Measuring Costs of Cardiovascular Disease Prevention for Patients with Familial Hypercholesterolemia in Administrative Claims Data.

INTRODUCTION: Familial hypercholesterolemia is a common genetic condition that significantly increases an individual's risk of cardiovascular events such as heart attack, stroke, and cardiac death and is a candidate for population-wide screening programs. Economic analyses of strategies to identify and treat familial hypercholesterolemia are limited by a lack of real-world cost estimates for screening services and medications for reducing cardiovascular risk in this population. METHODS: We estimated the cost of lipid panel testing in patients with hyperlipidemia and the cost of statins, ezetimibe, and PCKS9 inhibitors in patients with familial hypercholesterolemia from a commercial claims database and report costs and charges per panel and prescription by days' supply. RESULTS: The mean cost for a 90-day supply for statins was $183.33, 2.3 times the mean cost for a 30-day supply at $79.35. PCSK9 inhibitors generated the highest mean costs among medications used by patients with familial hypercholesterolemia. CONCLUSIONS: Lipid testing and lipid-lowering medications for cardiovascular disease prevention generate substantial real-world costs which can be used to improve cost-effectiveness models of familial hypercholesterolemia screening and care management.

A regional analysis of payer and provider views on cholesterol management: PCSK9 inhibitors as an illustrative alignment model.

BACKGROUND: Multiple barriers exist for appropriate use of the proprotein convertase subtilisin/kexin type 9 enzyme inhibitors (PCSK9i) in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH) with inadequately controlled hypercholesterolemia despite standard therapies. Among these barriers, high payer rejection rates and inadequate prior authorization (PA) documentation by providers hinder optimal use of PCSK9i. OBJECTIVES: To (a) identify and discuss provider and payer discordances on barriers to authorization and use of PCSK9i based on clinical and real-world evidence and (b) align understanding and application of clinical, cost, safety, and efficacy data of PCSK9i. METHODS: Local groups of 3 payers and 3 providers met in 6 separate locations across the United States through a collaborative project of AMCP and PRIME Education. Responses to selected pre- and postmeeting survey questions measured changes in attitudes and beliefs regarding treatment barriers, lipid thresholds for considering PCSK9i therapy, and tactics for improving PA processes. Statistical analysis of inter- and intragroup changes in attitudes were performed by Cox proportional hazards test and Fisher's exact test for < 5 variables. RESULTS: The majority of providers and payers (67%-78%) agreed that high patient copayments and inadequate PA documentation were significant barriers to PCSK9i usage. However, payers and providers differed on beliefs that current evidence does not support PCSK9i cost-effectiveness (6% providers, 56% payers; P = 0.003) and that PA presents excessive administrative burden (72% providers, 44% payers; P = 0.09) Average increases pre- to postmeeting were noted in provider beliefs that properly documented PA forms expedite access to PCSK9i (22%-50% increase) and current authorization criteria accurately distinguish patients who benefit most from PCSK9i (6%-22%). Payers decreased in their belief that current authorization criteria accurately distinguish benefiting patients (72%-50%). Providers and payers increased in their belief that PCSK9i are cost-effective (44%-61% and 28%-50%, respectively) and were more willing to consider PCSK9i at the low-density lipoprotein cholesterol threshold of > 70 mg/dL for patients with ASCVD (78%-83% and 44%-67%, respectively) or FH (22%-39% and 22%-33%). Payers were more agreeable to less stringent PA requirements for patients with FH (33%-72%, P = 0.019) and need for standardized PA requirements (50%-83%, P = 0.034); these considerations remained high (89%) among providers after the meeting. Most participants supported educational programs for patient treatment adherence (83%) and physician/staff PA processes (83%-94%). CONCLUSIONS: Provider and payer representatives in 6 distinct geographic locations provided recommendations to improve quality of care in patients eligible for PCSK9i. Participants also provided tactical recommendations for streamlining PA documentation processes and improving awareness of PCSK9i cost-effectiveness and clinical efficacy. The majority of participants supported development of universal, standardized patient eligibility criteria and PA forms. DISCLOSURES: The study reported in this article was part of a continuing education program funded by an independent educational grant awarded by Sanofi US and Regeneron Pharmaceuticals to PRIME Education. The grantor had no role in the study design, execution, analysis, or reporting. AMCP received grant funding from PRIME to assist in the study, as well as in writing the manuscript. McCormick, Bhatt, Bays, Taub, Caldwell, Guerin, Steinhoff, and Ahmad received an honorarium from PRIME for serving as faculty for the continuing education program. McCormick, Bhatt, Bays, Taub, Caldwell, Guerin, Steinhoff, and Ahmad were involved as participants in the study. Bhatt discloses the following relationships: Advisory board: Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma, Regado Biosciences; Board of directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data monitoring committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); Site co-investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded research: FlowCo, Merck, Novo Nordisk, Takeda. Bays' research site has received research grants from 89Bio, Acasti, Akcea, Allergan, Alon Medtech/Epitomee, Amarin, Amgen, AstraZeneca, Axsome, Boehringer Ingelheim, Civi, Eli Lilly, Esperion, Evidera, Gan and Lee, Home Access, Janssen, Johnson and Johnson, Lexicon, Matinas, Merck, Metavant, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, Selecta, TIMI, and Urovant. Bays has served as a consultant/advisor for 89Bio, Amarin, Esperion, Matinas, and Gelesis, and speaker for Esperion. McCormick, Caldwell, Guerin, Ahmad, Singh, Moreo, Carter, Heggen, and Sapir have nothing to disclose.

The economic impact of familial hypercholesterolemia on productivity.

BACKGROUND: Familial hypercholesterolemia (FH) is a common inherited cause for premature coronary artery disease that increases suffering and disability in affected people. However, the extent to which FH impacts work productivity at a population level is unclear. OBJECTIVE: We aimed to quantify the burden of heterozygous FH (HeFH) in terms of productivity-adjusted life years (PALYs) lost to HeFH in Australia. METHODS: A life-table model was constructed to quantify years of life and PALYs lived by Australians with HeFH (prevalence 1 in 300) and of working age (aged 20-69 years). Follow-up was simulated until age 70 years. The model was then resimulated, but assuming the cohort did not have HeFH. Increased cardiovascular mortality and reduction in productivity attributable to HeFH were sourced from published data. Differences in total years of life, quality-adjusted life years, and PALYs lived by the "HeFH cohort" and the same cohort without HeFH ("non-HeFH cohort") reflected the quality-adjusted life years and PALYs lost due to HeFH. All future costs and outcomes were discounted by 5% annually. RESULTS: In 2017, an estimated 51,587 people of working age in Australia (0.33%) had HeFH. Over their working lifetime, we predicted that 2950 excess cardiovascular deaths occurred in the current Australian population of working age individuals with HeFH, resulting in a loss of 24,727 years of life. In terms of productivity, HeFH led to the loss of 24,954 PALYs over the working lifetime. Based on gross domestic product (GDP) per full-time equivalent worker, this equated to a total of AUD 5.23 billion in lost GDP over the working lifetime, with an average of AUD 101,366 lost per person. A relative reduction of 20% in cardiovascular deaths (as can be achieved with adequate cholesterol control) would lead to 1113 PALYs and AUD 233 million in GDP saved in the HeFH cohort. CONCLUSION: The impact of HeFH on work productivity is significant. Screening and prevention strategies tailored early in life are likely to exert not only a positive impact on health but also the economy.

A Retrospective Chart Review Evaluating Efficacy, Tolerability, and Cost of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i) in Older Adults.

INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are proven to have profound lowering of low-density lipoprotein cholesterol (LDL-C) in patients with clinical atherosclerotic cardiovascular disease or familial hypercholesterolemia. AIM: The primary purpose of this study was to evaluate PCSK9i utilization in older adults, with a focus on efficacy outcomes within 6 months of initiation. Secondary outcomes included tolerability, out-of-pocket expenses (OPE), and barriers to initiation of therapy. METHODS: We conducted a retrospective chart review of patients ≥ 65 years prescribed PCSK9i therapy by a pharmacist-run lipid clinic within a cardiology practice. RESULTS: A total of 136 older adults were prescribed PCSK9i therapy for a Food and Drug Administration-approved indication between September 2015 and March 2019 with 98 patients included in the analyses. In terms of efficacy, 51 patients who took ≥ 3 doses of PCSK9i with baseline and follow-up lipid panels were assessed. On average, LDL-C reduced by 60% (169-67 mg/dL, p < 0.001). For tolerability, 15 patients reported treatment-emergent side effects, resulting in 10 therapy discontinuations. For the cost analysis, 72 patients reported anticipated OPE for 1 month of therapy. Ultimately 17 patients were approved for manufacturer patient assistance with $0 OPE and 31 patients utilized insurance coverage to obtain therapy reporting a median OPE of $9 United States Dollars ($0-$450). The main barrier to initiation was high OPE. CONCLUSIONS: PCSK9i are effective at lowering LDL-C in older adults. Tolerability was high among patients without a history of statin intolerance. PCSK9i remain high-cost medications to both insurance companies and patients in terms of cost-sharing responsibilities.

Economic evaluation of lipid lowering with PCSK9 inhibitors in patients with familial hypercholesterolemia: Methodological aspects.

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have proved to reduce low density lipoprotein cholesterol levels in numerous clinical trials. In two large clinical trials, PCSK9 inhibitor treatment reduced the risk of cardiovascular disease. Our aim was to explore the impact of varying assumptions about clinical effectiveness on health and economic outcomes for patients with familial hypercholesterolemia. METHODS: We used a previously published and validated Norwegian model for cardiovascular disease. The model was updated with recent data from the world's second largest registry of patients with genetically confirmed familial hypercholesterolemia. We performed analyses for 24 different subgroups of patients based on age, gender, statin tolerance and previous history of cardiovascular disease. RESULTS: In 1 out of 24 subgroups, PCSK9 inhibitors were cost-effective when effectiveness was modelled using direct relative efficacy as reported in the FOURIER trial. When using assumptions, as suggested in a recent consensus statement from the European Atherosclerosis Society, 14 subgroups were cost-effective. CONCLUSIONS: Cost-effectiveness of PCSK9 inhibitors depends highly on assumptions regarding effectiveness. Basing assumptions only on randomised controlled trials, and not taking into account varying effects based on baseline cholesterol level, results in much fewer groups being cost-effective.

Hidden Burden of Electronic Health Record-Identified Familial Hypercholesterolemia: Clinical Outcomes and Cost of Medical Care.

Background Familial hypercholesterolemia ( FH ), is a historically underdiagnosed, undertreated, high-risk condition that is associated with a high burden of cardiovascular morbidity and mortality. In this study, we use a population-based approach using electronic health record ( EHR )-based algorithms to identify FH . We report the major adverse cardiovascular events, mortality, and cost of medical care associated with this diagnosis. Methods and Results In our 1.18 million EHR- eligible cohort, International Classification of Diseases, Ninth Revision ( ICD -9) code-defined hyperlipidemia was categorized into FH and non- FH groups using an EHR algorithm designed using the modified Dutch Lipid Clinic Network criteria. Major adverse cardiovascular events, mortality, and cost of medical care were analyzed. A priori associated variables/confounders were used for multivariate analyses using binary logistic regression and linear regression with propensity score-based weighted methods as appropriate. EHR FH was identified in 32 613 individuals, which was 2.7% of the 1.18 million EHR cohort and 13.7% of 237 903 patients with hyperlipidemia. FH had higher rates of myocardial infarction (14.77% versus 8.33%; P<0.0001), heart failure (11.82% versus 10.50%; P<0.0001), and, after adjusting for traditional risk factors, significantly correlated to a composite major adverse cardiovascular events variable (odds ratio, 4.02; 95% CI, 3.88-4.16; P<0.0001), mortality (odds ratio, 1.20; CI, 1.15-1.26; P<0.0001), and higher total revenue per-year (incidence rate ratio, 1.30; 95% CI, 1.28-1.33; P<0.0001). Conclusions EHR -based algorithms discovered a disproportionately high prevalence of FH in our medical cohort, which was associated with worse outcomes and higher costs of medical care. This data-driven approach allows for a more precise method to identify traditionally high-risk groups within large populations allowing for targeted prevention and therapeutic strategies.

Comparative aspects of the care of familial hypercholesterolemia in the "Ten Countries Study".

BACKGROUND: There is a lack of information on the health care of familial hypercholesterolemia (FH). OBJECTIVE: The objective of this study was to compare the health care of FH in countries of the Asia-Pacific region and Southern Hemisphere. METHODS: A series of questionnaires were completed by key opinion leaders from selected specialist centers in 12 countries concerning aspects of the care of FH, including screening, diagnosis, risk assessment, treatment, teaching/training, and research; the United Kingdom (UK) was used as the international benchmark. RESULTS: The estimated percentage of patients diagnosed with the condition was low (overall <3%) in all countries, compared with ∼15% in the UK. Underdetection of FH was associated with government expenditure on health care (Ï° = 0.667, P < .05). Opportunistic and systematic screening methods, and the Dutch Lipid Clinic Network criteria were most commonly used to detect FH; genetic testing was infrequently used. Noninvasive imaging of coronary calcium and/or carotid plaques was underutilized in risk assessment. Patients with FH were generally not adequately treated, with <30% of patients achieving guideline recommended low-density lipoprotein cholesterol targets on conventional therapies. Treatment gaps included suboptimal availability and use of lipoprotein apheresis and proprotein convertase subtilsin-kexin type 9 inhibitors. A deficit of FH registries, training programs, and publications were identified in less economically developed countries. The demonstration of cost-effectiveness for cascade screening, genetic testing, and specialized treatments were significantly associated with the availability of subsidies from the health care system (Ï° = 0.571-0.800, P < .05). CONCLUSION: We identified important gaps across the continuum of care for FH, particularly in less economically developed countries. Wider implementation of primary and pediatric care, telehealth services, patient support groups, education/training programs, research activities, and health technology assessments are needed to improve the care of patients with FH in these countries.

Universal screening at age 1-2 years as an adjunct to cascade testing for familial hypercholesterolaemia in the UK: A cost-utility analysis.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is widely underdiagnosed. Cascade testing (CT) of relatives has been shown to be feasible, acceptable and cost-effective in the UK, but requires a supply of index cases. Feasibility of universal screening (US) at age 1-2 years was recently demonstrated. We examined whether this would be a cost-effective adjunct to CT in the UK, given the current and plausible future undiagnosed FH prevalence. METHODS: Seven cholesterol and/or mutation-based US ±â€¯reverse cascade testing (RCT) alternatives were compared with no US in an incremental analysis with a healthcare perspective. A decision model was used to estimate costs and outcomes for cohorts exposed to the US component of each strategy. RCT case ascertainment was modelled using recent UK CT data, and probabilistic Markov models estimated lifetime costs and health outcomes for the cohorts screened under each alternative. 1000 Monte Carlo simulations were run for each model, and average outcomes reported. Further uncertainty was explored deterministically. Threshold analysis investigated the association between undiagnosed FH prevalence and cost-effectiveness. RESULTS: A strategy involving cholesterol screening followed by diagnostic genetic testing and RCT was the most cost-effective modelled (incremental cost-effectiveness ratio (ICER) versus no US £12,480/quality adjusted life year (QALY); probability of cost-effectiveness 96·8% at £20,000/QALY threshold). Cost-effectiveness was robust to both deterministic sensitivity analyses and threshold analyses that modelled ongoing case ascertainment at theoretical maximum levels. CONCLUSIONS: These findings support implementation of universal cholesterol screening followed by diagnostic genetic testing and RCT for FH, under a UK conventional willingness-to-pay threshold.

Cost-utility analysis of searching electronic health records and cascade testing to identify and diagnose familial hypercholesterolaemia in England and Wales.

BACKGROUND AND AIMS: The cost effectiveness of cascade testing for familial hypercholesterolaemia (FH) is well recognised. Less clear is the cost effectiveness of FH screening when it includes case identification strategies that incorporate routinely available data from primary and secondary care electronic health records. METHODS: Nine strategies were compared, all using cascade testing in combination with different index case approaches (primary care identification, secondary care identification, and clinical assessment using the Simon Broome (SB) or Dutch Lipid Clinic Network (DLCN) criteria). A decision analytic model was informed by three systematic literature reviews and expert advice provided by a NICE Guideline Committee. RESULTS: The model found that the addition of primary care case identification by database search for patients with recorded total cholesterol >9.3 mmol/L was more cost effective than cascade testing alone. The incremental cost-effectiveness ratio (ICER) of clinical assessment using the DLCN criteria was £3254 per quality-adjusted life year (QALY) compared with case-finding with no genetic testing. The ICER of clinical assessment using the SB criteria was £13,365 per QALY (compared with primary care identification using the DLCN criteria), indicating that the SB criteria was preferred because it achieved additional health benefits at an acceptable cost. Secondary care identification, with either the SB or DLCN criteria, was not cost effective, alone (dominated and dominated respectively) or combined with primary care identification (£63, 514 per QALY, and £82,388 per QALY respectively). CONCLUSIONS: Searching primary care databases for people at high risk of FH followed by cascade testing is likely to be cost-effective.

Parent-child genetic testing for familial hypercholesterolaemia in an Australian context.

AIM: The aim of this study was to evaluate the clinical outcome of parent-child testing for familial hypercholesterolaemia (FH) employing genetic testing and the likely additional cost of treating each child. METHODS: Parent-child testing for gene variants causative of FH was carried out according to Australian guidelines. The number of new cases detected, the low-density lipoprotein (LDL)-cholesterol that best predicted a mutation and the proportional reduction in LDL-cholesterol following statin treatment was evaluated. Treatment costs were calculated as the cost per mmol/L reduction in LDL-cholesterol. RESULTS: A total of 126 adult patients, known to have a pathogenic mutation causative of FH, and their children were studied. From 244 children identified, 148 (60.7%) were genetically screened; 84 children were identified as mutative positive (M+) and 64 as mutative negative. Six of the M+ children were already on statin treatment; 40 were subsequently treated with low-dose statins, with LDL-cholesterol falling significantly by 38% (P < 0.001). The estimated cost per mmol/L reduction of LDL-cholesterol of a child receiving statins from ages 10 to 18 years is AU$1361, which can potentially be cost-effective. An LDL-cholesterol threshold of 3.5 mmol/L had a sensitivity of 92.8% and specificity of 96.6% for the detection of a mutation. CONCLUSION: Genetic testing of children of affected parents with FH is an effective means of detecting new cases of FH. Cascade testing can enable early statin therapy with significant reductions in LDL-cholesterol concentration.

The cost-effectiveness of screening strategies for familial hypercholesterolaemia in Poland.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) elevates the cholesterol level and increases the risk of coronary events and death. Early detection and treatment reduce this risk. We aimed to determine the cost-effectiveness of FH screening in Poland in children, first job takers, and after an acute coronary syndrome (ACS) event, each followed by a cascade screening in the relatives of the positively-diagnosed subjects. METHODS: A decision tree was constructed to model the diagnosis process. We considered scenarios with and without genetic testing. A life-time Markov was built to investigate the effectiveness (life years gained, LYG; and quality-adjusted life years, QALY) and cost (public payer perspective) of treatment in FH-affected subjects. The clinical benefits result from early treatment reducing the risk of coronary heart disease (and death, in result). Model parameters were based on published data and experts' opinions. The costs (patients visits, tests, drugs) were estimated from the National Health Fund data and other publicly-available sources. RESULTS: Screening ACS patients below 55/65 years of age in men/women is the most cost-effective strategy: the cost of one LYG (QALY) amounts to 100 EUR (110 EUR). Removing the age limit or using genetic tests reduced cost-effectiveness; nonetheless, all strategies remained cost effective: the cost of one LYG or QALY was <5040 EUR, much lower than the official threshold of ca. 29,800 EUR/QALY. CONCLUSIONS: Screening for FH is highly cost-effective in Poland. The strategies are complementary, and using a combination thereof is recommended.

Budget Impact Analysis of PCSK9 Inhibitors for the Management of Adult Patients with Heterozygous Familial Hypercholesterolemia or Clinical Atherosclerotic Cardiovascular Disease.

OBJECTIVE: The aim of this study was to assess the budget impact of introducing the proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) alirocumab and evolocumab to market for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular (CV) disease requiring additional lowering of low-density lipoprotein cholesterol (LDL-C). METHODS: A 3-year model estimated the costs of lipid-modifying therapy (LMT) and CV events to a hypothetical US health plan of 1 million members, comparing two scenarios-with and without the availability of PCSK9i as add-on therapy to statins. Proportions of patients with uncontrolled LDL-C despite receiving statins, and at risk of CV events, were estimated from real-world data. Total undiscounted annual LMT costs (2017 prices, including PCSK9i costs of $14,563.50), dispensing and healthcare costs, including the costs of CV events, were estimated for all prevalent patients in the target population, based on baseline risk factors. Maximum PCSK9i utilization of 1-5% over 3 years according to risk group (following the same pattern as current ezetimibe use), and 5-10% as a secondary scenario, were assumed. RESULTS: Total healthcare budget impacts per target patient (and per member) per month for years 1, 2 and 3 were $3.62($0.10), $7.22($0.20) and $10.79($0.30), respectively, assuming 1-5% maximum PCSK9i utilization, and $15.81($0.44), $31.52($0.88) and $47.12($1.31), respectively, assuming 5-10% utilization. Results were sensitive to changes in model timeframe, years to maximum PCSK9i utilization and PCSK9i costs. CONCLUSIONS: The budget impact of PCSK9i as add-on therapy to statins for patients with hypercholesterolemia is relatively low compared with published estimates for other specialty biologics. Drug cost rebates and discounts are likely to further reduce budget impact.

PCSK9 Inhibitors Show Value for Patients and the US Health Care System.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved by the US Food and Drug Administration (FDA) as cholesterol-lowering therapies for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease. OBJECTIVES: To estimate the long-term health and economic value of PCSK9 inhibitors for Americans (51 years and older). METHODS: We conducted simulations using the Future Elderly Model, an established dynamic microsimulation model to project the lifetime outcomes for the US population aged 51 years and older. Health effects estimates and confidence intervals from published meta-analysis studies were used to project changes in life expectancy, quality-adjusted life-years, and lifetime medical spending resulting from the use of PCSK9 inhibitors. We considered two treatment scenarios: 1) current FDA eligibility and 2) an extended eligibility scenario that includes patients with no pre-existing cardiovascular disease but at high risk. We assumed that the price of PCSK9 inhibitors was discounted by 35% in the first 12 years and by 57% thereafter, with gradual uptake of the drug in eligible populations. RESULTS: Use of PCSK9 inhibitors by individuals covered by current FDA approval would extend life expectancy at the age of 51 years by an estimated 1.1 years and would yield a lifetime net value of $5800 per person. If use was extended to those at high risk for cardiovascular disease, PCSK9 inhibitors would generate a lifetime net benefit of $14,100 per person. CONCLUSIONS: Expanded access to PCSK9 inhibitors would offer positive long-term net value for patients and the US health care system at the current discounted prices.

Cost-effectiveness of Evolocumab in Patients With High Cardiovascular Risk in Spain.

PURPOSE: Our objective was to assess the cost-effectiveness of evolocumab in patients at high risk of cardiovascular (CV) events from the Spanish National Health System perspective. METHODS: A Markov model was used to assess the cost-effectiveness (incremental [∆] cost per ∆ quality-adjusted life-year [QALY]; or cost utility) of evolocumab plus standard of care (SoC; statins) versus SoC, assuming lifetime treatment. Cohorts with baseline LDL-C >100 mg/dL and familial hypercholesterolemia (FH) or CV event history (secondary prevention [SP]) were considered. Lifetime CV event rates were predicted either (1) using risk equations considering local risk factors (Spanish Familial Hypercholesterolemia Cohort Study) adjusted to reflect the increased risk of FH patients or (2) using CV event rates from local registries (Information System for the Development of Research in Primary Care) for SP patients. LDL-C relative reductions from evolocumab trials (Evolocumab 140 mg Q2W (bi-weekly) and 420 mg QM (monthly)) were converted into CV event reductions using rate ratios per millimole per liter (mmol/L; 38.67 mg/dL) from a meta-analysis of statin trials (Cholesterol Treatment Trialists' Collaboration). FINDINGS: Predicted 10-year/lifetime CV risks were 50%/95% (FH) and 62%/82% (SP) for SoC and 27%/83% (FH) and 44%/69% (SP) for evolocumab plus SoC. Predicted 10-year/lifetime major CV event risks were 42%/86% (FH) and 47%/67% (SP) for SoC and 21%/68% (FH) and 31%/52% (SP) for evolocumab plus SoC. Predicted per patient-year rates of non-fatal/fatal CV events were 2.2/0.8 (FH) and 1.1/0.6 (SP) for SoC and 1.2/0.6 (FH) and 0.7/0.5 (SP) for evolocumab plus SoC. Predicted CV event reductions per mmol/L were 17% (FH) and 15% (SP). Evolocumab treatment was associated with increased QALYs and costs compared with SoC (FH: ∆cost, €65,369; ∆QALY, 2.12; incremental cost-effectiveness ratio [ICER], €30,893; SP: ∆cost, €42,266; ∆QALY, 0.93; ICER, €45,340). IMPLICATIONS: Evolocumab plus to SoC may provide a cost-effective option for LDL-C lowering in FH and SP patients in Spain.

Cost effectiveness of cascade testing for familial hypercholesterolaemia, based on data from familial hypercholesterolaemia services in the UK.

AIMS: Familial hypercholesterolaemia (FH) is a vastly under-diagnosed genetic disorder, associated with early development of coronary heart disease and premature mortality which can be substantially reduced by effective treatment. Patents have recently expired on high-intensity statins, reducing FH treatment costs. We build a model using UK data to estimate the cost effectiveness of DNA testing of relatives of those with monogenic FH. METHODS AND RESULTS: A Markov model was used to estimate the cost effectiveness of cascade testing, using data from UK cascade services. The estimated incremental cost effectiveness ratio (ICER) was £5806 and the net marginal lifetime cost per relative tested was £2781. More than 80% of lifetime costs were diagnosis-related and incurred in the 1st year. In UK services, 23% of 6396 index cases were mutation-positive. For each mutation-positive index case, 1.33 relatives were tested, resulting overall in a rate of 0.31 tested relatives per tested index case. If the number of relatives tested per tested index case rose to 3.2 (projected by National Institute for Health and Care Excellence in 2008) the ICER would reduce to £2280 and lifetime costs to £1092. CONCLUSION: Cascade testing of relatives of those with suspected FH is highly cost effective. The current Europe-wide high levels of undiagnosed FH, and associated morbidity and mortality, mean adoption of cascade services should yield substantial quality of life and survival gains.

Design of the Familial Hypercholesterolaemia Australasia Network Registry: Creating Opportunities for Greater International Collaboration.

Familial Hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipoprotein metabolism that leads to premature coronary heart disease. There are over 65,000 people estimated to have FH in Australia, but many remain undiagnosed. Patients with FH are often under-treated, but with early detection, cascade family testing and adequate treatment, patient outcomes can improve. Patient registries are key tools for providing new information on FH and enhancing care worldwide. The development and design of the FH Australasia Network Registry is a crucial component in the comprehensive model of care for FH, which aims to provide a standardized, high-quality and cost-effective system of care that is likely to have the highest impact on patient outcomes. Informed by stakeholder engagement, the FH Australasia Network Registry was collaboratively developed by government, patient and clinical networks and research groups. The open-source, web-based Rare Disease Registry Framework was the architecture chosen for this registry owing to its open-source standards, modular design, interoperability, scalability and security features; all these are key components required to meet the ever changing clinical demands across regions. This paper provides a high level blueprint for other countries and jurisdictions to help inform and map out the critical features of an FH registry to meet their particular health system needs.

Challenges in the health economics of familial hypercholesterolemia.

PURPOSE OF REVIEW: Implementation of effective interventions often requires evidence regarding value, that is, whether they are worth what we pay for them. This review explores recent evidence concerning cost-effectiveness in familial hypercholesterolemia, and discusses the cause of, and likelihood of solutions to, the paucity of such evidence. RECENT FINDINGS: Cost-effectiveness analysis in familial hypercholesterolemia has been limited almost exclusively to adult populations. However, there is growing evidence that childhood intervention offers substantial benefit in terms of downstream health gains. Statin therapy in adults has been demonstrated to be cost-effective, but the range of novel agents that might be used will require de novo economic evaluation alongside exploration of their effect and safety profile. SUMMARY: The familial hypercholesterolemia field has limited evidence regarding cost-effectiveness, which limits optimum allocation of resources. Economic evaluations are necessary to appraise new agents and optimal timing of management approaches. Evaluations often have substantial data demands; consequentially, their applicability to medical decision-making or policy will be partly determined by the availability of data, particularly those providing information about the long-term trajectory of health benefit from familial hypercholesterolemia treatment.

A new electronic screening tool for identifying risk of familial hypercholesterolaemia in general practice.

OBJECTIVE: To evaluate the performance of a new electronic screening tool (TARB-Ex) in detecting general practice patients at potential risk of familial hypercholesterolaemia (FH). METHODS: Medical records for all active patients seen between 2012 and 2014 (n=3708) at a large general practice in Perth, Western Australia were retrospectively screened for potential FH risk using TARB-Ex. Electronic extracts of medical records for patients identified with potential FH risk (defined as Dutch Lipid Clinic Network Criteria (DLCNC) score ≥5) through TARB-Ex were reviewed by a general practitioner (GP) and lipid specialist. High-risk patients were recalled for clinical assessment to determine phenotypic FH diagnosis. Performance was evaluated against a manual record review by a GP in the subset of 360 patients with high blood cholesterol (cholesterol ≥7 mmol/L or low-density lipoprotein cholesterol ≥4.0 mmol/L). RESULTS: Thirty-two patients with DLCNC score ≥5 were identified through electronic screening compared with 22 through GP manual review. Sensitivity was 95.5% (95% CI 77.2% to 99.9%), specificity was 96.7% (95% CI 94.3% to 98.3%), negative predictive accuracy was 99.7% (95% CI 98.3% to 100%) and positive predictive accuracy was 65.6% (95% CI 46.9% to 8%). Electronic screening was completed in 10 min compared with 60 h for GP manual review. 10 of 32 patients (31%) were considered high risk and recalled for clinical assessment. Six of seven patients (86%) who attended clinical assessment were diagnosed with phenotypic FH on examination. CONCLUSIONS: TARB-Ex screening is a time-effective and cost-effective method of systematically identifying potential FH risk patients from general practice records for clinical follow-up.

An economic evaluation alongside a randomized controlled trial evaluating an individually tailored lifestyle intervention compared with usual care in people with familial hypercholesterolemia.

BACKGROUND: Cost-effectiveness analyses provide insight in the use of lifestyle interventions. To evaluate the cost-effectiveness of a lifestyle intervention compared to usual care in people with Familial Hypercholesterolemia, 340 people with FH were randomized to the intervention or control group. LDL cholesterol, quality of life and costs were measured at 0 and 12 months. Cost-effectiveness analyses were performed from a healthcare perspective using bootstrapping techniques. RESULTS: Non-significant decreases in LDL cholesterol and quality of life were found. The mean between-group difference in costs was €-237 (95% CI -1,386 to 130). The incremental cost-effectiveness ratios were 1,729 per 1 mmol/l LDL cholesterol and 145,899 per QALY gained. Assumed that the small non-significant decrease in LDL cholesterol is attributed to the intervention, the probability of cost-effectiveness of the intervention compared to usual care was 91% per 1 mmol/l LDL cholesterol reduction and 75% per QALY gained at a ceiling ratio of €20,000. CONCLUSIONS: The intervention is not cost-effective. TRIAL REGISTRATION: NTR1899, date 07-07-2009.