Diagnosis Of Atherosclerotic Cardiovascular Disease Research Articles

Impact of an integrated clinical and specialty pharmacy service model on access to PCSK9 inhibitor therapy

Background: Despite the proven benefits of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in dramatically lowering low-density lipoprotein cholesterol (LDL-C) levels, access to these costly medications remains challenging. A recent nationwide report of over 51,000 patients prescribed a PCSK9 inhibitor found that only 47% of patients gained insurance approval, with an average time to approval of 29 days. Vanderbilt Specialty Pharmacy (VSP) developed a model to streamline insurance approval and increase patient access to evolocumab and alirocumab.Objectives: To evaluate the time to PCSK9 inhibitor approval and factors that impact time to approval in an integrated specialty pharmacy model.Methods: A single-center, retrospective cohort study of patients prescribed a PCSK9 inhibitor by a Vanderbilt University Medical Center provider between 1 September 2015 and 1 December 2016 was conducted. The primary endpoint was days to treatment approval from first provider treatment request. Secondary endpoints were patient, prescriber, and clinical factors related to treatment approval. Descriptive statistics, univariate, and multivariable Cox regression analyses were performed to evaluate the impact of specified factors on the time to treatment approval.Results: VSP gained access to PCSK9 inhibitor treatment through insurers in 264 patients during the study period. The majority were male (52%) with a mean age of 62 (SD ±11) and mean baseline LDL-C of 162mg/dL (SD ±57). The median time to medication approval was 7 days, ranging of 0–266. Mean time to medication approval was 17 days (SD ±25). On univariate analysis, older patients (≥65) were significantly more likely to achieve approval earlier compared to those <65 years (p = .031) as were patients prescribed PCSK9 therapy for atherosclerotic cardiovascular disease (ASCVD) (p < .001). The time to medication approval was longer when a prior authorization (PA) was required (HR 0.17, SD ±0.5; p < .001) or a first level appeal was required (HR 0.28, SD ±0.04; p < .001). On multivariable analysis, older age, the requirement of a PA, and the requirement of a first level appeal remained significant predictors to the time to medication approval (p < .001).Conclusions: The VSP model of an integrated clinical pharmacist and pharmacy technician expedited the time to PCSK9 inhibitor access and initiation. As expected, the need for a prior authorization or appeal increased the time to approval. However, age and diagnosis of ASCVD positively impacted time to approval.

Abstract 240: Association of Depression Risk With Patient Experience, Healthcare Expenditure and Health Resource Utilization Among Adults With Atherosclerotic Cardiovascular Disease

Background: Approximately 20% of patients with atherosclerotic cardiovascular disease (ASCVD) suffer from depression. Currently, these two conditions are the most common causes of disability in high-income countries and projected to become so for all countries by 2030. Depression is a risk marker for ASCVD and associated with worse health outcomes. In a nationally representative US adult population, we evaluate patient experience, healthcare expenditure and resource utilization among non-depressed ASCVD patients based on their risk for depression. Methods: The 2004-2015 Medical Expenditure Panel Survey (MEPS), a nationally representative sample was the basis for our study. We included adults ≥18 years with a diagnosis of ASCVD, ascertained by ICD9 codes and/or self-reported data and excluded those with a diagnosis of Depression, identified by ICD9 code 311. Individuals were stratified by depression risk (based on the Patient Health Questionnaire-2): Two-part econometric model was used to study cost data, and regression models for all other associations, adjusted for ASCVD risk factors. Results: The study sample consisted of 16,136 ASCVD patients without the diagnosis of depression (aged 67 ± 10 years, 55% male), translating into 179.2 million US adults, of which 8.6% (15.5 million US adults) had a high risk for depression. Individuals with high vs. low risk for depression had higher overall and out-of-pocket healthcare expenditures ($1,200 &amp; $353, respectively; both p &lt; 0.001). Additionally, those with high risk had higher odds for hospitalizations [OR 1.75 (1.75, 2.32)], poor self-perceived health status [OR 4.83 (3.28, 7.12)], poor patient-provider communication scores [OR 2.44 (1.93, 3.09)], poor patient satisfaction [OR 3.33 (1.64, 6.77)], and significantly worse healthcare-related quality of life measures than those with low risk for depression (Table). Conclusion: Among ASCVD patients without a diagnosis of depression, individuals with a greater risk for depression were more likely to report worse healthcare experience, increased resource utilization and higher healthcare spending. To enhance health outcomes and increase healthcare efficiency, more aggressive screening for depression risk to promote improved recognition and intervention are needed among this vulnerable population.

Patient-reported adherence to statin therapy, barriers to adherence, and perceptions of cardiovascular risk.

BackgroundPatient reports of their adherence behaviors, concerns about statins, and perceptions of atherosclerotic cardiovascular disease (ASCVD) risk could inform approaches for improving adherence to statin therapy. We examined these factors and their associations with adherence.MethodsWe conducted telephone interviews among a stratified random sample of adults receiving statins within an integrated delivery system (N = 730, 81% response rate) in 2010. We sampled equal numbers of individuals in three clinical risk categories: those with 1) coronary artery disease; 2) diabetes or other ASCVD diagnosis; and 3) no diabetes or ASCVD diagnoses. We assessed 15 potential concerns about and barriers to taking statins, and perceived risk of having a heart attack in the next 10 years (0–10 scale). We calculated the proportion of days covered (PDC) by statins in the last 12 months using dispensing data and used multivariate logistic regression to examine the characteristics associated with non-adherence (PDC<80%). Analyses were weighted for sampling proportions.ResultsSixty-one percent of patients with PDC<50% reported not filling a new prescription, splitting or skipping statins, or stopping refilling statins in the last 12 months vs. 15% of those with PDC≥80% (p<0.05). The most commonly reported concerns about statins were preferring to lower cholesterol with lifestyle changes (66%), disliking medications in general (59%), and liver or kidney problems (31%); having trouble remembering to take statins (9%) was the most common reason for taking less than prescribed. In multivariate analyses, clinical risk categories were not significantly associated with odds of non-adherence; however, those with higher perceived risk of heart attack were less likely to be non-adherent.ConclusionsPatient-reported medication-taking behaviors were correlated with statin PDC and those with lower perceived cardiovascular risk were less likely to be adherent. These findings highlight the importance of eliciting from and educating patients on their adherence behaviors and ASCVD risks.

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

PurposeThe 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 methodsThis 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.ResultsA 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.ConclusionPatients 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.

Paleogenetic study on the 17th century Korean mummy with atherosclerotic cardiovascular disease.

While atherosclerotic cardiovascular disease (ASCVD) is known to be common among modern people exposed to various risk factors, recent paleopathological studies have shown that it affected ancient populations much more frequently than expected. In 2010, we investigated a 17th century Korean female mummy with presumptive ASCVD signs. Although the resulting report was a rare and invaluable conjecture on the disease status of an ancient East Asian population, the diagnosis had been based only on anatomical and radiological techniques, and so could not confirm the existence of ASCVD in the mummy. In the present study, we thus performed a paleogenetic analysis to supplement the previous conventional diagnosis of ASCVD. In aDNA extracted from the same Korean mummy, we identified the risk alleles of seven different SNPs (rs5351, rs10757274, rs2383206, rs2383207, rs10757278, rs4380028 and rs1333049) that had already been revealed to be the major risk loci of ASCVD in East Asian populations. The reliability of this study could be enhanced by cross-validation using two different analyses: Sanger and SNaPshot techniques. We were able to establish that the 17th century Korean female had a strong genetic predisposition to increased risk of ASCVD. The current paleogenetic diagnosis, the first of its kind outside Europe, re-confirms its utility as an adjunct modality for confirmatory diagnosis of ancient ASCVD.

Trends in prescribing rate of statins at discharge and modifiable factors in patients with atherosclerotic cardiovascular disease.

Tremendous effort has been invested in reducing the prevalence of atherosclerotic cardiovascular disease (ASCVD) in China. Meanwhile, accumulating evidence has emerged to show the benefits of statins in the prevention of cardiovascular disease. The present study investigated the change trends of statins prescription at discharge among patients with ASCVD in recent years, differences across subtypes of ASCVD, and associated factors. The study included 51,972 patients with a discharge diagnosis of ASCVD who were hospitalized in West China Hospital from 2008 to 2014. Trends of statins prescription rates between subtypes of ASCVD were compared and potential influential factors were explored. The overall statins prescription rate in patients with ASCVD was 58.8%. Adjusted odds ratios (ORs) of increase in prescription rate per year were 1.15 (95% CI 1.13-1.17, p<0.001), 1.14 (95% CI 1.10-1.17, p<0.001), 1.19 (95% CI 1.16-1.23; p<0.001), 1.14 (95% CI 1.09-1.19; p<0.001), and 1.13 (95% CI 1.09-1.17; p<0.001) for ASCVD, coronary artery disease, cerebrovascular disease, peripheral arterial disease (PAD), and polyvascular disease, respectively; no significant differences in trends were detected among ASCVD subtypes. However, statins prescription rates were persistently lower in cerebrovascular disease and PAD than the other two subtypes. Discharge departments, together with other physician-related and patient-related characteristics were associated with statins utilization. In conclusion, between 2008 and 2014, statins prescription rate in patients with ASCVD was not optimal. The increasing trends in statins prescription among patients with ASCVD subtypes were similar but the differences did not decrease. Consciousness of integrated and successive medical care should be strengthened in China.

Predicting Cardiovascular Events in Familial Hypercholesterolemia: The SAFEHEART Registry (Spanish Familial Hypercholesterolemia Cohort Study).

Although risk factors for atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH) have been described, models for predicting incident ASCVD have not been reported. Our aim was to use the SAFEHEART registry (Spanish Familial Hypercholesterolemia Cohort Study) to define key risk factors for predicting incident ASCVD in patients with FH. SAFEHEART is a multicenter, nationwide, long-term prospective cohort study of a molecularly defined population with FH with or without previous ASCVD. Analyses to define risk factors and to build a risk prediction equation were developed, and the risk prediction equation was tested for its ability to discriminate patients who experience incident ASCVD from those who did not over time. We recruited 2404 adult patients with FH who were followed up for a mean of 5.5 years (SD, 3.2 years), during which 12 (0.5%) and 122 (5.1%) suffered fatal and nonfatal incident ASCVD, respectively. Age, male sex, history of previous ASCVD, high blood pressure, increased body mass index, active smoking, and low-density lipoprotein cholesterol and lipoprotein(a) levels were independent predictors of incident ASCVD from which a risk equation with a Harrell C index of 0.85 was derived. The bootstrap resampling (100 randomized samples) of the original set for internal validation showed a degree of overoptimism of 0.003. Individual risk was estimated for each person without an established diagnosis of ASCVD before enrollment in the registry by use of the SAFEHEART risk equation, the modified Framingham risk equation, and the American College of Cardiology/American Heart Association ASCVD Pooled Cohort Risk Equations. The Harrell C index for these models was 0.81, 0.78, and 0.8, respectively, and differences between the SAFEHEART risk equation and the other 2 were significant (P=0.023 and P=0.045). The risk of incident ASCVD may be estimated in patients with FH with simple clinical predictors. This finding may improve risk stratification and could be used to guide therapy in patients with FH. URL: http://clinicaltrials.gov. Unique identifier: NCT02693548.

Abstract 112: Statin Utilization in the Outpatient Clinic of a University Based Residency Training Program

Background: Current guidelines released in 2013 recommend statins for five specific patient groups including persons with clinical atherosclerotic cardiovascular disease (ASCVD) and diabetes. National estimates of statin utilization in 2012 report statin use in persons with ASCVD at 58.8% and 63.5% among persons with diabetes. A recent review also showed suboptimal statin prescription rates prior to 2013, with only 23% being prescribed a statin at goal dose. Our goal was to assess statin prescriptions in a large resident run outpatient clinic and identify factors affecting statin prescriptions as potential targets for intervention to improve compliance with the guidelines. Methods: We obtained data from the medical record data warehouse of a primary care outpatient clinic within a large safety-net hospital from Jan–Dec 2015. The clinic is predominantly run by internal medicine residents and supervised by general internal medicine attending physicians. Patients with a diagnosis of ASCVD and diabetes were identified and electronic medical records abstraction was done to identify persons who were prescribed a statin (regardless of dose). Bivariate analyses were conducted to identify potential factors affecting statin prescriptions. Results: Our patient population was predominantly African American, representing more than 70% of our clinic patients. We found 87% of persons with ASCVD and 70% of persons with diabetes were on statin. We found no differences in statin prescriptions by demographic characteristics among persons with ASCVD. Among patients with diabetes, younger age (p&lt;0.01), female sex (p&lt;0.05), non-black race (p&lt;0.05) and private insurance/lack of insurance (p&lt;0.01) were associated with a lower likelihood of being prescribed a statin. Conclusion: Statin prescriptions among patients with ASCVD and diabetes appear to be higher in our patient population compared to prior national estimates, however statin prevalence remains suboptimal. Our next steps are to begin a targeted educational intervention for residents in the continuity clinic and ultimately demonstrate that resident driven intervention is an effective way to increase compliance with the guidelines.

Missed Opportunities for Primary Prevention of Cardiovascular Disease in an HIV Clinic

Background Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death among people living with HIV (PLWH). PLWH have a high prevalence of ASCVD risk factors, including hypertension (HTN), dyslipidemia, diabetes mellitus (DM), elevated BMI, smoking, physical inactivity, and poor diet.Methods Setting—Urban Ryan White funded clinic in Columbia, SC providing care to about 2200 PLWH. A retrospective chart review was performed on a sample of patients ≥40 years old. Patients were eligible if they did not have a known diagnosis of ASCVD, had ≥ 3 visits in the last 3 years, and at least 1 visit in the past 12 months. Data regarding demographics, comorbidities, lab values, medications, and recent blood pressures were abstracted. Data were collected on assessment and intervention for smoking, weight loss, diet, and exercise. Objectives of this study were to: (1) determine the prevalence of ASCVD risk factors among patients without known ASCVD; (2) estimate the proportion of patients who received appropriate pharmacologic and lifestyle interventions. ResultsCharts were reviewed in random order until 100 charts had the required variables to calculate the 10-year ASCVD risk (Figure 1). These complete charts were similar in demographic characteristics to the clinic population. Of the complete charts, 66% met BMI criteria for being obese or overweight; but < 30% of these patients had documentation of the diagnosis, or received appropriate intervention for diet, exercise, or weight loss. HTN was diagnosed in 42% of patients, and 52% of these were adequately controlled. An additional 9% met criteria for HTN but did not carry the diagnosis. Documented diagnosis of DM was surprisingly low at <5%. Nurses assessed smoking in 100% of patients, and the majority of smokers received an intervention. Based on current guidelines, less than 25% of eligible patients were prescribed a statin (Figure 2). To our concern, none of the patients with LDL ≥190 mg/dL or DM had evidence of statin therapy.Conclusion Although > 85% of clinic patients have an undetectable HIV viral load, there were multiple missed opportunities for primary prevention of cardiovascular disease, including interventions for smoking cessation, diet and exercise, and guideline based anti-HTN and statin therapy.Figure 1:Disclosures A. Jones, Proctor & Gamble: Stock, Dividend. CVS Health Corp: Stock, Dividend. Johnson & Johnson: Stock, Dividend. Baxter Inc.: Stock, Dividend. Becton-Dickinson: Stock, Dividend. United Health Group: Stock, Dividend

Antihyperlipidemic Medication Treatment Patterns and Statin Adherence Among Patients with ASCVD in a Managed Care Plan After Release of the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol.

The American College of Cardiology (ACC) and American Heart Association (AHA) released a new blood cholesterol treatment guideline in November 2013. It is unknown how the new recommendations have affected cholesterol medication use and adherence in a commercial health plan. To evaluate the effect of the 2013 guideline release on antihyperlipidemic treatment patterns and statin adherence in patients with atherosclerotic cardiovascular disease (ASCVD) compared with a historical control group. This study was a historical cohort analysis of adult patients (aged 21-75 years) with clinical ASCVD enrolled in a SelectHealth commercial health plan. Patients were included in the guideline implementation cohort if they had a medical claim with an ICD-9-CM diagnosis of ASCVD in the year before the November 2013 ACC/AHA guideline release. The index date was defined as the first outpatient medical claim with an ICD-9-CM for ASCVD in the first 6 months after the guideline was released. Patients were required to have continuous enrollment for ≥ 1 year before and after the index date. These same criteria were applied to patients exactly 4 years earlier to identify a historical control group. Patients meeting these criteria formed the antihyperlipidemic treatment patterns cohort. Of these, patients who also had ≥1 pharmacy claim for a statin in the 1-year pre- and post-index periods were included in the statin adherence cohort. Antihyperlipidemic treatment patterns were assessed using pharmacy claims for antihyperlipidemic medications in the 1-year pre- and post-index periods. Antihyperlipidemic medication claims were classified as a nonstatin cholesterol medication, low-intensity statin, moderate-intensity statin, or high-intensity statin. To address differences in pre-index antihyperlipidemic medications between the guideline implementation and historical control groups, patients were randomly matched 1:1 based on pre-index classification in a post hoc analysis. Post-index antihyperlipidemic classifications were compared between groups using a Stuart-Maxwell test. The change in mean statin adherence (proportion of days covered [PDC]) was compared within and between groups using paired and independent t-tests, respectively. The proportion of adherent patients (PDC ≥ 0.80) in the pre- and post-index periods was compared between groups using a chi-square test. A multivariable logistic regression was used to compare the likelihood of being adherent in the post-index period while controlling for pre-index adherence and other potential confounders. A total of 7,818 adult members with ASCVD in the index period and 1 year before the index period were identified. Of those, 1,841 patients met the criteria to be included in the analysis, and 1,526 patients were matched on antihyperlipidemic classification and included in the antihyperlipidemic treatment patterns analysis. Baseline characteristics were similar, although the guideline implementation group was younger (58.3 vs. 60.5 years, P < 0.001), and more were male (74.8% vs. 71.3%, P = 0.106) than the historical control group. In the matched cohort, there was a significant difference in the post-index antihyperlipidemic classification (P < 0.001), which appeared to be a result of the difference in nonstatin cholesterol medications (guideline 6.9% vs. historical 13.0%) and high-intensity statins (guideline 23.7% vs. historical 16.3%). Of the 1,841 patients in the antihyperlipidemic treatment patterns cohort, 919 patients met inclusion criteria for the statin adherence analysis. Although PDC decreased over time in both groups, significantly more patients in the guideline implementation group were adherent in the post-index period than the historical control group (66.5% vs. 57.3%, respectively; P = 0.005). Additionally, patients in the guideline implementation group were more likely than the historical control to be adherent in the post-index period when adjusting for potential confounders (OR = 1.49, 95% CI = 1.10-2.03; P = 0.011). Since the release of the updated ACC/AHA treatment guideline, more commercial health plan patients with ASCVD used high-intensity statins and fewer used nonstatin cholesterol medications than historical controls. Additionally, since the guideline release, more patients are adherent to statin therapy than historical controls. This study provides managed care organizations with valuable information regarding the effect of the 2013 ACC/AHA guideline. No outside funding or services were received for this work. Outside of the current study, Bellows has received research funding from Biogen Idec, Regeneron Pharmaceuticals, Myriad Genetic Laboratories, Shire Development, and Bristol-Myers Squibb and an honorariam from Avanir Pharmaceuticals. Voelker received summer intern support from Pfizer and the AMCP Foundation during the time of this study. The remaining authors have nothing to disclose. All authors contributed to study concept and design and to the revision of the manuscript. Bellows, Olsen, and Voelker collected the data, assisted by Wander; data interpretation was performed primarily by Bellows, along with Olsen and Voelker and assisted by Wander. The manuscript was primarily written by Bellows, along with the other authors.

Potential Clinical Impact of Abdominal Aortic Calcification on Bone Density Lateral Spine Images

Abdominal aortic calcification (AAC) predicts incident atherosclerotic cardiovascular disease (ASCVD) events and can be accurately identified on densitometric lateral spine images obtained at the time of bone densitometry. Our objective was to estimate the proportion of patients referred for bone densitometry who have a high level of AAC and are not already known to have ASCVD or to be at high risk for ASCVD. AAC was scored on densitometric lateral spine images of 2168 individuals blinded to clinical diagnoses or risk factors using the 24-point Framingham scale. We ascertained preexisting ASCVD diagnoses and risk factors using electronic health record data. We used the risk calculator of the American Heart Association (AHA) and the American College of Cardiology (ACC) to estimate the 10-yr risk of hard ASCVD outcomes (myocardial infarction, death caused by coronary heart disease, or nonfatal or fatal stroke). A high level of AAC (AAC score ≥5) was present in 41 (6.1%, 95% confidence interval [CI]: 4.4%–8.2%) of those aged less than 65 yr, in 253 (23.1%, 95% CI: 20.7%–25.7%) of those aged 65–74 yr, and in 153 (37.8%, 95% CI: 33.0%–42.7%) of those aged 75–80 yr. Among those aged 65–74 yr, 16.9% (95% CI: 14.7%–19.3%) had a high level of AAC and no prior clinical diagnosis of ASCVD, but only 2.4% had a high level of AAC and a predicted 10-yr risk of hard ASCVD outcomes <7.5%. AAC is common among those aged 65 yr and older who were referred for bone densitometry and had no known ASCVD, although these individuals can also be recognized as being at intermediate to high risk using the AHA-ACC ASCVD risk calculator. Further studies regarding the impact of identification of AAC on provider and patient cardiovascular disease risk management choices are warranted.

Abstract P069: Modifiable Risk Factors as Drivers of Pharmaceutical Expenditures Among US Adults with Atherosclerotic Heart Disease: 2012 Medical Expenditure Panel Survey

Background: Atherosclerotic Cardiovascular disease (ASCVD) remains the leading cause of deaths and costs in the US. Despite advancements in therapies, no study has evaluated drivers of pharmaceutical expenditures among individuals with ASCVD. We aimed to assess the economic impact of modifiable risk factors (MRF) on overall pharmaceutical expenditures among ASCVD patients. Methods: We studied the 2012 Medical Expenditure Panel Survey (MEPS) data of adults aged ≥40 years with Body Mass Index ≥18.5Kg/m2 and ICD-9 diagnosis of ASCVD (410, 413, 414, 433, 434, 435, 436, 437, 440, 443, and 447). Using total pharmacy expenditure variable in MEPS as our primary outcome, marginal and actual expenditures associated with predictors were estimated using a two-part econometric model with probit and glm, family(gamma) link (log). Results: Based on the 2012 MEPS, an estimated 140.7 million people in US are aged ≥40 years. An estimated 15.4 million had ASCVD (69±15 years; 41% female). Overall, total pharmaceutical expenditure among those with ASCVD was $52.7 billion (95% CI: $44.2-62.0 billion), which accounted for 33.7% of total pharmaceutical expenditures. Individuals with ASCVD had $1,847 (95% CI: $1,655 - 2,038) incremental pharmaceutical expenditure vs. those without it (p&lt;0.001). The two-part econometric model showed that all MRF independently impacted incremental expenditure. By aggregates of MRF, 50% had 2-3; 39% had 4-6; and the rest (11%) had one or none. The estimated pharmaceutical expenditures was lower with favorable MRF status irrespective of comorbid conditions. In adjusted analyses, as compared to those with ≥4 MRF, those with 2-3 had $1,881 (95% CI: $1,242 -2,521) and those with 0-1 MRF had $2,669 (95% CI: $2,317 - 3,020) lower pharmaceutical costs, respectively. Conclusion: Our study results suggest attainment of favorable modifiable risk status as delineated in AHA 2020 Impact goals can have a beneficial impact on pharmaceutical costs, which accounts for significant proportion of overall healthcare expenditure.

Abstract 18904: VARSITY Study (VA Retrospective study of Statin IntensiTY): Utilizing a Large VA Cohort to Determine the Actual Clinical Response of LDL Reduction After Initiating Statin Therapy in Newly Diagnosed ASCVD

Background: According to the 2013 ACC/AHA Blood Cholesterol Guideline (BCGL), high-intensity statin therapy (HIST) is recommended in individuals with newly diagnosed atherosclerotic cardiovascular disease (ASCVD) and this therapy is expected to lower LDL by &gt;50%. These recommendations come from multiple studies which demonstrated that the reduction in major vascular events was proportional to the absolute LDL reduction. This retrospective study utilized a large VA cohort to report the LDL reduction with the initiation of statin therapy after an initial diagnosis of ASCVD. Methods: A national cohort of VA patients with a new diagnosis of ASCVD and subsequent initiation of statin therapy was constructed. The most proximate LDL measured within 12 weeks before (PreLDL) and 4-12 weeks after (PostLDL) initiation of statin therapy were recorded. Patients with a prior diagnosis of ASCVD, a prior prescription for any lipid lowering drug, or a prior prescription for immunosuppressant agents were excluded. The statin doses were categorized as high-, moderate- or low-intensity as defined in the 2013 BCGL. Results: This cohort consisted of 92,755 VA patients with an initial ASCVD diagnosis from 5/1992 to 7/2014. The cohort was 97% male, 19% ethnic minority, and the average age was 66.7 (± 10.9) years. The average PreLDL was 129.8 (±35.1), the average PostLDL was 94.2 (±31.7) mg/dl, and only 2.5% were prescribed HIST. The results are summarized in Table 1. Conclusion: This cohort study examined statin intensity and LDL reduction after the initial diagnosis of ASCVD. HIST was rarely prescribed as initial therapy and in a majority of these patients the expected &gt;50% LDL reduction was not achieved. This study suggests the need for additional research to explore the factors contributing to a &gt;50% reduction in LDL following the initiation of statin therapy in patients with ASCVD, and that the monitoring of response to HIST may be clinically important.

Healthcare resource utilization and costs in working-age patients with high-risk atherosclerotic cardiovascular disease: findings from a multi-employer claims database

Objective:Patients with coronary artery disease with diabetes, a history of acute coronary syndromes, cerebrovascular atherosclerotic disease, or peripheral arterial disease are at particularly high risk for a cardiovascular (CV) event and can be defined as having high-risk atherosclerotic cardiovascular disease (ASCVD). The objective of this study is to examine healthcare resource utilization (HRU) and total healthcare costs (THC) for patients with ASCVD in a commercially insured population.Methods:A retrospective cohort study was conducted using a large, US employer-based, claims database. Patients with an ASCVD diagnosis between October 1, 2008 to September 30, 2009 who met eligibility requirements were included. All-cause and ASCVD-related HRU and THC for the first and second year of follow-up were examined for all patients and by the number of arterial beds affected. Adjusted THC were compared across groups with and without polyvascular disease.Results:The analysis included 152,290 patients with ASCVD. Use of CV-related medications, hospitalizations, and office visits were highest among patients with three arterial beds affected. Mean all-cause THC for patients with ASCVD were ∼$19,000 per patient in Year 1 or Year 2, with medical costs as the main driver. ASCVD-related THC were also similar for Year 1 ($8699) and Year 2 ($7925) across all patients. Adjusted all-cause and ASCVD-related THC for both years were greatest for patients with three affected arterial beds compared with one or two affected beds (p < 0.001 for each comparison).Conclusions:This is the first study in a managed care setting to systematically estimate all-cause and ASCVD-related THC for an aggregated population of ASCVD patients at high risk for a CV event. The economic burden of ASCVD in working-age patients in the US is substantial. Significantly higher HRU and costs were found in patients with polyvascular disease compared with those with only one affected bed.

Abstract 338: Patterns of Lipid Lowering Medication Use among Patients with Atherosclerotic Cardiovascular Disease

Background: The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the treatment of hypercholesterolemia marked a departure from previously established guidelines in regards to pharmacologic therapy. This study identified patients with atherosclerotic cardiovascular disease (ASCVD) using the new guidelines, and examined their patterns of lipid lowering medication (LLM) use in a real-world environment. Methods: This retrospective cohort study utilized claims data from the HealthCore Integrated Research Database (HIRD SM ). Newly diagnosed ASCVD patients aged ≥18 years were identified between 1/1/2007 and 11/30/2012 (index date=first ASCVD diagnosis date). Patients had both ≥ 12 months pre- and post- index health plan enrollment and no LLM use at baseline. Index LLM was identified based on earliest fill of LLM within 6 months after the index date. Index LLM dose titration, discontinuation, switch, and augmentation were examined among monotherapy initiators only. Descriptive statistics were used to examine patterns of LLM use at 12 and 36 months follow-up among all patients and those with ≥36 months post-index health plan enrollment respectively. Results: The study identified 128,017 ASCVD patients with a mean age of 59 years, 43.1% (55,136 of 128,017) female, and 48.8% (62,493 of 128,017) with ≥36 months follow-up. Within 6 months after the index date, 7.8% (9,929 of 128,017) initiated high-intensity statin monotherapy; 27.8% (35,634 of 128,017) moderate/low-intensity statin monotherapy; 1.6% (2,024 of 128,017) non-statin monotherapy; 1.4% (1,770 of 128,017) combination therapy; and 61.4% (78,660 of 128,017) had no fills for any LLM. Among monotherapy initiators over 12 and 36 months follow-up, 8.8% (4,180 of 47,587) and 12.4% (2,635 of 21,198) had up-titration of index LLM, 54.5% (25,938 of 47,587) and 77.8% (16,488 of 21,198) discontinued index LLM, 9.6% (4,579 of 47,587) and 13.9% (2,935 of 21,198) switched their index LLM, and 3.0% (1,403 of 47,587) and 2.8% (586 of 21,198) augmented index LLM. Among all patients over 12 and 36 months follow-up, 41.4% (53,049 of 128,017) and 49.7% (31,057 of 62,493) had statins, 10.6% (13,522 of 128,017) and 13.0% (8,134 of 62,493) had high-intensity statins, 5.8% (7,361of 128,017) and 12.8% (7,989 of 62,493) had ≥2 types of statins, 4.9% (6,253 of 128,017) and 9.3% (5,798 of 62,493) had both statins and non-statin LLMs, and 56.9% (72,897 of 128,017) and 47.9% (29,923 of 62,493) had no LLM. Conclusions: Few patients initiated a high-intensity statin within 6 months of ASCVD diagnosis and at 12 months and 36 months follow-up. Our findings suggest that treatment for ASCVD patients was not optimal in relation to the recent ACC/AHA guideline recommendations and significant modifications in prescribing patterns should be made towards use of high-intensity statins to improve treatment outcomes.

Abstract 15920: The Prevalence of Atherosclerotic Disease in Those With Connective Tissue Disease as a Function of Age, Race, and Traditional Risk Factors

Background: Atherosclerosis is a multifactorial disease with an intrinsic inflammatory component, but it may also be influenced by systemic inflammation. There is cardiovascular risk associated with rheumatoid arthritis (RA), but there is still a need to clarify the contributions of traditional risk factors in those with inflammatory connective tissue diseases (CTD, which includes RA) in the development of atherosclerotic cardiovascular disease (ASCVD). It would also be useful to identify particular groups of patients that are at disproportionately greater conferred risk for ASCVD owing to their CTD. For these reasons, a cross-sectional analysis of a diverse patient population could help develop finer ASCVD risk estimations in those with and without CTD. Results: A systematically queried warehouse of de-identified data from over a quarter-million adult patients at our urban medical center over the past six years showed that prevalence of ASCVD steadily increases with age, consistent with rates found in other large cohorts, in both white and African-American patients. Amongst the ~9,000 patients with CTD (RA, other inflammatory polyarthropathy, lupus, Sjögren’s syndrome, systemic sclerosis, dermatomyositis, polymyositis), the overall prevalence of ASCVD was higher than amongst those without CTD with a rate ratio of 1.9 [95% CI 1.8-2.1] for white patients and 3.3 [95% CI 3.1-3.5] for African-American patients. Subgroup analysis revealed that the rate ratio was particularly high for young adults, and especially young African-American patients (ages 18-44; rate ratio for women: 10.7 [95% CI 8.5-13.5], for men: 9.9 [95% CI 6.8-14.5]). Rate ratios of ASCVD in those with vs. without CTD declined with age as traditional risk factors became more prevalent. Importantly, in those without any documented traditional risk factors (smoking, hypertension, diabetes, dyslipidemia), a diagnosis of ASCVD was found nearly three times more frequently in those with CTD than without [rate ratio 2.9, 95% CI 2.4-3.5]. Conclusions: CTD is associated with increased ASCVD rates, and major traditional risk factors do not fully account for these increased rates. African-Americans and young adults have a disproportionately strengthened association between CTD and ASCVD.

Atherosclerotic Cardiovascular Disease in Hospitalized Patients With Systemic Sclerosis: Higher Mortality Than Patients With Lupus and Rheumatoid Arthritis

Systemic sclerosis (SSc; scleroderma) patients have an increased risk for atherosclerotic cardiovascular disease (ASCVD), possibly mediated through inflammatory and fibrotic mechanisms affecting the macrovasculature and microvasculature. We utilized the US Nationwide Inpatient Sample to assess the frequency of and mortality risk associated with ASCVD among hospitalized SSc patients. We examined the frequency and mortality associated with primary diagnoses and procedures related to ASCVD among adult SSc patients using data from 1993 to 2007. Using multivariate logistic regression (controlling for age, sex, nonelective admission, and modified Charlson Comorbidity Index), we compared the odds of death among hospitalized SSc patients with ASCVD to those with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), as well as to a control group that excluded patients with connective tissue diseases. A total of 308,452 hospitalizations of SSc patients were included, of which 5.4% were associated with a primary ASCVD diagnosis or procedure. ASCVD-related SSc hospitalizations were more likely to result in death compared with non-ASCVD SSc hospitalizations (odds ratio [OR] 1.3, 95% confidence interval [95% CI] 1.1-1.4). Multivariate analyses showed that ASCVD-related SSc hospitalizations were more likely to result in death than similar hospitalizations of SLE (OR 1.5, 95% CI 1.2-1.8), RA (OR 2.3, 95% CI 1.9-2.8), and control patients (OR 1.4, 95% CI 1.2-1.8) with ASCVD. SSc patients with ASCVD have higher in-hospital mortality than comparable groups of SLE and RA patients with ASCVD. Further research to elucidate the specific mechanisms underlying ASCVD in SSc is necessary.

Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound

We report the development and validation of an intravascular rotary catheter for bimodal interrogation of arterial pathologies. This is based on a point-spectroscopy scanning time-resolved fluorescence spectroscopy technique enabling reconstruction of fluorescence lifetime images (FLIm) and providing information on arterial intima composition and intravascular ultrasound (IVUS) providing information on arterial wall morphology. The catheter design allows for independent rotation of the ultrasonic and optical channels within an 8 Fr outer diameter catheter sheath and integrates a low volume flushing channel for blood removal in the optical pathways. In the current configuration, the two channels consist of (a) a standard 3 Fr IVUS catheter with single element transducer (40 MHz) and (b) a side-viewing fiber optic (400 μm core). Experiments conducted in tissue phantoms showed the ability of the catheter to operate in an intraluminal setting and to generate coregistered FLIm and IVUS in one pull-back scan. Current results demonstrate the feasibility of the catheter for simultaneous bimodal interrogation of arterial lumen and for generation of robust fluorescence lifetime data under IVUS guidance. These results facilitate further development of a FLIm-IVUS technique for intravascular diagnosis of atherosclerotic cardiovascular diseases including vulnerable plaques.

The Role of Matrix Metalloproteinases in Atherothrombosis

The matrix metalloproteinase (MMP) family of enzymes is involved in arterial wall extracellular matrix degradation and remodeling. The latter activities have been implicated in a number of normal and pathologic processes, such as atherosclerotic lesion formation and progression, plaque destabilization and rupture, but also in plaque stabilization and healing. As a result, the MMPs have been explored as both therapeutic targets and diagnostic tools for the treatment and diagnosis of atherosclerotic cardiovascular diseases. In this review, we summarize experimental findings, genetic associations, and the biomarker potential of MMPs in atherothrombosis. In addition, the regulation and expression of MMPs in atherosclerotic plaques is discussed, with an emphasis on the role of lipid-derived inflammatory mediators as modulators of MMP activity.