Clinical characteristics and management of patients with nonalcoholic steatohepatitis in a real-world setting: analysis of the Ipsos NASH therapy monitor database.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is the more severe, inflammatory type of nonalcoholic fatty liver disease (NAFLD). NASH, a leading indication for liver transplantation, is growing in prevalence. The extent of liver fibrosis, ranging from fibrosis stage (FS) of none (F0) to cirrhosis (F4), is a strong predictor of health outcomes. There is little information on patient demographics and clinical characteristics by fibrosis stage and NASH treatment outside of academic medical centers. METHODS: We conducted a cross-sectional observational study using Ipsos' syndicated NASH Therapy Monitor database, consisting of medical chart audits provided by sampled NASH-treating physicians in the United States in 2016 (n = 174) and 2017 (n = 164). Data was collected online. RESULTS: Of 2,366 patients reported on by participating physicians and included in the analysis, 68% had FS F0-F2, 21% had bridging fibrosis (F3), and 9% had cirrhosis (F4). Common comorbidities were type 2 diabetes (56%), hyperlipidemia (44%), hypertension (46%), and obesity (42%). Patients with more advanced fibrosis scores (F3-F4) had higher comorbidity rates than patients with F0-F2. Commonly used diagnostic tests included ultrasound (80%), liver biopsy (78%), AST/ALT ratio (43%), NAFLD fibrosis score (25%), transient elastography (23%), NAFLD liver fat score (22%), and Fatty Liver Index (19%). Most commonly prescribed medications were vitamin E (53%), statins (51%), metformin (47%), angiotensin converting enzyme inhibitors (28%), and beta blockers (22%). Medications were commonly prescribed for reasons other than their known effects. CONCLUSION: Physicians in this study, drawn from a spectrum of practice settings, relied on ultrasound and liver biopsy for diagnosis and vitamin E, statins, and metformin for pharmacological treatment of NASH. These findings imply poor adherence to guidelines in the diagnosis and management of NAFLD and NASH. Nonalcoholic steatohepatitis (NASH) is a liver disease caused by excess fat in the liver which can lead to liver inflammation and scarring (fibrosis), ranging from stage F0 (no scarring) to F4 (advanced scarring). The stage of liver scarring can predict the likelihood of future health problems, including liver failure and liver cancer. However, we do not fully understand how patient characteristics may vary at different stages of liver scarring. We looked at medical information from physicians treating patients diagnosed with NASH to understand how patient characteristics might differ based on the severity of their liver scarring. The majority (68%) of patients were stage F0-F2, with 30% having advanced scarring (F3-F4). In addition to NASH, many patients also had type 2 diabetes, high cholesterol, high blood pressure, and obesity. Patients with more advanced scarring (F3-F4) were more likely to have these diseases than patients with less severe disease (F0-F2). Diagnosis of NASH by participating physicians was based on tests including imaging (ultrasound, CT scan, MRI), liver biopsy, blood tests, and whether patients had other conditions that would put them at risk for NASH. The medications that the doctors prescribed most often to their patients included vitamin E and drugs to treat high cholesterol, high blood pressure, or diabetes. Medications were frequently prescribed for reasons other than their known effects. By understanding how patient characteristics vary by stages of liver scarring and how NASH is currently managed may help guide the evaluation and treatment of NASH when NASH-specific therapies become available.

Comorbidities among patients with cancer who do and do not develop febrile neutropenia during the first chemotherapy cycle.

Patients receiving myelosuppressive chemotherapy with certain comorbidities are at increased risk of febrile neutropenia. A comprehensive evaluation of febrile neutropenia-related comorbidities across cancers is needed. This study compared comorbidity prevalence among patients with cancer who did and did not develop febrile neutropenia during the first chemotherapy cycle. This case-control study used administrative claims from adult patients with non-Hodgkin lymphoma or breast, lung, colorectal, ovarian, or gastric cancer who received chemotherapy between 2007 and 2012. Each patient who developed febrile neutropenia (case) was matched with up to four patients without febrile neutropenia (controls) by cancer type, metastasis, chemotherapy regimen, age group, and sex. For each comorbidity (identified in the year before chemotherapy began), the adjusted odds ratio (aOR) for febrile neutropenia by cancer type was evaluated using conditional logistic regression models adjusted for potential confounding factors. Of 31,331 eligible patients, 672 developed febrile neutropenia in the first chemotherapy cycle. A total of 3312 febrile neutropenia cases and matched controls were analyzed. Across tumor types, comorbidity prevalence was higher in patients who developed febrile neutropenia than in those without febrile neutropenia. Among patients with breast cancer, osteoarthritis was more prevalent in patients with febrile neutropenia (aOR, 1.85; 95% CI, 1.07 to 3.18). Among patients with non-Hodgkin lymphoma, renal disease was more prevalent in patients with febrile neutropenia (aOR, 2.25; 95% CI, 1.23 to 4.11). Patients who developed febrile neutropenia in the first chemotherapy cycle presented with comorbidities more often than otherwise similar patients who did not develop febrile neutropenia. These findings warrant further investigation and support the inclusion of comorbidities into febrile neutropenia risk models.

Incidence of skin and soft tissue infections in ambulatory and inpatient settings, 2005-2010.

BACKGROUND: The emergence of community-associated methicillin-resistant S. aureus was associated with dramatically increased skin and soft tissue infection (SSTI) incidence in the first few years of the 21(st) century in the U.S. However, subsequent trends are poorly understood. METHODS: We examined ambulatory and inpatient data of over 48 million persons years aged 0-64 years from the HealthCore Integrated Research Database (HIRD) between 2005 and 2010. Data were extracted from medical, pharmacy, and eligibility databases. We quantified SSTI incidence, type, and complications and comparative incidence trends for urinary tract infections (UTIs) and pneumonia. RESULTS: A total of 2,301,803 SSTIs were identified. Most SSTIs (95 %) were treated in the ambulatory setting and most (60 %) were categorized as abscesses or cellulitis. During the study period, SSTI incidence remained relatively stable from 47.9 (95 % CI: 47.8-48.1) cases/1,000 PY in 2005 to 48.5 cases/1,000 PY (95 % CI: 48.3-48.6) in 2010). Persons aged 45-64 years had the highest incidence of both ambulatory-treated and inpatient-treated SSTIs (51.2 (95 % CI: 51.1-51.3) and 3.87 (95 % CI: 3.84-3.90) cases/1,000 PY, respectively). SSTI complications such as myositis, gangrene, and sepsis occurred in 0.93 % (95 % CI: 0.92-0.94 %) and 16.92 % (95 % CI: 16.87-16.97 %) of ambulatory-treated and inpatient-treated patients, respectively. SSTI incidence was approximately twice that of UTIs and tenfold of that of pneumonia. CONCLUSIONS: Among our large, diverse population of persons less than 65 years, SSTI incidence 2005 through 2010 has remained relatively constant at approximately 4.8 SSTIs per 100 person years, suggesting that previously observed increases in SSTI incidence remain sustained.

The clinical and economic burdens of metabolic dysfunction-associated steatohepatitis.

AIMS: This study aimed to assess and compare the health care resource utilization (HCRU) and medical cost of metabolic dysfunction-associated steatohepatitis (MASH) by disease severity based on Fibrosis-4 Index (FIB-4) score among US adults in a real-world setting. MATERIALS AND METHODS: This observational cohort study used claims data from the Healthcare Integrated Research Database (HIRD) to compare all-cause, cardiovascular (CV)-related, and liver-related HCRU, including hospitalization, and medical costs stratified by FIB-4 score among patients with MASH (identified by International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code K75.81). Hospitalization and medical costs were compared by FIB-4 score using generalized linear regression with negative binomial and gamma distribution models, respectively, while controlling for confounders. RESULTS: The cohort included a total of 5,104 patients with MASH and comprised 3,162, 1,343, and 599 patients with low, indeterminate, and high FIB-4 scores, respectively. All-cause hospitalization was significantly higher in the high FIB-4 cohort when compared with the low FIB-4 reference after covariate adjustment (rate ratio, 1.63; 95% CI, 1.32-2.02; p < .0001). CV-related hospitalization was similar across all cohorts; however, CV-related costs were 1.26 times higher (95% CI, 1.11-1.45; p < .001) in the indeterminate cohort and 2.15 times higher (95% CI, 1.77-2.62; p < .0001) in the high FIB-4 cohort when compared with the low FIB-4 cohort. Patients with indeterminate and high FIB-4 scores had 2.97 (95% CI, 1.78-4.95) and 12.08 (95% CI, 7.35-19.88) times the rate of liver-related hospitalization and were 3.68 (95% CI, 3.11-4.34) and 33.73 (95% CI, 27.39-41.55) times more likely to incur liver-related costs, respectively (p < .0001 for all). LIMITATIONS: This claims-based analysis relied on diagnostic coding accuracy, which may not capture the presence of all diseases or all care received. CONCLUSIONS: High and indeterminate FIB-4 scores were associated with significantly higher liver-related clinical and economic burdens than low FIB-4 scores among patients with MASH.

MASH is a serious liver disease that can lead to fibrosis, cirrhosis, and other complications. There is a need to understand the impact of disease severity on the burden of MASH. Health care claims data were used to assess the use of medical resources, including hospitalization, and medical costs among patients with 3 different levels of severity of MASH, as assessed via FIB-4 score. FIB-4 is a widely available non-invasive marker of severity. Rates of all-cause, cardiovascular-related and liver-related hospitalization and medical costs were several-fold higher in patients with high disease severity of MASH than those with low disease severity of MASH.

Evaluating the burden of illness of metabolic dysfunction-associated steatohepatitis in a large managed care population: The ETHEREAL Study.

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH; formerly nonalcoholic steatohepatitis) is the inflammatory form of metabolic dysfunction-associated steatotic liver disease (formerly nonalcoholic fatty liver disease). MASH is a progressive disease associated with increased risk for many hepatic and extra-hepatic complications such as cirrhosis, hepatocellular carcinoma, the requirement for liver transplantation, and cardiovascular (CV)-related and kidney-related complications. It is important to understand the clinical and economic burden of MASH. OBJECTIVES: To assess and compare the clinical and economic burdens of MASH in adults with the non-MASH population in a real-world setting. METHODS: This observational, retrospective study used the Healthcare Integrated Research Database (HIRD), which contains health care claims data for commercially insured and Medicare Advantage health plan members across the United States. All-cause, CV-related, and liver-related medical costs and health care resource utilization were evaluated in patients with at least 2 diagnoses of MASH during the patient identification period (October 1, 2016, to April 30, 2022) and compared with a non-MASH cohort 1:1 matched on age, Quan Charlson Comorbidity Index, region of residence, and health plan type and length of enrollment. Generalized linear regression with negative binomial and γ distribution models were used to compare health care resource utilization and medical costs, respectively, while controlling for confounders. Covariate-adjusted all-cause, CV-related, and liver-related hospitalization rate ratios and medical cost ratios were assessed and compared for the MASH and matched non-MASH cohorts. RESULTS: A total of 18,549 patients with MASH were compared with 18,549 matched patients in the non-MASH cohort. After adjusting for covariates, MASH was associated with significantly higher rates of hospitalization and higher medical costs compared with the non-MASH cohort. When compared with the non-MASH cohort, patients with MASH had 1.22 (95% CI = 1.15-1.30; P < 0.0001) times higher rates of all-cause hospitalization, 1.13 (95% CI = 1.03-1.24; P = 0.008) times higher rates of CV-related hospitalization, and 7.22 (95% CI = 4.91-10.61; P < 0.0001) times higher rates of liver-related hospitalization. Similarly, all-cause medical costs were 1.26 (95% CI = 1.22-1.30; P < 0.0001) times higher, CV-related medical costs were 1.66 (95% CI = 1.59-1.73; P < 0.0001) times higher, and liver-related medical costs were 7.79 (95% CI = 7.42-8.17; P < 0.0001) times higher among patients with MASH. CONCLUSIONS: Compared with those of the non-MASH cohort with similar age, Quan Charlson Comorbidity Index, health plan, region of residence, and duration of enrollment, patients with MASH had significantly higher all-cause, CV-related, and liver-related hospitalizations and medical costs.

Use of Concurrent Anti-diabetes Medications in Patients With Type 2 Diabetes in Clinical Practice in the United States.

PURPOSE: This report describes the use of combination therapy in patients with type 2 diabetes mellitus (T2DM) who had been initially prescribed metformin in the United States. METHODS: Retrospective claims data from a de-identified database were used to identify individuals aged ≥18 years with ≥1 claim for a metformin-containing regimen dated between January 1, 2018, and December 31, 2018. Demographics, insurance type, and prescriber type were compared among subgroups receiving two (dual) or three or more (triple+) anti-diabetes therapies. All analyses were descriptive; no formal comparisons were conducted. FINDINGS: Data from 353,062 patients were included. Demographic and other baseline characteristics were similar between the groups receiving dual or triple+ therapy (n = 213,871 and 139,191, respectively). A small age difference was observed between patients receiving dual versus triple+ therapy (mean [SD], 66.5 [11.8] and 65.8 [10.8] years, respectively). Mean (SD) glycosylated hemoglobin levels were lower among patients receiving dual therapy versus triple+ therapy: 7.6% (1.7) versus 8.0% (1.7). The most frequent combination was metformin plus a sulfonylurea (33.4%). The percentage receiving combination therapy with newer treatments was relatively low, and slightly greater in younger patients. Total health care costs were similar with dual and triple+ therapies. IMPLICATIONS: The current descriptive analysis demonstrated generally similar features, with regard to the evaluated factors, in cohorts receiving dual versus triple+ T2DM therapy. However, differences between unmeasured factors could exist and require further evaluation. These findings, based on data from a cohort of patients from clinical practice who had initially been prescribed metformin, provide a useful snapshot of current prescribing practices and can be used to inform future research and evidence-based policy decisions.

Cardiovascular risk prediction model and stratification in patients with type 2 diabetes enrolled in a Medicare Advantage plan.

BACKGROUND: Cardiovascular (CV) risk tools have been developed both nationally and internationally to identify patients at risk for developing CV disease or experiencing a CV event. However, these tools vary widely in the definitions of endpoints, the time at which the endpoints are measured, patient populations, and their validity. The primary limitation of some of the most commonly utilized tools is the lack of specificity for a type 2 diabetes (T2D) population and/or among older patients. OBJECTIVE: To develop a predictive model within an older population of patients with T2D to identify patients at risk for CV events. METHODS: This retrospective cohort study used claims, laboratory, and enrollment data during the 2011-2018 study period. Patients with T2D were identified based on diagnoses and/or medications from 2012-2013. The patient cohort was split into 3 different datasets. The holdout dataset included only those patients residing in the northeastern United States. The rest of the sample was then randomly split: 70% for the training dataset, which were used to fit the predictive model, and 30% for the test dataset to assess internal validity. The primary outcome was the first composite CV event defined as at least 1 of the following: inpatient hospitalization for myocardial infarction, ischemic stroke, unstable angina, or heart failure; or any evidence of revascularization. A survival model for the composite outcome was fitted with baseline demographic and clinical characteristics prognostic for the dependent variable utilizing augmented backwards elimination. For assessing model performance, accuracy, sensitivity, specificity, and the c-statistic were used. Patients were ranked as having a low, moderate, or high probability of a future CV event. RESULTS: A total of 362,791 patients were identified. The holdout dataset included only those patients residing in the northeastern United States (n = 8,303). There were 248,142 patients included in the training dataset and 106,346 patients in the test dataset. The proportion with at least 1 observed composite CV event was 20.9%. The final model included 42 variables. The c-statistic was 0.68, and the accuracy, sensitivity, and specificity were approximately 63%. Results were consistent across the training, test, and holdout samples. The optimal cut points minimizing the difference in sensitivity and specificity for low-, moderate-, and high-risk future CV events were determined to be less than 0.18, 0.18-0.63, and greater than 0.63, respectively, in the training dataset at 5 years. The 5-year observed event risk was 11%, 27%, and 51% for patients classified as low, moderate, and high risk of a future CV event, respectively. CONCLUSIONS: A model predicting CV events among older patients with T2D using administrative claims to identify those at risk may be used for focusing interventions to prevent future events. DISCLOSURES: This study was funded by Boehringer Ingelheim (BI) and conducted as part of the BI-Humana Research Collaboration. Caplan is employed by Humana Healthcare Research, Inc., a wholly owned subsidiary of Humana Inc., which received fees to conduct the study from the sponsor BI. At the time of the study, Hayden and Harvey were employees of Humana Healthcare Research, Inc. Additionally, Prewitt, who owns stock in Humana Inc, and Chiguluri are employees of Humana Inc. Kattan, associated with the Cleveland Clinic in Ohio, served as a consultant to BI, and Pimple and Goss are employees of BI. Luthra was employed by BI for the duration of the study. Portions of this work were accepted as an abstract and presented as a poster at the American Diabetes Association 2020 virtual meeting, June 12-16, 2020.

Assessing risk of future cardiovascular events, healthcare resource utilization and costs in patients with type 2 diabetes, prior cardiovascular disease and both.

BACKGROUND: Description of risk of cardiovascular (CV) events associated with diabetes is evolving. This US-based real-world study estimated risk of future CV events and heart failure (HF) from type 2 diabetes (T2DM) only, prior CV events only or T2DM plus prior CV events, versus controls, and evaluated healthcare resource utilization (HCRU) and costs. METHODS AND MATERIALS: This retrospective cohort study queried claims and mortality data for 638,301 patients: T2DM only (377,205); prior CV events only (130,964); both T2DM and prior CV events (130,132); and matched (1:1) controls, during 1 January 2012-31 December 2012. Cardiovascular diagnoses/events and death were assessed individually, and as composite endpoint (myocardial infarction [MI], stroke, transient ischemic attack [TIA], peripheral artery disease [PAD]), during follow-up, ending 31 July 2018. RESULTS: Adjusting for age and gender, patients with T2DM only were 1.6, prior CV events only 2.5 and T2DM plus prior CV events 3.8 times likelier to have primary composite CV events relative to controls, p < .001. HF development was elevated across all three cohorts. Adjusted results showed inpatient admissions for T2DM only, CV events only and T2DM plus prior CV events were 1.37, 2.76 and 3.63 times greater than controls, respectively. All-cause healthcare costs were highest in the T2DM plus prior CV events cohort ($2783 per patient per month [PPPM]) followed by the prior CV events only ($1910 PPPM) and T2DM only cohorts ($1343 PPPM), and controls ($825 PPPM). Adjusted all-cause total costs were 1.48 for T2DM only, 1.49 for prior CV events only and 1.93 for T2DM plus prior CV events times higher compared to controls. CONCLUSION: In this large and geographically broad US based cohort, CV risk for T2DM patients was elevated, as was the risk for patients with prior CV events, while patients with T2DM plus prior CV events had the highest risk of future CV events. The substantial clinical and economic burden of CV events and HF in patients with both T2DM and prior CV events suggest a need for an integrated treatment and targeted intervention across both conditions.

Spirometry evaluation to assess performance of a claims-based predictive model identifying patients with undiagnosed COPD.

BACKGROUND: A claims-based model to predict patients likely to have undiagnosed COPD was developed by Moretz et al in 2015. This study aims to assess the performance of the aforementioned model using prospectively collected spirometry data. METHODS: A study population aged 40-89 years enrolled in a Medicare Advantage plan with prescription drug coverage or commercial health plan and without a claim for COPD diagnosis was identified from April 1, 2012 to March 31, 2016 in the Humana claims database. This population was stratified into subjects likely or unlikely to have undiagnosed COPD using the claims-based predictive model. Subjects were randomly selected for spirometry evaluation of FEV1 and FVC. The predictive model was validated using airflow limitation ratio (FEV1/FVC <0.70). RESULTS: A total of 218 subjects classified by the predictive model as likely and 331 not likely to have undiagnosed COPD completed spirometry evaluation. Those predicted to have undiagnosed COPD had a higher mean age (70.2 vs 67.9 years, P=0.0012) and a lower mean FEV1/FVC ratio (0.724 vs 0.753, P=0.0002) compared to those predicted not to have undiagnosed COPD. Performance metrics for the predictive model were: area under the curve =0.61, sensitivity =52.5%, specificity =64.6%, positive predictive value =33.5%, and negative predictive value =80.1%. CONCLUSION: The claims-based predictive model identifies those not at risk of having COPD eight out of ten times, and those who are likely to have COPD one out of three times.

Initiation of triple therapy maintenance treatment among patients with COPD in the US.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD. Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated. Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy. Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines. PATIENTS AND METHODS: This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013. Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2. A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity. RESULTS: Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy. In Cohort 2, 30,493 COPD patients (mean age =64.7 years) who initiated triple therapy were identified. Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1), 40.8% moderate (GOLD 2), 22.5% severe (GOLD 3), and 2.3% very severe (GOLD 4). Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4. CONCLUSION: In this large US claims database study, one-quarter of all treated COPD patients received triple therapy. Although triple therapy is recommended for the most severe COPD patients, spirometry is infrequently assessed, and a majority of the patients who receive triple therapy may have only mild/moderate disease. Any potential overprescribing of triple therapy may lead to unnecessary costs to the patient and health care system.

Differences in Health Care Use and Costs Among Patients With Cancer Receiving Intravenous Chemotherapy in Physician Offices Versus in Hospital Outpatient Settings.

PURPOSE: The current shift in site of care from community oncology practices to the hospital outpatient department to deliver oncology services may have significant implications for the economic and clinical outcomes of cancer care. Therefore, this study compares health care use and costs among patients with cancer receiving intravenous (IV) chemotherapy in physician offices (PO) versus in hospital outpatient settings (HOP). METHODS: This retrospective study, which was based on medical and pharmacy claims data, included patients (age, 18 to 64 years) initiating IV chemotherapy/biologic treatment between January 1, 2006, and August 31, 2012, who were diagnosed with early or metastatic breast cancer, metastatic lung cancer, metastatic colorectal cancer, or non-Hodgkin lymphoma or chronic lymphocytic leukemia. Patients were assigned to PO or HOP groups on the basis of where they received > 95% of their IV cancer therapy. RESULTS: The study sample included 18,740 patients (12,899 PO; 5,841 HOP) who had a mean age of 51.6 years and a Deyo-Charlson Comorbidity Index score of 5.37. Overall office visits (21.8 ± 13.8 PO v 21.2 ± 12.9, P < .005) and outpatient services (50.8 ± 35.5 PO v 48.5 ± 33.6, P < .001) were higher in the PO group than in the HOP group. Cancer-related inpatient hospitalizations (0.6 ± 1.2 PO v 0.7 ± 1.4 HOP, P = .002) were lower in the PO group than in the HOP group. Although quality-of-care metrics were similar between the HOP and PO groups, follow-up all-cause costs ($82,773 PO v $122,473 HOP) and cancer-related health care costs ($69,037 PO v $108,177 HOP) were higher in the HOP group than in the PO group. CONCLUSION: Despite similar resource use, all-cause and cancer-related health care costs in HOP were significantly higher compared with those in PO settings.

Clinical outcomes and medication adherence in acute coronary syndrome patients with and without type 2 diabetes mellitus: a longitudinal analysis 2006-2011.

BACKGROUND: The presence of type 2 diabetes mellitus magnifies the risks associated with acute coronary syndrome (ACS), increasing the risk of recurrent cardiovascular events (CVEs) and doubling the risk of death. Managing cardiovascular risk factors has little effect on lowering the mortality risk in patients with type 2 diabetes. OBJECTIVE: To evaluate the relationship between type 2 diabetes mellitus and subsequent CVEs and medication adherence following ACS hospitalization. METHODS: Patients with ACS were identified using ICD-9-CM codes for acute myocardial infarction or unstable angina. The risk of subsequent CVEs was assessed at 1 and 3 years after the index ACS event based on type 2 diabetes status, adjusting for baseline demographic characteristics, comorbidities, medication use, and index ACS characteristics. RESULTS: Of 140,903 patients with ACS (mean age 66.8 years, 58.6% male), 27.4% had type 2 diabetes. During follow-up, 22.0% had subsequent CVEs (26.2% type 2 diabetes, 19.0% nondiabetes). After adjusting for other covariates, type 2 diabetes was associated with increased risk of subsequent CVEs by 9.7% at 1 year and 10.2% at 3 years (both P < 0.001). Most patients were not revascularized at first recurrence after index ACS discharge (79.2% type 2 diabetes, 77.5% nondiabetes). Patients with type 2 diabetes had statistically significant higher adherence rates for antiplatelet agents at 1 year and antihypertensives at 1 and 3 years versus nondiabetes patients. Persistence was higher in the type 2 diabetes group for antihypertensives and in the nondiabetes group for antiplatelet agents and statins. CONCLUSIONS: This analysis demonstrates that patients with type 2 diabetes have a higher risk of subsequent CVEs following an initial event versus those without diabetes, despite evidence of higher treatment persistence for certain medications. Adherence rates remained suboptimal, suggesting a continuing need for patient education.