Quality of Life in Patients With Chronic Limb-Threatening Ischemia Treated With Revascularization.

BACKGROUND: In the BEST-CLI trial (Best Endovascular Versus Best Surgical Therapy for Patients With Chronic Limb-Threatening Ischemia), a prespecified secondary objective was to assess the effects of revascularization strategy on health-related quality of life (HRQoL). METHODS: Patients with chronic limb-threatening ischemia were randomized to surgical bypass (Bypass) or endovascular intervention (Endo) in 2 parallel trials. Cohort 1 included patients with single-segment great saphenous vein; cohort 2 included those lacking suitable single-segment great saphenous vein. HRQoL was assessed over the trial duration using Vascular Quality-of-Life (VascuQoL), European Quality-of-Life-5D (EQ-5D), the Short Form-12 (SF-12) Physical Component Summary (SF-12 PCS), SF-12 Mental Component Summary (SF-12 MCS), Utility Index Score (SF-6D R2), and numeric rating scales of pain. HRQoL was summarized by cohort and compared within and between groups using mixed-model linear regression. RESULTS: A total of 1193 and 335 patients in cohorts 1 and 2 with a mean follow-up of 2.9 and 2.0 years, respectively, were analyzed. In cohort 1, HRQoL significantly improved from baseline to follow-up for both groups across all measures. For example, mean (SD) VascuQoL scores were 3.0 (1.3) and 3.0 (1.2) for Bypass and Endo at baseline and 4.7 (1.4) and 4.8 (1.5) over follow-up. There were significant group differences favoring Endo when assessed with VascuQoL (difference, -0.14 [95% CI, -0.25 to -0.02]; P=0.02), SF-12 MCS (difference, -1.03 [95% CI, -1.89 to -0.18]; P=0.02), SF-6D R2 (difference, -0.01 [95% CI, -0.02 to -0.001]; P=0.03), numeric rating scale pain at present (difference, 0.26 [95% CI, 0.03 to 0.49]; P=0.03), usual level during previous week (difference, 0.26 [95% CI, 0.04 to 0.48]; P=0.02), and worst level during previous week (difference, 0.29 [95% CI, 0.02 to 0.56]; P=0.04). There was no difference between treatment arms on the basis of EQ-5D (difference, -0.01 [95% CI, -0.03 to 0.004]; P=0.12) or SF-12 PCS (difference, -0.41 [95% CI, -1.2 to 0.37]; P=0.31). In cohort 2, HRQoL also significantly improved from baseline to the end of follow-up for both groups based on all measures, but there were no differences between Bypass and Endo on any measure. CONCLUSIONS: Among patients with chronic limb-threatening ischemia deemed eligible for either Bypass or Endo, revascularization resulted in significant and clinically meaningful improvements in HRQoL. In patients with an available single-segment great saphenous vein for bypass, but not among those without one, Endo was statistically superior on some HRQoL measures; however, these differences were below the threshold of clinically meaningful difference.

Pragmatic guidance for embedding pragmatic clinical trials in health plans: Large simple trials aren't so simple.

BACKGROUND: There are unique opportunities related to the design and conduct of pragmatic trials embedded in health insurance plans, which have longitudinal data on member/patient demographics, dates of coverage, and reimbursed medical care, including prescription drug dispensings, vaccine administrations, behavioral healthcare encounters, and some laboratory results. Such trials can be large and efficient, using these data to identify trial-eligible patients and to ascertain outcomes. METHODS: We use our experience primarily with the National Institutes of Health Pragmatic Trials Collaboratory Distributed Research Network, which comprises health plans that participate in the US Food & Drug Administration's Sentinel System, to describe lessons learned from the conduct and planning of embedded pragmatic trials. RESULTS: Information is available for research on more than 75 million people with commercial or Medicare Advantage health plans. We describe three studies that have used or plan to use the Network, as well as a single health plan study, from which we glean our lessons learned. CONCLUSIONS: Studies that are conducted in health plans provide much-needed evidence to drive clinically meaningful changes in care. However, there are many unique aspects of these trials that must be considered in the planning, implementation, and analytic phases. The type of trial best suited for studies embedded in health plans will be those that require large sample sizes, simple interventions that could be disseminated through health plans, and where data available to the health plan can be leveraged. These trials hold potential for substantial long-term impact on our ability to generate evidence to improve care and population health.

Baseline modern medical management in the BEST-CLI trial.

OBJECTIVES: The use of optimal medical therapy (OMT) in patients with chronic limb-threatening ischemia (CLTI) has not been well-studied. The Best Endovascular vs Best Surgical Therapy in Patients with CLTI study (BEST-CLI) is a multicenter, randomized, controlled trial sponsored by the National Institutes of Health comparing revascularization strategies in patients with CLTI. We evaluated the use of guideline-based OMT among patients with CLTI at the time of their enrollment into the trial. METHODS: A multidisciplinary committee defined OMT criteria related to blood pressure and diabetic management, lipid-lowering and antiplatelet medication use, and smoking status for patients enrolled in BEST-CLI. Status reports indicating adherence to OMT were provided to participating sites at regular intervals. Baseline demographic characteristics, comorbid medical conditions, and use of OMT at trial entry were evaluated for all randomized patients. A linear regression model was used to identify the relationship of predictors to the use of OMT. RESULTS: At the time of randomization (n = 1830 total enrolled), 87% of patients in BEST-CLI had hypertension, 69% had diabetes, 73% had hyperlipidemia, and 35% were currently smoking. Adherence to four OMT components (controlled blood pressure, not currently smoking, use of one lipid-lowering medication, and use of an antiplatelet agent) was modest. Only 25% of patients met all four OMT criteria; 38% met three, 24% met two, 11% met only one, and 2% met none. Age ≥80 years, coronary artery disease, diabetes, and Hispanic ethnicity were positively associated, whereas Black race was negatively associated, with the use of OMT. CONCLUSIONS: A significant proportion of patients in BEST-CLI did not meet OMT guideline-based recommendations at time of entry. These data suggest a persistent major gap in the medical management of patients with advanced peripheral atherosclerosis and CLTI. Changes in OMT adherence over the course of the trial and their impact on clinical outcomes and quality of life will be assessed in future analyses.

Lipid-lowering treatment among older patients with atherosclerotic cardiovascular disease.

BACKGROUND: The contemporary uptake of lipid-lowering therapies (LLT), including more intensive treatment with high-intensity statins and non-statin LLT, among U.S. older adults (≥75 years old) with ASCVD is unknown. METHODS: In this multicenter retrospective cohort study of a large geographically diverse sample of commercially insured U.S. older adults with ASCVD, we assessed treatment with LLT. Secondary measures included LDL-C above target ≥70 mg/dl, persistence and adherence to therapy. RESULTS: Treatment with statins, high-intensity statins, ezetimibe, and PCSK9 inhibitors was assessed in 194,503 older adults (49.9% female) with known ASCVD on January 31st, 2019. 49.3% of older adults with ASCVD were on any statin, with 16.6% receiving a high-intensity statin and 32.7% on low-or moderate-intensity statins. Treatment with ezetimibe (2.4%) or PCSK9 inhibitors (0.24%) was rare and 62.6% of the overall cohort had an LDL-C above target at ≥70 mg/dl. Patients on high-intensity statins were more frequently male, had a diagnosis of coronary artery disease, and were more frequently seen by a cardiologist compared with those on low-or moderate-intensity statins and untreated individuals (p < 0.0001). The majority of older adults on high-intensity statins remained on therapy at 12 months (91.9%) and 85.7% had ≥75% adherence to treatment. CONCLUSIONS: Less than half of eligible older adults with ASCVD are on statins and only a minority of patients are receiving more intensive lipid-lowering to improve outcomes.

Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia.

BACKGROUND: Patients with chronic limb-threatening ischemia (CLTI) require revascularization to improve limb perfusion and thereby limit the risk of amputation. It is uncertain whether an initial strategy of endovascular therapy or surgical revascularization for CLTI is superior for improving limb outcomes. METHODS: In this international, randomized trial, we enrolled 1830 patients with CLTI and infrainguinal peripheral artery disease in two parallel-cohort trials. Patients who had a single segment of great saphenous vein that could be used for surgery were assigned to cohort 1. Patients who needed an alternative bypass conduit were assigned to cohort 2. The primary outcome was a composite of a major adverse limb event - which was defined as amputation above the ankle or a major limb reintervention (a new bypass graft or graft revision, thrombectomy, or thrombolysis) - or death from any cause. RESULTS: In cohort 1, after a median follow-up of 2.7 years, a primary-outcome event occurred in 302 of 709 patients (42.6%) in the surgical group and in 408 of 711 patients (57.4%) in the endovascular group (hazard ratio, 0.68; 95% confidence interval [CI], 0.59 to 0.79; P<0.001). In cohort 2, a primary-outcome event occurred in 83 of 194 patients (42.8%) in the surgical group and in 95 of 199 patients (47.7%) in the endovascular group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06; P = 0.12) after a median follow-up of 1.6 years. The incidence of adverse events was similar in the two groups in the two cohorts. CONCLUSIONS: Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar. (Funded by the National Heart, Lung, and Blood Institute; BEST-CLI ClinicalTrials.gov number, NCT02060630.).

High-Intensity Statin Use Among Patients With Atherosclerosis in the U.S.

BACKGROUND: Preventive therapy among patients with established atherosclerotic cardiovascular disease (ASCVD) is generally underused. Whether new guideline recommendations and a focus on implementation have improved the use of high-intensity statins is unknown. OBJECTIVES: This study sought to evaluate the patterns and predictors of statin use among patients with ASCVD. METHODS: In this retrospective cohort study, pharmacy and medical claims data from a commercial health plan were queried for patients with established ASCVD between January 31, 2018, and January 31, 2019. Statin use on an index date of January 31, 2019, was evaluated, as was 12-month adherence and discontinuation. Multivariable logistic regression was used to determine independent associations with statin use of varying intensities. RESULTS: Of the 601,934 patients with established ASCVD, 41.7% were female, and the mean age was 67.5 ± 13.3 years. Overall, 22.5% of the cohort were on a high-intensity statin, 27.6% were on a low- or moderate-intensity statin, and 49.9% were not on any statin. In multivariable analysis, younger patients, female patients, and those with higher Charlson comorbidity score were less likely to be prescribed any statin. Among statin users, female patients, older patients, and those with peripheral artery disease were less likely to be on a high-intensity formulation, whereas a cardiology encounter in the prior year increased the odds. The majority of high-intensity stain users achieved high levels of adherence. CONCLUSIONS: Substantial underuse of statins persists in a large, insured, and contemporary cohort of patients with ASCVD from the United States. In particular, concerning gaps in appropriate statin use remain among younger patients, women, and those with noncoronary ASCVD.

Awareness, Knowledge, and Utility of RCT Data vs RWE: Results From a Survey of US Cardiologists: Real-world Evidence in Clinical Decision Making.

Real-world evidence (RWE) provides a potential rich source of additional information to the body of data available from randomized clinical trials (RCTs), but there is a need to understand the strengths and limitations of RWE before it can be applied to clinical practice. To gain insight into current thinking in clinical decision making and utility of different data sources, a representative sampling of US cardiologists selected from the current, active Fellows of the American College of Cardiology (ACC) were surveyed to evaluate their perceptions of findings from RCTs and RWE studies and their application in clinical practice. The survey was conducted online via the ACC web portal between 12 July and 11 August 2017. Of the 548 active ACC Fellows invited as panel members, 173 completed the survey (32% response), most of whom were board certified in general cardiology (n = 119, 69%) or interventional cardiology (n = 40, 23%). The survey results indicated a wide range of familiarity with and utilization of RWE amongst cardiologists. Most cardiologists were familiar with RWE and considered RWE in clinical practice at least some of the time. However, a significant minority of survey respondents had rarely or never applied RWE learnings in their clinical practice, and many did not feel confident in the results of RWE other than registry data. These survey findings suggest that additional education on how to assess and interpret RWE could help physicians to integrate data and learnings from RCTs and RWE to best guide clinical decision making.

A Pragmatic Clinical Trial to Compare the Real-World Effectiveness of V-Go versus Standard Delivery of Insulin in Patients with Advanced Type 2 Diabetes.

BACKGROUND: Many patients with type 2 diabetes mellitus (T2DM) do not have adequate glycemic control, leading to poor patient outcomes and high healthcare costs. OBJECTIVE: This prospective pragmatic clinical trial evaluated V-Go, a wearable insulin delivery device, compared with standard treatment optimization (STO) among insulin-treated patients with T2DM in a real-world, community-based practice setting. METHODS: Study sites, rather than individual patients, were randomized to V-Go or STO via cluster randomization. Patients were treated according to routine clinical practice and followed up to 4 months. T2DM medications and supplies were purchased utilizing usual insurance and co-pay systems. The primary analysis was an unadjusted treatment group comparison of glycosylated hemoglobinA1c (HbA1c) change from baseline to end of study (EOS). A cost of therapy analysis was completed on patients who had received comparable baseline T2DM treatment with multiple daily basal-bolus insulin injections (MDI). RESULTS: Analysis included 415 patients (169 V-Go, 246 STO) enrolled from 52 US sites. Mean baseline HbA1c (9.6%) was higher in V-Go (9.9%, range 8.0% - 14.2%) than STO (9.3%, range 7.9% - 13.9%, p <.001). HbA1c decreased from baseline to EOS in both V-Go (-1.0%, p<.001) and STO (-0.5%, p<.001); V-Go had significantly larger decrease (p=.002). V-Go had a significant reduction (p<.001) in mean insulin total daily dose (TDD; 0.76 U/kg baseline, 0.57 U/kg EOS), not seen in STO (0.72 U/kg baseline and EOS). The MDI group included 95 (56.2%) V-Go and 113 STO (45.9%) patients. Mean baseline HbA1c was significantly higher in V-Go (9.9%) than STO (9.4%). V-Go also experienced larger decrease in HbA1c from baseline (-1.0%) than STO (-0.36%) (p=.006) with a decrease in TDD, while STO TDD remained unchanged. EOS mean per patient per day cost of diabetes treatment was lower for V-Go ($30.59) vs STO ($32.20) (p=.006). V-Go was more cost effective than STO ($24.02 per 1% drop in HbA1c vs $58.86, respectively). CONCLUSIONS: This pragmatic clinical trial demonstrated improved HbA1c levels, lower cost, and decreased insulin dose in patients with T2DM initiating V-Go vs STO in a real-world community-based practice setting. Observed baseline HbAlc indicated use of V-Go in more difficult to manage diabetes patients.

Clinical characteristics, patterns of lipid-lowering medication use, and health care resource utilization and costs among patients with atherosclerotic cardiovascular disease.

PURPOSE: The aim of this study was to investigate real-world patient characteristics, medication use, and health care resource utilization (HCRU) and costs among patients with clinical atherosclerotic cardiovascular disease (ASCVD) as defined by 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, to examine burden of disease and unmet needs, such as potential undertreatment. PATIENTS AND METHODS: This retrospective cohort study utilized a nationally representative managed care database to identify newly diagnosed ASCVD patients between January 1, 2007, and November 30, 2012 (index = first ASCVD diagnosis date) in the USA. Patients had ≥12-month pre-index (baseline) and ≥12-month post-index (follow-up) health plan enrollment and no baseline lipid-lowering medication (LLM). Patient characteristics, LLM utilization patterns, HCRU, and costs were examined for all patients and by subgroups based on LLM use pattern and/or follow-up low-density lipoprotein cholesterol (LDL-C) levels. RESULTS: A total of 128,017 ASCVD patients were identified with a mean (SD) age of 59 (13) years, 43.1% female, and 48.8% with ≥36-month follow-up. Within 12-month follow-up, 10.6% had high-intensity statins and 56.9% had no LLM fills. Baseline mean (SD) all-cause costs were $8,852 ($25,608). At 12-month follow-up, mean (SD) all-cause and ASCVD-related costs were $31,443 ($54,040) and $20,289 ($45,159), respectively. The 36-month analyses showed similar distributions. Multivariable analyses showed that age, gender, region, health insurance type, baseline comorbidities, baseline use of specific medications, baseline lipid profiles, and index ASCVD type were significantly associated with all-cause and ASCVD-related health care costs. CONCLUSION: Patients have nonoptimal treatment for ASCVD and substantial HCRU and costs associated with residual risk. Unmet needs and cost burdens of ASCVD patients merit additional investigation.

Barriers to PCSK9 inhibitor prescriptions for patients with high cardiovascular risk: Results of a healthcare provider survey conducted by the National Lipid Association.

BACKGROUND: Statin therapy is recommended for reducing atherosclerotic cardiovascular disease (ASCVD) risk. Significant risk can remain because of insufficient clinical response or statin intolerance. Proprotein convertase subtilisin/kexin type-9 (PCSK9) therapy lowers low-density lipoprotein cholesterol and has recently been shown to lower ASCVD events. OBJECTIVE: The aim of the study was to assess the barriers and challenges experienced with the access and approval reimbursement process for PCSK9 inhibitor prescriptions. METHODS: In 2016, the National Lipid Association conducted an online survey on PCSK9 inhibitor use and barriers to prescription among experienced healthcare workers who provide care to high-risk patients with ASCVD or familial hypercholesterolemia (FH). RESULTS: There were 434 respondent healthcare workers with extensive experience in treating lipid disorders. PCSK9 inhibitors are considered by 71.3% of respondent providers with statin-intolerant patients. There were high rates (>85%) of initial denial. The major barriers to approvals were insurer processes, provider documentation (inadequate documentation of maximally tolerated statin dose, diagnostic criteria for FH, number of statins failed if statin intolerant and most recent low-density lipoprotein cholesterol), and administrative burden (time, staff, paperwork, and appeals). Provider approval rates for getting ≥75% patients approved were higher for FH (43%) than for ASCVD patients (36%). Among providers with good approval rates, documentation was the most critical factor. Barriers more difficult to overcome include perceived higher threshold requirements by payers, drugs not on formulary, and drug costs. CONCLUSIONS: Healthcare providers encounter significant barriers to PCSK9 inhibitor prescriptions; many of these are related to documentation issues and can be overcome with checklists, staff support, and experience.

Initiation Patterns of Statins in the 2 Years After Release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Management Guideline in a Large US Health Plan.

BACKGROUND: The purpose of this study was to characterize changes in statin utilization patterns in patients newly initiated on therapy in the 2 years following the release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol management guideline in a large US health plan population. METHODS AND RESULTS: This retrospective, observational study used administrative medical and pharmacy claims data to identify patients newly initiated on statin therapy over 4 quarters prior to and 8 quarters following the release of the guideline (average N/quarter=3596). Patients were divided into the 4 statin benefit groups (SBGs) based on risk factors and laboratory lipid levels as defined in the guideline: SBG1 (with atherosclerotic cardiovascular disease [ASCVD]; N=1046/quarter), SBG2 (without ASCVD, with low-density lipoprotein cholesterol ≥190 mg/dL; N=454/quarter), SBG3 (without ASCVD, aged 40-75 years, with diabetes mellitus, low-density lipoprotein cholesterol 70-189 mg/dL; N=1391/quarter), SBG4 (no ASCVD or diabetes mellitus, age 40-75 years, low-density lipoprotein cholesterol 70-189 mg/dL, estimated 10-year ASCVD risk of ≥7.5%; N=705/quarter). Demographic variables, statin utilization patterns, lipid levels, and comorbidities were analyzed for pre- and postguideline periods. Postguideline, gradually increased high-intensity statin initiation occurred in SBG1, SBG2, and in SBG3 patients with 10-year ASCVD risk ≥7.5%. Moderate- to high-intensity statin initiation gradually increased among SBG4 patients. Recommended-intensity statin choice changed to a greater degree among patients treated by specialty care physicians. Regarding sex, target-intensity statin initiation was lower in women in all groups before and after guideline release. CONCLUSIONS: Prescriber implementation of the guideline recommendations has gradually increased, with the most marked change in the increased initiation of high-intensity statins in patients with ASCVD and in those treated by a specialist.

Lipid-lowering treatment modifications among patients with hyperlipidemia and a prior cardiovascular event: a US retrospective cohort study.

BACKGROUND: Numerous studies demonstrate that, even with use of statins, many patients are unable to meet their LDL-C goals. This study examined modifications to statin and/or ezetimibe therapy among patients with hyperlipidemia and prior history of cardiovascular (CV) events in a US commercially insured population. METHODS: Adults (age ≥18 years) initiating statins and/or ezetimibe between 1 January 2007 and 31 December 2008 were identified from HealthCore Integrated Research Database. The index date was the initiation date of statins and/or ezetimibe. All patients had ≥1 medical claims related to myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, coronary artery bypass graft, or percutaneous coronary intervention within 12 months prior to the index date. Treatment modifications to statins and/or ezetimibe initiated on the index date (index therapy) included permanent discontinuation of any lipid lowering therapy (LLT), rechallenge, switching, subtraction, augmentation, and dose changes. RESULTS: Among 17,902 patients, around 90% initiated with statin monotherapy, followed by statin and ezetimibe combination (3.0%: 18-64 years; 3.8%: ≥65 years). Ten percent or less initiated on high intensity statins. Most common treatment modifications were rechallenging index therapy (25.2%: 18-64 years, 27.0%: ≥65 years), switching (27.5%: 18-64 years, 24.6%: ≥65 years), and permanent discontinuation of any LLT (18.6%: 18-64 years, 21.0%: ≥65 years). Only 10% of patients in both groups underwent dose escalation. CONCLUSIONS: Real-world evidence indicates that few high-risk patients initiate therapy with high-intensity statins. More than 50% of patients underwent a rechallenge or switching. Despite high CVD risk profile, approximately 20% of patients permanently discontinued any LLT. Key limitations: Pharmacy claims do not provide information on whether patients who had a pharmacy fill actually took the medication as prescribed. It is unknown whether rechallenge was a simple delay in filling a prescription or an actual rechallenge of their index therapy. Reasons for treatment discontinuations or modifications were unavailable in claims data.

Cost Effectiveness of Achieving Targets of Low-Density Lipoprotein Particle Number Versus Low-Density Lipoprotein Cholesterol Level.

A recent analysis of a commercially insured US population found fewer cardiovascular disease (CVD) events in high-risk patients attaining low levels of low-density lipoprotein (LDL), as measured by LDL particle number (LDL-P) versus low LDL cholesterol (LDL-C). Here, we investigated the cost effectiveness of LDL-lowering therapy guided by LDL-P. Patients were selected from the HealthCore Integrated Research Database and followed for 12 to 36 months. Patients who achieved LDL-P <1,000 nmol/l were placed into the LDL-P cohort, whereas those without LDL-P tests, but who achieved LDL-C <100 mg/dl, were placed into the LDL-C cohort. CVD-related costs included all health plan paid amounts related to CVD events or lipid management. Cost effectiveness was assessed through incremental cost-effectiveness ratios, defined as difference in total costs across the cohorts divided by difference in CVD events, measured over follow-up. Each cohort included 2,094, 1,242, and 705 patients over 12-, 24-, and 36-month follow-up. Patients in the LDL-P cohort received more aggressive lipid-lowering therapy and had fewer CVD events during follow-up compared to patients in the LDL-C cohort. This led to greater pharmacy costs and lower medical costs over time. Incremental cost-effectiveness ratio estimates ranged from $23,131 per CVD event avoided at 12 months to $3,439 and -$4,555 at 24- and 36-month follow-up, suggesting a high likelihood that achieving LDL-P <1,000 nmol/l is cost effective. In conclusion, LDL-lowering therapy guided by LDL-P was demonstrated to be cost effective, with greater clinical and economic benefit seen over longer time horizons and with the increased use of generic statins.

Bidirectional Data Collaborations in Distributed Research.

INTRODUCTION: The need for collaborations with bidirectional data exchange within and across distributed research networks has increased. CURRENTLY EXISTING ACTIVITIES: This commentary will present currently publically available activities including the Sentinel Initiative, the Patient-Centered Outcomes Research Network (PCORnet), and the NIH Research Collaboratory. CURRENT TECHNICAL AND GOVERNANCE CHALLENGES: Even with the advances made in this arena, several technical and governance challenges remain including the evolution of clinically rich data sources and modes of care, availability of longitudinal data resources through data linkage, and the processes to share data and link data resources while ensuring privacy and proprietary control of data. PERSPECTIVE: These activities will require enhanced levels of trust between entities involved in the delivery of healthcare (Trust 2.0) in addition to the trust health plans and health systems have with patients (Trust 1.0). Recent public funding announcements and public access to data resources will likely improve the landscape of bidirectional data collaborations in distributed research.

Clinical Characteristics and Unmet Need Among Patients with Atherosclerotic Cardiovascular Disease Stratified by Statin Use.

BACKGROUND: The American College of Cardiology (ACC)/American Heart Association (AHA) 2013 guidelines for blood cholesterol treatment recommend high-intensity statins for adults with atherosclerotic cardiovascular disease (ASCVD). Currently, little is known about the real-world patient characteristics of ASCVD, as well as the clinical and economic consequences of different treatment options for this disease. OBJECTIVES: To compare the demographic, clinical, and economic characteristics of patients with clinical ASCVD who started therapy with high-intensity statins, low-/moderate-intensity statins, or no statins in usual-care settings based on data primarily before the release of the ACC/AHA 2013 guidelines. METHODS: This retrospective, observational cohort study used claims data from US commercial health plans from January 2006 to June 2014 to identify patients with ASCVD (ie, acute coronary syndrome, coronary heart disease, ischemic stroke, or peripheral arterial disease). High-intensity, low-/moderate-intensity statin users and non-statin users were selected based on the presence of a corresponding prescription fill. The index date was defined as the first statin fill date for the statin cohorts and the earliest eligibility date for clinical ASCVD for the non-statin users group. The follow-up outcomes, including treatment patterns, cardiovascular (CV) events, and healthcare utilization and costs, were assessed after matching the high-intensity statin and low-/moderate-intensity statin initiators. RESULTS: A total of 273,308 patients with ASCVD were included in the study; of these, 104,649 were statin initiators and 168,659 non-statin users. Only 8.8% (N = 24,106) of the total population initiated high-intensity statins. Patient adherence (defined as proportion of days covered ≥80%) to statin therapy was low in the matched high-intensity statin and low-/moderate-intensity statin cohorts (27.0% vs 26.4%, respectively). Approximately 16% of the patients in either of the matched cohorts had at least 1 CV event during the available follow-up period. CONCLUSION: The low percentage of patients who initiated high-intensity statin therapy, low adherence to statin therapy, and high rates of CV events during the follow-up period suggest a substantial unmet need among patients with ASCVD in the real-world setting. The demographic and clinical heterogeneity across the cohorts suggests significant variability in physician perception of the appropriate use of statins and may provide an opportunity to improve care and health outcomes in these high-risk patients.

Frequency of Attainment of Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol Goals in Cardiovascular Clinical Practice (from the National Cardiovascular Data Registry PINNACLE Registry).

Studies have found that non-high-density lipoprotein cholesterol (non-HDL-C) is a superior marker for coronary heart disease compared to low-density lipoprotein cholesterol (LDL-C). Little is known about achievement of non-HDL-C goals outside clinical trials. Within a population of 146,064 patients with dyslipidemia in the PINNACLE Registry and a subgroup of 36,188 patients with diabetes mellitus (DM), we examined the proportion of patients and patient characteristics associated with having LDL-C, non-HDL-C, and both LDL-C and non-HDL-C levels at National Cholesterol Education Program goals. LDL-C, non-HDL-C, and both LDL-C and non-HDL-C goals in the overall cohort were achieved by 73%, 73.4%, and 68.9% patients, respectively. Significant predictors of meeting all 3 goals were age, male gender, statin, nonstatin, and combined statin plus nonstatin use. Patients with co-morbidities of hypertension, previous stroke or transient ischemic attack, peripheral arterial disease, myocardial infarction, and smoking were less likely to have LDL-C, non-HDL-C, and both LDL-C and non-HDL-C levels at National Cholesterol Education Program goal. In the overall cohort, patients with DM were less likely to meet non-HDL-C and both LDL-C and non-HDL-C goals. In the subgroup of patients with DM, predictors of meeting lipid goals were similar to the overall cohort. In conclusion, these data suggest contemporary treatment patterns by cardiologists successfully achieve lipid goals in most patients. Younger, female patients and those with atherosclerotic cardiovascular disease and risk factors, such as hypertension and DM, are less likely to achieve goals and may require more careful follow-up after statin initiation. Both LDL-C and non-HDL-C goals are achieved in <70% of patients, suggesting room for improvement if a goal-targeted individualized strategy is adopted.

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.

Cardiovascular risk in patients achieving low-density lipoprotein cholesterol and particle targets.

OBJECTIVES: Previous research suggests that LDL particle number (LDL-P) may be a better tool than LDL cholesterol (LDL-C) to guide LDL-lowering therapy. Using real-world data, this study has two objectives: [1] to determine the incidence of CHD across LDL-P thresholds; and [2] to compare CHD/stroke events among patients achieving comparably low LDL-P or LDL-C levels. METHODS: A claims analysis was conducted among high-risk patients identified from the HealthCore Integrated Research Database(SM). The impact of LDL levels on risk was compared across cohorts who achieved LDL-P <1000 nmol/L or LDL-C <100 mg/dL. Cohorts were matched to balance demographic and comorbidity differences. RESULTS: Among 15,569 patients with LDL-P measurements, the risk of a CHD event increased by 4% for each 100 nmol/L increase in LDL-P level (HR 1.04; 95% CI 1.02-1.05, p < .0001). The comparative analysis included 2,094 matched patients with ≥12 months of follow-up, 1,242 with ≥24 months and 705 with ≥36 months. At all time periods, patients undergoing LDL-P measurement were more likely to receive intensive lipid-lowering therapy and had a lower risk of CHD/stroke than those in the LDL-C cohort (HR: 0.76; 95% CI: 0.61-0.96; at 12 months). CONCLUSIONS: In this real-world sample of commercially insured patients, higher LDL-P levels were associated with increased CHD risk. Moreover, high-risk patients who achieved LDL-P <1000 nmol/L received more aggressive lipid-lowering therapy than patients achieving LDL-C <100 mg/dL, and these differences in lipids and therapeutic management were associated with a reduction in CHD/stroke events over 12, 24 and 36 months follow-up.

The INITIATOR study: pilot data on real-world clinical and economic outcomes in US patients with type 2 diabetes initiating injectable therapy.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) progression often results in treatment intensification with injectable therapy to maintain glycemic control. Using pilot data from the Initiation of New Injectable Treatment Introduced after Anti-diabetic Therapy with Oral-only Regimens study, real-world treatment patterns among T2DM patients initiating injectable therapy with insulin glargine or liraglutide were assessed. METHODS: This was a retrospective analysis of claims from the OptumInsight™ (OI; January 1, 2010 to July 30, 2010) and HealthCore(®) (HC; January 1, 2010 to June 1, 2010) health insurance databases. Baseline characteristics, health care resource utilization, and costs were compared between adults with T2DM initiating injectable therapy with insulin glargine pen versus liraglutide. Follow-up outcomes, including glycated hemoglobin A1c (A1C), hypoglycemia, health care utilization, and costs, were assessed. RESULTS: At baseline, almost one in three liraglutide patients (OI, n = 363; HC, n = 521) had A1C <7.0%, while insulin glargine patients (OI, n = 498; HC, n = 1,188) had poorer health status, higher A1C (insulin glargine: 9.8% and 9.1% versus liraglutide: 7.9% and 7.7%, OI and HC, respectively, both P < 0.001), and were less likely to be obese (insulin glargine: 10.8% and 9.2% versus liraglutide: 17.4% and 18.8%, OI and HC, respectively, both P < 0.01). The percentage of patients experiencing a hypoglycemic event was numerically higher for insulin pen use for both cohorts (OI 4.4% versus 3.0%; HC 6.2% versus 2.3%). During follow-up, in the insulin glargine cohort, annualized diabetes-related costs remained unchanged ($8,344 versus $7,749 OI, and $7,094 versus $7,731 HC), despite a significant increase in pharmacy costs, due to non-significant decreases in medical costs, while the liraglutide cohort had a significant increase in annualized diabetes-related costs ($4,510 versus $7,731 OI, and $4,136 versus $7,111 HC; both P < 0.001) due to a non-significant increase in medical costs coupled with a significant increase in pharmacy costs. CONCLUSION: These descriptive data identified differences in demographic and baseline clinical characteristics among patients initiating injectable therapies. The different health care utilization and cost patterns warrant further cost-effectiveness analysis.