Clinical management and primary prevention of suspected coronary artery disease guided by computed tomography.

AIMS: Despite the well established role of coronary computed tomography angiography (CCTA) as a diagnostic gatekeeper, the yield of subsequent invasive coronary angiographies (ICA) remains low. We evaluated the adherence of CCTA integration in clinical management and primary prevention therapy. METHODS: We retrospectively analyzed patients referred for ICA after CCTA without known coronary artery disease (CAD) or structural cardiac pathologies. Based on computed tomography (CT) findings, patients were classified as appropriately or inappropriately referred to ICA, equaling Coronary Artery Disease - Reporting and Data System (CAD-RADS) categories 0-2 (<50% stenosis) and 3-5 (>50% stenosis), respectively. CT exams were compared regarding invasive findings and revascularizations. Integration of CT results into primary prevention measures was analyzed and compared to measures taken after ICA. RESULTS: Of 1005 patients referred for ICA, 81 (8.1%) had no obstructive CT findings and therefore no ICA indication. ICA inappropriate patients did not differ in symptom characteristics, but had a significantly lower revascularization rate (3.7% vs. 42.1%, P < 0.0001) compared with patients appropriately referred to ICA. In patients with indication for lipid-lowering therapy after the CCTA statin rate was 53.1% and significantly increased after ICA to 76.4% (P < 0.0001). In CCTA, obstructive findings in proximal-only lesions did not increase the revascularization rate (45.6% vs. 42.1%, P = 0.11) but missed nonproximal relevant stenoses (15.0% vs. 2.5%, P < 0.0001) compared with obstructive findings in all segments. CONCLUSION: The overall rate of inappropriateness was low, but there is relevant statin underutilization in eligible patients due to a lack of CT findings integration. Both ICA referrals and primary preventive therapy could be improved by the implementation of CT results based on CAD-RADS recommendations.

Atherosclerotic cardiovascular disease thresholds for statin initiation among people living with HIV in Thailand: A cost-effectiveness analysis.

BACKGROUND: People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (ASCVD) compared to their uninfected peers. Expanding statin use may help alleviate this burden. We evaluated the cost-effectiveness of reducing the recommend statin initiation threshold for primary ASCVD prevention among PLHIV in Thailand. METHODS: Our decision analytic microsimulation model randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database (data collected between 1/January/2013 and 1/September/2019). Direct medical costs and quality-adjusted life-years were assigned in annual cycles over a lifetime horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. The study population included PLHIV aged 35-75 years, without ASCVD, and receiving antiretroviral therapy. Statin initiation thresholds evaluated were 10-year ASCVD risk ≥10% (control), ≥7.5% and ≥5%. RESULTS: A statin initiation threshold of ASCVD risk ≥7.5% resulted in accumulation of 0.015 additional quality-adjusted life-years compared with an ASCVD risk threshold ≥10%, at an extra cost of 3,539 Baht ($US113), giving an incremental cost-effectiveness ratio of 239,000 Baht ($US7,670)/quality-adjusted life-year gained. The incremental cost-effectiveness ratio comparing ASCVD risk ≥5% to ≥7.5% was 349,000 Baht ($US11,200)/quality-adjusted life-year gained. At a willingness-to-pay threshold of 160,000 Baht ($US5,135)/quality-adjusted life-year gained, a 30.8% reduction in the average cost of low/moderate statin therapy led to the ASCVD risk threshold ≥7.5% becoming cost-effective compared with current practice. CONCLUSIONS: Reducing the recommended 10-year ASCVD risk threshold for statin initiation among PLHIV in Thailand would not currently be cost-effective. However, a lower threshold could become cost-effective with greater preference for cheaper statins.

Independent and Joint Effects of Testosterone Replacement Therapy and Statins use on the Risk of Prostate Cancer Among White, Black, and Hispanic Men.

The associations of testosterone therapy (TTh) and statins use with prostate cancer remain conflicted. However, the joint effects of TTh and statins use on the incidence of prostate cancer, stage and grade at diagnosis, and prostate cancer-specific mortality (PCSM) have not been studied.We identified White (N = 74,181), Black (N = 9,157), and Hispanic (N = 3,313) men diagnosed with prostate cancer in SEER-Medicare 2007-2016. Prediagnostic prescription of TTh and statins was ascertained for this analysis. Weighted multivariable-adjusted conditional logistic and Cox proportional hazards models evaluated the association of TTh and statins with prostate cancer, including statistical interactions between TTh and statins.We found that TTh (OR = 0.74; 95% CI, 0.68-0.81) and statins (OR = 0.77; 95% CI, 0.0.75-0.88) were inversely associated with incident prostate cancer. Similar inverse associations were observed with high-grade and advanced prostate cancer in relation to TTh and statins use. TTh plus statins was inversely associated with incident prostate cancer (OR = 0.53; 95% CI, 0.48-0.60), high-grade (OR = 0.43; 95% CI, 0.37-0.49), and advanced prostate cancer (OR = 0.44; 95% CI, 0.35-0.55). Similar associations were present in White and Black men, but among Hispanics statins were associated with PCSM.Prediagnostic use of TTh or statins, independent or combined, was inversely associated with incident and aggressive prostate cancer overall and in NHW and NHB men. Findings for statins and aggressive prostate cancer are consistent with previous studies. Future studies need to confirm the independent inverse association of TTh and the joint inverse association of TTh plus statins on risk of prostate cancer in understudied populations. PREVENTION RELEVANCE: The study investigates a potential interaction between TTh and statin and its effect on incident and aggressive prostate cancer in men of different racial and ethnic backgrounds. These results suggest that among NHW and non-Hispanic Black men TTh plus statins reduced the odds of incident prostate cancer, high-grade and advance stage prostate cancer.

National Trends in Statin Use among the United States Nursing Home Population (2011-2016).

BACKGROUND: Little is known about trends in statin use in United States (US) nursing homes. OBJECTIVES: The aim of this study was to describe national trends in statin use in nursing homes and evaluate the impact of the introduction of generic statins, safety warnings, and guideline recommendations on statin use. METHODS: This study employed a repeated cross-sectional prevalence design to evaluate monthly statin use in long-stay US nursing home residents enrolled in Medicare fee-for-service using the Minimum Data Set 3.0 and Medicare Part D claims between April 2011 and December 2016. Stratified by age (65-75 years, ≥ 76 years), analyses estimated trends and level changes with 95% confidence intervals (CI) following statin-related events (the availability of generic statins, American Heart Association/American College of Cardiology guideline updates, and US FDA safety warnings) through segmented regression models corrected for autocorrelation. RESULTS: Statin use increased from April 2011 to December 2016 (65-75 years: 38.6-43.3%; ≥ 76 years: 26.5% to 30.0%), as did high-intensity statin use (65-75 years: 4.8-9.5%; ≥ 76 years: 2.3-4.5%). The introduction of generic statins yielded little impact on the prevalence of statins in nursing home residents. Positive trend changes in high-intensity statin use occurred following national guideline updates in December 2011 (65-75 years: ß = 0.16, 95% CI 0.09-0.22; ≥ 76 years: ß = 0.09, 95% CI 0.06-0.12) and November 2013 (65-75 years: ß = 0.11, 95% CI 0.09-0.13; ≥ 76 years: ß = 0.04, 95% CI 0.03-0.05). There were negative trend changes for any statin use concurrent with FDA statin safety warnings in March 2012 among both age groups (65-75 years: ß trend change = - 0.06, 95% CI - 0.10 to - 0.02; ≥ 76 years: ß trend change = - 0.05, 95% CI - 0.08 to - 0.01). The publication of the results of a statin deprescribing trial yielded a decrease in any statin use among the ≥ 76 years age group (ß level change = - 0.25, 95% CI - 0.48 to - 0.09; ß trend change = - 0.03, 95% CI - 0.04 to - 0.01), with both age groups observing a positive trend change with high-intensity statins (65-75 years: ß = 0.11, 95% CI 0.02-0.21; ≥ 76 years: ß = 0.05, 95% CI 0.01-0.09). CONCLUSION: Overall, statin use in US nursing homes increased from 2011 to 2016. Guidelines and statin-related events appeared to impact use in the nursing home setting. As such, statin guidelines and messaging should provide special consideration for nursing home populations, who may have more risk than benefit from statin pharmacotherapy.

Physician variation in the de-adoption of ineffective statin and fibrate therapy.

OBJECTIVE: To describe physicians' variation in de-adopting concurrent statin and fibrate therapy for type 2 diabetic patients following a reversal in clinical evidence. DATA SOURCES: We analyzed 2007-2015 claims data from OptumLabs® Data Warehouse, a longitudinal, real-world data asset with de-identified administrative claims and electronic health record data. STUDY DESIGN: We modeled fibrate use among Medicare Advantage and commercially insured type 2 diabetic statin users before and after the publication of the ACCORD lipid trial, which found statins and fibrates were no more effective than statins alone in reducing cardiovascular events among type 2 diabetic patients. We modeled fibrate use trends with physician random effects and physician characteristics such as age and specialty. DATA EXTRACTION: We identified patient-year-quarters with one year of continuous insurance enrollment, type 2 diabetes diagnoses, and fibrate use. We designated the physician most responsible for patients' diabetes care based on evaluation and management visits and prescriptions of glucose-lowering drugs. PRINCIPAL FINDINGS: Fibrate use increased by 0.12 percentage points per quarter among commercial patients (95% CI, 0.10 to 0.14) and 0.17 percentage points per quarter among Medicare Advantage patients (95% CI, 0.13 to 0.20) before the trial and then decreased by 0.16 percentage points per quarter among commercial patients (95% CI, -0.18 to -0.15) and 0.05 percentage points per quarter among Medicare Advantage patients (95% CI, -0.06 to -0.03) after the trial. However, 45% of physicians treating commercial patients and 48% of physicians treating Medicare Advantage patients had positive trends in prescribing following the trial. Physicians' characteristics did not explain their variation (pseudo R2  = 0.000). CONCLUSION: On average, physicians decreased fibrate prescribing following the ACCORD lipid trial. However, many physicians increased prescribing following the trial. Observable physician characteristics did not explain variations in prescribing. Future research should examine whether physicians vary similarly in other de-adoption settings.

Impact of changing reimbursement criteria on statin treatment patterns among patients with atherosclerotic cardiovascular disease or cardiovascular risk factors.

WHAT IS KNOWN AND OBJECTIVE: Starting 1 August 2013, the eligible cholesterol level for statin reimbursement in patients with atherosclerotic cardiovascular disease (ASCVD) or cardiovascular disease (CVD)-related risk factors changed from LDL-C ≥ 130 mg/dl (or TC ≥ 200 mg/dl) to LDL-C ≥ 100 mg/dl (or TC ≥ 160 mg/dl) in Taiwan, which may modify clinician prescribing behaviours. We aimed to evaluate the impact of changing reimbursement criteria on statin treatment patterns. METHODS: A before-after cohort design was conducted using Taiwan's National Health Insurance Research Database. Differences in statin treatment patterns between the pre- and postregulation periods were compared. Two prespecified study cohorts were identified to examine the impacts of this change on those who need statins for "secondary prevention" (patients newly diagnosed with ASCVD) and those who need statins for "primary prevention" (patients newly diagnosed with CVD-related risk factors, such as diabetes mellitus [DM]). Treatment patterns measured in this study included initiation, discontinuation, switching, dose increase, dose decrease and dose maximization. RESULTS: The proportion of patients who initiated statins during the postregulation period was higher than that of patients who initiated statins during the preregulation period (eg coronary heart disease (CHD) patients, pre- vs. postregulation: 41.23% vs. 48.25%). Notably, only 30%-40% of patients initiated statin use in the postregulation period across different conditions. In addition, the proportion of patients who discontinued statins remained very high. Even in the postregulation period, more than half of CHD patients discontinued statins during the 1-year follow-up period (eg CHD patients, pre- vs. postregulation: 59.07% vs. 52.75%). WHAT IS NEW AND CONCLUSION: The new reimbursement criteria started on 1 August 2013 seemed to lower the barriers of access to the first statin prescription among patients with CHD, cerebrovascular disease (CBVD) and DM. Nevertheless, the proportion of patients who initiated statin use was suboptimal, and the proportion of patients who discontinued statins was very high in the postregulation period.

Effects of adherence to pharmacological secondary prevention after acute myocardial infarction on health care costs - an analysis of real-world data.

BACKGROUND: Acute myocardial infarction (AMI), a major source of morbidity and mortality, is also associated with excess costs. Findings from previous studies were divergent regarding the effect on health care expenditure of adherence to guideline-recommended medication. However, gender-specific medication effectiveness, correlating the effectiveness of concomitant medication and variation in adherence over time, has not yet been considered. METHODS: We aim to measure the effect of adherence on health care expenditures stratified by gender from a third-party payer's perspective in a sample of statutory insured Disease Management Program participants over a follow-up period of 3-years. In 3627 AMI patients, the proportion of days covered (PDC) for four guideline-recommended medications was calculated. A generalized additive mixed model was used, taking into account inter-individual effects (mean PDC rate) and intra-individual effects (deviation from the mean PDC rate). RESULTS: Regarding inter-individual effects, for both sexes only anti-platelet agents had a significant negative influence indicating that higher mean PDC rates lead to higher costs. With respect to intra-individual effects, for females higher deviations from the mean PDC rate for angiotensin-converting enzyme (ACE) inhibitors, anti-platelet agents, and statins were associated with higher costs. Furthermore, for males, an increasing positive deviation from the PDC mean increases costs for ß-blockers and a negative deviation decreases costs. For anti-platelet agents, an increasing deviation from the PDC-mean slightly increases costs. CONCLUSION: Positive and negative deviation from the mean PDC rate, independent of how high the mean was, usually negatively affect health care expenditures. Therefore, continuity in intake of guideline-recommended medication is important to save costs.

Assessing the association between medication adherence, as defined in quality measures, and disease-state control, health care utilization, and costs in a retrospective database analysis of Medicare supplemental beneficiaries using statin medications.

BACKGROUND: Adherence to medication, and related health and economic outcomes, is becoming increasingly important as populations age and as the number of Americans managing chronic conditions increases. The Pharmacy Quality Alliance (PQA) statin medication adherence measure is used in Medicare star ratings to evaluate health plan performance. Yet, limited evidence exists that investigates the association between statin medication adherence, as specified in the PQA adherence quality measure, and disease-state control, health care utilization, and costs. OBJECTIVE: To determine the association between adherence (≥80% proportion of days covered) and disease-state control, health care utilization, and health care costs for Medicare supplemental beneficiaries using statin medications eligible for inclusion in the PQA statin adherence quality measure. METHODS: This retrospective study used a cohort of eligible beneficiaries for inclusion in the PQA statin adherence measure with low-density lipoprotein (LDL) laboratory values from IBM MarketScan Medicare Supplemental Research Databases (2009-2015). A logistic regression model assessed the association between adherence and LDL control (controlled individuals had LDL levels ≤ 100 mg/dL). Health care utilization and costs during a 1-year period, from first statin medication claim, were compared between adherent and nonadherent groups using generalized linear models with log link and negative binomial distribution (utilization) or gamma distribution (costs), adjusting for covariates. Beta coefficients were used to compute cost ratios (CR) and rate ratios (RR). Cohort characteristics were assessed using t-tests, Wilcoxon rank sum tests, or chi-square tests. An a priori alpha level of 0.001 was used. RESULTS: The study cohort consisted of 77,174 beneficiaries, of whom 58,668 (76.0%) were classified as adherent to their statin medications. After controlling for other factors, odds of disease-state control were approximately 2 times higher among medication adherent beneficiaries compared with their nonadherent counterparts (OR = 2.192; 95% CI = 2.109-2.278). Multivariable analyses showed adherers experienced 4.7% fewer outpatient (RR = 0.953; 95% CI = 0.940-0.965) and 27.5% fewer inpatient (RR = 0.725; 95% CI = 0.687-0.766) visits; had 9.9% lower outpatient (CR = 0.901; 95% CI = 0.885-0.916) and 28.3% lower inpatient (CR = 0.717; 95% CI = 0.705-0.729) costs; 14.7% lower total costs (CR = 0.853; 95% CI =0.838-0.868); and 7.0% higher prescription drug costs (CR = 1.070; 95% CI = 1.052-1.089) than nonadherers. Adherence to statin medications was associated with a reduction in total costs of $157.32 per member per month. CONCLUSIONS: This retrospective database analysis demonstrated that statin adherence was associated with approximately twice the odds of having a controlled disease state compared with nonadherence in a large Medicare sample. Adherent beneficiaries had fewer outpatient and inpatient visits (lower utilization), lower outpatient and inpatient costs, and lower total costs, a calculated savings of $157.32 per member per month, despite having higher prescription drug costs. Finally, these results provide important new information by demonstrating that adherence (≥ 80%) is associated with lower health care costs in a short (1-year) time frame. DISCLOSURES: Funding for this study was provided by Pharmacy Quality Alliance; Merck & Co. (Kenilworth, NJ); and SinfoniaRx. All authors except Pickering and Black were employed by the University of Arizona College of Pharmacy or the Mel & Enid Zuckerman College of Public Health at the time of this study. Pickering is employed by the Pharmacy Quality Alliance, and Black is employed by Merck & Co. Chinthammit also reports employment with Eli Lilly and Company, and Campbell reports employment with the Pharmacy Quality Alliance. Axon reports grants from Arizona Department of Health Services, unrelated to this work. Warholak reports grants from Novartis and the Arizona Department of Health Services, unrelated to this work. This research was presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Annual Meeting 2019, May 18-22, 2019, in New Orleans, LA.

An Evaluation of Statin Use Among Patients with Type 2 Diabetes at High Risk of Cardiovascular Events Across Multiple Health Care Systems.

BACKGROUND: Patients with more than one chronic condition often receive care from several providers and facilities, which may lead to fragmentation of care. Poor care coordination in dual health care system use has been associated with increased emergency department visits, hospitalizations, and costs. OBJECTIVE: Dual health care system use is increasing among veterans, and we sought to evaluate the effect of dual health care system use on statin treatment in veterans with type 2 diabetes at high risk of cardiovascular events, using varying degrees of Centers for Medicare & Medicaid Services (CMS) services. METHODS: This was a 10-year retrospective longitudinal cohort study of national clinical and administrative data that included 689,138 veterans with type 2 diabetes who were aged 65 years or older on January 1, 2006. Patients were followed from January 1, 2007, until December 31, 2016. Administrative and clinical data from the Veterans Health Administration's (VHA) Corporate Data Warehouse were merged with CMS inpatient, outpatient, and pharmacy data. Statin use was defined as any therapy and subcategorized as high versus low or moderate intensity per the American College of Cardiology/American Heart Association guidelines. Marginal generalized estimating equation-type models for longitudinal data were used to model the association between dual health care utilization status (< 50%, 50%-80%, and > 80% VHA utilization, with the first group serving as the reference group) and statin use after adjusting for measured covariates. RESULTS: The mean ages at baseline for each group were similar and ranged between 75.4 and 76.9 years. For the outcome of any statin use, the group with < 50% VHA utilization was significantly less likely to receive statin therapy compared with the group with > 80% VHA utilization (OR = 0.26, 95% CI = 0.26-0.26), while the group with 50%-80% VHA utilization was slightly more likely (OR = 1.05, 95% CI = 1.04-1.07). Similarly, for the high-intensity versus low-/moderate-intensity or no statins outcome, the group with < 50% VHA utilization was significantly less likely to receive a high-intensity statin compared with the group with > 80% VHA utilization (OR = 0.56, 95% CI = 0.55-0.57), while the group with 50%-80% VHA utilization was only slightly less likely (OR = 0.95, 95% CI =0.94-0.96). CONCLUSIONS: Among veterans with diabetes at high risk of cardiovascular events, dual health care system utilization status appeared to affect statin use. We observed lower odds for any statin use and high-intensity statin therapy among the cohort with the lowest degree of VHA utilization (i.e., < 50%). Interventions to increase statin use among veterans at high risk of cardiovascular events with lower degrees of VHA utilization should be explored. DISCLOSURES: This study was supported by a grant funded by the Department of Veterans Affairs' Health Services Research and Development Service and was undertaken at the Health Equity and Rural Outreach Center (HEROIC) at Ralph H. Johnson Veteran Affairs Medical Center, Charleston, SC. The authors report no potential conflicts of interest relevant to this article. This article represents the views of the authors and not those of the Medical University of South Carolina or Veteran Health Administration.

Inclisiran, the billion-dollar drug, to lower LDL cholesterol - is it worth it?

INTRODUCTION: If statins are unsuccessful at achieving the LDL cholesterol level goal in subjects with hypercholesterolemia, non-statin therapy should be added to reduce cardiovascular morbidity and mortality. The first inhibitors of proprotein convertase substilisin-kexin type 9 (PCSK9) were human monoclonal antibodies and these reduced LDL cholesterol and cardiovascular events. Inclisiran is a small interfering RNA molecule (siRNAs) directed against PCSK9. AREAS COVERED: This key paper evaluation focuses on Phase 3 trials that assess inclisiran in the treatment of hypercholesterolemia and heterozygous familial hypercholesterolemia. EXPERT OPINION: To date, the findings with inclisiran have been very promising as it causes large decreases in LDL cholesterol with few adverse effects. However, there are some limitations to its widespread use. Firstly, cardiovascular outcomes trials have not been completed, so we do not know how inclisiran compares to the PCSK9 monoclonal antibodies, which, seem to me, to only have a modest effect on cardiovascular outcomes. Secondly, a major problem with the PCSK9 monoclonal antibodies is that they are expensive, and their use is often discontinued or not pursued, which can leave the subjects intended for treatment at high cardiovascular risk. At present, it is not clear whether similar problems around cost will apply to inclisiran.

Discontinuing statins or not in the elderly? Study protocol for a randomized controlled trial.

BACKGROUND: The risk/benefit ratio of using statins for primary prevention of cardiovascular (CV) events in elderly people has not been established. The main objectives of the present study are to assess the cost-effectiveness of statin cessation and to examine the non-inferiority of statin cessation in terms of mortality in patients aged 75 years and over, treated with statins for primary prevention of CV events. METHODS: The "Statins in the elderly" (SITE) study is an ongoing 3-year follow-up, open-label comparative multi-centre, randomized clinical trial that is being conducted in two parallel groups in outpatient primary care offices. Participants meeting the following criteria are included: people aged 75 years and older being treated with statins as primary prevention for CV events, who provide informed consent. After randomization, patients in the statin-cessation strategy are instructed to withdraw their treatment. In the comparison strategy, patients continue their statin treatment at the usual dosage. The cost-effectiveness of the statin-cessation strategy compared to continuing statins will be estimated through the incremental cost per quality-adjusted life years (QALYs) gained at 36 months, from the perspective of the French healthcare system. Overall mortality will be the primary clinical endpoint. We assumed that the mortality rate at 3 years will be 15%. The sample size was computed to achieve 90% power in showing the non-inferiority of statin cessation, assuming a non-inferiority margin of 5% of the between-group difference in overall mortality. In total, the SITE study will include 2430 individuals. DISCUSSION: There is some debate on the value of statins in people over 75 years old, especially for primary prevention of CV events, due to a lack of evidence of their efficacy in this population, potential compliance-related events, drug-drug interactions and side effects that could impair quality of life. Data from clinical trials guide the initiation of medication therapy for primary or secondary prevention of CV disease but do not define the timing, safety, or risks of discontinuing the agents. The SITE study is one of the first to examine whether treatment cessation is a cost-effective and a safe strategy in people of 75 years and over, formerly treated with statins. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02547883. Registered on 11 September 2015.

Association of combination statin and antihypertensive therapy with reduced Alzheimer's disease and related dementia risk.

BACKGROUND: Hyperlipidemia and hypertension are modifiable risk factors for Alzheimer's disease and related dementias (ADRD). Approximately 25% of adults over age 65 use both antihypertensives (AHTs) and statins for these conditions. While a growing body of evidence found statins and AHTs are independently associated with lower ADRD risk, no evidence exists on simultaneous use for different drug class combinations and ADRD risk. Our primary objective was to compare ADRD risk associated with concurrent use of different combinations of statins and antihypertensives. METHODS: In a retrospective cohort study (2007-2014), we analyzed 694,672 Medicare beneficiaries in the United States (2,017,786 person-years) who concurrently used both statins and AHTs. Using logistic regression adjusting for age, socioeconomic status and comorbidities, we quantified incident ADRD diagnosis associated with concurrent use of different statin molecules (atorvastatin, pravastatin, rosuvastatin, and simvastatin) and AHT drug classes (two renin-angiotensin system (RAS)-acting AHTs, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), vs non-RAS-acting AHTs). FINDINGS: Pravastatin or rosuvastatin combined with RAS-acting AHTs reduce risk of ADRD relative to any statin combined with non-RAS-acting AHTs: ACEI+pravastatin odds ratio (OR) = 0.942 (CI: 0.899-0.986, p = 0.011), ACEI+rosuvastatin OR = 0.841 (CI: 0.794-0.892, p<0.001), ARB+pravastatin OR = 0.794 (CI: 0.748-0.843, p<0.001), ARB+rosuvastatin OR = 0.818 (CI: 0.765-0.874, p<0.001). ARBs combined with atorvastatin and simvastatin are associated with smaller reductions in risk, and ACEI with no risk reduction, compared to when combined with pravastatin or rosuvastatin. Among Hispanics, no combination of statins and RAS-acting AHTs reduces risk relative to combinations of statins and non-RAS-acting AHTs. Among blacks using ACEI+rosuvastatin, ADRD odds were 33% lower compared to blacks using other statins combined with non-RAS-acting AHTs (OR = 0.672 (CI: 0.548-0.825, p<0.001)). CONCLUSION: Among older Americans, use of pravastatin and rosuvastatin to treat hyperlipidemia is less common than use of simvastatin and atorvastatin, however, in combination with RAS-acting AHTs, particularly ARBs, they may be more effective at reducing risk of ADRD. The number of Americans with ADRD may be reduced with drug treatments for vascular health that also confer effects on ADRD.

Patients with coronary artery disease after acute myocardial infarction: effects of continuous enrollment in a structured Disease Management Program on adherence to guideline-recommended medication, health care expenditures, and survival.

OBJECTIVE: Acute myocardial infarction (AMI) carries increased risk of mortality and excess costs. Disease Management Programs (DMPs) providing guideline-recommended care for chronic diseases seem an intuitively appealing way to enhance health outcomes for patients with chronic conditions such as AMI. The aim of the study is to compare adherence to guideline-recommended medication, health care expenditures and survival of patients enrolled and not enrolled in the German DMP for coronary artery disease (CAD) after an AMI from the perspective of a third-party payer over a follow-up period of 3 years. METHODS: The study is based on routinely collected data from a regional statutory health insurance fund (n = 15,360). A propensity score matching with caliper method was conducted. Afterwards guideline-recommended medication, health care expenditures, and survival between patients enrolled and not enrolled in the DMP were compared with generalized linear and Cox proportional hazard models. RESULTS: The propensity score matching resulted in 3870 pairs of AMI patients previously and continuously enrolled and not enrolled in the DMP. In the 3-year follow-up period the proportion of days covered rates for ACE-inhibitors (60.95% vs. 58.92%), anti-platelet agents (74.20% vs. 70.66%), statins (54.18% vs. 52.13%), and ß-blockers (61.95% vs. 52.64%) were higher in the DMP group. Besides that, DMP participants induced lower health care expenditures per day (€58.24 vs. €72.72) and had a significantly lower risk of death (HR: 0.757). CONCLUSION: Previous and continuous enrollment in the DMP CAD for patients after AMI is a promising strategy as it enhances guideline-recommended medication, reduces health care expenditures and the risk of death.

High-fat diet induced alteration in lipid enzymes and inflammation in cardiac and brain tissues: Assessment of the effects of Atorvastatin-loaded nanoparticles.

Treatment with Lipitor is associated with several adverse impacts. Here we investigated the effects of low Lipitor nanoparticles (atorvastatin calcium nanopartilcle [AC-NP]), with size less than 100 , on enzymes of lipid metabolism and inflammation in cardiac, hepatic, and brain tissues of hypercholestremic adult male rats. Adult male rats were divided into five experimental groups. In group 1, the intact control (normal pellet diet), animals were fed a normal control diet; the other four groups were fed a high-fat diet (HFD) for 6 weeks. After 6 weeks, groups from 2 to 5 were assigned as a positive control (HFD), HFD + Lipitor, HFD + AC-NP-R1, or HFD + AC-NP-R2. Different treatments were administrated orally for two regimen periods (R1 daily and R2 once every 3 days). The treatment was conducted for two consecutive weeks. The HFD group faced a significant elevation in 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), associated with a significant reduction in low-density lipoprotein receptor (LDL-R) along with cholesterol 7 α-hydroxylase enzyme in hepatic tissues, compared with the control group. Also, the HFD group induced hepatic, cardiac, and brain inflammation, evidenced by increased hepatic oxidative stress markers and cardiac homocysteine, together with elevated proinflammatory cytokines interleukin-1ß (IL-1ß) and IL-6 levels in brain tissue, compared with the control group. Different AC-NP treatments significantly augmented both mRNA LDL-R and mRNA 7α-hydroxylase expression in hepatic tissues, associated with significant depletion in mRNA HMG-CoA expression, compared with HFD + Lipitor. The inflammation symptoms were ameliorated by the AC-NP treatments, compared to HFD + Lipitor. Lipitor encapsulation in NP formulation results in increased efficiency and reduced dose-related adverse effects known to be associated with the Lipitor chronic administration.

Adoption of coronary artery disease - Reporting and Data System (CAD-RADS™) and observed impact on medical therapy and systolic blood pressure control.

BACKGROUND: CAD-RADS was developed to standardize communication of per-patient maximal stenosis on coronary CT angiography (CCTA) and provide treatment recommendations and may impact primary prevention care and resource utilization. The authors sought to evaluate CAD-RADS adoption on preventive medical therapy and risk factor control amongst a mixed provider population. METHODS: Statins, aspirin (ASA), systolic blood pressure and, when available, lipid panel changes were abstracted for 1796 total patients undergoing CCTA in the 12 months before (non-standard reporting, NSR, cohort) and after adoption of the CAD-RADS reporting template. Only initiation of a medication in a treatment naïve patient, escalation from baseline dose, or transition to a higher potency was considered an escalation/initiation in lipid therapy. RESULTS: The CAD-RADS reporting template was utilized in 83.7% (751/897) of CCTAs after the CAD-RADS adoption period. After adjusting for any coronary artery disease (CAD) on CCTA, statin initiation/escalation was more commonly observed in the CAD-RADS cohort (aOR 1.46; 95%CI 1.12-1.90, p = 0.005), driven by higher rates of new statin initiation (aOR 1.79; 95%CI 1.23-2.58, p = 0.002). This resulted in a higher observed rates of total cholesterol improvement in the CAD-RADS cohort (58% vs 49%, p = 0.016). New ASA initiation was similar between reporting templates after adjustment for CAD on CCTA (aOR 1.40; 95%CI 0.97-2.02, p = 0.069). The ordering provider's specialty (cardiology vs non-cardiology) did not significantly impact the observed differences in initiation/escalation of statins and ASA (pinteraction = NS). CONCLUSIONS: Adoption of CAD-RADS reporting was associated with increased utilization of preventive medications, regardless of ordering provider specialty.

Generic atorvastatin and rosuvastatin in the South Korean market: time of introduction in relation to manufacturer characteristics.

Background: The competition for and market dynamics of generic medicines can be understood by analyzing manufacturers' behavior. In this study, we analyzed the various types of generic atorvastatin and rosuvastatin that were introduced onto the South Korean market from 2002 to 2018 and their corresponding manufacturers. Methods: Based on publicly available data, we selected drugs containing atorvastatin and rosuvastatin as active ingredients for the analysis. We calculated the time between the date of marketing approval for the first generic and that of the remaining generics. Then, we categorized manufacturers that marketed generics into first movers and latecomers. Results: We confirmed that many manufacturers have marketed generic drugs in South Korea and that manufacturers can be categorized as first movers and latecomers. Interestingly, latecomers account for a large portion of the manufacturers of generics, and they have entered the market steadily, even after the market matured with a number of manufacturers. Additionally, the characteristics of the manufacturers were closely related to manufacturers' behaviors in the market. Conclusions: The order-of-entry effect, which is commonly observed in other markets, is marginal in the South Korean market, and this phenomenon is mainly explained by the rare price competition among generic manufacturers.

Assessment of Transporter Polymorphisms as a Factor in a BCRP Drug Interaction Study With Lanabecestat.

Lanabecestat is a human ß-site amyloid precursor protein-cleaving enzyme 1 inhibitor in development to slow disease progression in patients with early Alzheimer's disease. The study evaluated the breast cancer resistance protein (BCRP) inhibition potential of lanabecestat on the pharmacokinetics (PK) of rosuvastatin, a probe for BCRP activity, in healthy white subjects who were not carriers of SLCO1B1 (c.521T>C), not homozygotes for ABCG2 (c.421C>A or c.34G>A), and not heterozygotes of ABCG2 (c.421C>A and c.34G>A). The safety of lanabecestat + rosuvastatin, the effects of rosuvastatin on the PK of lanabecestat, and the effects of multiple genetic polymorphisms on rosuvastatin exposure were assessed. Geometric mean ratios of the maximum observed rosuvastatin concentration (Cmax ), area under the rosuvastatin concentration-versus-time curve (AUC) from time 0 to infinity, and time of maximum observed drug concentration (tmax ) when rosuvastatin was administered alone and with lanabecestat were contained within 0.8-1.25, as were lanabecestat AUC at steady state and tmax at steady state when lanabecestat was administered alone or with rosuvastatin. Lanabecestat Cmax at steady state increased 8% in the presence of rosuvastatin. Except for an approximately 80% increase of rosuvastatin AUC (P < .05) in the heterozygotes of ABCG2 c.421C>A relative to the CC genotype, there were no statistically significant associations between rosuvastatin exposure and polymorphisms assessed. Lanabecestat + rosuvastatin was associated with few treatment-emergent adverse events, all of which resolved and were mild. Lanabecestat does not meaningfully impact BCRP activity; therefore, restriction of concomitant administration with BCRP substrates, such as rosuvastatin, may be unnecessary.

The impact of a pharmacist-driven, collaborative practice on diabetes management in an Urban underserved population: a mixed method assessment.

The objective of this manuscript is to describe the results of a pharmacist-driven, Type 2 diabetes targeted, collaborative practice within an urban, underserved federally qualified health center. Pharmacists within a primary care team managed patients with chronic illnesses utilizing a collaborative practice agreement. Pharmacists, pharmacy residents, and supervised students provided care for patients with Type 2 diabetes. The first visit incorporated past medical history, medication reconciliation, determination of adherence and patient knowledge of diabetes pathophysiology, care plan, including diet and exercise, medications, and possible complications. Pharmacists had the authority to optimize medications and order laboratory tests and referrals. Diabetes, hypertension, and medication use outcomes data were collected and analyzed to assess the impact of clinical pharmacy services. Patient and provider satisfaction were assessed via surveys and focus group interviews. Ninety-nine patients were included in the evaluation. The mean A1c level was 9.8% at baseline and 8.4% at follow-up (p< .05). There were significant improvements in patient attainment of A1c <9%, ACE Inhibitor/angiotensin receptor blocker and statin use, and tobacco cessation at follow-up (p< .05). Eleven providers who responded to the satisfaction survey answered 73% of the questions with strongly agree. The seven patients who participated in the satisfaction survey, and focus group were satisfied with the care they received from the pharmacists. The focus group highlighted similar personal goals, barriers, and interests in nutrition education. Working as part of a collaborative care team, pharmacists were able to have a significant impact on improving the health outcomes of patients with Type 2 diabetes and patient and provider perceptions of the vital role of pharmacists.

Impact of Star Rating Medication Adherence Measures on Adherence for Targeted and Nontargeted Medications.

BACKGROUND: In 2012, Medicare incorporated medication adherence targeting oral antidiabetic medications, renin-angiotensin system (RAS) antagonists, and statins as highly weighted components in its Star Ratings Program. In the same year, health plans began receiving quality bonus payments for higher star ratings. OBJECTIVE: We aimed to assess how these policy changes affected adherence to targeted and other chronic disease medications in the United States. METHODS: We performed interrupted time series analyses to assess monthly changes in medication adherence from 2010 to 2016 using health plans' Medicare claims submitted to a large pharmacy benefits manager. We conducted 2 sets of analyses. The first examined whether policy changes affected adherence to the 3 targeted therapy classes, and the second assessed the association between policy changes and adherence to 5 chronic disease classes not targeted by star ratings. For the second analysis, we further compared adherence between members who concomitantly used and did not use targeted medications. RESULTS: For star-ratings analyses, we studied 240 811 members on oral antidiabetic medications, 500 958 on RAS antagonists, and 471 135 on statins. Adherence for all star rating-targeted and nontargeted medications increased after 2012 (P < .001). Oral antidiabetic, statin, and RAS antagonist adherence was, respectively, 11.2%, 3.7%, and 8.1% higher than adherence without policy changes (P < .001). Nontargeted antihypertensive and antihyperlipidemic adherence trends were higher among those concomitantly on star rating-targeted medications compared with those who were not (P < .001). CONCLUSIONS: As policy makers strive to identify optimal quality measures for improving healthcare delivery, it is important to consider that incentives can promote improved performance in both targeted measures and related outcomes.