Flexible Approaches Based on Multistate Models and Microsimulation to Perform Real-World Cost-Effectiveness Analyses: An Application to Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors.

OBJECTIVES: This study aims to show the application of flexible statistical methods in real-world cost-effectiveness analyses applied in the cardiovascular field, focusing specifically on the use of proprotein convertase subtilisin-kexin type 9 inhibitors for hyperlipidemia. METHODS: The proposed method allowed us to use an electronic health database to emulate a target trial for cost-effectiveness analysis using multistate modeling and microsimulation. We formally established the study design and provided precise definitions of the causal measures of interest while also outlining the assumptions necessary for accurately estimating these measures using the available data. Additionally, we thoroughly considered goodness-of-fit assessments and sensitivity analyses of the decision model, which are crucial to capture the complexity of individuals' healthcare pathway and to enhance the validity of this type of health economic models. RESULTS: In the disease model, the Markov assumption was found to be inadequate, and a "time-reset" timescale was implemented together with the use of a time-dependent variable to incorporate past hospitalization history. Furthermore, the microsimulation decision model demonstrated a satisfying goodness of fit, as evidenced by the consistent results obtained in the short-term horizon compared with a nonmodel-based approach. Notably, proprotein convertase subtilisin-kexin type 9 inhibitors revealed their favorable cost-effectiveness only in the long-term follow-up, with a minimum willingness to pay of 39 000 Euro/life years gained. CONCLUSIONS: The approach demonstrated its significant utility in several ways. Unlike nonmodel-based or alternative model-based methods, it enabled to (1) investigate long-term cost-effectiveness comprehensively, (2) use an appropriate disease model that aligns with the specific problem under study, and (3) conduct subgroup-specific cost-effectiveness analyses to gain more targeted insights.

Strong Association Between Migraine and Transient Global Amnesia: A National Inpatient Sample Analysis.

The purpose of this article was to explore sex- and race-specific variables and comorbidities associated with transient global amnesia (TGA) using a nationally representative database. Data were obtained from the Nationwide Inpatient Sample using ICD-9 and procedure codes. Descriptive and survey logistic regression analyses were conducted and adjusted for influence of comorbidities, demographic characteristics, and hospitalization-related factors. Patients with migraines were 5.98 times more likely to also have a diagnosis of TGA compared with patients without migraines. Similarly, patients with TGA were more likely to have hypertension, precerebral disease, and hyperlipidemia. The odds of being diagnosed with TGA was lower among African Americans and Hispanics as well as among patients classified as Asian/Other, compared with Caucasians. TGA was associated with lower hospital charges ($14,242 versus $21,319), shorter hospital stays (mean days: 2.49 [SE=0.036] versus 4.72 [SE=0.025]), and routine hospital discharges (91.4% versus 74.5%). Patients with migraines and patients classified as Caucasian had higher odds of being diagnosed with TGA. All minority populations showed a lower rate of diagnosis that fell short of statistical significance.

A Cost Analysis of Universal versus Targeted Cholesterol Screening in Pediatrics.

OBJECTIVE: To compare the number of children needed to screen to identify a case of childhood dyslipidemia and estimate costs under universal vs targeted screening approaches. STUDY DESIGN: We constructed a decision-analytic model comparing the health system costs of universal vs targeted screening for hyperlipidemia in US children aged 10 years over a 1-year time horizon. Targeted screening was defined by family history: dyslipidemia in a parent and/or early cardiovascular disease in a first-degree relative. Prevalence of any hyperlipidemia (low-density lipoprotein [LDL] ≥130 mg/dL) and severe hyperlipidemia (LDL ≥190 mg/dL or LDL ≥160 mg/dL with family history) were obtained from published estimates. Costs were estimated from the 2016 Maryland Medicaid fee schedule. We performed sensitivity analyses to evaluate the influence of key variables on the incremental cost per case detected. RESULTS: For universal screening, the number needed to screen to identify 1 case was 12 for any hyperlipidemia and 111 for severe hyperlipidemia. For targeted screening, the number needed to screen was 7 for any hyperlipidemia and 49 for severe hyperlipidemia. The incremental cost per case detected for universal compared with targeted screening was $1980 for any hyperlipidemia and $32 170 for severe hyperlipidemia. CONCLUSIONS: Our model suggests that universal cholesterol screening detects hyperlipidemia at a low cost per case, but may not be the most cost-efficient way to identify children with severe hyperlipidemia who are most likely to benefit from treatment.

Hyperlipidemia and Medical Expenditures by Cardiovascular Disease Status in US Adults.

BACKGROUND: Hyperlipidemia is a major risk factor for cardiovascular disease (CVD), affecting 73.5 million American adults. Information about health care expenditures associated with hyperlipidemia by CVD status is needed to evaluate the economic benefit of primary and secondary prevention programs for CVD. METHODS: The study sample includes 48,050 men and nonpregnant women ≥18 from 2010 to 2012 Medical Expenditure Panel Survey. A 2-part econometric model was used to estimate annual hyperlipidemia-associated medical expenditures by CVD status. The estimation results from the 2-part model were used to calculate per-capita and national medical expenditures associated with hyperlipidemia. We adjusted the medical expenditures into 2012 dollars. RESULTS: Among those with CVD, per person hyperlipidemia-associated expenditures were $1105 [95% confidence interval (CI), $877-$1661] per year, leading to an annual national expenditure of $15.47 billion (95% CI, $5.23-$27.75 billion). Among people without CVD, per person hyperlipidemia-associated expenditures were $856 (95% CI, $596-$1211) per year, resulting in an annual national expenditure of $23.11 billion (95% CI, $16.09-$32.71 billion). Hyperlipidemia-associated expenditures were attributable mostly to the costs of prescription medication (59%-90%). Among people without CVD, medication expenditures associated with hyperlipidemia were $13.72 billion (95% CI, $10.55-$15.74 billion), higher in men than in women. CONCLUSIONS: Hyperlipidemia significantly increased medical expenditures and the increase was higher in people with CVD than without. The information on estimated expenditures could be used to evaluate and develop effective programs for CVD prevention.

Clinical and economic burden associated with cardiovascular events among patients with hyperlipidemia: a retrospective cohort study.

BACKGROUND: Annual direct costs for cardiovascular (CV) diseases in the United States are approximately $195.6 billion, with many high-risk patients remaining at risk for major cardiovascular events (CVE). This study evaluated the direct clinical and economic burden associated with new CVE up to 3 years post-event among patients with hyperlipidemia. METHODS: Hyperlipidemic patients with a primary inpatient claim for new CVE (myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, coronary artery bypass graft, percutaneous coronary intervention and heart failure) were identified using IMS LifeLink PharMetrics Plus data from January 1, 2006 through June 30, 2012. Patients were stratified by CV risk into history of CVE, modified coronary heart disease risk equivalent, moderate- and low-risk cohorts. Of the eligible patients, propensity score matched 243,640 patients with or without new CVE were included to compare healthcare resource utilization and direct costs ranging from the acute (1-month) phase through 3 years post-CVE date (follow-up period). RESULTS: Myocardial infarction was the most common CVE in all the risk cohorts. During the acute phase, among patients with new CVE, the average incremental inpatient length of stay and incremental costs ranged from 4.4-6.2 days and $25,666-$30,321, respectively. Acute-phase incremental costs accounted for 61-75% of first-year costs, but incremental costs also remained high during years 2 and 3 post-CVE. CONCLUSIONS: Among hyperlipidemic patients with new CVE, healthcare utilization and costs incurred were significantly higher than for those without CVE during the acute phase, and remained higher up to 3 years post-event, across all risk cohorts.

Estimating the future burden of cardiovascular disease and the value of lipid and blood pressure control therapies in China.

BACKGROUND: Lifestyle and dietary changes reflect an ongoing epidemiological transition in China, with cardiovascular disease (CVD) playing an ever-increasing role in China's disease burden. This study assessed the burden of CVD and the potential value of lipid and blood pressure control strategies in China. METHODS: We estimated the likely burden of CVD between 2016 and 2030 and how expanded use of lipid lowering and blood pressure control medication would impact that burden in the next 15 years. Accounting for the costs of drug use, we assessed the net social value of a policy that expands the utilization of lipid and blood pressure lowering therapies in China. RESULTS: Rises in prevalence of CVD risk and population aging would likely increase the incidence of acute myocardial infarctions (AMIs) by 75 million and strokes by 118 million, while the number of CVD deaths would rise by 39 million in total between 2016 and 2030. Universal treatment of hypertension and dyslipidemia patients with lipid and blood pressure lowering therapies could avert between 10 and 20 million AMIs, between 8 and 30 million strokes, and between 3 and 10 million CVD deaths during the 2016-2030 period, producing a positive social value net of health care costs as high as $932 billion. CONCLUSIONS: In light of its aging population and epidemiological transition, China faces near-certain increases in CVD morbidity and mortality. Preventative measures such as effective lipid and blood pressure management may reduce CVD burden substantially and provide large social value. While the Chinese government is implementing more systematic approaches to health care delivery, prevention of CVD should be high on the agenda.

Reducing Medication Costs to Prevent Cardiovascular Disease: A Community Guide Systematic Review.

INTRODUCTION: Hypertension and hyperlipidemia are major cardiovascular disease risk factors. To modify them, patients often need to adopt healthier lifestyles and adhere to prescribed medications. However, patients' adherence to recommended treatments has been suboptimal. Reducing out-of-pocket costs (ROPC) to patients may improve medication adherence and consequently improve health outcomes. This Community Guide systematic review examined the effectiveness of ROPC for medications prescribed for patients with hypertension and hyperlipidemia. METHODS: We assessed effectiveness and economics of ROPC for medications to treat hypertension, hyperlipidemia, or both. Per Community Guide review methods, reviewers identified, evaluated, and summarized available evidence published from January 1980 through July 2015. RESULTS: Eighteen studies were included in the analysis. ROPC interventions resulted in increased medication adherence for patients taking blood pressure and cholesterol medications by a median of 3.0 percentage points; proportion achieving 80% adherence to medication increased by 5.1 percentage points. Blood pressure and cholesterol outcomes also improved. Nine studies were included in the economic review, with a median intervention cost of $172 per person per year and a median change in health care cost of -$127 per person per year. CONCLUSION: ROPC for medications to treat hypertension and hyperlipidemia is effective in increasing medication adherence, and, thus, improving blood pressure and cholesterol outcomes. Most ROPC interventions are implemented in combination with evidence-based health care interventions such as team-based care with medication counseling. An overall conclusion about the economics of the intervention could not be reached with the small body of inconsistent cost-benefit evidence.

Effect of the Medicare Part D coverage gap on medication use among patients with hypertension and hyperlipidemia.

BACKGROUND: Prior studies of the Medicare Part D coverage gap are limited in generalizability and scope. OBJECTIVE: To determine the effect of the coverage gap on drugs used for asymptomatic (antihypertensive and lipid-lowering drugs) and symptomatic (pain relievers, acid suppressants, and antidepressants) conditions in elderly patients with hypertension and hyperlipidemia. DESIGN: Quasi-experimental study using pre-post design and contemporaneous control group. SETTING: Medicare claims files from 2005 and 2006 for 5% random sample of Medicare beneficiaries. PATIENTS: Part D plan enrollees with hypertension or hyperlipidemia aged 65 years or older who had no coverage, generic-only coverage, or both brand-name and generic coverage during the gap in 2006. Patients who were fully eligible for the low-income subsidy served as the control group. MEASUREMENTS: Monthly 30-day supply prescriptions available, medication adherence, and continuous medication gaps of 30 days or more for antihypertensive or lipid-lowering drugs; monthly 30-day supply prescriptions available for pain relievers, acid suppressants, or antidepressants before and after coverage gap entry. RESULTS: Patients with no gap coverage had a decrease in monthly antihypertensive and lipid-lowering drug prescriptions during the coverage gap. Nonadherence also increased in this group (antihypertensives: odds ratio [OR], 1.60 [95% CI, 1.50 to 1.71]; lipid-lowering drugs: OR, 1.59 [CI, 1.50 to 1.68]). The proportion of patients with no gap coverage who had continuous medication gaps in lipid-lowering medication use and antihypertensive use increased by an absolute 7.3% (OR, 1.38 [CI, 1.29 to 1.46]) and 3.2% (OR, 1.35 [CI, 1.25 to 1.45]), respectively, because of the coverage gap. Decreases in use were smaller for pain relievers and antidepressants and larger for acid suppressants in patients with no gap coverage. Patients with generic-only coverage had decreased use of cardiovascular medications but no change in use of drugs for symptomatic conditions. No measures changed in the brand-name and generic coverage groups. Results of sensitivity analyses were consistent with the main findings. LIMITATION: Because this study was nonrandomized, unobserved differences may still exist between study groups. CONCLUSION: The Part D coverage gap was associated with decreased use of medications for hypertension and hyperlipidemia in patients with no gap coverage and generic-only gap coverage. The proposed phasing out of the gap by 2020 will benefit such patients; however, use of low-value medications may also increase. PRIMARY FUNDING SOURCE: Penn-Pfizer Alliance and American Heart Association.

Cost-effectiveness of Icosapent Ethyl for High-risk Patients With Hypertriglyceridemia Despite Statin Treatment.

Importance: The Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial (REDUCE-IT) demonstrated the efficacy of icosapent ethyl (IPE) for high-risk patients with hypertriglyceridemia and known cardiovascular disease or diabetes and at least 1 other risk factor who were treated with statins. Objective: To estimate the cost-effectiveness of IPE compared with standard care for high-risk patients with hypertriglyceridemia despite statin treatment. Design, Setting, and Participants: An in-trial cost-effectiveness analysis was performed using patient-level study data from REDUCE-IT, and a lifetime analysis was performed using a microsimulation model and data from published literature. The study included 8179 patients with hypertriglyceridemia despite stable statin therapy recruited between November 21, 2011, and May 31, 2018. Analyses were performed from a US health care sector perspective. Statistical analysis was performed from March 1, 2018, to October 31, 2021. Interventions: Patients were randomly assigned to IPE, 4 g/d, or placebo and were followed up for a median of 4.9 years (IQR, 3.5-5.3 years). The cost of IPE was $4.16 per day after rebates using SSR Health net cost (SSR cost) and $9.28 per day with wholesale acquisition cost (WAC). Main Outcomes and Measures: Main outcomes were incremental quality-adjusted life-years (QALYs), total direct health care costs (2019 US dollars), and cost-effectiveness. Results: A total of 4089 patients (2927 men [71.6%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive IPE, and 4090 patients (2895 men [70.8%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive standard care. Treatment with IPE yielded more QALYs than standard care both in trial (3.34 vs 3.27; mean difference, 0.07 [95% CI, 0.01-0.12]) and over a lifetime projection (10.59 vs 10.35; mean difference, 0.24 [95% CI, 0.15-0.33]). In-trial, total health care costs were higher with IPE using either SSR cost ($18 786) or WAC ($24 544) than with standard care ($17 273; mean difference from SSR cost, $1513 [95% CI, $155-$2870]; mean difference from WAC, $7271 [95% CI, $5911-$8630]). Icosapent ethyl cost $22 311 per QALY gained using SSR cost and $107 218 per QALY gained using WAC. Over a lifetime, IPE was projected to be cost saving when using SSR cost ($195 276) compared with standard care ($197 064; mean difference, -$1788 [95% CI, -$9735 to $6159]) but to have higher costs when using WAC ($202 830) compared with standard care (mean difference, $5766 [95% CI, $1094-$10 438]). Compared with standard care, IPE had a 58.4% lifetime probability of costing less and being more effective when using SSR cost and an 89.4% probability of costing less than $50 000 per QALY gained when using SSR cost and a 72.5% probability of costing less than $50 000 per QALY gained when using WAC. Conclusions and Relevance: This study suggests that, both in-trial and over the lifetime, IPE offers better cardiovascular outcomes than standard care in REDUCE-IT participants at common willingness-to-pay thresholds.

Medical utilization and costs associated with statin adherence in Medicaid enrollees with type 2 diabetes.

BACKGROUND: Statin adherence is a serious problem in patients with hyperlipidemia. However, it is not clear whether statin adherence is associated with medical utilization or health-care costs. OBJECTIVE: To study statin adherence and assess associated medical utilization and health-care costs in patients with type 2 diabetes, based on a national Medicaid database. METHODS: A retrospective claims-based study was conducted using the records of patients with type 2 diabetes with comorbid hyperlipidemia who were continuously enrolled in Medicaid from January 2004 to December 2006. All data were drawn from MarketScan Medicaid Database, including inpatient, outpatient, and drug claims. The eligible patients starting statins in 2005 were followed for 1 year to measure medication use, hospitalization, outpatient visits, emergency department (ED) visits, and health-care costs based on Medicaid medical and drug claims. Adherence was measured by medication possession ratio (MPR). Multiple regression analyses were implemented to assess statin adherence-associated outcomes, including medical utilization (risks for hospitalization and ED visits), all-cause costs, and hyperlipidemia-related medical costs. RESULTS: A total of 1705 eligible patients with type 2 diabetes and hyperlipidemia were identified. The average adherence rate to statins (MPR) at 1 year was 0.61, and 37% of the patients (n=624) were adherent to statins (MPR≥0.8). Regression analyses indicated that diabetic patients who were adherent to statins showed lower risks for hospitalization (OR 0.80; 95% CI 0.636 to 0.966) and ED visits (OR 0.71; 95% CI 0.519 to 0.812) and decreased all-cause medical costs by 15% (p<0.05) and hyperlipidemia-related medical costs by 12% (p<0.05). CONCLUSIONS: Our study found high prevalence of nonadherence to statins in Medicaid patients with type 2 diabetes. Adherence to statins (MPR≥0.8) was associated with reduced medical utilization and lower medical costs.

Economic burden of comorbidities in patients with psoriasis is substantial.

BACKGROUND: Psoriasis is frequently associated with comorbidities. OBJECTIVE: To estimate the incremental economic burden associated with comorbidities in patients with psoriasis, accounting for psoriasis severity. METHODS: Patients continuously enrolled ≥6 months after a randomly selected psoriasis diagnosis date were selected from the Ingenix Impact National Managed Care Database (1999-2004). Comorbidities identified during the 6-month study included: psoriatic arthritis, cardiovascular disease, depression, diabetes, hyperlipidemia, hypertension, obesity, cerebrovascular diseases and peripheral vascular disease. Resource utilization and costs during the 6-month follow-up period were compared for patients with ≥1 comorbidity vs. those without and for patients with a specific comorbidity vs. those without. Adjusted incidence rate ratios (IRRs) and odds ratios (ORs) were estimated for resource utilization using negative binomial and logistic regression models, respectively. Adjusted incremental costs associated with comorbidities were reported using general linear models with log-link and gamma distributions or two-part models. Models controlled for age, sex and psoriasis severity. RESULTS: A total of 114,512 patients were included; 51% had ≥1 comorbidity. Hyperlipidemia (27%) and hypertension (25%) were most prevalent. Patients with comorbidities were more likely to experience urgent care [OR (95% confidence interval (CI))=1.58 (1.51-1.65)] than patients without comorbidities. They also had significantly greater hospitalization rates [IRR (95% CI)=2.27 (2.13-2.42)] and outpatient visits [IRR (95% CI)=1.53 (1.52-1.55)]. Compared with patients who did not have comorbidities, patients with comorbidities incurred $2184 (P<0.001) greater total costs. CONCLUSION: Comorbidities present a significant economic burden in patients with psoriasis.

The impact of Medicare Part D on medication adherence among older adults enrolled in Medicare-Advantage products.

BACKGROUND: Little is known about how Medicare Part D affects the medication refill adherence for cardiovascular and diabetes medications, particularly among beneficiaries without prior drug coverage. OBJECTIVES: To evaluate Medicare Part D's effect on medication adherence among beneficiaries with hyperlipidemia, hypertension, and/or diabetes enrolled in Medicare Advantage products. RESEARCH DESIGN: We used a quasi-experimental pre-post design, with 3 treatment groups and a comparison group, to assess the effect of Part D on several measures of adherence to prescription medications. SUBJECTS: Adults aged 65 or older with hyperlipidemia, hypertension, and/or diabetes in 2003 continuously enrolled between 2004 and 2007 in a large Pennsylvania insurer's Medicare Advantage products. MEASURES: Medication possession ratios (MPR), good adherence with MPR >0.8, and intensity of treatment measured by average daily counts of pills per day of treatment. RESULTS: Part D improved MPRs in the group without prior drug coverage by 13.4 percentage points (95% CI, 10.1-16.8), 17.9 (95% CI, 13.7-22.1), and 13.5 (95% CI, 11.5-15.5) for those with hyperlipidemia, diabetes, and hypertension, respectively. Adherence improved less in the other 2 groups with limited prior drug benefits. Although the proportion of beneficiaries in the intervention groups who attained good adherence levels increased after Part D, less than 50%, 68%, and 78% of beneficiaries with hyperlipidemia, diabetes, and hypertension, respectively, attained good adherence. CONCLUSION: Part D increased adherence to medications that reduce the risk of cardiovascular events for patients with hypertension, diabetes, and hyperlipidemia. This should improve the health of the elderly people in the long run.

Food insecurity is associated with chronic disease among low-income NHANES participants.

Food insecurity refers to the inability to afford enough food for an active, healthy life. Numerous studies have shown associations between food insecurity and adverse health outcomes among children. Studies of the health effects of food insecurity among adults are more limited and generally focus on the association between food insecurity and self-reported disease. We therefore examined the association between food insecurity and clinical evidence of diet-sensitive chronic disease, including hypertension, hyperlipidemia, and diabetes. Our population-based sample included 5094 poor adults aged 18-65 y participating in the NHANES (1999-2004 waves). We estimated the association between food insecurity (assessed by the Food Security Survey Module) and self-reported or laboratory/examination evidence of diet-sensitive chronic disease using Poisson regression. We adjusted the models to account for differences in age, gender, race, educational attainment, and income. Food insecurity was associated with self-reported hypertension [adjusted relative risk (ARR) 1.20; 95% CI, 1.04-1.38] and hyperlipidemia (ARR 1.30; 95% CI, 1.09-1.55), but not diabetes (ARR 1.19; 95% CI, 0.89-1.58). Food insecurity was associated with laboratory or examination evidence of hypertension (ARR 1.21; 95% CI, 1.04-1.41) and diabetes (ARR 1.48; 95% CI, 0.94-2.32). The association with laboratory evidence of diabetes did not reach significance in the fully adjusted model unless we used a stricter definition of food insecurity (ARR 2.42; 95% CI, 1.44-4.08). These data show that food insecurity is associated with cardiovascular risk factors. Health policy discussions should focus increased attention on ability to afford high-quality foods for adults with or at risk for chronic disease.

The modeled lifetime cost-effectiveness of published adherence-improving interventions for antihypertensive and lipid-lowering medications.

OBJECTIVE: We sought to compare the cost-effectiveness of different interventions that have been shown to improve adherence with antihypertensive and lipid-lowering therapy, by combining a burden of nonadherence model framework with literature-based data on adherence-improving interventions. METHODS: MEDLINE was reviewed for studies that evaluated ≥1 adherence intervention compared with a control, used an adherence measure other than self-report, and followed patients for ≥6 months. Effectiveness was assessed as Relative Improvement, ratio of adherence with an intervention versus control. Costs, standardized to 12 months and adjusted to 2007 US$, and effectiveness estimates for each intervention were entered into a previously published model designed to measure the burden of nonadherence with antihypertensive and lipid-lowering medications, in a hypertensive population. Outputs included direct medical costs and incremental costs per quality-adjusted life-year (QALY) gained. RESULTS: After screening, 23 eligible adherence-improving interventions were identified from 18 studies. Relative Improvement ranged from 1.13 to 3.60. After eliminating more costly/less effective interventions, two remained. Self-monitoring, reminders, and educational materials incurred total health-care costs of $17,520, and compared with no adherence intervention, had an incremental cost-effectiveness ratio (ICER) of $4984 per QALY gained. Pharmacist/nurse management incurred total health-care costs of $17,896, and versus self-monitoring, reminders, and education had an ICER of $6358 per QALY gained. CONCLUSIONS: Of published interventions shown to improve adherence, reminders and educational materials, and a pharmacist/nurse management program, appear to be cost-effective and should be considered before other interventions. Understanding relative cost-effectiveness of adherence interventions may guide design and implementation of efficient adherence-improving programs.

The cost and effectiveness of adherence-improving interventions for antihypertensive and lipid-lowering drugs*.

AIMS: Adherence to cardiovascular medications is poor. Accordingly, interventions have been proposed to improve adherence. However, as intervention-associated costs are rarely considered in full, we sought to review the effectiveness and costs associated with different adherence-improving interventions for cardiovascular disease therapies. METHODS: We reviewed MEDLINE to update a prior review of interventions to improve adherence with antihypertensive and/or lipid-lowering therapy covering January 1972 to June 2002, to add studies published from July 2002 to October 2007. Eligible studies evaluated > or = 1 intervention compared with a control, used measures other than self-report, reported significant improvement in adherence and followed patients for > or = 6 months. Effectiveness was measured as relative improvement (RI), the ratio of adherence in the intervention group to the control group. Costs were calculated based on those reported in the analysis, if available or estimated based on resource use described. All costs were truncated to 6 months and adjusted to 2007 US$. RESULTS: Of 755 new articles, five met all eligibility criteria. Combining with the prior review gave 23 interventions from 18 studies. RI in adherence ranged from 1.11 to 4.65. Six-month intervention costs ranged from $10 to $142 per patient. Reminders had the lowest effectiveness (RI: 1.11-1.14), but were least costly ($10/6 months). Case management was most effective (RI: 1.23-4.65), but the most costly ($90-$130/6 months). CONCLUSIONS: Generally, we found a positive association between intervention costs and effectiveness. Therefore, consideration of intervention costs, along with the benefits afforded to adherence, may help guide the design and implementation of adherence-improving programs.

The economic consequences of non-adherence to lipid-lowering therapy: results from the Anglo-Scandinavian-Cardiac Outcomes Trial.

BACKGROUND: Adherence to lipid-lowering therapy in clinical practice is less than ideal. Analysis of registry data has indicated that this is associated with poor outcomes. The objective of the present analysis was to assess the impact of high adherence to drug (defined as > 80% of days covered), compared with low adherence to drug (< 50% of days covered) in terms of risk of events and long-term economic consequences. DESIGN: Open-label follow up of a randomised placebo-controlled trial in hypertensive patients. METHODS: Cox proportional hazards and Poisson regression models were used to assess the hazard ratio of patients with high adherence compared with low adherence while controlling for cardiovascular risk. A Markov model was used to predict the long-term costs and health outcomes associated with poor adherence during the follow-up period. RESULTS: Both statistical models indicated that high adherence is associated with improved prognosis [Cox model: 0.75; 95% confidence interval (CI): 0.56-0.98, Poisson model hazard ratio: 0.73; 95% CI: 0.58-0.98]. Discounted at 3.5% per year, the Markov model predicts that as a consequence of higher adherence during the follow-up period, costs would be higher (1689 pounds per patient compared with 1323 pounds per patient) because of higher drug costs, but the projected survival and quality-adjusted survival (QALY) would also be longer (10.83 compared with 10.81 life years and 8.13 compared with 8.11 QALYs). CONCLUSION: Given the higher risk of cardiovascular events associated with low adherence shown here, measures to improve adherence are an important part of the prevention of cardiovascular disease.

Association Between Poverty and Appropriate Statin Prescription for the Treatment of Hyperlipidemia in the United States: An Analysis From the ACC NCDR PINNACLE Registry.

BACKGROUND: Poverty is associated with a higher risk of myocardial infarction and cardiac death, both of which are decreased by treatment of hyperlipidemia. There may be differences in the appropriate treatment of hyperlipidemia between richer and poorer Americans. In this study, we aimed to evaluate the association between income level and appropriate lipid-lowering therapy. METHODS: We identified outpatient visits in the National Cardiovascular Data Registry's Practice Innovation and Clinical Excellence (PINNACLE) Registry and determined appropriateness of lipid-lowering therapy among patients in different income quintiles (Quintile 5 being the highest income quintile). Logistic regression at the patient level was performed to evaluate the independent association of income and the primary outcome of appropriate statin therapy. The analysis was repeated before and after November 2013 given a change in guideline definitions. RESULTS: The study included 1,655,723 patients. Overall, 68-73% of patients were treated appropriately under the ATP III Guidelines and 57-62% of patients were treated appropriately under the ACC/AHA Guidelines. Patients in the wealthiest quintile had higher odds of appropriate statin therapy under both guidelines relative to patients in the poorest quintile (OR 1.06 [1.05-1.07] for ATP III and OR 1.03 [1.01-1.04] for ACC/AHA). In the whole sample, patients with higher estimated income had a small but significant increased likelihood of appropriate statin therapy (point-biserial correlation 0.035 [p < 0.001] for ATP III and 0.026 [p < 0.001] for ACC/AHA). CONCLUSIONS: Here we describe a small association between appropriate statin use and income. Further investigation into barriers in the use of evidence-based therapies in poorer populations is needed.

Rationale and design of the Study Assessing the Effect of Cardiovascular Medications Provided as Low-cost, Evidence-based Generic Samples (SAMPLES) trial.

BACKGROUND: Highly effective generic cardiovascular medications are frequently underused, leading to greater overall drug costs and cost-related nonadherence. OBJECTIVE: We sought to assess an intervention to stimulate appropriate generic cardiovascular drug use without creating administrative or financial barriers that may impede essential medication use. TRIAL DESIGN: The SAMPLES (Study Assessing the Effect of Cardiovascular Medications Provided as Low-cost, Evidence-based Generic Samples) trial is a clustered, randomized controlled trial of the effect of providing physicians with free generic samples of hydrochlorothiazide for hypertensive patients and simvastatin for patients with hyperlipidemia. We will randomize 660 primary care physicians in Pennsylvania, clustered by physician practice, to receive free samples for both conditions or to receive no samples. We will use data on filled prescriptions obtained from a state-sponsored prescription drug assistance program to perform an intention-to-treat evaluation of the impact of the intervention on physician prescribing behavior (proportion of prescriptions that are generic) and patient adherence. Secondary outcomes will include physician adherence to established guidelines and overall prescription drug costs. CONCLUSION: This trial will define the potential role of an innovative approach to stimulate clinically appropriate cost-effective prescribing. We will determine whether free generic samples can reduce overall drug costs as well as out-of-pocket costs to the patient without sacrificing efficacy and whether this approach results in improved adherence to essential cardiovascular medications. This intervention may also improve adherence to practice guidelines and improve the quality of care received. If effective, this strategy could be used broadly by private insurers or government payers aiming to stimulate more cost-effective and higher-quality care.