1–10], mean 6.8±7.7). Chinese patients were more likely to experience delays from last known well to hospital arrival (median 1318 [330–3209] versus 644 [142–2055] minutes), less likely to receive thrombolytic therapy (2.5% versus 8.1%), and more likely to experience treatment delays (door‐to‐needle time median 95 [72–112] versus 62 [49–85] minutes). Adherence to early and discharge antithrombotics, smoking cessation counseling, and dysphagia screening were relatively high (eg >80%) in both countries. Large gaps existed between China and the United States with regard to the administration of thrombolytics within 3 hours (18.3% versus 83.6%), door‐to‐needle time ≤60 minutes (14.6% versus 48.0%), deep venous thrombosis prophylaxis (65.0% versus 97.8%), anticoagulation for atrial fibrillation (21.0% versus 94.4%), lipid treatment (66.3% versus 95.8%), and rehabilitation assessment (58.8% versus 97.4%). Conclusions We found significant differences in clinical characteristics and gaps in adherence for certain performance measures between China and the United States. Additional efforts are needed for continued improvements in acute stroke care and secondary prevention in both nations, especially China.

Background Chronic kidney disease (CKD) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow‐up data were included (N=9019). CKD was defined as an estimated creatinine clearance

Background The 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommended testing low‐density lipoprotein cholesterol (LDL‐C) to identify untreated patients with LDL‐C ≥190 mg/dL, assess lipid‐lowering therapy adherence, and consider nonstatin therapy. We sought to determine whether clinician lipid testing practices were consistent with these guidelines. Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry enrolled primary and secondary prevention patients from 140 US cardiology, endocrinology, and primary care offices in 2015 and captured demographic data, lipid treatment history, and the highest LDL‐C level in the past 2 years. Core laboratory lipid levels were drawn at enrollment. Among 7627 patients, 2787 (36.5%) had no LDL‐C levels measured in the 2 years before enrollment. Patients without chart‐documented LDL‐C levels were more often women, nonwhite, uninsured, and non–college graduates (all P

Background Physician shortages and reimbursement changes have led to greater use of advanced practice providers (APPs). Prevalence of and outcomes associated with APP care following myocardial infarction are unknown. Methods and Results We examined outpatient cardiology or primary care visits within 90 days post‐myocardial infarction among 29 477 Medicare‐insured patients aged ≥65 years from 364 hospitals in Acute Coronary Treatment Intervention Outcomes Network Registry. We compared medication adherence, all‐cause readmission risk, mortality, and major adverse cardiovascular events between patients seen by APPs versus physicians only. Overall, 11% of myocardial infarction patients were treated by an APP. Patients seen by APPs were more likely to have diabetes mellitus (37% versus 33%) and heart failure (20% versus 16%), be discharged to a nursing facility (21% versus 13%) and had more outpatient visits within 90 days post‐discharge (median 6 versus 5, P

Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA2DS2VASc=1) (or women with CHA2DS2VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these “low‐risk” patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low‐risk CHA2DS2VASc scores. Methods and Results We compared characteristics, treatment strategies, and outcomes among patients with a CHA2DS2VASc=0, CHA2DS2VASc=1, females with a CHA2DS2VASc=2, and CHA2DS2VASc ≥2 in ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA2DS2VASc ≥2 patients (84.2%), those with a CHA2DS2VASc=0 (60.3%), 1 (69.9%), and females with a CHA2DS2VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation (P

Background The Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS2°P), a 0‐to‐9‐point system based on the presence/absence of 9 clinical factors, was developed to classify the risk of major adverse cardiovascular events (MACE) (a composite of cardiovascular death, recurrent myocardial infarction, or ischemic stroke) among patients with a recent myocardial infarction. Its performance has not been examined internationally outside of a clinical trial setting. Methods and Results We evaluated the performance of TRS2°P for predicting MACE in 53 599 patients with recent myocardial infarction in 5 international cohorts from New Zealand, South Korea, Sweden, and the United States participating in the Chronic Kidney Disease Prognosis Consortium. Overall, there were 19 444 cases of MACE across 5 cohorts over a mean follow‐up of 5 years, and the overall MACE rate ranged from 5.0 to 18.4 (per 100 person‐years). The TRS2°P showed modest calibration (Brier score ranged from 0.144 to 0.173) and discrimination (C‐statistics >0.61 in all studies except 1 from Korea with 0.55) across cohorts relative to its original Brier score of 0.098 and C‐statistic of 0.67 in the derived data set. Although there was some heterogeneity across cohorts, the 9 predictors in the TRS2°P were generally associated with higher MACE risk, with strongest associations observed (meta‐analyzed adjusted hazard ratio 1.6–1.7) for history of heart failure, age ≥75 years, and prior stroke, followed by peripheral artery disease, kidney dysfunction, diabetes mellitus, and hypertension (hazard ratio 1.3–1.4). Prior coronary bypass graft surgery and smoking did not reach statistical significance (hazard ratio ≈1.1). Conclusions TRS2°P, a simple scoring system with 9 routine clinical factors, was modestly predictive of secondary events when applied in patients with recent myocardial infarction from diverse clinical and geographic settings.

Background There is limited information about the long‐term survival of older patients after myocardial infarction (MI). Methods and Results CRUSADE (Can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines) was a registry of MI patients treated at 568 US hospitals from 2001 to 2006. We linked MI patients aged ≥65 years in CRUSADE to their Medicare data to ascertain long‐term mortality (defined as 8 years post index event). Long‐term unadjusted Kaplan–Meier mortality curves were examined among patients stratified by revascularization status. A landmark analysis conditioned on surviving the first year post‐MI was conducted. We used multivariable Cox regression to compare mortality risks between ST‐segment–elevation myocardial infarction and non–ST‐segment–elevation myocardial infarction patients. Among 22 295 MI patients ≥ age 65 years (median age 77 years), we observed high rates of evidence‐based medication use at discharge: aspirin 95%, β‐blockers 94%, and statins 81%. Despite this, mortality rates were high: 24% at 1 year, 51% at 5 years, and 65% at 8 years. Eight‐year mortality remained high among patients who underwent percutaneous coronary intervention (49%), coronary artery bypass graft (46%), and among patients who survived the first year post‐MI (59%). Median survival was 4.8 years (25th, 75th percentiles 1.1, 8.5); among patients aged 65–74 years it was 8.2 years (3.3, 8.9) while for patients aged ≥75 years it was 3.1 years (0.6, 7.6). Eight‐year mortality was lower among ST‐segment–elevation myocardial infarction than non–ST‐segment–elevation myocardial infarction patients (53% versus 67%); this difference was not significant after adjustment (hazard ratio 0.94, 95% confidence interval, 0.88–1.00). Conclusions Long‐term mortality remains high among patients with MI in routine clinical practice, even among revascularized patients and those who survived the first year.

BackgroundIntensive care unit (ICU) use for initially stable patients presenting with non–ST‐segment–elevation myocardial infarction (NSTEMI) varies widely across hospitals and minimally correlates with severity of illness. We aimed to develop a bedside risk score to assist in identifying high‐risk patients with NSTEMI for ICU admission. Methods and ResultsUsing the Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry linked to Medicare data, we identified patients with NSTEMI aged ≥65 years without cardiogenic shock or cardiac arrest on presentation. Complications requiring ICU care were defined as subsequent development of cardiac arrest, shock, high‐grade atrioventricular block, respiratory failure, stroke, or death during the index hospitalization. We developed and validated a model and integer risk score (Acute Coronary Treatment and Intervention Outcomes Network (ACTION) ICU risk score) that uses variables present at hospital admission to predict requirement for ICU care. Of 29 973 patients with NSTEMI, 4282 (14%) developed a complication requiring ICU‐level care, yet 12 879 (43%) received care in an ICU. Signs or symptoms of heart failure, initial heart rate, initial systolic blood pressure, initial troponin, initial serum creatinine, prior revascularization, chronic lung disease, ST‐segment depression, and age had statistically significant associations with requirement for ICU care after adjusting for other risk factors. The ACTION ICU risk score had a C‐statistic of 0.72. It identified 11% of patients as having very high risk (>30%) of developing complications requiring ICU care and 49% as having low likelihood (

Background Oral anticoagulation (OAC) reduces stroke risk in atrial fibrillation, but bleeding is a frequent side effect. The decision to discontinue or modify medication regimens in response to a bleeding event may differ according to bleeding site and severity. Methods and Results We used data from a large, national outpatient registry, ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation; 2010–2011), to evaluate event characteristics and OAC management following the first bleeding event occurring during follow‐up. Bleeding events were classified into 3 categories: (1) International Society of Thrombosis and Hemostasis major bleeding, (2) clinically relevant nonmajor bleeding requiring medical attention, and (3) nuisance bleeding not requiring medical attention (eg, bruising, hemorrhoidal bleeding). Of 9743 patients enrolled in ORBIT‐AF with follow‐up data, 510 (3.23/100 subject‐years) experienced a major bleed, 615 (3.90/100 subject‐years), experienced a clinically relevant nonmajor bleed, and 1558 (9.87/100 subject‐years) experienced a nuisance bleed, among first bleeds over 2 years. Nearly one third of patients (31.6%) discontinued OAC therapy following a major bleeding event, 12.7% following a clinically relevant nonmajor bleed, and 4.5% following a nuisance bleed. Compared with those who experienced a clinically relevant nonmajor or nuisance bleed, patients who experienced a major bleed were more likely to be black and female and to have a history of heart failure and stroke. Those who discontinued were more likely to have central nervous system or gastrointestinal bleeding than those who persisted on OAC therapy. Conclusions Overall, 1 in 3 patients who experienced a major bleed was no longer anticoagulated after the event. Those who discontinued OAC were more likely to have central nervous system or gastrointestinal bleeding than those who persisted on OAC.

Background Ticagrelor is a P2Y12 receptor inhibitor with superior clinical efficacy compared with clopidogrel. However, it is associated with reduced efficacy when combined with a high‐dose aspirin. Methods and Results Patients in the acute coronary treatment and intervention outcomes network (ACTION) Registry‐Get With The Guidelines (GWTG) with acute myocardial infarction from October 2013 through December 2014 were included in the study (167 455 patients; 622 sites). We evaluated temporal trends in the prescription of P2Y12 inhibitors, and identified factors associated with ticagrelor use at discharge. Among patients discharged on ticagrelor and aspirin (21 262 patients), we evaluated the temporal trends and independent factors associated with high‐dose aspirin prescription at discharge. Ticagrelor prescription at discharge increased significantly from 12% to 16.7% (P

BackgroundCurrent statin use and symptoms among older adults in routine community practice have not been well characterized since the release of the 2013 American College of Cardiology/American Heart Association guideline. Methods and ResultsWe compared statin use and dosing between adults >75 and ≤75 years old who were eligible for primary or secondary prevention statin use without considering guideline‐recommended age criteria. The patients were treated at 138 US practices in the Patient and Provider Assessment of Lipid Management (PALM) registry in 2015. Patient surveys also evaluated reported symptoms while taking statins. Multivariable logistic regression models examined the association between older age and statin use and dosing. Among 6717 people enrolled, 1704 (25%) were >75 years old. For primary prevention, use of any statin or high‐dose statin did not vary by age group: any statin, 62.6% in those >75 years old versus 63.1% in those ≤75 years old (P=0.83); high‐dose statin, 10.2% versus 12.3% in the same groups (P=0.14). For secondary prevention, older patients were slightly less likely to receive any statin (80.1% versus 84.2% [P=0.003]; adjusted odds ratio, 0.81; 95% confidence interval, 0.66–1.01 [P=0.06]), but were much less likely to receive a high‐intensity statin (23.5% versus 36.2% [P75 years versus younger patients, yet older patients were less likely to receive high‐intensity statins for secondary prevention. Statins appear to be similarly tolerated in older and younger adults.

BackgroundMineralocorticoid receptor antagonist (MRA) therapy may be beneficial to patients with atrial fibrillation (AF), but little is known about their use in patients with AF and subsequent outcomes. Methods and ResultsIn order to better understand MRA use and subsequent outcomes, we performed a retrospective cohort study of the contemporary ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry. AF progression and cardiovascular outcomes were compared using propensity‐matched Cox proportional hazards modeling according to MRA use at baseline and new MRA use at follow‐up versus patients with no MRA use. Among 7012 patients with nonpermanent AF, 320 patients were taking MRA at enrollment, and 416 patients initiated MRA use during follow‐up. The mean patient age was 72.5 years, 56.3% were men, and 70.4% had paroxysmal AF. Among all patients taking MRAs, 434 (59.0%) had heart failure, 655 (89.0%) had hypertension, and 380 (51.6%) had both. After adjustment, new MRA use was not associated with reduced AF progression (hazard ratio, 1.18; 95% confidence interval, 0.88–1.58; P=0.27) but showed a trend towards lower risk of stroke, transient ischemic attack, or systemic embolism (hazard ratio, 0.17; 95% confidence interval, 0.02–1.23; P=0.08). Results were similar for a comparison of new MRA users and baseline MRA users compared with nonusers. ConclusionsIn community‐based outpatients with AF, the majority of MRA use was for heart failure and hypertension. MRA use also trended towards lower adjusted stroke risk. Future studies should test the hypothesis that MRA use may decrease the risk of stroke in patients with AF.

BackgroundGuidelines recommend P2Y12 inhibitor therapy for 1 year after myocardial infarction (MI), yet little guidance is provided on antiplatelet management for patients with recurrent ischemic events during that year. We describe changes in P2Y12 inhibitor type among patients with recurrent ischemic events in the first year after MI. Methods and ResultsThe TRANSLATE‐ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study enrolled 12 365 patients with MI treated with percutaneous coronary intervention. We examined whether P2Y12 inhibitor choice changed among patients with recurrent MI, stent thrombosis, and/or unplanned revascularization during the first year after MI, and modeled factors associated with P2Y12 inhibitor intensification (changing clopidogrel to prasugrel or ticagrelor). In the first year after MI, 1414 patients (11%) had a total of 1740 recurrent ischemic events (771 recurrent MIs, 969 unplanned revascularizations, and 165 stent thromboses). Median time to the first recurrent ischemic event was 154 days (25th–75th percentiles, 55–287 days). Of those with recurrent ischemic events, 101 of 1092 (9.3%) occurring in clopidogrel‐treated patients led to P2Y12 inhibitor intensification. Recurrent events involving stent thrombosis or MI were the strongest factors associated with P2Y12 inhibitor intensification, yet only 40% of patients with stent thrombosis and 14% of patients with recurrent MI had P2Y12 inhibitor intensification. Increasing age and longer time from the index MI were associated with lower likelihood for intensification. ConclusionsFew patients after MI with a recurrent ischemic event who were taking clopidogrel switched to a more potent P2Y12 inhibitor, even after stent thrombosis events. Specific guidance is needed for patients who have recurrent ischemic events, particularly when closely spaced. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503.

BackgroundNon–vitamin K antagonist oral anticoagulants (NOACs) are indicated for stroke prevention in atrial fibrillation (AF) but require lower doses in certain patients. We sought to describe the frequency, appropriateness (according to Food and Drug Administration labeling), and outcomes of patients prescribed reduced doses of NOACs in community practice. Methods and ResultsWe analyzed data from the ORBIT‐AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II) registry, a prospective, national, observational registry of AF patients. Among 7925 AF patients receiving NOACs, we assessed patterns of use of reduced NOAC doses and associated cardiovascular and bleeding outcomes at median follow‐up of 1 year. Overall, 6636 patients (84%) received a NOAC at standard dose, which was consistent with US Food and Drug Administration labeling in 6376 (96%). Reduced NOAC dose was prescribed to 1289 (16% overall), which was consistent with Food and Drug Administration labeling in only 555 patients (43%). Compared with those whose NOAC dose was appropriately reduced, patients receiving inappropriate dose reductions were younger (median age 79 versus 84, P

BackgroundThe 2013 American College of Cardiology/American Heart Association cholesterol guidelines recommend high‐intensity statins for patients after myocardial infarction (MI) rather than treating to a low‐density lipoprotein cholesterol goal, as the previous ATP III (Adult Treatment Panel third report) guidelines had advised. Methods and ResultsTo evaluate the frequency of postdischarge lipid testing and high‐intensity statin use among MI patients discharged on a statin during the ATP III guidelines era, we linked ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry data to Medicare claims for 11 046 MI patients aged ≥65 years who were discharged alive on a statin from 347 hospitals (2007–2009). Multivariable regression was used to evaluate the association between lipid testing and 1‐year high‐intensity statin use. Only 21% of MI patients were discharged on a high‐intensity statin. By 90 days after MI, 44% of patients discharged on a statin underwent lipid testing (43% on low‐ or moderate‐intensity statins and 49% on high‐intensity statins; P=0.001). Follow‐up lipid testing rates were 47% among patients with in‐hospital low‐density lipoprotein cholesterol ≥100 mg/dL and 47% among newly prescribed statin recipients. By 1 year, only 14% of patients were on high‐intensity statins. Only 4% of patients discharged on low‐ or moderate‐dose statin were uptitrated to high intensity; postdischarge lipid testing was associated with a slightly higher likelihood of high‐intensity statin use by 1 year (5.4% versus 2.9%, adjusted odds ratio: 1.92; 95% confidence interval, 1.52–2.41). ConclusionsPrevious guidelines recommended low‐density lipoprotein cholesterol goal‐directed statin therapy, but lipid testing and high‐intensity statin use were infrequent after MI. The American College of Cardiology/American Heart Association guidelines may promote more intensive cardiovascular risk reduction by eliminating treatment dependence on lipid testing.