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The limitations of the explanatory clinical trial framework include the high expense of implementing explanatory trials, restrictive entry criteria for participants, and redundant logistical processes. These limitations can result in slow evidence generation that is not responsive to population health needs, yielding evidence that is not generalizable. Clinically integrated trials, which integrate clinical research into routine care, represent a potential solution to this challenge and an opportunity to support learning health systems. The operational and design features of clinically integrated trials include a focused scope, simplicity in design and requirements, the leveraging of existing data structures, and patient participation in the entire trial process. These features are designed to minimize barriers to participation and trial execution and reduce additional research burdens for participants and clinicians alike. Broad adoption and scalability of clinically integrated trials are dependent, in part, on continuing regulatory, healthcare system, and payer support. This analysis presents a framework of the strengths and challenges of clinically integrated trials and is based on a multidisciplinary expert "Think Tank" panel discussion that included representatives from patient populations, academia, non-profit funding agencies, the U.S. Food and Drug Administration, and industry., Competing Interests: Disclosures Dr. Peters is supported by the National Heart Lung and Blood Institute (T32HL069749) and has received honoraria from Cytokinetics. Dr. Jones has received grants from Bayer, Boehringer Ingelheim, and Merck. Dr. Broedl is an employee of Boehringer Ingelheim. Dr. Hornik received a research grant from Before Brands and consulting fees from SC Pharma. Dr. Knowlton received a salary from Intermountain Health Care. Dr. Krofah had leadership roles in Protas, the Reagan Udall Foundation, Clinical Trials Transformation Initiative (CTTI), Duke Margolis Center for Health Policy, Alliance for a Stronger FDA, Patient Focused Medicines Development (PFMD), and Medical Device Innovation Consortium (MDIC). Dr. Landray received grants from Janssen, FluLab, Schmidt Futures, Google Ventures, the National Institute for Health Research, UK Research & Innovation, Wellcome, and the Bill & Melinda Gates Foundation, as well as study drugs from Regeneron, Roche, AbbVie, and GSK. Dr. Rockhold received grants from the NIH, PCORI, BMS, AstraZeneca, American Regent, the Gates Foundation, and Eidos and consulting fees from Janssen, Clover, Doctor Evidence, and Intercept. He also participated on Data Safety Monitoring Boards for Lilly, AstraZeneca, Merck, Gilead, Novartis, Icosavax, Sanofi, UCB, Amgen, Biogen, BMS, Pulmocide, Alkermes, and Diurnal. He had an unpaid leadership role for the Frontier Science Foundation. He has stock or stock options for GSK, Clover, Athira, Doctor Evidence, DataVant, Spencer Health Solutions, and Adaptic Health. Dr. Roessig is a full-time employee of Bayer AG. Dr. Rothman has received grants from PCORI, the CDC, NIH, and AHRQ. Lesley Schofield is an employee of Novartis and has stock or stock options from Novartis. Dr. Tenaerts is an employee of Medable, Inc., and has a stock option grant with Medable, Inc. Dr. Tenaerts also received an honorarium for participation on a data monitoring committee., (Copyright © 2024. Published by Elsevier Inc.)

The global pharmaceutical industry portfolio is skewed towards cancer and rare diseases due to more predictable development pathways and financial incentives. In contrast, drug development for major chronic health conditions that are responsible for a large part of mortality and disability worldwide is stalled. To examine the processes of novel drug development for common chronic health conditions, a multistakeholder Think Tank meeting, including thought leaders from academia, clinical practice, non-profit healthcare organizations, the pharmaceutical industry, the Food and Drug Administration (FDA), payors as well as investors, was convened in July 2022. Herein, we summarize the proceedings of this meeting, including an overview of the current state of drug development for chronic health conditions and key barriers that were identified. Six major action items were formulated to accelerate drug development for chronic diseases, with a focus on improving the efficiency of clinical trials and rapid implementation of evidence into clinical practice., Competing Interests: Conflict of interest Konstantin A. Krychtiuk: advisory boards Novartis, Sanofi, Amgen; speaker fees Amgen, Daichii Sankyo, Zoll Medical Tomas LG Andersson: employed by AstraZeneca, owns stock in AstraZeneca, travel support by AstraZeneca Ulrike Bodesheim employed by Bayer AG; Javed Butler: Consulting fees: 3ivelabs, Abbott, Amgen, American Regent, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Edwards, Element, Faraday, G3 Pharmaceutical, Imbria, Impulse Dynamics, Innolife, Inventiva, Ionis, Janssen, LivaNova, Lexicon, Medtronic, Merck, Novartis, Novo Nordisk, Otsuka, Occlutech, PharmaCosmos, Roche, Sanofi, Secretome, Sequana, Tricog, Vifor; Speaker Fees: Novartis, Boehringer Ingelheim-Lilly, Astra Zeneca, Impulse Dynamics; Lesley H Curtis: Fees Boehringer Ingleheim, NIH, and Regeneron Pharmaceuticals Mitchell Elkind: Grants: Roche; Lecture Fees: Atria Academy of Science and Medicine; Travel Support: American Heart Association; Adrian F. Hernandez: Consulting fees Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, CSL Behring, Cytokinetics, Eli Lilly, Intellia Therapeutics, Merck, Novartis, Novo Nordisk, Prolaio; Grants/Contracts: American Regent, AstraZeneca, Bayer, Boehringer Ingelheim, Intellia Therapeutics, Merck, Novartis, Novo Nordisk, Verily; Christoph Hornik: None declared; Gary H Lyman: Consulting Fees: Sandoz, Astra Zeneca, Beyond Spring, G1 Therapeutics, Merck, Partners Healthcare, ER Squibb, Samsung, Fresenius Kabi; Pooja Khatri: grants from Cerenovus; serving on the scientific advisory boards of Lumosa; Shionogi, Bayer, and Basking Biosciences; andreceiving online publication royalties from UpToDate; Michael Mbagwu: Stocks in Verana Health as employee Masahiro Murakami: employed by Eli Lilly; Gwen Nichols: None declared; Lothar Roessig: employed by Bayer; Anne Quinn Young: None declared; Richard L. Schilsky Consulting Fees: Cellworks, EQRx, Zephyr AI, Clarified Precision Medicine, Illumina, Member, DSMB, Baseline Study sponsored by Verily Chairman, Scientific Advisory Board, Ontario Institute for Cancer Research Member, Strategic External Advisory Committee for Canadian Cancer Trials Group Chairman, Board of Directors, Reagan-Udall Foundation for the FDA, Member, Board of Directors, Friends of Cancer Research, Member, Board of Directors, Leap Therapeutics; Neha Pagidipati: Research support from Alnylam, Amgen, Boehringer Ingelheim, Eggland's Best, Eli Lilly, Novartis, Novo Nordisk, Verily Life Sciences; Consultation/Advisory Panels for Bayer, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Esperion, AstraZeneca, Merck, Novartis, and Novo Nordisk; Executive Committee member for trials sponsored by Novo Nordisk and by Amgen; DSMB for trials sponsored by J+J and Novartis; Medical advisory board for Miga Health., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: PAD increases the risk of cardiovascular mortality and limb loss, and disparities in treatment and outcomes have been described. However, the association of patient-specific characteristics with variation in outcomes is less well known., Methods: Patients with PAD from Duke University Health System (DUHS) between January 1, 2015 and March 31, 2016 were identified. PAD status was confirmed through ground truth adjudication and predictive modeling using diagnosis codes, procedure codes, and other administrative data. Symptom severity, lower extremity imaging, and ankle-brachial index (ABI) were manually abstracted from the electronic health record (EHR). Data was linked to Centers for Medicare and Medicaid Services data to provide longitudinal follow up. Primary outcome was major adverse vascular events (MAVE), a composite of all-cause mortality, myocardial infarction (MI), stroke, lower extremity revascularization and amputation., Results: Of 1,768 patients with PAD, 31.6% were asymptomatic, 41.2% had intermittent claudication (IC), and 27.3% had chronic limb-threatening ischemia (CLTI). At 1 year, patients with CLTI had higher rates of MAVE compared with asymptomatic or IC patients. CLTI and Medicaid dual eligibility were independent predictors of mortality. CLTI and Black race were associated with amputation., Conclusions: Rates of MAVE were highest in patients with CLTI, but patients with IC or asymptomatic disease also had high rates of adverse events. Black and Medicaid dual-eligible patients were disproportionately present in the CLTI subgroup and were at higher risk of amputation and mortality, respectively. Future studies must focus on early identification of high-risk patient groups to improve outcomes in patients with PAD., (Copyright © 2021. Published by Elsevier Inc.)

Background: Medicare insurance claims may provide an efficient means to ascertain follow-up of older participants in clinical research. We sought to determine the accuracy and completeness of claims- versus site-based follow-up with clinical event committee (+CEC) adjudication of cardiovascular outcomes., Methods: We performed a retrospective study using linked Medicare and Duke Database of Clinical Trials data. Medicare claims were linked to clinical data from 7 randomized cardiovascular clinical trials. Of 52,476 trial participants, linking resulted in 5,839 (of 10,497 linkage-eligible) Medicare-linked trial participants with fee-for-service A and B coverage. Death, myocardial infarction (MI), stroke, and revascularization incidences were compared using Medicare inpatient claims only, site-reported events (+CEC) only, or a combination of the 2. Randomized treatment effects were compared as a function of whether claims-based, site-based (+CEC), or a combined system was used for event detection., Results: Among the 5,839 study participants, the annual event rates were similar between claims- and site-based (+CEC) follow-up: death (overall rate 5.2% vs 5.2%; adjusted κ 0.99), MI (2.2% vs 2.3%; adjusted κ 0.96), stroke (0.7% vs 0.7%; adjusted κ 0.99), and any revascularization (7.4% vs 7.9%; adjusted κ 0.95). Of events detected by claims yet not reported by CEC, a minority were reported by sites but negatively adjudicated by CEC (39% of MIs and 18% of strokes). Differences in individual case concordance led to higher event rates when claims- and site-based (+CEC) systems were combined. Randomized treatment effects were similar among the 3 approaches for each outcome of interest., Conclusions: Claims- versus site-based (+CEC) follow-up identified similar overall cardiovascular event rates despite meaningful differences in the events detected. Randomized treatment effects were similar using the 2 methods, suggesting claims data could be used to support clinical research leveraging routinely collected data. This approach may lead to more effective evidence generation, synthesis, and appraisal of medical products and inform the strategic approaches toward the National Evaluation System for Health Technology., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Emerging data suggest that neck circumference (NC) is associated with cardiometabolic risk factors. Limited research is available regarding the association between NC and cardiovascular outcomes in African Americans., Methods: Using data from the Jackson Heart Study, we included participants with recorded NC measurements at baseline (2000-2004). Baseline characteristics for the included population were summarized by tertiles of NC. We then calculated age- and sex-adjusted cumulative incidence of clinical cardiovascular outcomes and performed Cox proportional-hazards with stepwise models., Results: Overall, 5,290 participants were categorized into tertiles of baseline NC defined as ≤37 cm (n = 2179), 38-40 cm (n = 1552), and >40 cm (n = 1559). After adjusting for age and sex, increasing NC was associated with increased risk of heart failure (HF) hospitalization (cumulative incidence = 13.4% [99% CI, 10.7-16.7] in the largest NC tertile vs 6.5% [99% CI, 4.7-8.8] in the smallest NC tertile), but not mortality, stroke, myocardial infarction, or coronary heart disease (all P ≥ .1). Following full risk adjustment, there was a nominal increase in the risk of HF hospitalization with increasing NC, but this was not statistically significant (hazard ratio per 1-cm increase, 1.04 [99% CI, 0.99-1.10], P = .06)., Conclusions: In this large cohort of African American individuals, a larger NC was associated with increased risk for HF hospitalization following adjustment for age and sex, but this risk was not statistically significant after adjusting for other clinical variables. Although NC is not independently associated with increased risk for cardiovascular events, it may offer prognostic information particularly related to HF hospitalization., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Electronic health records (EHRs) can be a major tool in the quest to decrease costs and timelines of clinical trial research, generate better evidence for clinical decision making, and advance health care. Over the past decade, EHRs have increasingly offered opportunities to speed up, streamline, and enhance clinical research. EHRs offer a wide range of possible uses in clinical trials, including assisting with prestudy feasibility assessment, patient recruitment, and data capture in care delivery. To fully appreciate these opportunities, health care stakeholders must come together to face critical challenges in leveraging EHR data, including data quality/completeness, information security, stakeholder engagement, and increasing the scale of research infrastructure and related governance. Leaders from academia, government, industry, and professional societies representing patient, provider, researcher, industry, and regulator perspectives convened the Leveraging EHR for Clinical Research Now! Think Tank in Washington, DC (February 18-19, 2016), to identify barriers to using EHRs in clinical research and to generate potential solutions. Think tank members identified a broad range of issues surrounding the use of EHRs in research and proposed a variety of solutions. Recognizing the challenges, the participants identified the urgent need to look more deeply at previous efforts to use these data, share lessons learned, and develop a multidisciplinary agenda for best practices for using EHRs in clinical research. We report the proceedings from this think tank meeting in the following paper., (Copyright © 2018 Elsevier, Inc. All rights reserved.)

Background: On May 20, 2016, US professional organizations in cardiology published joint treatment guidelines recommending the use of angiotensin-receptor neprilysin inhibitor (ARNI) for eligible patients with heart failure with reduced ejection fraction (HFrEF). Using data from the Get With The Guidelines-Heart Failure registry, we evaluated the early impact of this update on temporal trends in ARNI prescription., Methods: We analyzed patients with HFrEF who were eligible for ARNI prescription (EF ≤40%, no contraindications) and hospitalized from February 20, 2016, through August 19, 2016-allowing for 13weeks before and after guideline publication. We quantified trends in ARNI use associated with guidelines publication with an interrupted time-series design using logistic regression and accounting for correlations within hospitals using general estimating equation methods., Results: Of 7,200 eligible patient hospitalizations, 51.9% were discharged in the period directly preceding publication of the guidelines, and 48.1% were discharged after. Odds ratios of ARNI prescription at discharge were significantly higher in the postguideline period compared with the preguideline period in adjusted models (adjusted odds ratio 1.29, 95% CI 1.06-1.57, P=.01). However, there was no significant interaction between observed and expected ARNI use after guideline publication (P interaction =.14). Results were consistent using a 6-month before and after time frame., Conclusions: The model suggested a small increase in ARNI use in HF patients being discharged from the hospital immediately after guideline release. However, the publication of national guidelines recommending ARNI use seemed to have little influence on the adoption of this evidence-based medication in the first 3 to 6months., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Non-adherence to medications is common and leads to suboptimal outcomes. Non-adherence can be intentional (e.g., deciding to skip dosages) or unintentional (e.g., forgetting), yet few studies have distinguished these reasons. An improved understanding of the reasons for non-adherence could inform the development of effective interventions., Methods and Results: We analyzed data from African Americans in the Jackson Heart Study who were prescribed medications for one or more chronic conditions. Participants were grouped by patient-reported adherence with non-adherence categorized as being intentional, unintentional or both. We used modified Poisson regression models to examine the factors associated with types of non-adherence. Of 2933 participants taking medication, 2138 (72.9%) reported non-adherence with 754 (35.3%) reporting only unintentional non-adherence, 263 (12.3%) only intentional non-adherence, and 1121 (52.4%) both. Factors independently associated with intentional non-adherence included female sex and depressive symptoms while factors associated with unintentional non-adherence included younger age and separated relationship status. Unintentional and intentional non-adherence was more common among participants taking anti-arrhythmic and anti-asthmatic medications, respectively. Higher levels of global perceived stress was associated with both types of non-adherence. The adjusted models for intentional and unintentional non-adherence had c-statistics of 0.65 and 0.66, respectively, indicating modest discrimination., Conclusion: Specific patient factors and individual medication classes were associated with distinct patterns of intentional and unintentional non-adherence, yet the overall modest discrimination of the models suggests contributions from other unmeasured factors. These findings provide a construct for understanding reasons for non-adherence and provide rationale to assess whether personalized interventions can improve adherence., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Heart failure with preserved ejection fraction may be associated with chronotropic incompetence, but little is known about the incidence and prevalence of permanent pacemaker use in this population or factors associated with its use., Methods: We analyzed patients with heart failure with preserved ejection fraction (ie, left ventricular ejection fraction greater than 40%) from the ADHERE registry (2001-2006) linked with Medicare claims. We described the use of both prevalent and incident permanent pacemakers in heart failure with preserved ejection fraction and determined factors associated with pacemaker use with logistic regression models., Results: Among 13,881 patients with heart failure with preserved ejection fraction, 3136 (22.6%) had a permanent pacemaker, and of these patients, 636 had a permanent pacemaker implanted during hospitalization. Permanent pacemaker use was more common among older patients (81 vs 79 years; P < .001), men (38% vs 34%; P < .001), patients with atrial fibrillation (58% vs 36%; P < .001), and patients with wider QRS duration (140 ms vs 94 ms; P < .001). Rates of digoxin, aldosterone antagonist, and loop diuretic use were slightly higher in patients with a permanent pacemaker compared with patients with no permanent pacemaker. Factors associated with both prevalent and incident pacemaker use included age, fast or slow heart rate, atrial fibrillation, and lower body mass index., Conclusions: Use of permanent pacemakers is relatively common among patients with heart failure with preserved ejection fraction., (Copyright © 2018. Published by Elsevier Inc.)

Background: Studies have shown that access to routine medical care is associated with the prevention, diagnosis, and treatment of chronic diseases. However, studies have not examined whether patient-reported difficulties in access to care are associated with rehospitalization in patients with cardiovascular disease., Methods: Electronic medical records and a standardized survey were used to examine cardiovascular patients admitted to a large medical center from January 1, 2015 through January 10, 2017 (n=520). All-cause readmission within 30 days of discharge was the primary outcome for analysis. Logistic regression models were used to examine the association between access to care and 30-day readmission while adjusting for patient demographics, socioeconomic status, healthcare utilization, and health status., Results: Nearly 1-in-6 patients (15.7%) reported difficulty in accessing routine medical care; and those who were younger, male, non-white, uninsured, with heart failure, and had low social support were significantly more likely to report difficulty. Patients who reported difficulty in accessing care had significantly higher rates of 30-day readmission than patients who did not report difficulty (33.3% vs. 17.9%; P=.001); and the risks remained largely unchanged after accounting for nearly two dozen covariates (unadjusted odds ratio [OR]=2.29; 95% CI, 1.46-3.60 vs. adjusted OR=2.17; 95% CI, 1.29-3.66). Risks for readmission were especially high for patients who reported issues with transportation (OR=3.24; 95% CI, 1.28-8.16) and scheduling appointments (OR=3.56; 95% CI, 1.43-8.84), but not for other reasons (OR=1.47; 95% CI, 0.61-3.54)., Conclusions: Cardiovascular patients who reported difficulty in accessing routine care had substantial risks of readmission within 30 days after discharge. These findings have important implications for identifying high-risk patients and developing interventions to improve access to routine medical care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

MitraClip is an approved therapy for mitral regurgitation (MR); however, health care resource utilization pre- and post-MitraClip remains understudied., Methods: Patients with functional and degenerative MR at high surgical risk in the EVEREST II High-Risk Registry and REALISM Continued-Access Study were linked to Medicare data. Pre- and post-MitraClip all-cause death, stroke, myocardial infarction, heart failure (HF), and bleeding hospitalizations were identified. Inpatient costs, adjusted to 2010 US dollars, were calculated, and event rate ratios and cost ratios were estimated with multivariable modeling., Results: Among 403 linked patients, the mean age was 80 years, 60% were male, mean baseline left ventricular ejection fraction was 49.6%, 83.3% were New York Heart Association class III/IV, 78.2% were MR grade 3+/4+, and 63.3% had functional MR. All-cause hospitalization decreased from 1,854 to 1,435/1,000 person-years (P<.001). HF hospitalization decreased following MitraClip (749 vs 332/1000 person-years, P<.001), but bleeding increased (199 vs 298/1000 person-years, P<.001). Changes in stroke and myocardial infarction were not statistically significant. Overall mean Medicare costs per patient were similar pre- and post-MitraClip, although there was a significant decrease in mean costs among those that survived a full year after MitraClip ($18,131 [SD $25,130] vs $11,679 [SD $22,486], P=.02)., Conclusions: MitraClip was associated with a reduced rate of all-cause and HF hospitalizations and an increased rate of bleeding hospitalizations. One-year Medicare costs were reduced in those who survived a full year after the MitraClip procedure. Payors and providers seeking to reduce HF hospitalizations and associated Medicare costs may consider MitraClip among appropriate patients likely to survive 1 year., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Apparent treatment-resistant hypertension (aTRH) is associated with an increased risk of adverse cardiovascular outcomes. We studied the frequency and intensity of care for aTRH among participants aged 65 years and older in the US-based REGARDS study linked with Medicare claims., Methods: Blood pressure (BP) was measured twice and averaged. aTRH was defined by the use of ≥3 classes of antihypertensive medication and uncontrolled BP (UaTRH, systolic/diastolic BP ≥140/90 mmHg), or ≥4 classes with controlled BP (CaTRH). Participants were categorized as not having aTRH (no aTRH), CaTRH or UaTRH., Results: Among 4650 participants with hypertension, 468 (10.1%) had UaTRH, 247 (5.3%) had CaTRH, and 3935 (84.6%) had hypertension but did not have aTRH. For hypertension-related visits, those with UaTRH saw primary care physicians and cardiologists more frequently than those without aTRH (mean primary care visits per year: 2.77 vs 2.27, P<.001; cardiologists: 0.50 vs 0.35, P=.014). Among those with UaTRH, CaTRH, and no aTRH, respectively 73.5%, 68.0%, and 67.5% had >1 hypertension-related visit per year. Among those with UaTRH, males vs females (prevalence ratio=0.78; 95% CI 0.69-0.89), whites vs blacks (0.88; 95% CI 0.78-0.99), and current smokers vs non-smokers (0.66; 95% CI 0.48-0.89) were less likely to receive >1 hypertension-related visit per year. Diagnostic intensity, measured by testing for end organ damage and secondary hypertension, was similar between groups., Conclusions: Many people with UaTRH are not seen more than once per year for hypertension and may benefit from increased care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Unlabelled: There is no consensus regarding whether to use antithrombotic medications in patients with peripheral artery disease after lower-extremity peripheral vascular intervention., Objectives: The main hypothesis is that significant variation exists regarding use of antithrombotic medications after lower-extremity peripheral vascular intervention. We sought to examine the patterns of postprocedural antithrombotic medication use and associated factors in Medicare patients., Methods: We measured rates of P2Y12 inhibitor use after peripheral vascular intervention in a 100% national sample of Medicare beneficiaries with Part D prescription drug coverage. We used logistic regression modeling to examine associations between patient and clinical factors and P2Y12 inhibitor use., Results: Between 2010 and 2012, a total of 85,830 patients underwent peripheral vascular intervention and had prescription drug claims. Overall, 18.3% of patients were treated with an oral anticoagulant, 19.1% received no P2Y12 inhibitor, 30.8% received a P2Y12 inhibitor before and after the procedure, 6.2% received a P2Y12 inhibitor for up to 30 days after the procedure, and 25.6% received a P2Y12 inhibitor for more than 30 days after the procedure. After adjustment, factors associated with P2Y12 inhibitor use included male sex; black race; history of renal disease, dementia, or heart failure; physician specialty; and clinical setting of the procedure. We observed a strong interaction effect between clinical setting and physician specialty (P < .001)., Conclusions: One-fifth of patients who underwent lower-extremity peripheral vascular intervention did not fill a prescription for a P2Y12 inhibitor. Patients whose operators were surgeons or radiologists had lower odds of P2Y12 inhibitor use. More research to determine the optimal use and duration of antithrombotic medications after the procedure is warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: A subset of patients hospitalized with acute heart failure experiences in-hospital worsening heart failure, defined as persistent or worsening signs or symptoms requiring an escalation of therapy., Methods: We analyzed data from the Acute Decompensated Heart Failure National Registry (ADHERE) linked to Medicare claims to develop and validate a risk model for in-hospital worsening heart failure. Our definition of in-hospital worsening heart failure included events such as escalation of medical therapy (eg, inotropic medications) >12hours after admission. We considered candidate risk prediction variables routinely assessed at admission, including age, medical history, biomarkers, and renal function. We used logistic regression with robust standard errors to generate a risk model in a 66% random derivation sample; we validated the model in the remaining 34%. We evaluated the calibration and discrimination of the model in both samples., Results: We evaluated 23,696 patients hospitalized with acute heart failure. Baseline characteristics were well matched in the derivation and validation samples, and the occurrence of in-hospital worsening heart failure was similar in both samples (15.4% and 15.6%, respectively). In the multivariable model, the strongest predictors of in-hospital worsening heart failure were increased troponin and creatinine. The model was well calibrated and had good discrimination in the derivation sample (c statistic, 0.74) and validation sample (c statistic, 0.72)., Conclusions: The ADHERE worsening heart failure risk model is a clinical tool with good discrimination for use in patients hospitalized with acute heart failure to identify those at increased risk for in-hospital worsening heart failure. This tool may be useful to target treatment strategies for patients at high risk for in-hospital worsening heart failure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Patients hospitalized with acute heart failure may experience worsening symptoms requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and postdischarge outcomes, but associations between the timing of worsening heart failure and outcomes are unknown., Methods: Using data from a large clinical registry linked to Medicare claims, we examined characteristics, outcomes, and costs of patients hospitalized for acute heart failure. We defined in-hospital worsening heart failure by the use of inotropes or intravenous vasodilators or initiation of mechanical circulatory support, hemodialysis, or ventilation. The study groups were early worsening heart failure (n = 1,990), late worsening heart failure (n = 4,223), complicated presentation (n = 15,361), and uncomplicated hospital course (n = 41,334)., Results: Among 62,908 patients, those with late in-hospital worsening heart failure had higher in-hospital and postdischarge mortality than patients with early worsening heart failure or complicated presentation. Those with early or late worsening heart failure had more frequent all-cause and heart failure readmissions at 30 days and 1 year, with resultant higher costs, compared with patients with an uncomplicated hospital course., Conclusion: Although late worsening heart failure was associated with the highest mortality, both early and late worsening heart failures were associated with more frequent readmissions and higher health care costs compared to uncomplicated hospital course. Prevention of worsening heart failure may be an important focus in the care of hospitalized patients with acute heart failure., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Although implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with out-of-hospital cardiac arrest, their effectiveness in survivors of "inhospital" cardiac arrest-a population with different arrest etiologies and higher illness acuity than out-of-hospital cardiac arrest-is unknown. We therefore sought to conduct a comparative effectiveness study of ICD therapy in survivors of inhospital cardiac arrest., Methods: We linked data from a national inpatient cardiac arrest registry with Medicare files and identified 1,200 adults from 267 hospitals between 2000 and 2008 who were discharged after surviving an inhospital cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia and who otherwise met traditional inclusion and exclusion criteria for secondary prevention ICD trials. The association between ICD treatment and long-term mortality was evaluated using an optimal match (≤4 controls for each ICD patient) propensity-score analysis., Results: Of 1,200 survivors, 343 (28.6%) received an ICD during the index hospitalization. Overall, 3-year mortality was 44.2%, with higher unadjusted mortality in the non-ICD versus the ICD group (46.9% vs 37.3%; log-rank; P < .001). After successfully matching 343 patients treated with ICDs with 823 untreated patients by propensity score, ICD treatment was associated with a 24% lower mortality rate (adjusted hazard ratio [HR] 0.76; 95% CI 0.60-0.97; P = .025). This lower mortality was mediated by lower rates of out-of-hospital deaths among ICD-treated patients (22.1% vs 30.8%; adjusted HR 0.71 [0.52-0.96]; P = .019), whereas deaths occurring during a readmission were similar (15.2% vs 16.1%; adjusted HR 0.89 [95% CI 0.60-1.32]; P = .56)., Conclusions: Implantable cardioverter-defibrillator therapy in survivors of inhospital cardiac arrest due to a pulseless ventricular rhythm is used uncommonly but associated with lower long-term mortality. Given that fewer than 3 in 10 eligible survivors are treated with ICDs after surviving an inhospital cardiac arrest, our findings highlight a potentially modifiable process of care, which could improve long-term survival in this high-risk population., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Catheter ablation for atrial fibrillation is used increasingly in older patients, yet the risks and benefits are not completely understood. With such uncertainty, local medical opinion may influence catheter ablation use., Methods: In a 100% sample of Medicare beneficiaries ≥65 years who underwent catheter ablation for atrial fibrillation between January 1, 2007, and December 31, 2009, we investigated variation in use by hospital referral region (HRR) for 20,176 catheter ablation procedures., Results: Across 274 HRRs, median age was 71.2 years (interquartile range 70.5-71.8), a median of 98% of patients were white, and a median of 39% of patients were women. The median age-standardized prevalence of atrial fibrillation was 77.1 (69.4-84.2) per 1,000 beneficiaries; the median rate of catheter ablation was 3.5 (2.4-4.9) per 1,000 beneficiaries. We found no significant associations between the rate of catheter ablation and prevalence of atrial fibrillation (P = .99), end-of-life Medicare expenditures per capita (P = .09), or concentration of cardiologists (P = .45) but a slight association with Medicare expenditures per capita (linear regression estimate 0.016; 95% CI 0.001-0.031; P = .04). Examined HRR characteristics explained only 2% of the variation in HRR-level rates of catheter ablation (model R(2) = 0.016)., Conclusion: The rate of catheter ablation for atrial fibrillation in older patients was low, varied substantially by region, and was not associated with the prevalence of atrial fibrillation, the availability of cardiologists, or end-of-life resource use and was only slightly associated with overall Medicare expenditures per capita., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Transient and persistent worsening renal function (WRF) may be associated with different risks during hospitalization for acute heart failure. We compared outcomes of patients hospitalized for acute heart failure with transient, persistent, or no WRF., Methods: We identified patients 65 years or older hospitalized with acute heart failure from a clinical registry linked to Medicare claims data. We defined WRF as an increase in serum creatinine of ≥ 0.3 mg/dL after admission. We further classified patients with WRF by the difference between admission and last recorded serum creatinine levels into transient WRF (< 0.3 mg/dL) or persistent WRF (≥ 0.3 mg/dL). We examined unadjusted rates and adjusted associations between 90-day outcomes and WRF status., Results: Among 27,309 patients, 18,568 (68.0%) had no WRF, 3,205 (11.7%) had transient WRF, and 5,536 (20.3%) had persistent WRF. Patients with WRF had higher observed rates of 90-day postdischarge all-cause readmission and 90-day postadmission mortality (P < .001). After multivariable adjustment, transient WRF (hazard ratio [HR] 1.19, 99% CI 1.05-1.35) and persistent WRF (HR 1.73, 99% CI 1.57-1.91) were associated with higher risks of 90-day postadmission mortality (P < .001 for both). Compared with transient WRF, persistent WRF was associated with a higher risk of 90-day postadmission mortality (HR 1.46, 99% CI 1.28-1.66, P < .001)., Conclusions: Transient and persistent WRF during hospitalization for acute heart failure were associated with higher adjusted risks for 90-day all-cause postadmission mortality. Patients with persistent WRF had worse outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The relative impact of atrial fibrillation on early outcomes of patients with heart failure with reduced or preserved ejection fraction (EF) is unknown., Methods: We conducted a retrospective cohort study of clinical registry data linked to Medicare claims for patients with heart failure with reduced or preserved EF stratified by presence of atrial fibrillation at admission. Outcomes of interest were all-cause mortality and readmission at 30days. We used Kaplan-Meier methods to estimate mortality and calculated cumulative incidence estimates of readmission. We used Cox proportional hazards models to examine associations between atrial fibrillation and 30-day outcomes., Results: Among 66,357 patients admitted to 283 hospitals between January 2001 and March 2006, 46% had atrial fibrillation (44% of patients with reduced EF and 48% of patients with preserved EF). After adjustment for other patient characteristics, atrial fibrillation was associated with a modestly higher risk of 30-day mortality (HR, 1.08; 95% CI, 1.03-1.14) and readmission (HR, 1.06; 95% CI, 1.02-1.11). In subgroup analyses, atrial fibrillation was associated with a higher risk of 30-day mortality (HR, 1.16; 95% CI, 1.08-1.25) among patients with preserved EF but not among patients with reduced EF. The association of atrial fibrillation with readmission did not differ by heart failure type (P=.37 for the interaction)., Conclusions: Atrial fibrillation was associated with higher 30-day mortality among patients with heart failure with preserved EF but not reduced EF. The association of atrial fibrillation with 30-day readmission was modest and did not differ by heart failure type., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Timing of initial treatment for acute decompensated heart failure (ADHF) varies across hospitals and its impact on outcomes remains poorly defined. We examined the association between time to first intravenous (IV) heart failure (HF) therapy and patient outcomes., Methods: Using the ADHERE-EM linked to Medicare claims data, we identified patients ≥65 years old who were hospitalized for ADHF and received IV HF therapy during index admission. Cox proportional hazard model was used to assess the association of time to treatment with a composite of 30-day all-cause mortality or re-admission. Generalized linear mixed models were used to examine the association of time to treatment with in-hospital all-cause mortality, index hospitalization length of stay, and total days alive and out-of-hospital at 30 days., Results: Of 6,971 patients, the median time to first IV HF therapy was 2.3-hours (interquartile range 1.1, 4.4). The cumulative incidence of 30-day all-cause mortality or readmission was 27.4%. After adjusting for covariates, time to treatment was not associated with increased risk of composite 30-day all-cause mortality or re-admission (HR 1.00; 95% CI 1.00-1.00; P = .221). However, every hour delay in treatment was associated with a modest increased risk of in-hospital mortality (adjusted OR 1.01; 95% CI 1.00-1.02; P = .001) and an approximately 1.4-hour increase in index admission length of stay (P < .001)., Conclusion: Among older patients presenting with ADHF, delay in initiating IV HF therapy was associated with modestly higher risk for in-hospital mortality and longer length of stay, but was not associated with 30-day outcomes., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Hospitals are challenged to reduce length of stay (LOS), yet simultaneously reduce readmissions for patients with heart failure (HF). This study investigates whether 30-day rehospitalization or an alternative measure of total inpatient days over an episode of care (EOC) is the best indicator of resource use, HF quality, and outcomes., Methods: Using data from the American Heart Association's Get With The Guidelines-Heart Failure Registry linked to Medicare claims, we ranked and compared hospitals by LOS, 30-day readmission rate, and overall EOC metric, defined as all hospital days for an HF admission and any subsequent admissions within 30 days. We divided hospitals into quartiles by 30-day EOC and 30-day readmission rates. We compared performance by EOC and readmission rate quartiles with respect to quality of care indicators and 30-day postdischarge mortality., Results: The population had a mean age of 80 ± 7.95 years, 45% were male, and 82% were white. Hospital-level unadjusted median index LOS and overall EOC were 4.9 (4.2-5.6) and 6.2 (5.3-7.4) days, respectively. Median 30-day readmission rate was 23.2%. Hospital HF readmission rate was not associated with initial hospital LOS, only slightly associated with total EOC rank (r = 0.26, P = .001), and inversely related to HF performance measures. After adjustment, there was no association between 30-day readmission and decreased 30-day mortality. In contrast, better performance on the EOC metric was associated with decreased odds of 30-day mortality., Conclusions: Although hospital 30-day readmission rate was poorly correlated with LOS, quality measures, and 30-day mortality, better performance on the EOC metric was associated with better 30-day survival. Total inpatient days during a 30-day EOC may more accurately reflect overall resource use and better serve as a target for quality improvement efforts., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Newly diagnosed atrial fibrillation (AF) during severe sepsis is associated with increased risks of in-hospital stroke and mortality. However, the prevalence, incidence, and risk factors associated with AF during the sepsis syndromes are unclear., Methods: We identified patients with preexisting, newly diagnosed, or no AF in a nationally representative 5% sample of Medicare beneficiaries hospitalized with sepsis between 2004 and 2007. We identified multivariable-adjusted demographic and clinical characteristics associated with development of newly diagnosed AF during a sepsis hospitalization., Results: A total of 60,209 beneficiaries had a sepsis hospitalization. Mean age was 80.2 years, 44.4% were men, and 83.1% were white. Atrial fibrillation occurred during 25.5% (95% CI 25.2-25.9) of sepsis hospitalizations, including 18.3% (18.0%-18.7%) with preexisting AF and 7.2% (7.0%-7.4%) with newly diagnosed AF. Patients with sepsis requiring intensive care had a greater risk of newly diagnosed AF (10.7%, 95% CI 10.3%-11.1%) compared with patients who did not require intensive care (4.4%, 4.2%-4.5%, P < .001). In multivariable analysis, factors associated with newly diagnosed AF during sepsis included older age, white race, acute organ dysfunction, intensive care unit admission, mechanical ventilation, right heart catheterization, diagnosis of endocarditis, and coronary artery bypass graft surgery. Cardiovascular comorbid conditions generally were not associated with increased risk for newly diagnosed AF during sepsis., Conclusions: Atrial fibrillation is common among critically ill patients with sepsis. Acute factors, rather than preexisting cardiovascular comorbid conditions, are associated with increased risk for newly diagnosed AF during sepsis, suggesting that mechanisms of newly diagnosed AF during sepsis may differ from the general population of patients with AF., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Aldosterone antagonist therapy is recommended for selected patients with heart failure and reduced ejection fraction. Adherence to therapy in the transition from hospital to home is not well understood., Methods: We identified patients with heart failure and reduced ejection fraction who were ≥65 years old, eligible for aldosterone antagonist therapy, and discharged home from hospitals in the Get With the Guidelines-Heart Failure registry between January 1, 2005, and December 31, 2008. We used Medicare prescription drug event data to measure adherence. Main outcome measures were prescription at discharge, outpatient prescription claim within 90 days, discontinuation, and adherence as measured with the medication possession ratio. We used the cumulative incidence function to estimate rates of initiation and discontinuation., Results: Among 2,086 eligible patients, 561 (26.9%) were prescribed an aldosterone antagonist at discharge. Within 90 days, 78.6% of eligible patients with a discharge prescription filled a prescription for the therapy, compared with 13.0% of eligible patients without a discharge prescription (P < .001). The median medication possession ratio was 0.63 over 1 year of follow-up. Among 634 patients who filled a prescription within 90 days of discharge, 7.9% discontinued therapy within 1 year., Conclusion: Most eligible patients were not prescribed aldosterone antagonist therapy at discharge from a heart failure hospitalization. Eligible patients without a discharge prescription seldom initiated therapy as outpatients. Most patients who were prescribed an aldosterone antagonist at discharge filled the prescription within 90 days and remained on therapy., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Despite demonstrated efficacy in randomized trials, aldosterone antagonist therapy is not used in many eligible patients with heart failure. Questions remain about its clinical effectiveness and safety for patients who are underrepresented in randomized trials and those at risk for hyperkalemia., Methods: The proposed study will evaluate the effectiveness of aldosterone antagonist therapy in eligible Medicare beneficiaries ≥ 65 years old hospitalized for heart failure between 2005 and 2008. Data are from the GWTG-HF registry linked with Medicare inpatient and prescription drug event files. We will use inverse probability-weighted estimators to assess differences in mortality, cardiovascular readmission, and readmission for hyperkalemia between patients who receive or do not receive aldosterone antagonist therapy., Results: The initial data set included 33,652 patients; 5,463 (16.2%) met all inclusion criteria. Compared with patients who did not meet the inclusion criteria, patients in the final cohort were more likely to be younger (77.3 vs 80.3 years) and male (63.8% vs 41.3%) and to have ischemic heart failure (74.2% vs 59.5%) (all P < .001). Mortality rates were 24.7% at 1 year and 50.7% at 3 years; cardiovascular readmission rates were 50.1% at 1 year and 65.2% at 3 years., Conclusions: The proposed study will evaluate the clinical effectiveness of aldosterone antagonist therapy in Medicare beneficiaries hospitalized for heart failure with reduced ejection fraction, an underrepresented population in clinical trials. By addressing this evidence gap, the study has the potential to inform clinical decision making and improve patient outcomes., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: We examined racial differences in patterns of care and resource use among Medicare beneficiaries with heart failure after enrollment in hospice., Methods: We conducted a retrospective cohort study of a 5% nationally representative sample of Medicare beneficiaries with heart failure who died between 2000 and 2008. Outcomes of interest included adjusted and unadjusted associations of race with hospice enrollment for any diagnosis, disenrollment, and resource use after enrollment., Results: The study population included 219,275 Medicare beneficiaries with heart failure, of whom 31.4% of white patients and 24.3% of nonwhite patients enrolled in hospice in the last 6 months of life (P < .001). Despite increasing rates of hospice use for both white and nonwhite patients, nonwhite patients were 20% less likely to enroll in hospice (adjusted relative risk, 0.80; 95% CI, 0.79-0.82). After enrollment, nonwhite patients were more likely to have an emergency department visit (42.6% vs 33.9%; P<.001), to be hospitalized (46.8% vs 38.5%; P<.001), and to have an intensive care unit stay (16.9% vs 13.3%; P<.001). These differences persisted after adjustment for patient characteristics. Nonwhite patients were also more likely to disenroll from hospice (11.6% vs 7.2%; P<.001). Among patients who remained in hospice until death, nonwhite patients had higher rates of acute care resource use and higher overall costs., Conclusion: Rates of hospice use have increased over time for both white and nonwhite patients. Nonwhite patients were less likely than white patients to enroll in hospice and had higher resource use after electing hospice care, regardless of disenrollment status., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Patients hospitalized with heart failure (HF) have elevated B-type natriuretic peptide (BNP) levels and increased risk for thromboembolic events. Associations between BNP level and thromboembolic events in patients with HF without atrial fibrillation (AF) are not well studied., Methods: We linked data from the ADHERE registry for 2003 through 2006 with Medicare claims to identify patients ≥65 years who were hospitalized with HF, did not have AF, and did not receive warfarin at discharge. We estimated rates of all-cause mortality, thromboembolic events, myocardial infarction (MI), and stroke using Kaplan-Meier methods and the cumulative incidence function. We used Cox models to assess associations between log BNP level and each outcome after adjustment for potential confounders., Results: The study population included 11,679 patients from 146 sites. Patients in the highest quartile of BNP level were older and more often male and African American. They had higher rates of coronary artery disease, renal insufficiency, and peripheral vascular disease and lower rates of diabetes mellitus and chronic obstructive pulmonary disease. After multivariable adjustment, each 30% increase in BNP level was associated with increased risks of death (hazard ratio 1.07, 95% CI 1.05-1.08) and MI (1.07, 1.04-1.10) but not thromboembolism or stroke., Conclusion: Higher BNP level upon admission with HF among older patients without AF was associated with increased risks of MI and mortality; however, higher BNP level was not associated with subsequent thromboembolism or stroke., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Study Objective: Although regionalized care for ST-segment elevation myocardial infarction (STEMI) has improved the use of timely reperfusion therapy, its effect on patient outcomes has been difficult to assess. Our objective is to explore temporal trends in STEMI mortality with the implementation of a statewide STEMI regionalization program (Reperfusion of Acute Myocardial Infarction in North Carolina Emergency Departments [RACE])., Methods: We compared trends in inpatient mortality among STEMI patients treated at North Carolina (NC) hospitals participating in the RACE program, relative to those not participating, using state inpatient claims data. Using Medicare claims data, we compared trends in 30-day mortality among Medicare beneficiaries in NC with those nationally. Logistic models with random effects were used to evaluate the association of the program with mortality., Results: From 2005 to 2007, inpatient mortality for 6,565 STEMI patients treated at NC hospitals participating in RACE decreased from 11.6% to 10.1% (risk difference -1.5%; 95% confidence interval [CI] -3.0% to 0.04%), whereas inpatient mortality among 5,850 STEMI patients treated at NC nonparticipating hospitals decreased from 10.2% to 8.6% (risk difference -1.6%; 95% CI -3.1% to 0.10%); (adjusted odds ratio 1.28; 95% CI 0.88 to 1.85 for temporal differences between groups). During the same period, 30-day STEMI mortality among Medicare beneficiaries decreased from 22.7% to 21.4% in NC (risk difference -1.28%; 95% CI -3.60% to 1.03%) and from 22.3% to 21.6% nationally (risk difference -0.71%, 95% CI -1.13% to -0.29%; adjusted odds ratio 0.99, 95% CI 0.85 to 1.15 for temporal differences between regions)., Conclusion: The initiation of a statewide STEMI collaborative care model was associated with a reduction in mortality rates according to claims data, yet these changes were similar to those seen nationally. Further study is needed to evaluate regionalized systems of STEMI care and to determine the role of claims data to evaluate population-based STEMI outcomes., (Copyright © 2011 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Background: Policy makers have proposed bundling payments for all heart failure (HF) care within 30 days of an HF hospitalization in an effort to reduce costs. Disease management (DM) programs can reduce costly HF readmissions but have not been economically attractive for caregivers under existing fee-for-service payment. Whether a bundled payment approach can address the negative financial impact of DM programs is unknown., Methods: Our study determined the cost-neutral point for the typical DM program and examined whether published HF DM programs can be cost saving under bundled payment programs. We used a decision analytic model using data from retrospective cohort studies, meta-analyses, 5 randomized trials evaluating DM programs, and inpatient claims for all Medicare beneficiaries discharged with an HF diagnosis from 2001 to 2004. We determined the costs of DM programs and inpatient care over 30 and 180 days., Results: With a baseline readmission rate of 22.9%, the average cost for readmissions over 30 days was $2,272 per patient. Under base-case assumptions, a DM program that reduced readmissions by 21% would need to cost $477 per patient to be cost neutral. Among evaluated published DM programs, 2 of the 5 would increase provider costs (+$15 to $283 per patient), whereas 3 programs would be cost saving (-$241 to $347 per patient). If bundled payments were broadened to include care over 180 days, then program saving estimates would increase, ranging from $419 to $1,706 per patient., Conclusions: Proposed bundled payments for HF admissions provide hospitals with a potential financial incentive to implement DM programs that efficiently reduce readmissions., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Clinical registries are used increasingly to analyze quality and outcomes, but the generalizability of findings from registries is unclear., Methods: We linked data from the Acute Decompensated Heart Failure National Registry (ADHERE) to 100% fee-for-service Medicare claims data. We compared patient characteristics and inpatient mortality of linked and unlinked ADHERE hospitalizations; patient characteristics, readmission, and postdischarge mortality of linked ADHERE patients to a random 20% sample of Medicare beneficiaries hospitalized for heart failure; and characteristics of Medicare sites participating and not participating in ADHERE., Results: Among 135,667 ADHERE records for eligible patients ≥ 65 years, we matched 104,808 (77.3%) records to fee-for-service Medicare claims, representing 82,074 patients. Linked hospitalizations were more likely than unlinked hospitalizations to involve women and white patients; there were no meaningful differences in other patient characteristics. In-hospital mortality was identical for linked and unlinked hospitalizations. In Medicare, ADHERE patients had slightly lower unadjusted mortality (4.4% vs 4.9% in-hospital, 11.2% vs 12.2% at 30 days, 36.0% vs 38.3% at 1 year [P < .001]) and all-cause readmission (22.1% vs 23.7% at 30 days, 65.8% vs 67.9% at 1 year [P < .001]). After risk adjustment, modest but statistically significant differences remained. ADHERE hospitals were more likely than non-ADHERE hospitals to be teaching hospitals, have higher volumes of heart failure discharges, and offer advanced cardiac services., Conclusion: Elderly patients in ADHERE are similar to Medicare beneficiaries hospitalized with heart failure. Differences related to selective enrollment in ADHERE hospitals and self-selection of participating hospitals are modest., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Background: Kidney disease is common among patients with heart failure, but relationships between worsening renal function (WRF) and outcomes after hospitalization for heart failure are poorly understood, especially among patients with preserved systolic function. We examined associations between WRF and 30-day readmission, mortality, and costs among Medicare beneficiaries hospitalized with heart failure., Methods: We linked data from a clinical heart failure registry to Medicare inpatient claims for patients >or=65 years old hospitalized with heart failure. We defined WRF as a change in serum creatinine >or=0.3 mg/dL from admission to discharge. Main outcome measures were readmission and mortality at 30 days after hospitalization and total inpatient costs., Results: Among 20,063 patients hospitalized with heart failure, WRF was common (17.8%) and more likely among patients with higher baseline comorbidity and more impaired renal function. In unadjusted analyses, WRF was associated with similar subsequent mean inpatient costs (USD 3,255 vs USD 3,277, P = .2) but higher readmission (21.8% vs 20.6%, P = .01) and mortality (10.0% vs 7.2%, P < .001). The differences persisted after adjustment for baseline patient and hospital characteristics (hazard of readmission 1.10 [95% CI 1.02-1.18], hazard of mortality 1.53 [95% CI 1.34-1.75]). Associations of WRF with readmission and mortality were similar between patients with reduced and preserved systolic function., Conclusions: Worsening renal function during hospitalization for heart failure is an independent predictor of early readmission and mortality in patients with reduced and preserved systolic function., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Background: Relationships between long-term use and level of dual antiplatelet therapy and outcomes after drug-eluting stent implantation are not well established., Methods: This is a retrospective cohort study of 9,256 patients receiving drug-eluting stents between January 2003 and August 2006. We classified patients according to tertiles of clopidogrel use during the 12 months after stent implantation. We used inverse probability weighting to account for differential selection into levels of clopidogrel use and logistic regression to estimate propensity scores for levels of clopidogrel use. We used Cox proportional hazards models to estimate effects of level of clopidogrel use on risk of bleeding events, death, and death or nonfatal myocardial infarction., Results: There were 3,102 patients in the high-use group, 3,069 in the medium-use group, and 3,085 in the low-use group. Compared with the high-use group, risk of death or nonfatal myocardial infarction was greater in the medium-use group (hazard ratio [HR] 1.46, 95% CI 1.09-1.99, P = .01) and the low-use group (HR 1.59, 95% CI 1.18-2.14, P = .002). The risk of bleeding events was lower in the medium-use group (HR 0.84, 95% CI 0.71-0.98, P = .03) and the low-use group (HR 0.77, 95% CI 0.65-0.90, P = .002)., Conclusions: Higher clopidogrel use 12 months after drug-eluting stent implantation was associated with a greater risk of subsequent bleeding events. Lower use was associated with a greater risk of death or nonfatal myocardial infarction.

Background: Previous studies have not confirmed associations between some current performance measures for inpatient heart failure processes of care and postdischarge outcomes. It is unknown if alternative measures are associated with outcomes., Methods: Using data for 20,441 Medicare beneficiaries in OPTIMIZE-HF from March 2003 through December 2004, which we linked to Medicare claims data, we examined associations between hospital-level processes of care and patient outcomes. Performance measures included any beta-blocker for patients with left ventricular systolic dysfunction (LVSD); evidence-based beta-blocker for patients with LVSD; warfarin for patients with atrial fibrillation; aldosterone antagonist for patients with LVSD; implantable cardioverter-defibrillator for patients with ejection fraction < or =35%; and referral to disease management. Outcome measures were unadjusted and adjusted associations of each process measure with 60-day and 1-year mortality and cardiovascular readmission at the hospital level., Results: Adjusted hazard ratios for 1-year mortality with a 10% increase in hospital- level adherence were 0.94 for any beta-blocker (95% CI, 0.90-0.98; P = .004), 0.95 for evidence-based beta-blocker (95% CI, 0.92-0.98; P = .004); 0.97 for warfarin (95% CI, 0.92-1.03; P = .33); 0.94 for aldosterone antagonists (95% CI, 0.91-0.98; P = .006); 0.92 for implantable cardioverter-defibrillator (95% CI, 0.87-0.98; P = .007); and 1.01 for referral to disease management (95% CI, 0.99-1.03; P = .21)., Conclusions: Several evidence-based processes of care are associated with improved outcomes, can discriminate hospital-level quality of care, and could be considered as clinical performance measures.

Background: Inpatient clinical registries generally have limited ability to provide a longitudinal perspective on care beyond the acute episode. We present a method to link hospitalization records from registries with Medicare inpatient claims data, without using direct identifiers, to create a unique data source that pairs rich clinical data with long-term outcome data., Methods and Results: The method takes advantage of the hospital clustering observed in each database by demonstrating that different combinations of indirect identifiers within hospitals yield a large proportion of unique patient records. This high level of uniqueness also allows linking without advance knowledge of the Medicare provider number of each registry hospital. We applied this method to 2 inpatient databases and were able to identify 81% of 39,178 records in a large clinical registry of patients with heart failure and 91% of 6,581 heart failure records from a hospital inpatient database. The quality of the link is high, and reasons for incomplete linkage are explored. Finally, we discuss the unique opportunities afforded by combining claims and clinical data for specific analyses., Conclusions: In the absence of direct identifiers, it is possible to create a high-quality link between inpatient clinical registry data and Medicare claims data. The method will allow researchers to use existing data to create a linked claims-clinical database that capitalizes on the strengths of both types of data sources.

Background: There is interest in measuring and comparing outcomes of percutaneous transluminal coronary angioplasty (PTCA) other than death, but there are no accepted methods for adjusting these outcomes for preprocedure differences in populations. We sought to identify independent predictors of functional outcome after PTCA., Methods and Results: We developed multivariate risk adjustment models for the 6-month postprocedure physical and mental health summary scores of the MOS SF-36. Complete data were available on 1182 patients undergoing PTCA at 12 institutions. The mean physical component score (PCS) of the SF-36 rose from 36.6 before PTCA to 43. 4 at 6 months after PTCA (P <.0001). Independent predictors of follow-up PCS were baseline PCS, a composite index of comorbidities, prior coronary bypass surgery, baseline MOS SF-36 mental component score (MCS), age, and recent thrombolysis. The model had an adjusted R(2) value of 0.357. The mean MCS rose from 48.5 before PTCA to 50.5 at 6 months after PTCA (P <.0001). Independent predictors of postprocedure mental health were baseline MCS, age, and heart failure. The predictive model for MCS had an adjusted R(2) value of 0.235., Conclusions: Preprocedure patient-reported functional status and select clinical variables are significantly associated with physical functioning and mental health 6 months after PTCA. The predictive power of these models, however, is probably insufficient to allow their use for comparisons among institutions or providers.