Obesity and metabolic syndrome in patients with heart failure with preserved ejection fraction: a cross-sectional analysis of the Veradigm Cardiology Registry.

BACKGROUND: The proportion of heart failure patients with preserved ejection fraction has been rising over the past decades and has coincided with increases in the prevalence of obesity and metabolic syndrome. The relationship between these interconnected comorbidities and heart failure with preserved ejection fraction (HFpEF) is still poorly understood. This study characterized obesity and metabolic syndrome among real-world patients with HFpEF. METHODS: We identified adults with heart failure in the Veradigm Cardiology Registry, previously the PINNACLE Registry, with a left ventricular ejection fraction measurement ≥ 50% between 01/01/2016 and 12/31/2019. Patients were stratified by obesity diagnosis and presence of metabolic syndrome (≥ 3 of the following: diabetes, hypertension, hyperlipidemia, and obesity). We captured baseline demographic and clinical characteristics and used multivariable logistic regression to examine the odds of having cardiac (atrial fibrillation, coronary artery disease, coronary artery bypass surgery, myocardial infarction, and stroke/transient ischemic attack) and non-cardiac (chronic kidney disease, chronic liver disease, and peripheral artery disease) comorbidities of interest. The models adjusted for age and sex, and the main covariates of interest were obesity and metabolic burden score (0-3 based on the presence of diabetes, hypertension, and hyperlipidemia). The models were run with and without an obesity*metabolic burden score interaction term. RESULTS: This study included 264,571 patients with HFpEF, of whom 55.7% had obesity, 52.5% had metabolic syndrome, 42.5% had both, and 34.3% had neither. After adjusting for age, sex, and burden of other metabolic syndrome-associated diagnoses, patients with HFpEF with obesity had lower odds of a diagnosis of other evaluated comorbidities relative to patients without obesity. The presence of metabolic syndrome in HFpEF appears to increase comorbidity burden as each additional metabolic syndrome-associated diagnosis was associated with higher odds of assessed comorbidities except atrial fibrillation. CONCLUSION: Obesity was common among patients with HFpEF and not always co-occurring with metabolic syndrome. Multivariable analysis suggested that patients with obesity may develop HFpEF in the absence of other driving factors such as cardiovascular disease or metabolic syndrome.

An Economic Evaluation of the Relationship Between Glycemic Control and Total Healthcare Costs for Adults with Type 2 Diabetes: Retrospective Cohort Study.

INTRODUCTION: Glycemic control is associated with better outcomes among individuals with type 2 diabetes (T2D). This research examines total US all-cause medical costs for adults with T2D with recommended glycemic control (HbA1c < 7%) compared to poor glycemic control (HbA1c ≥ 7%). METHODS: The study used administrative claims data linked to HbA1c laboratory test results from January 1, 2015 through June 30, 2021 to identify adults with T2D with a recorded HbA1c test. Patients with recommended glycemic control at index date were propensity score matched to patients with poor glycemic control. General linear models and two-part models were used to compare all-cause outpatient, drug, acute care and total costs for 1 year post index date. RESULTS: The study included 59,830 propensity-matched individuals. Results indicate that recommended glycemic control, compared to poor glycemic control, was associated with statistically significantly lower all-cause acute care ($23,868 ± $21,776 vs. $24,352 ± $22,223), drug ($10,277 ± $14,671 vs. $10,540 ± $14,928), and total medical costs ($41,381 ± $42,757 vs. $42,054 ± $43,422) but significantly higher outpatient costs ($7290 ± $12,028 vs. $7026 ± $11,587) (all p < 0.0001). Sensitivity analyses examined results based upon alternative HbA1c thresholds of ≤ 6.5% and < 8%. Results were generally robust to alternative HbA1c thresholds, with higher HbA1c thresholds associated with higher all-cause total costs as well as increased savings for having HbA1c below threshold. CONCLUSIONS: Glycemic control was associated with significantly lower all-cause total, drug, and acute care medical costs. Given the high prevalence of T2D in the USA, our results suggest potential economic benefits associated with glycemic control for healthcare providers.

Real-world primary nonadherence to antiobesity medications.

BACKGROUND: Primary nonadherence (PNA), when a medication is newly prescribed but not filled, has been identified as a major research gap potentially impacting the optimal treatment of patients with overweight and obesity who are newly prescribed antiobesity medications (AOMs). OBJECTIVES: To assess PNA among patients with newly prescribed AOMs and to examine factors associated with PNA to AOMs. METHODS: This was a retrospective study that used the Optum Integrated Clinical plus Claims database to identify individuals who had at least 1 prescription order for an AOM the US Food and Drug Administration approved for long-term use. Individuals with prescription orders between January 1, 2012, and February 28, 2019, were identified, and patient demographics, clinical characteristics, medication prescribed, baseline health care utilization, and obesity-related complications were described by PNA status. PNA was defined as no pharmacy claim for the AOM within 60 days of the date of the new prescription order as identified in electronic health record data. A multivariable logistic regression model was used to examine factors associated with PNA. RESULTS: The study sample included a total of 1,563 patients. The mean body mass index was 38.4 kg/m2; 10.7% were prescribed liraglutide 3.0 mg, 26.0% were prescribed lorcaserin, 36.3% of patients were prescribed naltrexone-bupropion, 5.4% were prescribed orlistat, and 21.6% were prescribed phentermine-topiramate. Most patients (91.1%) exhibited PNA, with only 8.9% filling their newly prescribed AOM within 60 days. Both the adherent and nonadherent groups were predominately female sex, White, and covered by commercial insurance. The mean age was similar between the 2 groups. Most obesity-related complications were less prevalent in the adherent group, although the Charlson comorbidity index score was similar between the 2 groups. After adjustment for patient demographics and clinical characteristics, there was not a statistically significant association between the specific AOM and PNA (P = 0.299). Patients with depression or living in the Midwest or South regions were at significantly increased risk of PNA. CONCLUSIONS: The rate of PNA to AOMs was very high, suggesting barriers in effective medical management of patients with overweight and obesity. Future research is warranted to understand reasons for PNA to AOMs and how to address these barriers. DISCLOSURES: Dr Kan, Dr Bae, Dr Dunn, and Dr Ahmad are employees of Eli Lilly and Company. Ms Buysman and Dr Gronroos are employees of Optum. Dr Swindle was an employee of Optum at the time the study was conducted and is currently employed at Evidera. Dr Bengtson is employed at Boehringer Ingelheim Pharmaceuticals, Inc. (Boehringer Ingelheim has no connection to this study), and during the conduct of this study was employed at Optum.

Five-year morbidity and mortality rates in a U.S. population with obesity with and without prediabetes.

AIMS: This research examines the prevalence of morbidity and mortality among people with obesity with or without prediabetes. METHODS: This observational study uses Optum® Market Clarity deidentified data from 2007 to 2020. Individuals with obesity without prediabetes (obesity only) were matched 1:1 to adults with prediabetes plus obesity based upon age, sex, race, ethnicity, and region. Age and sex adjusted prevalence rates and 95 % CIs were calculated for morbidity and mortality for each 365-day period post index date and over the entire 5-year post-period. RESULTS: After 5-years, the adjusted mortality rate was 10.1 % for adults with obesity plus prediabetes and 6.9 % for adults with obesity only (p < 0.05). Five years post index date, the prevalence of type 2 diabetes was 25.3 % for people with obesity plus prediabetes and 9.2 % for people with obesity only (p < 0.05). Prevalence rates after 5 years for atherosclerotic cardiovascular disease (13.1 % v 8.1 %), composite cardiovascular outcome (7.0 % v 4.4 %) and composite cardio-renal outcome (8.9 % v 5.0 %) were significantly higher for adults with obesity plus prediabetes compared to adults with obesity only (all p < 0.05). CONCLUSIONS: Results of this study indicate that the presence of prediabetes contributes to the development of additional morbidity and mortality in adults with obesity.

A Framework for Integrating Continuous Glucose Monitor-Derived Metrics into Economic Evaluations in Type 1 Diabetes.

Economic models in type 1 diabetes have relied on a change in haemoglobin A1c as the link between the blood glucose trajectory and long-term clinical outcomes, including microvascular and macrovascular disease. The landscape has changed in the past decade with the availability of regulatory approved, accurate and convenient continuous glucose monitoring devices and their ability to track patients' glucose levels over time. The data emerging from continuous glucose monitoring have enriched the clinical understanding of the disease and indirectly of patients' behaviour. This has triggered the development of new measures proposed to better define the quality of glycaemic control, beyond haemoglobin A1c. The objective of this paper is to review recent developments in clinical knowledge brought into focus with the application of continuous glucose monitoring devices, and to discuss potential approaches to incorporate the concepts into economic models in type 1 diabetes. Based on a targeted review and a series of multidisciplinary workshops, an influence diagram was developed that captures newer concepts (e.g. continuous glucose monitoring metrics) that can be integrated into economic models and illustrates their association with more established concepts. How the additional continuous glucose monitoring-based indicators of glycaemic control may contribute to economic modelling beyond haemoglobin A1c, and more accurately reflect the economic value of novel type 1 diabetes treatments, is discussed.

An Early Assessment of the Real-World Treatment Patterns of Type 2 Diabetes: A Comparison to the 2018 ADA/EASD Consensus Report Recommendations.

INTRODUCTION: Using the American Diabetes Association (ADA) Hyperglycemic Pharmacotherapy Guidelines for type 2 diabetes, we evaluated the medication use patterns in real-world patients with type 2 diabetes in the USA. METHODS: Health care claims among patients with type 2 diabetes were analyzed (IBM® MarketScan® 2007 to 2019 Commercial and Medicare Databases). Diabetes treatment patterns were evaluated for the total patient sample of 580,741 during the year 2019. Prior years' claims data were used to construct patient history and determine clinical groups per the 2018 ADA/EASD consensus statement: atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), heart failure (HF), hypoglycemia (hypo), and obesity. The recommended therapy use rates (RTUR) were calculated for clinical groups. Univariate chi-square tests were performed to compare RTUR within and outside clinical groups. Multivariate logistic regression was used to identify variables associated with recommended therapy use. RESULTS: A large proportion of patients belonged to multiple clinical groups; this was more common in the Medicare cohort. Each clinical group in the Commercial cohort had a substantially higher RTUR than in the Medicare cohort. However, no clinical group achieved > 40% RTUR. The RTUR was the highest in the CKD and obesity groups in the Commercial cohort and in the hypo and obesity groups in the Medicare cohort, but lowest in hypo and HF groups in the Commercial and Medicare cohorts, respectively. CONCLUSION: Prevalence of guideline-aligned treatment use in 2019 was low, particularly since many patients fit into multiple risk groups with established treatment benefits.

Bridging the Gap Between Self-Reported and Claims-Derived Adherence Measures for Basal Insulin Among Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: Complex or personalized insulin regimens challenge traditional adherence measures. Our objective was to develop an improved basal insulin (BI) adherence measure using both patient-reported and administrative claims data, resulting in a more complete measure. METHODS: Patients' self-reported BI utilization over the previous 12 months was linked with their claims data for the same period. Hybrid medication possession ratio (MPR) was derived by calculating expected days of insulin supply [total dispensed insulin units from claims over 12 months divided by self-reported total daily dose (TDD)]. The hybrid MPR was compared against traditional claims-based MPR, adjusted claims-based MPR, and patient-reported MPR. For all MPR measures, the adherence threshold was ≥ 0.8. A logistic model was used to predict non-adherence per hybrid MPR. The predicted model-based MPR was compared with existing measures in a larger cohort. RESULTS: The study sample consisted of 296 patients. TDD derived from claims was higher than self-reported TDD [77.9 (71.8) vs. 57.7 (38.3)], implying average dispensed insulin would last longer than claims-based days supply. Correspondingly, hybrid and MPRs adjusted for package size (56% and 71%, respectively) were higher than claims-based MPR (50%). Age, total claims-based days supply, retinopathy, adjusted MPR-based adherence, and non-insulin injectable use were key predictors of hybrid MPR-based adherence. Applying the claims-based prediction model to a larger cohort to test validity showed high correlations with predicted and adjusted MPR-based adherence. CONCLUSIONS: Traditional claims-based MPR underestimated adherence while adjusted MPR overestimated adherence when self-reported total daily dose was taken as benchmark insulin dose. The predicted model may help identify patients with poor basal insulin adherence. More research is needed to further confirm the findings. FUNDING: Eli Lilly and Company, Indianapolis, IN, USA.

Non-adherence to basal insulin among patients with type 2 diabetes in a US managed care population: Results from a patient survey.

The aim of this study was to assess insulin non-adherence among patients with type 2 diabetes (T2DM) to better understand relationships between adherence, basal insulin (BI) usage, and patient experiences. A cross-sectional survey of patients with T2DM using BI was conducted. Adherence was measured by the Morisky Medication Adherence Scale 8-Items (MMAS-8). Low adherence (LA) was defined as MMAS-8 score < 6, high adherence (HA) as MMAS-8 score = 8, and medium adherence as MMAS-8 score = 6 to < 8. Patients with MMAS-8 scores = 6 to < 8 were excluded from the analysis. Of 400 completed surveys, 395 patients (98.8%) completed all MMAS-8 items, 112 with LA, 134 with HA. Compared with HA patients, greater proportions of LA patients followed more complex BI dosing patterns (57.1% vs. 39.5%, P = 0.014), had some difficulty calculating their correct BI dose (40.2% vs. 6.8%, P < 0.001), reported having missed ≥1 dose per month (79.3% vs. 12.6%, P < 0.001), and temporarily stopped BI in the past year (23.2% vs. 0.7%, P < 0.001). In conclusion, understanding patients' experiences with BI therapy can help formulate strategies to improve adherence.

Clinical course of nonalcoholic fatty liver disease: an assessment of severity, progression, and outcomes.

PURPOSE: To identify the characteristics and initial disease severity of patients with nonalcoholic fatty liver disease (NAFLD) and assess incidence and risk factors for disease progression in a retrospective study. METHODS: Patients ≥18 years of age without alcoholism or other liver diseases (eg, hepatitis B/C) were selected from Geisinger Health System electronic medical record data from 2004 to 2015. Initial disease stage was stratified into uncomplicated NAFLD, advanced fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and liver transplant using clinical biomarkers, diagnosis, and procedure codes. Disease progression was defined as stage progression or death and analyzed via Kaplan-Meier plots and multistate models. RESULTS: In the NAFLD cohort (N=18,754), 61.5% were women, 39.0% had type 2 diabetes mellitus (T2DM), and the mean body mass index was 38.2±10.2 kg/m2. At index, 69.9% had uncomplicated NAFLD, 11.7% had advanced fibrosis, and 17.8% had cirrhosis. Of 18,718 patients assessed for progression, 17.3% progressed (11.0% had stage progression, 6.3% died without evidence of stage progression) during follow-up (median=842 days). Among subgroups, 12.3% of those without diabetes mellitus progressed vs 24.7% of those with T2DM. One-year mortality increased from 0.5% in uncomplicated NAFLD to 22.7% in HCC. After liver transplant, mortality decreased to 5.6% per year. CONCLUSIONS: In 2.3 years of follow-up, approximately 17% of patients progressed or died without evidence of stage progression. T2DM was associated with approximately twice the risk of disease progression, and mortality risk increased with disease stage. Early diagnosis and monitoring of disease progression, especially in patients with T2DM, is warranted.

Risk Factors for Nocturnal Hypoglycemia in Insulin-treated Patients With Type 2 Diabetes: A Secondary Analysis of Observational Data Derived From an Integrated Clinical Trial Database.

PURPOSE: A trade-off exists in most diabetes therapies between the benefits of good glycemic control and the morbidity of hypoglycemia. Balancing these factors to achieve desired outcomes is a key consideration for personalized diabetes therapy. Hypoglycemia at night (nocturnal hypoglycemia [NH]) is a common but often under-reported problem in insulin-treated patients with type 2 diabetes. To better understand the risk for NH, we pooled data from multiple clinical trials of insulin treatment and specifically examined NH risk factors in relation to glycemic goals. METHODS: Of 53 randomized trials involving insulin treatment, 18 trials that collected NH data were included. Risk factors associated with NH were identified by using gradient-boosting methods. A proportional hazards model was used to quantify the hazard ratio (HR) for risk factors. By modeling with individual patient data, a patient-level NH risk score distribution was created. Finally, results of the model were used to quantify an adjustment to the glycemic goal that would fully offset each risk factor, all other factors being equal. FINDINGS: Data pooling resulted in the inclusion of 7341 patients with type 2 diabetes from 18 randomized clinical trials. In the mean 6-month treatment period, 43% of patients experienced at least 1 episode of NH (mean [SD], 1.1 [1.5] events/month). Reduction of glycosylated hemoglobin (HbA1c) levels during the trial was a risk factor for NH (HR, 1.40 [95% CI, 1.38-1.43] per -1% of HbA1c). Higher baseline HbA1c level was a protective factor against NH (HR, 0.76 [95% CI, 0.74-0.77] per +1% of HbA1c); and the adjustment to HbA1c goal required to offset 1% higher baseline HbA1c was -0.825%. Patient characteristics for risk of NH included older age (HR, 1.02 [95% CI, 1.01-1.02]) per 1-year increase), female sex (HR, 1.18 [95% CI, 1.15-1.22]), black or African-American race (HR, 1.41 [95% CI, 1.33-1.50] vs white race), longer diabetes duration (HR, 1.02 [95% CI, 1.01-1.02] per 1-year increase), diabetic nephropathy (HR, 1.40 [95% CI, 1.27-1.54]), and concomitant sulfonylurea use (HR, 1.10 [95% CI, 1.05-1.15]). Asian race was associated with a lower risk of NH (HR, 0.50 [95% CI, 0.48-0.53] vs white race); this finding could be offset with a 2.03% adjustment to the HbA1c goal. IMPLICATIONS: Data on NH are scarce. By pooling multiple clinical trials, this study was able to evaluate patient-level data. A quantitative understanding of the trade-off between individual risk factors for NH and glycemic reduction may help clinicians to personalize patients' glycemic goals, while effectively managing NH risk. Limitations of the study include that patients were selected through inclusion/exclusion criteria and that patient compliance may be better in a trial setting. Validating the findings in the real world will be helpful.

Health-related quality of life burden of nonalcoholic steatohepatitis: a robust pragmatic literature review.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a form of chronic liver disease (CLD): patients have an increased risk of developing cirrhosis, liver failure, and complications (e.g. hepatocellular carcinoma). NASH has a high clinical burden, and likely impairs patients' health-related quality of life (HRQoL), but there are currently no licensed therapies. The objective of this robust pragmatic literature review was to identify and describe recent studies on the HRQoL burden of NASH from the patient perspective. METHODS: English-language primary research studies were identified that measured HRQoL in adults with NASH (population-based studies or clinical trials of pharmacological therapy). Searches were conducted in the following bibliographical databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), and Health Technology Assessment Database (HTA). Abstracts from selected congresses (2015/2016) were hand searched. Articles were assessed for relevance by two independent reviewers, and HRQoL data were extracted. RESULTS: A total of 567 de-duplicated abstracts were identified, and 20 full-text articles were reviewed. Eight studies were included: five quantitative, two interventional, and one qualitative. The quantitative and interventional studies measured HRQoL using the Short-Form 36 (SF-36) and the Chronic Liver Disease Questionnaire (CLDQ), and the qualitative study involved focus groups and individual interviews. Overall, the studies showed that NASH affects HRQoL, especially physical functioning, with many patients reporting being fatigued. In quantitative studies, overall, patients with NASH had a reduced HRQoL versus normative populations and nonalcoholic fatty liver disease (NAFLD) patients, but not versus chronic liver diseases. A longitudinal study showed that when weight loss was achieved, HRQoL improvement over 6 months was greater in patients with NASH versus NAFLD. Qualitative research suggested that, in addition to fatigue, other symptoms are also burdensome, having a broad negative impact on patients' lives. The impact of pharmacological treatment on HRQoL was explored in only two included studies. CONCLUSIONS: HRQoL is impaired in patients with NASH. Patients experience a range of symptoms, especially fatigue, and the impact on their lives is broad. Further research is needed to understand the HRQoL burden of NASH (e.g. assessing NASH-specific impacts not captured by SF-36 and CLDQ) and the impact of future NASH therapies on HRQoL.

The role of imperfect surrogate endpoint information in drug approval and reimbursement decisions.

Approval of new drugs is increasingly reliant on "surrogate endpoints," which correlate with but imperfectly predict clinical benefits. Proponents argue surrogate endpoints allow for faster approval, but critics charge they provide inadequate evidence. We develop an economic framework that addresses the value of improvement in the predictive power, or "quality," of surrogate endpoints, and clarifies how quality can influence decisions by regulators, payers, and manufacturers. For example, the framework shows how lower-quality surrogates lead to greater misalignment of incentives between payers and regulators, resulting in more drugs that are approved for use but not covered by payers. Efficient price-negotiation in the marketplace can help align payer incentives for granting access based on surrogates. Higher-quality surrogates increase manufacturer profits and social surplus from early access to new drugs. Since the return on better quality is shared between manufacturers and payers, private incentives to invest in higher-quality surrogates are inefficiently low.

Evaluating health-related quality of life in type 1 diabetes: a systematic literature review of utilities for adults with type 1 diabetes.

BACKGROUND AND AIMS: Type 1 diabetes is a chronic condition associated with micro- and macrovascular complications that have a notable impact on health-related quality of life, the magnitude of which can be quantified via the use of utility values. The aim of this review was to conduct a systematic literature review to identify and compare published health state utility values for adults with type 1 diabetes both, with and without diabetes-related complications. METHODS: Literature searches of the PubMed, EMBASE, and Cochrane Library databases were performed to identify English language studies on adults with type 1 diabetes, published from 2000 onward, reporting utility values for patients with or without diabetes-related complications or assessing the impact of changes in HbA1c or body mass index on quality of life. For inclusion, studies were required to report utilities elicited using validated methods. RESULTS: A total of 20 studies were included in the final review that included utility values elicited using the EuroQuol five dimensions questionnaire (n=9), 15D questionnaire (n=2), Quality of Well-Being scale (n=4), time trade-off (n=3), and standard gamble (n=2) methods. For patients with no complications, reported utility values ranged from 0.90 to 0.98. Complications including stroke (reported disutility range, -0.105 to -0.291), neuropathy (range, -0.055 to -0.358), and blindness (range, -0.132 to -0.208) were associated with the largest decrements in utility values. The magnitude of utility values and utility decrements was influenced by the assessment method used. CONCLUSION: Complications lead to impaired health-related quality of life in patients with type 1 diabetes, the magnitude of which is influenced by the method used to determine utilities. There is currently a lack of utility data for certain complications of type 1 diabetes, meaning that many economic evaluations have relied on a combination of type 1 and type 2 diabetes utilities, despite differences between the conditions and populations, or type 1 diabetes-specific utilities derived from different instruments.

Treatment progression in sulfonylurea and dipeptidyl peptidase-4 inhibitor cohorts of type 2 diabetes patients on metformin.

BACKGROUND: Metformin is an oral antidiabetic drug (OAD) widely used as first-line therapy in type 2 diabetes (T2D) treatments. Numerous treatment pathways after metformin failure exist. It is important to understand how treatment choices influence subsequent therapy progressions. This retrospective study compares adherence to, persistence with, and treatment progression in sulfonylurea (SU) and dipeptidyl peptidase-4 (DPP-4) inhibitor patient cohorts with T2D on metformin. METHODS: Using health insurance claims data, matched patient cohorts were created and OAD use was compared in patients with T2D initiating SU or DPP-4 inhibitors (index drugs) since January 1, 2010, to December 31, 2010, with background metformin therapy. Propensity score matching adjusted for possible selection bias. Persistence was measured via Cox regression as days to a ≥60-day gap in index drug possession; adherence was defined as proportion of days covered (PDC) ≥80%. Evolving treatment patterns were traced at 6-month intervals for 24 months following index drug discontinuation. RESULTS: From among 19,621 and 7,484 patients in the SU and DPP-4 inhibitor cohorts, respectively, 6,758 patient pairs were matched. Persistence at 12 months in the SU cohort was 48.0% compared to 52.5% for the DPP-4 inhibitor cohort. PDC adherence (mean [SD]) during the 12-month follow-up period was 63.3 (29.7) for the SU cohort and 65.5 (28.7) for the DPP-4 inhibitor cohort. PDC ≥80% was 40.5% and 43.4% in the SU and DPP-4 inhibitor cohorts, respectively. A higher percentage of patients in the SU cohort remained untreated. Following index drug discontinuation, monotherapy was more common in the SU cohort, while use of two or three OADs was more common in the DPP-4 inhibitor cohort. Insulin therapy initiation was higher in the SU cohort. CONCLUSION: Slightly better adherence and persistence were seen in the DPP-4 inhibitor cohort. Adherence and persistence remain a challenge to many patients; understanding therapy progression will help identify target areas for intervention and improvement.

Comparative resource utilization and costs for patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with clopidogrel or prasugrel.

PURPOSE: Results of a study of bleeding events and other inhospital outcomes with the use of clopidogrel versus prasugrel in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) are reported. METHODS: Demographic and clinical data on adults hospitalized for ACS, managed with PCI, and treated with clopidogrel or prasugrel during a two-year period were extracted from a large hospital claims database. Bleeding rates, hospital length of stay (LOS), and total hospital costs during the index hospitalization were evaluated. RESULTS: The study sample consisted of 75,297 patients who received clopidogrel and 9,477 who received prasugrel. The unadjusted bleeding rates were 5.7% with clopidogrel use and 3.2% with prasugrel use (p < 0.0001). After propensity score stratification to adjust for selection bias, rates of bleeding events were not significantly different between clopidogrel- and prasugrel-treated patients (odds ratio, 0.90; 95% confidence interval [CI], 0.80-1.02; p = 0.0949). The adjusted mean ± S.D. hospital LOS was 0.22 day lower (95% CI, 0.15-0.28; p < 0.001) with the use of prasugrel versus clopidogrel, and adjusted total mean hospital costs were $375 less for prasugrel-treated patients (p = 0.003). CONCLUSION: After adjustments for demographic and clinical characteristics, rates of inhospital bleeding in patients who received prasugrel and those who received clopidogrel were not significantly different. The adjusted analyses showed that the mean hospital LOS was shorter and total mean hospital costs were lower for patients treated with prasugrel.

Cardiovascular risk profiles in Type 2 diabetes and the impact of geographical setting.

Cardiovascular (CV) disease is a leading morbidity and mortality in Type 2 diabetes (T2DM). Previous studies have shown geographic differences in the prevalence of CV and renal diseases. A literature review of longitudinal (≥5 years) studies including ≥1000 T2DM patients and reporting CV endpoints was performed to compare risk profiles. Key differences between geographies included a relatively higher prevalence of microalbuminuria in East Asian relative to North American and European patients, which in turn is an important CV risk factor. Patients from East Asia also have a relatively higher incidence of stroke and lower incidence of coronary heart disease. Overall, there are differences in CV risk in T2DM patients between different regions and that long-term studies from Africa, the Middle East and Latin America are lacking.

Point-of-care platelet reactivity determination with VerifyNow-P2Y12 following administration of clopidogrel or prasugrel: data from a real-world, clinical care inpatient setting.

OBJECTIVES: To describe VerifyNow-P2Y12 (VN-P2Y12, Accumetrics, San Diego, CA) results from patients treated with either clopidogrel or prasugrel who were seeking care in a hospital setting. BACKGROUND: VN-P2Y12 is a point-of-care device that measures platelet reactivity to adenosine diphosphate. Past assessments of thienopyridine therapy utilizing VN-P2Y12 have largely come from clinical trial settings. There are limited data from real-world settings. METHODS: Electronic medical record data from Huntsville Hospital (Huntsville, AL) for those who underwent VN-P2Y12 testing for clopidogrel or prasugrel between January 1, 2009 and October 31, 2010 were analyzed. The VN-P2Y12 data included P2Y12 reaction units (PRUs) and device-reported percentage of inhibition. Descriptive analyses were conducted with t tests, and a logistic regression model was estimated to assess the association between patient characteristics and the likelihood of platelet nonresponse. RESULTS: In total, 2882 tests (2476 with clopidogrel and 406 with prasugrel) were analyzed. For clopidogrel and prasugrel, respectively, mean PRU standard deviation (SD) was 206 (90) and 107 (93; P < 0.0001) and mean % inhibition (SD) was 31% (26%) and 63% (31%; P < 0.0001). Treatment with clopidogrel alone (odds ratio [OR] = 5.25; P < 0.0001), being non-Caucasian (OR = 1.48; P = 0.0440), obese (OR = 1.49; P = 0.0010), anemic (OR = 3.29; P < 0.0001), diabetic (OR = 1.75; P < 0.0001), and having a history of myocardial infarction (OR = 1.57; P < 0.0001) were significant predictors of having PRU ≥ 235. CONCLUSION: This real-world data analysis shows results that are consistent with clinical trial results, namely that compared with clopidogrel, prasugrel is associated with significantly lower PRU and greater percentage of inhibition, regardless of age, race, gender, diabetes, obesity, or proton pump inhibitor use.

Real-world observations with prasugrel compared to clopidogrel in acute coronary syndrome patients treated with percutaneous coronary intervention in the United States.

OBJECTIVES: To compare 30 and 90 day real-world acute myocardial infarction (AMI) and bleeding related rehospitalization rates in acute coronary syndrome (ACS) patients receiving percutaneous coronary intervention (PCI; ACS-PCI) treated with clopidogrel or prasugrel. RESEARCH DESIGN AND METHODS: Using the Premier hospital database, ACS-PCI patients receiving a drug-eluting (DES) or bare-metal (BMS) stent and clopidogrel or prasugrel from July 2009 to June 2011 were analyzed. Patients were included based on the prasugrel US prescribing information (USPI), excluding patients with a history of transient ischemic attack/stroke and patients ≥75 years without diabetes or prior MI. The primary endpoint was 30 day adjusted AMI rehospitalization rate. Secondary endpoints included 90 day AMI and 30 and 90 day bleeding-related rehospitalization rates. Treatment comparisons were adjusted using propensity score stratification. RESULTS: At the index event, prasugrel patients (N = 9404) differed from clopidogrel patients (N = 74,163) by having a lower risk of comorbid conditions associated with bleeding, being more likely younger and male, having ST-elevation MI and receiving a DES. For clopidogrel and prasugrel, respectively, the observed AMI-related rehospitalization rates were 4.7% and 3.9% at 30 days (p < 0.0001) and 6.3% and 5.1% at 90 days (p < 0.0001). After adjustment, prasugrel was associated with ∼10% lower odds of AMI-related rehospitalization (30 days: OR = 0.892 [95% CI: 0.798, 0.998]; 90 days, OR = 0.901 [95% CI: 0.817, 0.994]). Adjusted bleeding-related rehospitalization rates were similar to each other (OR = 1.035 at 30 days [95% CI: 0.765, 1.399]; OR = 0.922 at 90 days [95% CI: 0.725, 1.172]). STUDY LIMITATIONS: Treatment adherence was not assessed. Bleeding events not resulting in a hospitalization (e.g. office, outpatient, or emergency room visits), deaths outside the hospital, or readmissions to a hospital outside of the Premier alliance were not captured in the database. CONCLUSIONS: The different patient characteristics between prasugrel- and clopidogrel-treated patients suggest physicians are more selective in choosing patients for prasugrel than recommended in the prasugrel USPI. However, after adjustment for these differences, 30 and 90 day AMI rehospitalization rates were lower for prasugrel-treated patients compared to clopidogrel-treated patients, with no difference in adjusted bleeding-related rehospitalization rates.

Physician preferences for extra-glycemic effects of type 2 diabetes treatments.

INTRODUCTION: The purpose of this study was to quantify United States (US) and United Kingdom (UK) physicians' preferences for attributes of type 2 diabetes treatments. METHODS: Samples of general practitioners (GPs) and endocrinologists in the US (n = 204) and the UK (n = 200) completed a discrete-choice experiment in which respondents chose between pairs of hypothetical type 2 diabetes treatments in a series of trade-off questions. The questions described hypothetical injectable treatments with differing levels of attributes, such as glucose control and treatment side effects. Relative importance of attributes was estimated by a multivariate regression model for limited dependent variables. These results were used to calculate how the predicted probability of choosing hypothetical type 2 diabetes treatments varies with changes in given attributes. RESULTS: The most important attributes to physicians were glucose control, risk of a fatal myocardial infarction (MI), and weight change. For US physicians, glucose control was about twice as important as gastrointestinal side effects, 5 times more important than changes in depression symptoms, and 20 times more important than liver monitoring. For UK physicians, reduction in MI risk was about 1.5 times more important than glucose control, 2.5 times more important than gastrointestinal side effects, and 10 times more important than liver-monitoring requirements. Preferences were similar among physicians in the US and the UK and among GPs and endocrinologists. CONCLUSIONS: Physicians valued type 2 diabetes treatments that go beyond glycemic control, although mitigating different complications and comorbidities was not equally as important.

Rehospitalization following percutaneous coronary intervention for commercially insured patients with acute coronary syndrome: a retrospective analysis.

BACKGROUND: While prior research has provided important information about readmission rates following percutaneous coronary intervention, reports regarding charges and length of stay for readmission beyond 30 days post-discharge for patients in a large cohort are limited. The objective of this study was to characterize the rehospitalization of patients with acute coronary syndrome receiving percutaneous coronary intervention in a U.S. health benefit plan. METHODS: This study retrospectively analyzed administrative claims data from a large US managed care plan at index hospitalization, 30-days, and 31-days to 15-months rehospitalization. A valid Diagnosis Related Group code (version 24) associated with a PCI claim (codes 00.66, 36.0X, 929.73, 929.75, 929.78-929.82, 929.84, 929.95/6, and G0290/1) was required to be included in the study. Patients were also required to have an ACS diagnosis on the day of admission or within 30 days prior to the index PCI. ACS diagnoses were classified by the International Statistical Classification of Disease 9 (ICD-9-CM) codes 410.xx or 411.11. Patients with a history of transient ischemic attack or stroke were excluded from the study because of the focus only on ACS-PCI patients. A clopidogrel prescription claim was required within 60 days after hospitalization. RESULTS: Of the 6,687 ACS-PCI patients included in the study, 5,174 (77.4%) were male, 5,587 (83.6%) were <65 years old, 4,821 (72.1%) had hypertension, 5,176 (77.4%) had hyperlipidemia, and 1,777 (26.6%) had diabetes. At index hospitalization drug-eluting stents were the most frequently used: 5,534 (82.8%). Of the 4,384 patients who completed the 15-month follow-up, a total of 1,367 (31.2%) patients were rehospitalized for cardiovascular (CV)-related events, of which 811 (59.3%) were revascularization procedures: 13 (1.0%) for coronary artery bypass graft and 798 (58.4%) for PCI. In general, rehospitalizations associated with revascularization procedures cost more than other CV-related rehospitalizations. Patients rehospitalized for revascularization procedures had the shortest median time from post-index PCI to rehospitalization when compared to the patients who were rehospitalized for other CV-related events. CONCLUSIONS: For ACS patients who underwent PCI, revascularization procedures represented a large portion of rehospitalizations. Revascularization procedures appear to be the most frequent, most costly, and earliest cause for rehospitalization after ACS-PCI.