Shah, Nilay D.

OBJECTIVE To examine whether glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) are preferentially initiated among patients with cardiovascular disease, heart failure (HF), or nephropathy, where these drug classes have established benefit, compared with dipeptidyl peptidase 4 inhibitors (DPP-4i), for which corresponding benefits have not been demonstrated. RESEARCH DESIGN AND METHODS We retrospectively analyzed claims of adults with type 2 diabetes included in OptumLabs Data Warehouse, a deidentified database of commercially insured and Medicare Advantage beneficiaries, who first started GLP-1RA, SGLT2i, or DPP-4i therapy between 2016 and 2019. Using multinomial logistic regression, we examined the relative risk ratios (RRR) of starting GLP-1RA and SGLT2i compared with DPP-4i for those with a history of myocardial infarction (MI), cerebrovascular disease, HF, and nephropathy after adjusting for demographic and other clinical factors. RESULTS We identified 75,395 patients who started GLP-1RA, 58,234 who started SGLT2i, and 91,884 who started DPP-4i. Patients with prior MI, cerebrovascular disease, or nephropathy were less likely to start GLP-1RA rather than DPP-4i compared with patients without these conditions (RRR 0.83 [95% CI 0.78–0.88] for MI, RRR 0.77 [0.74–0.81] for cerebrovascular disease, and RRR 0.87 [0.84–0.91] for nephropathy). Patients with HF or nephropathy were less likely to start SGLT2i (RRR 0.83 [0.80–0.87] for HF and RRR 0.57 [0.55–0.60] for nephropathy). Both medication classes were less likely to be started by non-White and older patients. CONCLUSIONS Patients with cardiovascular disease, HF, and nephropathy, for whom evidence suggests a greater likelihood of benefiting from GLP-1RA and/or SGLT2i therapy, were less likely to start these drugs. Addressing this treatment/benefit paradox, which was most pronounced in non-White and older patients, may help reduce the morbidity associated with these conditions.

Background/Aims: The Pediatric Research Equity Act and Best Pharmaceuticals for Children Act are intended to promote the conduct of clinical trials that generate pediatric-specific evidence about drug safety and efficacy. This study assesses the quality of evidence generated through Pediatric Research Equity Act–mandated and Best Pharmaceuticals for Children Act–incentivized clinical trials of hematology/oncology drugs and characterizes subsequent changes in pediatric drug utilization rates. Methods: Trial characteristics (blinding, randomization, and comparator group) were determined for clinical trials that supported pediatric label changes. Using data from OptumLabs ® Data Warehouse, a de-identified administrative claims database, we calculated pediatric utilization rates for each drug. We calculated monthly utilization rates from January 2003 (or from the first month in which data were available) to December 2018. Results: We identified 11 hematology/oncology drugs that underwent pediatric label changes under the Pediatric Research Equity Act Pediatric Research Equity Act and/or Best Pharmaceuticals for Children Act, and we identified 15 trials supporting these changes. Of these trials, 36% (5/14) were randomized, 31% (4/13) were blinded, and 36% (5/14) used a comparator group. A median of 49 children (interquartile range 29.5) received the drug under investigation across these trials. Pediatric label changes were not associated with subsequent changes in pediatric drug utilization. Although some drugs saw increased pediatric use after gaining new pediatric indications, this pattern was not consistently observed. In addition, there was no evidence to suggest that drugs were utilized less frequently after they failed to receive pediatric indications. Conclusions: Clinical trials of hematology/oncology drugs conducted under the Pediatric Research Equity Act Pediatric Research Equity Act and Best Pharmaceuticals for Children Act generally have low methodological rigor, and the resulting label changes are not consistently associated with changes in pediatric utilization. Alternative regulatory strategies and study designs may be necessary to maximize the impact of newly generated knowledge on drug utilization.

INTRODUCTION: Obesity has been associated with adverse disease-related outcomes and inferior treatment response to biologic agents in patients with inflammatory bowel diseases (IBDs), but its impact on the risk of treatment-related complications is unknown. We performed a cohort study examining the association between obesity and risk of serious infections in biologic-treated patients with IBD. METHODS: Using an administrative claims database, in a cohort of biologic-treated patients with IBD between 2014 and 2018 with follow-up 1 year before and after treatment initiation, we compared the risk of serious infections (infections requiring hospitalization) between obese vs nonobese patients (based on validated administrative claims) using Cox proportional hazard analysis. RESULTS: We included 5,987 biologic-treated patients with IBD (4,881 on tumor necrosis factor-α antagonists and 1,106 on vedolizumab), of whom 524 (8.8%) were classified as obese. Of the 7,115 person-year follow-up, 520 patients developed serious infection. Risk of serious infection was comparable in obese vs nonobese patients (8.8% vs 8.5%; unadjusted hazard ratio, 1.15; 95% confidence interval, 0.86–1.54). After adjusting for age, comorbidities, disease characteristics, health care utilization, use of corticosteroids, immunomodulators, and opiates, obesity was not associated with an increased risk of serious infection (adjusted hazard ratio, 0.74 [95% confidence interval, 0.55–1.01]). Similar results were seen on stratified analysis by disease phenotype (Crohn's disease and ulcerative colitis) and index biologic therapy (tumor necrosis factor-α antagonists and vedolizumab). DISCUSSION: After adjusting for comorbid conditions and disease characteristics, obesity is not independently associated with an increased risk of serious infections in biologic-treated patients with IBD.

Objective: To characterize changes in rates of hospitalization for digoxin toxicity and trends in the associated mortality and readmission among older adults over a 12-year period in the United States. Methods: We studied 33,952,331 Medicare fee-for-service beneficiaries 65 years or older with a hospital discharge diagnosis of digoxin toxicity in the United States from 1999 to 2011. Outcome measures were rates of hospitalization for digoxin toxicity; in-hospital mortality; 30-day mortality; and 30-day readmission. Results: There were 20,957 hospitalizations for a principal or secondary diagnosis of digoxin toxicity between 1999 and 2011. The rate declined significantly from 15.2 per 100,000 person-years (95% confidence interval [CI]: 14.7-15.7) in 1999 to 2.1 per 100,000 person-years (95% CI: 1.9-2.3) in 2011 (p<0.001), representing an adjusted annual decline of 17.0% (95% CI: 16.2-17.0) (Figure 1). Between 1999 and 2011, the observed in-hospital and 30-day mortality rates associated with hospitalization for digoxin toxicity declined significantly, from 6.0% (95% CI: 5.2-6.8) to 3.3% (95% CI: 2.0-5.1) (p<0.01) and 14.0% (95% CI: 13.0-15.2) to 10.6% (95% CI: 8.2-13.4) (p<0.05), respectively, representing an annual decline for in-hospital mortality of 5.0% (95% CI: 3.7-7.2) and for 30-day mortality of 4.0% (95% CI: 3.1-5.7). The overall observed 30-day readmission rate declined significantly from 23.5% (95% CI: 22.1-24.9) in 1999 to 18.9% (95% CI: 15.6-22.3) in 2011 (p<0.05), but there was no significant decline in the adjusted annual change in 30-day readmission (1.0%, 95% CI: 0.0-1.7). Conclusions: In a national sample of Medicare beneficiaries, the rate of hospitalization for digoxin toxicity and subsequent mortality declined significantly between 1999 and 2011.

Background: The increasing prevalence of heart failure (HF) and high associated costs has spurred investigation of factors related to adverse outcomes in these patients. Reports to date present discrepant evidence regarding the link between depression and HF outcomes, and only scarce data related to healthcare utilization in the form of emergency department (ED) visits are available. Purpose: To evaluate the relationship of depression with healthcare utilization and death among HF patients in the community. Methods: Residents of Olmsted, Dodge, and Fillmore, MN counties with HF were prospectively recruited between October 2007 and December 2010, and completed a 9-item Patient Health Questionnaire (PHQ-9) for depression categorized as: none-minimal (PHQ-9 score 0-4), mild (5-9), or moderate-severe (≥10). Anderson-Gill models were used to determine if depression predicted hospitalizations and ED visits while proportional hazards regression estimated hazard ratios for death. Results: Among 411 HF patients (mean age 73±13, 58% male), 15% had moderate-severe depression, 27% mild, and 58% none-minimal. Over a mean follow-up of 1.5 years, 613 hospitalizations, 786 ED visits, and 75 deaths occurred. The risk of all adverse outcomes increased stepwise with increasing severity of depression (Table). After adjustment for key clinical characteristics, moderate-severe depression was associated with nearly a 2-fold increased risk of hospitalization and ED visits, and almost a 4-fold increased risk of death. These results are independent of coexisting comorbidities. Conclusions: Depression is frequent among HF patients in the community and independently predicts a significant increase in the use of healthcare resources and mortality. Greater attention to the recognition and management of depression in HF may improve clinical outcomes and decrease healthcare utilization and expenditures in these patients. Hazard Ratios (95%CI) for Hospitalizations and All-Cause Mortality by Severity of Depression None-Minimal Mild Moderate-Severe P for trend Hospitalizations Crude 1.00 (ref) 1.23 (0.91-1.66) 2.01 (1.39-2.89) <0.001 Fully-Adjusted * 1.00 (ref) 1.15 (0.86-1.54) 1.93 (1.37-2.71) 0.001 Emergency Department Visits Crude 1.00 (ref) 1.42 (1.03-1.96) 1.99 (1.42-2.79) <0.001 Fully-Adjusted * 1.00 (ref) 1.39 (1.00-1.93) 1.98 (1.40-2.79) <0.001 All-Cause Mortality Crude 1.00 (ref) 1.53 (0.87-2.68) 3.33 (1.95-5.70) <0.001 Fully-Adjusted * 1.00 (ref) 1.55 (0.88-2.74) 3.84 (2.21-6.68) <0.001 * Adjusted for age, sex, and Charlson comorbidity index

Objectives: Patient involvement in the choice of whether to undergo emergency department observation unit (EDOU) admission and cardiac stress testing or follow-up with a physician could increase knowledge, increase satisfaction, and safely decrease resource use. We test this hypothesis in a randomized trial. Methods: We developed and tested Chest Pain Choice, a decision aid that communicates the pre-test probability of an acute coronary syndrome (ACS) within 45 days and makes management options (EDOU admission and stress testing or 24-72 hr follow-up with a physician) explicit to the patient. Patients with a primary complaint of chest pain and no known coronary artery disease who were being considered for EDOU admission were eligible. Patient-clinician pairs were randomized to intervention (decision aid plus risk estimate) or usual care (no decision aid, no risk estimate). We used patient surveys and 30-day phone follow-up to assess the primary outcome (patient knowledge regarding their short-term risk for ACS), patient satisfaction, safety (delayed or missed ACS defined as acute myocardial infarction, ventricular arrhythmia, cardiogenic shock, or cardiac/unknown death), and resource use. Analysis was by intention to treat. Results: The 205 patients had the following characteristics: mean age (SD) 54.7 (11.8), 59% female, 36% history of HTN and 10% history of diabetes. Compared with usual care patients (n=104), patients receiving the decision aid (n=101) less frequently decided to be admitted to the EDOU for cardiac stress testing (58% vs 77%, absolute difference = 19%, 95% CI 6, 31), had a lower rate of stress testing (74% vs 90%, absolute difference = 16%, 95% CI 6, 26), greater knowledge of their exact pre-test probability of ACS (25% vs 1%, absolute difference = 24%, 95% CI 15, 33) and reported greater satisfaction with the decision-making process (strongly agree: 61% vs 40%, absolute difference = 21%, 95% CI 7, 33). There were no cases of delayed or missed ACS in either arm. Conclusion: Use of a decision aid in ED chest pain patients increased knowledge, increased satisfaction, and safely decreased resource use. In an era of health care reform, shared decision-making is a promising approach that may both increase patient engagement and decrease resource use.Funding(This research has received full or partial funding support from the American Heart Association, National Center)

Diabetes mellitus is considered to be a coronary heart disease (CHD) equivalent, with heart disease and stroke accounting for the majority of diabetes-related deaths. As a result, patients with diabetes require aggressive treatment of CHD risk factors, including dyslipidemia. In addition to targeted reduction of LDL cholesterol, current guidelines recommend addition of a fibrate (gemfibrozil, fenofibrate, or clofibrate) in patients with established CHD and atherogenic dyslipidemia: triglycerides (TG) 200-499 mg/dL and HDL cholesterol (HDL-C) ≤40 mg/dL. Fibrates have also been recommended for patients with TG ≥500 mg/dL to reduce risk of acute pancreatitis. Yet, data supporting the use of fibrates in these settings remains variable and inconclusive. We therefore sought to provide an in-depth analysis of patterns of fibrate use among patients with type 2 diabetes between 2001 and 2010. Using Ingenix administrative claims, we identified 71,161 patients age ≥18 years old with an established diagnosis of type 2 diabetes (ICD-9 250.XX) and ≥3 years of continuous enrollment who were newly initiated on a fibrate between 2001 and 2010. Lab results were available for a subset of 18,863 (26.5%) patients, who were included in final analysis. During each 2-year period, between 77.6% - 84.1% of patients had a lipid test performed within the preceding 12 months (p=0.59 for change in testing over time). The prevalence of atherogenic dyslipidemia increased over time, from 20.8% (2001-2002) to 41.2% (2009-2010); 4.84% rise per 2-year period (p=0.002). The prevalence of severe atherogenic dyslipidemia (HDL-C ≤40 mg/dL and TG ≥500 mg/dL), also increased over time, from 9.3% in 2001-2002 to 13.6% in 2009-2010; 1.17% rise per 2-year period (p=0.002). In contrast, percent of patients with TG ≥500 mg/dL decreased over time, from 20.5% in 2001-2002 to 16.7% in 2009-2010; 1.19% decline per 2-year period (p=0.03). Initiation of new fibrate therapy in treatment naïve patients with diabetes remained constant; 2.0% in 2001-2002 and 1.6% in 2009-2010 (p=0.93). Subgroup analysis of patients with atherogenic dyslipidemia also showed no significant change in fibrate initiation over time; 11.4% in 2001-2002 and 15.7% in 2009-2010 (p=0.3). Similarly, while there was a trend toward increased initiation of fibrates among patients with TG ≥500 mg/dL, this trend was not statistically significant (27.4% in 2001-2002 and 41.6% in 2009-2010; 3.34% change per 2-year period (p=0.09)). In conclusion, the prevalence of atherogenic dyslipidemia among patients with type 2 diabetes has increased significantly over the past decade. However, fibrate use in all patients with type 2 diabetes, including those specifically with atherogenic dyslipidemia, has remained constant throughout the observation period, despite lack of conclusive evidence supporting its use.

Objective: To understand the organization of cardiologists in the United States and territories with an emphasis on identifying the characteristics of practices where cardiologists practice. Data: The Healthcare Organization Services database, which provides information on the designation, specialties and business associations, or affiliations, of healthcare professionals across the US and territories. These data were updated as of September 2013. Methods: Cardiologists were defined as providers with an MD or DO, who have an active clinical practice, and either: (1) have Cardiology as primary specialty, or (2) who have Internal Medicine, Pediatrics or Family Medicine indicated as primary specialty, with Cardiology as secondary specialty. Cardiologists were linked to businesses and descriptive analyses were conducted to characterize the organization of cardiologists. Findings: We identified 33,745 cardiologists; 22,461 of these cardiologists had at least one affiliation with an ambulatory practice or independent physician association (AP/IPA), while 30,567 had at least one hospital affiliation. Approximately 57.6% (19,453 of 33,745) of cardiologists were affiliated with both the AP/IPA and hospital settings. The overwhelming majority of ambulatory practices linked to hospital-AP/IPA affiliated cardiologists are medical groups (7,839 of 9,838), while independent physician practices comprise the next largest category (1,498 of 9,838). Of the 7,839 medical groups, 3,809 are cardiology specialty, 1,316 are multispecialty group practices, and 2,060 are family practice, general practice, geriatric medicine, internal medicine, pediatric medicine or primary care. Among all non-multispecialty medical groups (n=6,523), 59.2% (3,862 of 6,523) have 1-2 affiliated cardiologists, 21.7% (1,413 of 6,523) have 3-5, 12.6% (821 of 6,523) have 6-10 and 6.5% (427 of 6,523) have more than 10 affiliated cardiologists. Focusing at the provider level, 17,639 hospital-AP/IPA cardiologists had any affiliation with a medical group (MG), with 12,840 cardiologists with any cardiology specialty MG affiliation, 3,215 with any multispecialty group practice MG affiliation, and 3,051 with any family practice, general practice, geriatric medicine, internal medicine, pediatric medicine or primary care MG affiliation. Overall, 15,476 hospital-AP/IPA cardiologists had any affiliation with at least one non-multi-specialty group practice (non-MSGP), with 4,279 affiliated with one or more non-MSGP(s) with 1-2 cardiologists, 4,378 with one or more non-MSGP(s) with 3-5 cardiologists, and 4,861 and 5,099 affiliated with one or more non-MSGP(s) with 6-10 and >10 cardiologists, respectively. Conclusion: The majority of cardiologists were affiliated with both a hospital and ambulatory practice or IPA. Of this subset, most cardiologists were affiliated with at least one group practice.