Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

BACKGROUND: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).

Significant variation in P2Y12 inhibitor use after peripheral vascular intervention in Medicare beneficiaries.

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.

Development and validation of a risk model for in-hospital worsening heart failure from the Acute Decompensated Heart Failure National Registry (ADHERE).

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.

Appropriate baseline laboratory testing following ACEI or ARB initiation by Medicare FFS beneficiaries.

BACKGROUND: Laboratory testing to identify contraindications and adverse drug reactions is important for safety of patients initiating angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Rates and predictors of appropriate testing among Medicare fee-for-service beneficiaries are unknown. PURPOSE: The study's purpose was to examine baseline laboratory testing rates, identify predictors of suboptimal testing, and assess the prevalence of abnormal creatinine and potassium among beneficiaries initiating ACE inhibitors or ARBs. DESIGN AND SUBJECTS: Retrospective cohort of 101 376 fee-for-service beneficiaries from 10 eastern US states in 1 July to 30 November 2011. MAIN MEASURES: Appropriate monitoring for serum creatinine or serum potassium was defined as evidence of an outpatient claim within 180 days before or 14 days after the index prescription fill date. KEY RESULTS: Thirty-eight percent of beneficiaries were men, 78% were White race, 26% had prevalent heart failure, and 89% had prevalent hypertension. Rates of appropriate baseline laboratory testing were 82.7% for potassium, 83.2% for creatinine, and 82.6% for both potassium and creatinine 180 days prior to initiation. In logistic regression, men (odds ratio [OR] = 1.15, 95% confidence interval [CI]: 1.11, 1.19), African-Americans (OR = 1.26, 95%CI: 1.20, 1.32), and beneficiaries with Alzheimer's disease and related disorders (OR = 1.22, 95%CI: 1.15, 1.28) or stroke (OR = 1.34, 95%CI: 1.26, 1.43) were more likely to experience suboptimal testing. At baseline, hyperkalemia was relatively uncommon (5.8%), and elevated creatinine values were rare (1.4%). CONCLUSIONS: Appropriate monitoring could be improved for African-American beneficiaries and beneficiaries with a history of stroke or Alzheimer's disease and related disorders initiating ACE inhibitors or ARBs. Copyright © 2016 John Wiley & Sons, Ltd.

TRENDS IN THE CARE AND OUTCOMES OF MEDICARE BENEFICIARIES WITH TYPE 2 DIABETES, 2002-2011.

OBJECTIVE: To summarize characteristics of Medicare beneficiaries with type 2 diabetes and to describe changing trends in care and outcomes. METHODS: We conducted a retrospective cohort study of a nationally representative 5% sample of fee-for-service Medicare beneficiaries 65 years and older with prevalent type 2 diabetes, between January 1, 2002, and December 31, 2011. The main outcome measures were diabetes-related screening tests, mortality, hospital admissions, dialysis, and lower extremity amputation. RESULTS: The average age of Medicare beneficiaries with diabetes was 76.5 years, 56% were women, and 83% were white. Screening practices in beneficiaries with diabetes improved from 2002 to 2011, with rising rates of foot exams, renal screening, hemoglobin A1c tests, and lipid profile tests. The prevalence of nephropathy and neuropathy increased. Although inpatient admissions declined from 2002 to 2011, diabetes-related emergency department visits increased. Amputation and end-stage renal disease remained static, while 1-year mortality declined over the study period. CONCLUSION: In this medically complex group of patients with high comorbidity, we observed improvements in screening practices and room for further improvement. Although the mortality rate decreased, other outcomes did not improve consistently. Health care resource has changed over time, with decreased hospital admissions and increased emergency department visits. ABBREVIATIONS: CCW = Chronic Conditions Data Warehouse ESRD = end-stage renal disease HbA1c = hemoglobin A1c HEDIS = Healthcare Effectiveness Data and Information Set ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification.

Linkage of Laboratory Results to Medicare Fee-for-Service Claims.

BACKGROUND: Medicare is the single largest purchaser of laboratory testing in the United States, yet test results associated with Medicare laboratory claims have historically not been available. OBJECTIVE: The purpose of this study was to describe both the linkage of laboratory results data to Medicare claims and the completeness of these results data. In a subgroup of beneficiaries initiating angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, we also demonstrate the generalizability of Medicare beneficiaries with laboratory values compared with those without laboratory values. We end with a discussion of the limitations and potential uses of these linked data. METHODS: We obtained information about laboratory orders and results for all Medicare fee-for-service beneficiaries in 10 eastern states who had outpatient laboratory tests conducted by a large national laboratory services vendor in 2011. Using a combination of direct identifiers and patient demographic characteristics, we linked patients in these laboratory data to Medicare beneficiaries, enabling us to associate test results with existing claims. RESULTS: Nearly all patients in the laboratory data were able to be linked to Medicare beneficiaries. There were over 2 million distinct beneficiaries with nearly 125 million specific test results in the laboratory data. For specific tests ordered in an outpatient or office setting in these 10 states, between 5% and 15% of them had linked laboratory data. Medicare beneficiaries initiating angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers who had laboratory results data had similar patient characteristics to those without results data. CONCLUSIONS: This novel linkage of laboratory results data to Medicare claims creates unprecedented opportunities for conducting comparative effectiveness research related to patient safety and quality.

Comparative effectiveness of cardiac resynchronization therapy with an implantable cardioverter-defibrillator versus defibrillator therapy alone: a cohort study.

BACKGROUND: Trials comparing implantable cardioverter-defibrillator (ICD) therapy with cardiac resynchronization therapy with a defibrillator (CRT-D) are limited to selected patients treated at centers with extensive experience. OBJECTIVE: To compare outcomes after CRT-D versus ICD therapy in contemporary practice. DESIGN: Retrospective cohort study using the National Cardiovascular Data Registry's ICD Registry linked with Medicare claims. SETTING: 780 U.S. hospitals implanting both CRT-D and ICD devices. PATIENTS: 7090 propensity-matched patients older than 65 years with reduced left ventricular ejection fraction (<0.35) and prolonged QRS duration on electrocardiography (≥120 ms) having CRT-D or ICD implantation between 1 April 2006 and 31 December 2009. MEASUREMENTS: Risks for death, readmission, and device-related complications over 3 years. RESULTS: Compared with ICD therapy, CRT-D was associated with lower risks for mortality (cumulative incidence, 25.7% vs. 29.8%; adjusted hazard ratio [HR], 0.82 [99% CI, 0.73 to 0.93]), all-cause readmission (cumulative incidence, 68.6% vs. 72.8%; adjusted HR, 0.86 [CI, 0.81 to 0.93]), cardiovascular readmission (cumulative incidence, 45.0% vs. 52.4%; adjusted HR, 0.80 [CI, 0.73 to 0.88]), and heart failure readmission (cumulative incidence, 24.3% vs. 29.4%; adjusted HR, 0.78 [CI, 0.69 to 0.88]). It was also associated with greater risks for device-related infection (cumulative incidence, 1.9% vs. 1.0%; adjusted HR, 1.90 [CI, 1.07 to 3.37]). The lower risks for heart failure readmission associated with CRT-D compared with ICD therapy were most pronounced among patients with left bundle branch block or a QRS duration at least 150 ms and in women. LIMITATIONS: Patients were not randomly assigned to treatment groups, and few patients could be propensity-matched. The findings may not extend to younger patients or those outside of fee-for-service Medicare. CONCLUSION: In older patients with reduced left ventricular ejection fraction and prolonged QRS duration, CRT-D was associated with lower risks for death and readmission than ICD therapy alone. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Adherence and persistence in the use of warfarin after hospital discharge among patients with heart failure and atrial fibrillation.

BACKGROUND: Postdischarge adherence and long-term persistence in the use of warfarin among patients with heart failure and atrial fibrillation without contraindications have not been fully described. METHODS AND RESULTS: We identified patients with heart failure and atrial fibrillation who were ≥ 65 years old, eligible for warfarin, and discharged home from hospitals in the Get With the Guidelines-Heart Failure registry from January 1, 2006, to December 31, 2009. We used linked Medicare prescription drug event data to measure adherence and persistence. The main outcome measures were rates of prescription at discharge, outpatient dispensing, discontinuation, and adherence as measured by the medication possession ratio. We hypothesized that adherence to warfarin would differ according to whether patients received the prescription at discharge. Among 2,691 eligible patients, 1,856 (69.0%) were prescribed warfarin at discharge. Patients prescribed warfarin at discharge had significantly higher prescription fill rates within 90 days (84.5% vs 12.3%; P < .001) and 1 year (91.6% vs 16.8%; P < .001) and significantly higher medication possession ratios (0.78 vs 0.63; P < .001). Among both previous nonusers and existing users, fill rates at 90 days and 1 year and possession ratios were significantly higher among those prescribed warfarin at discharge. CONCLUSIONS: One-third of eligible patients with heart failure and atrial fibrillation were not prescribed warfarin at discharge from a heart failure hospitalization, and few started therapy as outpatients. In contrast, most patients who were prescribed warfarin at discharge filled the prescription within 90 days and remained on therapy at 1 year.

Self-reported health parameters compared with clinician measurements: methods in practice-based research.

CONTEXT: Self-reported health data are used by health insurance companies to assess risk. Most studies show underreporting compared with clinical measurements. OBJECTIVE: To compare self-reported height, weight, blood pressure, waist circumference, and dietary intake with registered dietitian's (RD's) measures of the same parameters. DESIGN: This is a secondary analysis of data collected in a larger study on the benefits of Medical Nutrition Therapy from an RD for overweight and obese patients when provided free of charge through an insurance benefit. SETTING: Participants completed a health risk assessment survey at home, from which the self-reported measures were extracted. The clinical measurements were taken by an RD in the office during a visit for Medical Nutrition Therapy. PARTICIPANTS: Participants were 81.4% female, with a mean body mass index of 35.0. All were insured and had a least 1 visit with an RD. MAIN OUTCOME MEASURE(S): Main outcomes were correlation between self-reported and RD-measured height, weight, body mass index, blood pressure, and waist circumference. Blood pressure was categorized as normal or high and the κ statistic was used to examine category agreement between the 2 measures. Servings of food groups were compared between the 2 measures by examining cumulative percent within 0, 1, or 2 servings of the RD-measured value. RESULTS: The 2 measures of height and weight were highly correlated (0.974 and 0.986, respectively). Blood pressure was more weakly correlated and when categorized had low κ scores, as did servings of food groups. CONCLUSIONS: Height and weight were more closely correlated than in previous studies. In an insured population enrolled in a weight management program, self-reported measures may be accurate for determining program impact. Blood pressure may be better collected categorically than continuously. The necessity of food intake assessment on a risk assessment should be reconsidered.

Early intravenous heart failure therapy and outcomes among older patients hospitalized for acute decompensated heart failure: findings from the Acute Decompensated Heart Failure Registry Emergency Module (ADHERE-EM).

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.

Transitional adherence and persistence in the use of aldosterone antagonist therapy in patients with heart failure.

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.

Costs of newly diagnosed neovascular age-related macular degeneration among medicare beneficiaries, 2004-2008.

PURPOSE: To examine associations between newly diagnosed neovascular age-related macular degeneration and direct medical costs. METHODS: This retrospective observational study matched 23,133 Medicare beneficiaries diagnosed with neovascular age-related macular degeneration between 2004 and 2008 with a control group of 92,532 beneficiaries on the basis of age, sex, and race. The index date for each case-control set corresponded to the first diagnosis for the case. Main outcome measures were total costs per patient and age-related macular degeneration-related costs per case 1 year before and after the index date. RESULTS: Mean cost per case in the year after diagnosis was $12,422, $4,884 higher than the year before diagnosis. Postindex costs were 41% higher for cases than controls after adjustment for preindex costs and comorbid conditions. Age-related macular degeneration-related costs represented 27% of total costs among cases in the postindex period and were 50% higher for patients diagnosed in 2008 than in 2004. This increase was attributable primarily to the introduction of intravitreous injections of vascular endothelial growth factor antagonists. Intravitreous injections averaged $203 for patients diagnosed in 2004 and $2,749 for patients diagnosed in 2008. CONCLUSION: Newly diagnosed neovascular age-related macular degeneration was associated with a substantial increase in total medical costs. Costs increased over time, reflecting growing use of anti-vascular endothelial growth factor therapies.

QRS duration, bundle-branch block morphology, and outcomes among older patients with heart failure receiving cardiac resynchronization therapy.

IMPORTANCE: The benefits of cardiac resynchronization therapy (CRT) in clinical trials were greater among patients with left bundle-branch block (LBBB) or longer QRS duration. OBJECTIVE: To measure associations between QRS duration and morphology and outcomes among patients receiving a CRT defibrillator (CRT-D) in clinical practice. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of Medicare beneficiaries in the National Cardiovascular Data Registry's ICD Registry between 2006 and 2009 who underwent CRT-D implantation. Patients were stratified according to whether they were admitted for CRT-D implantation or for another reason, then categorized as having either LBBB or no LBBB and QRS duration of either 150 ms or greater or 120 to 149 ms. MAIN OUTCOMES AND MEASURES: All-cause mortality; all-cause, cardiovascular, and heart failure readmission; and complications. Patients underwent follow-up for up to 3 years, with follow-up through December 2011. RESULTS: Among 24 169 patients admitted for CRT-D implantation, 1-year and 3-year mortality rates were 9.2% and 25.9%, respectively. All-cause readmission rates were 10.2% at 30 days and 43.3% at 1 year. Both the unadjusted rate and adjusted risk of 3-year mortality were lowest among patients with LBBB and QRS duration of 150 ms or greater (20.9%), compared with LBBB and QRS duration of 120 to 149 ms (26.5%; adjusted hazard ratio [HR], 1.30 [99% CI, 1.18-1.42]), no LBBB and QRS duration of 150 ms or greater (30.7%; HR, 1.34 [99% CI, 1.20-1.49]), and no LBBB and QRS duration of 120 to 149 ms (32.3%; HR, 1.52 [99% CI, 1.38-1.67]). The unadjusted rate and adjusted risk of 1-year all-cause readmission were also lowest among patients with LBBB and QRS duration of 150 ms or greater (38.6%), compared with LBBB and QRS duration of 120 to 149 ms (44.8%; adjusted HR, 1.18 [99% CI, 1.10-1.26]), no LBBB and QRS duration of 150 ms or greater (45.7%; HR, 1.16 [99% CI, 1.08-1.26]), and no LBBB and QRS duration of 120 to 149 ms (49.6%; HR, 1.31 [99% CI, 1.23-1.40]). There were no observed associations with complications. CONCLUSIONS AND RELEVANCE: Among fee-for-service Medicare beneficiaries undergoing CRT-D implantation in clinical practice, LBBB and QRS duration of 150 ms or greater, compared with LBBB and QRS duration less than 150 ms or no LBBB regardless of QRS duration, was associated with lower risk of all-cause mortality and of all-cause, cardiovascular, and heart failure readmissions.

The incremental value of medical nutrition therapy in weight management.

OBJECTIVE: To evaluate the incremental cost of and health benefits attributable to medical nutrition therapy (MNT) for managed care members participating in an obesity-related health management program. DESIGN: Retrospective case-control. METHODOLOGY: Overweight or obese adult managed care members who utilized the MNT benefit (n = 291) were matched, using propensity score matching, with similar individuals (n = 1,104) who did not utilize the MNT benefit. Health outcomes data on weight, body mass index (BMI), waist circumference, and physical exercise were collected via surveys administered at baseline and approximately 2 years later. PRINCIPAL FINDINGS: Both groups experienced statistically significant reductions in weight, BMI, and waist circumference and increases in exercise frequency. Compared with matched controls, individuals who received MNT were about twice as likely to achieve a clinically significant reduction in weight, with an adjusted odds ratio of 2.2 (95% confidence interval, -1.7-2.9; P < .001). They also experienced greater average reductions in weight (3.1 vs. 1.4 kg; beta = -1.75; t[1314] = -2.21; P = .028) and were more likely to exercise more frequently after participating in the program (F[1,1358] = 4.07, P = .044). There was no difference between the groups in waist circumference. The MNT benefit was used by 5% of eligible members and cost $0.03 per member per month. CONCLUSION: MNT is a valuable adjunct to health management programs that can be implemented for a relatively low cost. MNT warrants serious consideration as a standard inclusion in health benefit plans.

Optimizing data integration in trials that use EHR data: lessons learned from a multi-center randomized clinical trial.

BACKGROUND: Despite great promise, trials that ascertain patient clinical data from electronic health records (EHR), referred to here as "EHR-sourced" trials, are limited by uncertainty about how existing trial sites and infrastructure can be best used to operationalize study goals. Evidence is needed to support the practical use of EHRs in contemporary clinical trial settings. MAIN TEXT: We describe a demonstration project that used EHR data to complement data collected for a contemporary multi-center pharmaceutical industry outcomes trial, and how a central coordinating center supported participating sites through the technical, governance, and operational aspects of this type of activity. We discuss operational considerations related to site selection, data extraction, site performance, and data transfer and quality review, and we outline challenges and lessons learned. We surveyed potential sites and used their responses to assess feasibility, determine the potential capabilities of sites and choose an appropriate data extraction strategy. We designed a flexible, multimodal approach for data extraction, enabling each site to either leverage an existing data source, create a new research datamart, or send all data to the central coordinating center to produce the requisite data elements. We evaluated site performance, as reflected by the speed of contracting and IRB approval, total patients enrolled, enrollment yield, data quality, and compared performance by data collection strategy. CONCLUSION: While broadening the type of sites able to participate in EHR-sourced trials may lead to greater generalizability and improved enrollment, sites with fewer technical resources may require additional support to participate. Central coordinating center support is essential to facilitate the execution of operational processes. Future work should focus on sharing lessons learned and creating reusable tools to facilitate participation of heterogeneous trial sites.

Design and rationale of a retrospective clinical effectiveness study of aldosterone antagonist therapy in patients with heart failure.

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.

Associations between aldosterone antagonist therapy and risks of mortality and readmission among patients with heart failure and reduced ejection fraction.

CONTEXT: Aldosterone antagonist therapy for heart failure and reduced ejection fraction has been highly efficacious in randomized trials. However, questions remain regarding the effectiveness and safety of the therapy in clinical practice. OBJECTIVE: To examine the clinical effectiveness of newly initiated aldosterone antagonist therapy among older patients hospitalized with heart failure and reduced ejection fraction. DESIGN, SETTING, AND PARTICIPANTS: Using clinical registry data linked to Medicare claims from 2005 through 2010, we examined outcomes of eligible patients hospitalized with heart failure and reduced ejection fraction. We used Cox proportional hazards models and inverse-weighted estimates of the probability of treatment to adjust for treatment selection bias. MAIN OUTCOME MEASURES: All-cause mortality, cardiovascular readmission, and heart failure readmission at 3 years, and hyperkalemia readmission at 30 days and 1 year. RESULTS: Among 5887 patients who met the inclusion criteria, the mean age was 77.6 years; of those 1070 (18.2%) started aldosterone antagonist therapy at discharge. Cumulative incidence rates among treated and untreated patients were 49.9% vs 51.2% (P = .62) for mortality; 63.8% vs 63.9% (P = .65) for cardiovascular readmission; and 38.7% vs 44.9% (P < .001) for heart failure readmission at 3 years; and 2.9% vs 1.2% (P < .001) for hyperkalemia readmission within 30 days and 8.9% vs 6.3% (P = .002) within 1 year. After inverse weighting for the probability of treatment, there were no significant differences in mortality (hazard ratio [HR], 1.04; 95% CI, 0.96-1.14; P = .32) and cardiovascular readmission (HR, 1.00; 95% CI, 0.91-1.09; P = .94). Heart failure readmission was lower among treated patients at 3 years (HR, 0.87; 95% CI, 0.77-0.98; P = .02). Readmission associated with hyperkalemia was higher with aldosterone antagonist therapy at 30 days (HR, 2.54; 95% CI, 1.51-4.29; P < .001) and 1 year (HR, 1.50; 95% CI, 1.23-1.84; P < .001). CONCLUSIONS: Initiation of aldosterone antagonist therapy at hospital discharge was not independently associated with improved mortality or cardiovascular readmission but was associated with improved heart failure readmission among eligible older patients with heart failure and reduced ejection fraction. There was a significant increase in the risk of readmission with hyperkalemia, predominantly within 30 days after discharge.

Medicare utilization, screening, and costs among participants in the Southeastern Diabetes Initiative: A population-based evaluation.

AIMS: Type 2 diabetes mellitus imposes significant burdens on patients and health care systems. Population-level interventions are being implemented to reach large numbers of patients at risk of or diagnosed with diabetes. We describe a population-based evaluation of the Southeastern Diabetes Initiative (SEDI) from the perspective of a payer, the Centers for Medicare & Medicaid Services (CMS). The purpose of this paper is to describe the population-based evaluation approach of the SEDI intervention from a Medicare utilization and cost perspective. METHODS: We measured associations between the SEDI intervention and receipt of diabetes screening (i.e., HbA1c test, eye exam, lipid profile), health care resource use, and costs among intervention enrollees, compared with a control cohort of Medicare beneficiaries in geographically adjacent counties. RESULTS: The intervention cohort had slightly lower 1-year screening in 2 of 3 domains (4% for HbA1c; 9% for lipid profiles) in the post-intervention period, compared with the control cohort. The SEDI intervention cohort did not have different Medicare utilization or total Medicare costs in the post-intervention period from surrounding control counties. CONCLUSIONS: Our analytic approach may be useful to others evaluating CMS demonstration projects in which population-level health is targeted for improvement in a well-defined clinical population.

The Effect of Clinical Care Location on Clinical Outcomes After Peripheral Vascular Intervention in Medicare Beneficiaries.

OBJECTIVES: Modifications in reimbursement rates by Medicare in 2008 have led to peripheral vascular interventions (PVI) being performed more commonly in outpatient and office-based clinics. The objective of this study was to determine the effects of this shift in clinical care setting on clinical outcomes after PVI. BACKGROUND: Modifications in reimbursement have led to peripheral vascular intervention (PVI) being more commonly performed in outpatient hospital settings and office-based clinics. METHODS: Using a 100% national sample of Medicare beneficiaries from 2010 to 2012, we examined 30-day and 1-year rates of all-cause mortality, major lower extremity amputation, repeat revascularization, and all-cause hospitalization by clinical care location of index PVI. RESULTS: A total of 218,858 Medicare beneficiaries underwent an index PVI between 2010 and 2012. Index PVIs performed in inpatient settings were associated with higher 1-year rates of all-cause mortality (23.6% vs. 10.4% and 11.7%; p < 0.001), major lower extremity amputation (10.1% vs. 3.7% and 3.5%; p < 0.001), and all-cause repeat hospitalization (63.3% vs. 48.5% and 48.0%; p < 0.001), but lower rates of repeat revascularization (25.1% vs. 26.9% vs. 38.6%; p < 0.001) when compared with outpatient hospital settings and office-based clinics, respectively. After adjustment for potential confounders, patients treated in office-based clinics remained more likely than patients in inpatient hospital settings to require repeat revascularization within 1 year across all specialties. There was also a statistically significant interaction effect between location of index revascularization and geographic region on the occurrence of all-cause hospitalization, repeat revascularization, and lower extremity amputation. CONCLUSIONS: Index PVI performed in office-based settings was associated with a higher hazard of repeat revascularization when compared with other settings. Differences in clinical outcomes across treatment settings and geographic regions suggest that inconsistent application of PVI may exist and highlights the need for studies to determine optimal delivery of PVI in clinical practice.

Significant Morbidity and Mortality Among Hospitalized End-Stage Liver Disease Patients in Medicare.

CONTEXT: For end-stage liver disease (ESLD) patients, care focuses on managing the life-threatening complications of portal hypertension, causing high resource utilization. OBJECTIVES: To describe the end-of-life trajectory of hospitalized ESLD patients in Medicare. METHODS: Using a 5% random sample of Medicare fee-for-service beneficiaries, we performed a retrospective cohort study, identifying hospitalized ESLD and heart failure (HF) patients (2007-2011). Index hospitalization end points included mortality, discharge to hospice, and length of stay. Postdischarge end points included all-cause mortality, rehospitalization, hospice enrollment, and days alive and out of hospital (DAOH). Follow-up was at one and three years after index hospitalization discharge. A reference cohort of decompensated HF patients was used for baseline comparison. RESULTS: At one year, the ESLD cohort (n = 22,311) had 209 DAOH; decompensated HF (n = 85,397) had 252 DAOH. Among ESLD patients, inpatient mortality was 13.5%; all-cause mortality was 64.9%. For these outcomes, rates were higher in those with ESLD than HF. In the ESLD group, rehospitalization rate was 59.1% (slightly lower than the HF group), hospice enrollment rate was 36.1%, and there were higher than expected cancer rates. For hospice-enrolled patients, the median length of time spent in hospice was nine days. The HF cohort had lower hospice enrollment, but more days enrolled. CONCLUSION: The results of this study show that morbidity and mortality rates associated with end of life in ESLD are substantial. There is an acute need for alternative approaches to manage the care of ESLD patients.