Antihypertensive drug use and the risk of dementia in patients with diabetes mellitus.

BACKGROUND: Diabetes and hypertension are independent risk factors for dementia, and hypertension may increase this risk in patients with diabetes. It is unclear whether antihypertensive drugs are associated with risk of dementia in these patients. METHODS: A retrospective study using a national cohort of beneficiaries of the Department of Veterans Affairs who have diabetes examined incidence of dementia over a 2-year follow-up period. Multivariate Cox proportional hazards regression model was used to estimate the unique effects of comorbid hypertension and antihypertensive medications on risk of dementia, after adjusting for several potential confounders. RESULTS: In all, 377,838 patients were studied (mean age: 75.53 ± 6.07 years). After adjustments were made for sociodemographic factors, duration of diabetes, comorbidity, and comedications, hypertension was associated with increased risk of developing dementia (hazard ratio [HR] = 1.08; 95% confidence interval [CI] = 1.03, 1.14). Antihypertensive medications decreased risk, ranging from 24% for angiotensin receptor blockers (ARBs) to 4% for ß-blockers. In a stratified analysis of patients without hypertension, angiotensin-converting enzyme inhibitors (HR = 0.81; 95% CI = 0.69, 0.94) and ARBs (HR = 0.55; 95% CI = 0.34, 0.88) continued to show protective effects. CONCLUSIONS: Comorbid hypertension was associated with increased risk of dementia, whereas antihypertensive medications, especially angiotensin-converting enzyme inhibitors and ARBs, were associated with reduced risk, even among patients without hypertension. Consequently, these agents may have potential therapeutic roles in delaying the onset of dementia in patients with diabetes.

COPD affects worker productivity and health care costs.

Purpose: This study aimed to measure the true burden of COPD by calculating incremental direct and indirect costs. Direct medical resource use, productivity metrics, and COPD-specific resource use and costs were also evaluated. Patients and methods: This was a retrospective, observational, matched cohort study using administrative claims data from the Truven Health MarketScan® Commercial Claims and Encounters and the Health and Productivity Management databases (2007-2010). Working-age (18-65 years) patients with COPD were identified as having at least one hospitalization or one emergency department visit or two outpatient visits. Patients in the non-COPD cohort did not have a diagnosis of COPD during the study period. Outcomes were evaluated in the first full calendar year after the year of identification (index). Results: Of the 5,701 patients with COPD identified, 3.6% patients were frequent exacerbators (≥2), 10.4% patients were infrequent exacerbators (1), and 86% patients were non-exacerbators (0). When compared with the 17,103 patients without COPD, the incremental direct cost of COPD was estimated at $6,246/patient/year (95% confidence interval: $4,620, $8,623; P<0.001). Loss in productivity was significantly greater in patients with COPD, with an average of 5 more days/year of absence from work and incremental indirect costs from short-term disability of $641 (P<0.001). Direct costs for frequent exacerbators ($17,651/year) and infrequent exacerbators ($14,501/year) were significantly higher than those for non-exacerbators ($11,395, P<0.001). Conclusion: Working-age patients with COPD incur statistically significantly higher direct and indirect costs and use more resources compared with those who do not have COPD.

Estimation of Missed Statin Prescription Use in an Administrative Claims Dataset.

BACKGROUND: Nonadherence to statin medications is associated with increased risk of cardiovascular disease and poses a challenge to lipid management in patients who are at risk for atherosclerotic cardiovascular disease. Numerous studies have examined statin adherence based on administrative claims data; however, these data may underestimate statin use in patients who participate in generic drug discount programs or who have alternative coverage. OBJECTIVE: To estimate the proportion of patients with missing statin claims in a claims database and determine how missing claims affect commonly used utilization metrics. METHODS: This retrospective cohort study used pharmacy data from the PharMetrics Plus (P+) claims dataset linked to the IMS longitudinal pharmacy point-of-sale prescription database (LRx) from January 1, 2012, through December 31, 2014. Eligible patients were represented in the P+ and LRx datasets, had ≥1 claim for a statin (index claim) in either database, and had ≥ 24 months of continuous enrollment in P+. Patients were linked between P+ and LRx using a deterministic method. Duplicate claims between LRx and P+ were removed to produce a new dataset comprised of P+ claims augmented with LRx claims. Statin use was then compared between P+ and the augmented P+ dataset. Utilization metrics that were evaluated included percentage of patients with ≥ 1 missing statin claim over 12 months in P+; the number of patients misclassified as new users in P+; the number of patients misclassified as nonstatin users in P+; the change in 12-month medication possession ratio (MPR) and proportion of days covered (PDC) in P+; the comparison between P+ and LRx of classifications of statin treatment patterns (statin intensity and patients with treatment modifications); and the payment status for missing statin claims. RESULTS: Data from 965,785 patients with statin claims in P+ were analyzed (mean age 56.6 years; 57% male). In P+, 20.1% had ≥ 1 missing statin claim post-index; 13.7% were misclassified as nonstatin users; and 14.9% were misclassified as new statin users. MPR was higher in the augmented P+ dataset versus the P+ dataset alone for all patients (79.4% vs. 76.7%, P < 0.001) and new users (61.4% vs. 58.7%, P < 0.001). Similarly, mean PDC was higher in the P+ dataset augmented with LRx versus the P+ dataset alone for all patients (76.0% vs. 74.0%, P < 0.001) and new users (58.5% vs. 56.5%, P < 0.001). Most patients received moderate-intensity statins; few changes in dose, intensity, or discontinuation of statins were observed when the P+ dataset was augmented. The most common reasons for missing data were payment by an alternate third-party program (66.3%) and use of cash, coupon, or discount cards (18.7%). CONCLUSIONS: Augmenting commercial claims data with point-of-sale data provides a more accurate assessment of statin use than claims data alone. DISCLOSURES: This study was funded by Amgen, which contributed to data interpretation and manuscript preparation. Wade, Hill, and De are employees of QuintilesIMS, which received funding from Amgen for work on this study. Patel and Harrison are employees of Amgen and own Amgen stock/stock options. Study concept and design were contributed by Wade, Hill, Patel, and Harrison. De took the lead in data collection, along with the other authors, and all authors contributed to data analysis. The manuscript was written and revised by all the authors.

Ezetimibe Use and LDL-C Goal Achievement: A Retrospective Database Analysis of Patients with Clinical Atherosclerotic Cardiovascular Disease or Probable Heterozygous Familial Hypercholesterolemia.

BACKGROUND: Ezetimibe is recommended by clinical practice guidelines as a second-line therapy for lowering low-density lipoprotein cholesterol (LDL-C) levels, but little is known about its use and effectiveness in real-world populations. OBJECTIVE: To understand the real-world impact of adding or switching to ezetimibe on LDL-C goal achievement in patients with clinical atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH). METHODS: Patients aged ≥ 18 years with an LDL-C measurement available between January 1, 2013, and June 30, 2014, were identified using the Inovalon MORE 2 database; this included commercial, health insurance exchange, Medicare Advantage, and managed Medicaid patients. The index date was the date of the first LDL-C measurement. Patients were required to have evidence of clinical ASCVD or probable HeFH based on ICD-9-CM codes and ≥ 1 outpatient pharmacy claim for a statin in the 1-year pre-index period, as well as continuous medical and pharmacy coverage for 1 year pre- and post-index. Patients who added ezetimibe to existing statin therapy or switched to ezetimibe within 90 days post-index LDL-C measurement were identified in order to replicate the typical time a clinician takes to assess the use of ezetimibe. The primary outcome was the proportion of patients who met the LDL-C goal of < 70 mg/dL within the follow-up period. LDL-C goal achievement was evaluated by baseline LDL-C level groupings: < 70 mg/dL, 70-99 mg/dL, 100-129 mg/dL, or ≥ 130 mg/dL; and across 4 patient diagnosis categories: all patients, ASCVD only, probable HeFH only, and ASCVD and probable HeFH. Descriptive analyses were reported. Categorical variables were summarized as the number of and corresponding percentage of patients. Continuous variables were presented as the mean and SD of the number of observations and median and range where appropriate. RESULTS: Of 125,330 patients who met selection criteria, mean age was 70.1 (SD = 9.9) years and mean LDL-C baseline was 90.7 (SD = 34.0) mg/dL. Over one half of patients (70%) were receiving statin therapy. Within the post-index time frame, 1.05% (n = 1,309) of patients added or switched to ezetimibe. Of these, 26% achieved LDL-C goal during the 90-day follow-up (59.5% did not achieve goal and 14.4% did not have a follow-up lab value). Therapeutic targets were reached by 30% of patients with baseline LDL-C levels of 70-99 mg/dL; 14% of those with baseline LDL-C of 100-129 mg/dL; and 7% of those with baseline LDL-C of ≥ 130 mg/dL. Achievement of LDL-C goals also varied by baseline diagnosis category. CONCLUSIONS: The addition of or switch to ezetimibe therapy was associated with a relatively small percentage of LDL-C goal achievement (< 70 mg/dL) in patients with clinical ASCVD and/or HeFH, even among patients with baseline LDL-C between 70 and 99 mg/dL. To provide superior individualized care for patients with hyperlipidemia, there is a potential role for newer therapies in lipid lowering, such as PCSK9 inhibitors, in appropriate high-risk populations. DISCLOSURES: This study was sponsored by Amgen. Menzin, Yu, and Stern are employees of Boston Health Economics, which was contracted by Amgen to perform this study. Aggarwal is a former employee of Boston Health Economics. Boatman, Patel, and Harrison are employees and stockholders of Amgen. Study concept and design were contributed by Menzin, Aggarwal, Harrison, and Patel. Aggarwal, Stern, and Yu collected the data. Data interpretation was performed by Aggarwal, Harrison, Patel, and Boatman. The manuscript was written and revised primarily by Aggarwal, with assistance from the other authors.

Cost-effectiveness analysis of umeclidinium/vilanterol for the management of patients with moderate to very severe COPD using an economic model.

BACKGROUND: Bronchodilators such as long-acting muscarinic antagonists (LAMAs) and long-acting ß2-agonists (LABAs) are central to the pharmacological management of COPD. Dual bronchodilation with umeclidinium/vilanterol (UMEC/VI; 62.5/25 µg) is a novel LAMA/LABA combination approved for maintenance treatment for patients with COPD. OBJECTIVE: The objective of this study was to assess the cost-effectiveness of maintenance treatment with UMEC/VI compared with tiotropium (TIO) 18 µg, open dual LAMA + LABA treatment, or no long-acting bronchodilator treatment in patients with moderate to very severe COPD. METHODS: A Markov model was developed to estimate the costs and outcomes associated with UMEC/VI treatment in patients with moderate to very severe COPD (GSK study number: HO-13-13411). Clinical efficacy, costs, utilities, and mortality obtained from the published literature were used as the model inputs. Costs are presented in US dollars based on 2015 prices. The model outputs are total costs, drug costs, other medical costs, number of COPD exacerbations, and quality-adjusted life-years (QALYs). Costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratios were calculated. One-way and probabilistic sensitivity analyses were conducted to assess the effects of changing parameters on the uncertainty of the results. RESULTS: UMEC/VI treatment for moderate to very severe COPD was associated with lower lifetime medical costs ($82,344) compared with TIO ($88,822), open dual LAMA + LABA treatment ($114,442), and no long-acting bronchodilator ($86,751). Fewer exacerbations were predicted to occur with UMEC/VI treatment compared with no long-acting bronchodilator treatment. UMEC/VI provided an 0.11 and 0.25 increase in QALYs compared with TIO and no long-acting bronchodilator treatment, and as such, dominated these cost-effectiveness analyses. Sensitivity analyses confirmed that the results were robust. CONCLUSION: The results from this model suggest that UMEC/VI treatment would be dominant compared with TIO and no long-acting bronchodilator treatment, and less costly than open dual LAMA + LABA treatment in patients with moderate to very severe COPD.

Indirect costs in chronic obstructive pulmonary disease: a review of the economic burden on employers and individuals in the United States.

OBJECTIVE: To review and summarize existing literature on the indirect burden of chronic obstructive pulmonary disease (COPD) in the US. METHODS: Medline, Scopus, and OvidSP databases were searched using defined search terms to identify relevant studies. Eligible studies were published in English between January 2000 and April 2012 and calculated the indirect burden of COPD in a US population in terms of prevalence, incidence or costs of productivity loss, disability, morbidity, or mortality. RESULTS: Of 53 studies identified, eleven met eligibility criteria, with data years spanning 1987-2009. Estimates of workforce participation range from 56% to 69% among individuals with COPD and from 65% to 77% among individuals without COPD. Approximately 13%-18% of those with COPD are limited in the amount or type of work they can do and one-third or more experience general activity limitation. Estimates of restricted activity days range from 27-63 days per year. Estimates of mean annual sick leave and/or disability days among employed individuals with COPD range from 1.3-19.4 days. Estimates of bed confinement range from 13-32 days per year. Estimated mean annual indirect costs were $893-$2,234/person (US dollars) with COPD ($1,521-$3,348 in 2010 [US dollars]) and varied with the population studied, specific cost outcomes, and economic inputs. In studies that assessed total (direct and indirect) costs, indirect costs accounted for 27%-61% of total costs, depending on the population studied. CONCLUSIONS: COPD is associated with substantial indirect costs. The disease places a burden on employers in terms of lost productivity and associated costs and on individuals in terms of lost income related to absenteeism, activity limitation, and disability. Consideration of indirect as well as direct costs is necessary to gain a more complete view of the societal burden of COPD.