Publications

This study uses National Health and Nutrition Examination Survey data to evaluate whether patients enrolled in the clinical trials that support the American College of Cardiology/American Heart Association (ACC/AHA) guideline are representative of the US adult population recommended additional pharmacotherapy by the ACC/AHA guideline.

BACKGROUND: Whether passively collected data can substitute for adjudicated outcomes to reproduce the magnitude and direction of treatment effect observed in cardiovascular clinical trials is not well known.

METHODS: We linked adults ≥65 years of age in the HiR (US CoreValve Pivotal High Risk) and SURTAVI trials (Surgical or Transcatheter Aortic Valve Replacement in Intermediate-Risk Patients) to 100% Medicare inpatient claims, January 1, 2011, to December 31, 2016. Primary (eg, death and stroke) and secondary trial end points were compared across treatment arms (eg, transcatheter aortic valve replacement [TAVR] versus surgical aortic valve replacement [SAVR]) using trial-adjudicated outcomes versus outcomes derived from claims at 1 year (HiR) or 2 years (SURTAVI).

RESULTS: Among 600 linked HiR participants (linkage rate, 80.0%), the rate of the trial's primary end point of all-cause mortality occurred in 13.7% of patients receiving TAVR and 16.4% of patients receiving SAVR at 1 year by using both trial data (hazard ratio, 0.84 [95% CI, 0.65-1.09]; P=0.33) and claims data (hazard ratio, 0.86 [95% CI, 0.66-1.11]; P=0.34; interaction P value=0.80). Noninferiority of TAVR relative to SAVR was seen by using both trial- and claims-based outcomes (Pnoninferiority<0.001 for both). Among 1005 linked SURTAVI trial participants (linkage rate, 60.5%), the trial's primary end point was 12.9% for TAVR and 13.1% for SAVR using trial data (hazard ratio, 1.08 [95% CI, 0.79-1.48]; P=0.90), and 11.3% for TAVR and 12.5% for SAVR patients using claims data (hazard ratio, 1.02 [95% CI, 0.73-1.41]; P=0.58; interaction P value=0.89). TAVR was noninferior to SAVR when compared using both trial and claims (Pnoninferiority<0.001 for both). Rates of procedural secondary outcomes (eg, aortic valve reintervention, pacemaker rates) were more closely concordant between trial and claims data than nonprocedural outcomes (eg, stroke, bleeding, cardiogenic shock).

CONCLUSIONS: In the HiR and SURTAVI trials, ascertainment of trial primary end points using claims reproduced both the magnitude and direction of treatment effect in comparison with adjudicated event data, but nonfatal and nonprocedural secondary outcomes were not as well reproduced. Use of claims to substitute for adjudicated outcomes in traditional trial treatment comparisons may be valid and feasible for all-cause mortality and certain procedural outcomes but may be less suitable for other end points.

IMPORTANCE: Individuals with low socioeconomic status (SES) bear a disproportionate share of the coronary heart disease (CHD) burden, and CHD remains the leading cause of mortality in low-income US counties.

OBJECTIVE: To estimate the excess CHD burden among individuals in the United States with low SES and the proportions attributable to traditional risk factors and to other factors associated with low SES.

DESIGN, SETTING, AND PARTICIPANTS: This computer simulation study used the Cardiovascular Disease Policy Model, a model of CHD and stroke incidence, prevalence, and mortality among adults in the United States, to project the excess burden of early CHD. The proportion of this excess burden attributable to traditional CHD risk factors (smoking, high blood pressure, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, type 2 diabetes, and high body mass index) compared with the proportion attributable to other risk factors associated with low SES was estimated. Model inputs were derived from nationally representative US data and cohort studies of incident CHD. All US adults aged 35 to 64 years, stratified by SES, were included in the simulations.

EXPOSURES: Low SES was defined as income below 150% of the federal poverty level or educational level less than a high school diploma.

MAIN OUTCOMES AND MEASURES: Premature (before age 65 years) myocardial infarction (MI) rates and CHD deaths.

RESULTS: Approximately 31.2 million US adults aged 35 to 64 years had low SES, of whom approximately 16 million (51.3%) were women. Compared with individuals with higher SES, both men and women in the low-SES group had double the rate of MIs (men: 34.8 [95% uncertainty interval (UI), 31.0-38.8] vs 17.6 [95% UI, 16.0-18.6]; women: 15.1 [95% UI, 13.4-16.9] vs 6.8 [95% UI, 6.3-7.4]) and CHD deaths (men: 14.3 [95% UI, 13.0-15.7] vs 7.6 [95% UI, 7.3-7.9]; women: 5.6 [95% UI, 5.0-6.2] vs 2.5 [95% UI, 2.3-2.6]) per 10 000 person-years. A higher burden of traditional CHD risk factors in adults with low SES explained 40% of these excess events; the remaining 60% of these events were attributable to other factors associated with low SES. Among a simulated cohort of 1.3 million adults with low SES who were 35 years old in 2015, the model projected that 250 000 individuals (19%) will develop CHD by age 65 years, with 119 000 (48%) of these CHD cases occurring in excess of those expected for individuals with higher SES.

CONCLUSIONS AND RELEVANCE: This study suggested that, for approximately one-quarter of US adults aged 35 to 64 years, low SES was substantially associated with early CHD burden. Although biomedical interventions to modify traditional risk factors may decrease the disease burden, disparities by SES may remain without addressing SES itself.

BACKGROUND: Individuals experiencing homelessness have higher hospitalization and mortality rates compared with the housed. Whether they also experience higher readmission rates, and if readmissions vary by region or cause of hospitalization is unknown.

OBJECTIVE: Evaluate the association of homelessness with readmission rates across multiple US states.

DESIGN: Retrospective analysis of administrative claims PATIENTS: All inpatient hospitalizations in Florida, Massachusetts, and New York from January 2010 to October 2015 MAIN MEASURES: Thirty- and 90-day readmission rates KEY RESULTS: Out of a total of 23,103,125 index hospitalizations, 515,737 were for patients who were identified as homeless at the time of discharge. After adjusting for cause of index hospitalization, state, demographics, and clinical comorbidities, 30-day and 90-day readmission rates were higher for index hospitalizations in the homeless compared with those in the housed group. The difference in 30-day readmission rates between homeless and housed groups was the largest in Florida (30.4% vs. 19.3%; p < 0.001), followed by Massachusetts (23.5% vs. 15.2%; p < 0.001) and New York (15.7% vs. 13.4%; p < 0.001) (combined 17.3% vs. 14.0%; p < 0.001). Among the most common causes of hospitalization, 30-day readmission rates were 4.1 percentage points higher for the homeless group for mental illness, 4.9 percentage points higher for diseases of the circulatory system, and 2.4 percentage points higher for diseases of the digestive system.

CONCLUSIONS: After adjusting for demographic and clinical characteristics, homelessness is associated with significantly higher 30- and 90-day readmission rates, with a significant variation across the three states. Interventions to reduce the burden of readmissions among individuals experiencing homelessness are urgently needed. Differences across states point to the potential of certain public policies to impact health outcomes for individuals experiencing homelessness.

OBJECTIVES: The aim of this study was to evaluate the performance of administrative claims in ascertaining trial clinical events committee-adjudicated outcomes in the U.S. CoreValve studies.

BACKGROUND: Real-world data offer tremendous opportunity to improve outcome ascertainment in clinical trials. However, little is known about the validity of outcomes ascertained using real-world data to capture trial endpoints.

METHODS: Patients enrolled in 3 pivotal trials and 2 pre-market continued-access studies evaluating transcatheter aortic valve replacement were linked to Medicare fee-for-service inpatient claims. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa agreement statistic of claims to detect clinical endpoints and procedural complications in trial patients were calculated.

RESULTS: Claims accurately identified trial-adjudicated deaths (sensitivity, specificity, PPV, and NPV all >99.6%; kappa 1.00). Claims had good performance in identifying trial-adjudicated permanent pacemaker implantation (sensitivity 92.2%, specificity 99.1%, PPV 96.1%, NPV 98.2%, kappa 0.93) and aortic valve reintervention (sensitivity 84.4%, specificity 99.6%, PPV 69.1%, NPV 99.8%, kappa 0.76). Claims had more modest performance in ascertaining trial-adjudicated myocardial infarction (sensitivity 63.6%, specificity 97.2%, PPV 29.9%, NPV 99.3%, kappa 0.39) and acute kidney injury (sensitivity 70.2%, specificity 85.4%, PPV 38.2%, NPV 95.7%, kappa 0.41) and the poorest performance for identifying trial-adjudicated bleeding events (sensitivity 86.4%, specificity 36.8%, PPV 35.0%, NPV 86.3%, kappa 0.16).

CONCLUSIONS: Compared with trial-adjudicated outcomes, claims data performed well in ascertaining death and outcomes with procedural billing codes and more modestly in identifying other outcomes. Claims may be cautiously and selectively used to augment data collection in future cardiovascular device trials.