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.

Awareness, diagnosis and treatment of heterozygous familial hypercholesterolemia (HeFH) - Results of a US national survey.

BACKGROUND: HeFH is a common inherited disorder that leads to markedly elevated LDL-cholesterol from birth and premature cardiovascular disease. HeFH is frequently underdiagnosed and undertreated. OBJECTIVE: To compare how well primary care physicians and cardiologists recognize and treat HeFH. METHODS: The National Lipid Association surveyed 500 primary care physicians and 500 cardiologists in the US who have patients with baseline LDL-cholesterol ≥ 190 mg/dL. The survey was conducted between August 29 and September 30, 2019. RESULTS: For a hypothetical case of HeFH, 57% of cardiologists versus 43% of primary care physicians made the correct diagnosis (P<0.001). Among respondents, 21% of cardiologists versus 29% of primary care physicians have never made a diagnosis of HeFH in a patient with an LDL-cholesterol ≥ 190 mg/dL (P<0.004). Only 7% of cardiologists versus 5% of primary care physicians would refer to a lipid specialist (P=0.05). For additional LDL-cholesterol lowering after statins, 58% of cardiologists versus 48% of primary care physicians would prescribe a PCSK9 inhibitor (P=0.004); however, 30% of cardiologists versus 53% of primary care physicians have never prescribed a PSCK9 inhibitor in an HeFH patient (P<0.001). CONCLUSION: Although cardiologists compared to primary care physicians are somewhat more likely to recognize and treat HeFH patients according to guidelines, both physician specialties do not adequately recognize or treat HeFH. There is a need for more education and training in recognizing and treating HeFH, greater access to lipid specialists, and fewer barriers for PCSK9 inhibitor use.

Assessment of microvascular function and pharmacological regulation in genetically confirmed familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic lipid disorder leading to accelerated atherosclerosis, premature cardiovascular disease and death. Microvascular endothelial dysfunction is one of the earliest vascular pathology manifestations and may precede symptomatic atherosclerosis. METHODS: In this paper, microvascular endothelial function was assessed in FH patients and healthy controls using flow mediated skin fluorescence (FMSF), based on measurements of nicotinamide adenine dinucleotide fluorescence intensity during brachial artery occlusion (ischemic response, IR) and immediately after occlusion (hyperemic response, HR). Low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were used to assess its relation with microvascular parameters evaluated in vivo. RESULTS: LDL-C levels were significantly correlated to both HRmax (r = -0.548, p = 0.001) and HRindex (r = -0.514, p = 0.003). Similarly, there was a significant inverse correlation of TC levels and both HRmax (r = -0.538, p = 0.002) and HRindex (r = -0.512, p = 0.003). All FMSF parameters were found lower in FH patients compared to age- and sex-matched healthy controls. Hyperemic response (HRmax) was significantly higher in FH patients examined on statins compared to those without any lipid-lowering treatment (19.9 ± 3.1 vs. 16.4 ± 4.2 respectively, p = 0.022). CONCLUSIONS: This study shows that, in patients with FH, microvascular endothelial-dependent hyperemic response is impaired and inversely correlated to plasma cholesterol levels. Microvascular function was found better in FH patients receiving statins.

Cost-Effectiveness of Evolocumab Therapy for Myocardial Infarction: The Chinese Healthcare Perspective.

PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an indispensable lipid-lowering treatment option, but their cost-effectiveness has been questioned. This study aimed to perform a health economic evaluation of evolocumab versus placebo in patients with myocardial infarction (MI) in China. METHODS: A Markov cohort state-transition model was developed in decision analysis software to estimate the incremental cost-effectiveness ratio (ICER), defined as cost per quality-adjusted life-year (QALY) saved. The simulation subjects could undergo non-fatal MI and/or stroke, or vascular or non-vascular death event. We integrated the Chinese population-specific demographics and event rates with the risk reduction of evolocumab based on the FOURIER trial and/or lowering of low-density lipoprotein cholesterol (LDL-C). Age-related change, event costs and utilities were included from published sources. RESULTS: At its current list price [33,748 Chinese yuan (CNY) annually per person], the ICER for evolocumab therapy was 927,713 CNY per QALY gained when integrating the FOURIER trial with absolute reduction of LDL-C. The probability of cost-effectiveness of evolocumab versus placebo was 1.96%, with a generally accepted threshold of 212,676 CNY per QALY gained. A reduction in acquisition price by approximately 70% (to less than 10,255 CNY annually) was needed to be cost-effective. Alternative scenario analyses of therapeutic benefit showed that the ICER for evolocumab in MI patients with uncontrolled familial hypercholesterolemia (FH) was 187,736 CNY per QALY gained. CONCLUSION: Evolocumab in patients with MI was not cost-effective based on the price in 2019 in China; however, treatment with evolocumab was more favorable in MI patients with FH.

Awareness, treatment rates, and compliance to treatment in patients with serum LDL cholesterol higher than 250 mg/dL, and possible, probable, or definite familial hypercholesterolemia.

PURPOSE: Familial hypercholesterolemia (FH) is a genetic disease characterized by increased levels of low-density lipoprotein cholesterol (LDL-C). It is underdiagnosed and undertreated despite relatively high prevalance and significant association with increased mortality. We aimed to determine treatment status and compliance in patients with LDL-C ≥ 250 mg/dL and FH. DESIGN: Patients older than 18 years old and have a serum LDL-C ≥ 250 mg/dL between January 2010 to December 2016 were identified from the hospital database. A phone survey was performed. Demographic features, smoking status, alcohol use, exercise, cardiovascular disease (CVD), use of medication for dyslipidemia, and CVD and high cholesterol levels in the family were questioned. Dutch Lipid Clinical Network Criteria was used to classify patients. The study was registered to Clinicaltrials.gov in July 2020 (NCT04494464). RESULTS: 1365 patients with a LDL-C ≥ 250 mg/dL were identified. Patients that could not be reached and who refused to interview were excluded and the data of 367 patients were analyzed. There were 248 (67.6%) female and 119 (32.4%) male patients and mean age was 50.52 ± 11.66. LDL-C was ≥330 mg/dL in 50 (13.6%) and 250-329 mg/dL in 317 (86.4%) patients. Forty (10.9%) patients were classified as definite, 181 (49.3%) as probable and 146 (39.8%) as possible FH. 213 (58.0%) patients were not receiving lipid-lowering treatment, and 162 (76.1%) stated that medication was never recommended previously, 30 (14.1%) had stopped medication him/herself and 21 (9.8%) had stopped medication with the advice of the physician. Among patients with definite/probable FH, 84 (38.0%) had CVD and the rate of lipid-lowering drug use in these patients was 58.3%. CONCLUSION: A significant proportion of patients with LDL-C ≥ 250 mg/dL were not taking lipid-lowering drugs. Similar with many other studies, diagnosis, and treatment rates of FH patients were very low in our study. Further national studies are required to increase awareness of the disease in both physicians and patients.

Lipoprotein apheresis and PCSK9 inhibitors for severe familial hypercholesterolaemia: Experience from Australia and New Zealand.

INTRODUCTION: Severe familial hypercholesterolaemia (FH) causes premature disability and death due to atherosclerotic cardiovascular disease and is refractory to standard lipid-lowering therapies. Lipoprotein apheresis (LA) has long been a standard of care for patients with severe FH, but is invasive, expensive and time-consuming for patients and their caregivers. Newer drug therapies, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may reduce the need for LA. MATERIALS AND METHODS: We audited the records of 16 patients (eight homozygous, eight heterozygous) treated with LA in Australia and New Zealand, 14 of whom subsequently commenced PCSK9 inhibitor therapy. LA was performed by cascade filtration in all centres. RESULTS: LDL-cholesterol was acutely lowered by 69 ± 7% in patients with homozygous FH and by 72 ± 9% in those with heterozygous FH, representing time-averaged reductions of 36 ± 12% and 34 ± 5%, respectively. LA was well-tolerated, and patients reported comparable quality of life to population and disease-related norms. After commencement of PCSK9 inhibitors, four of seven patients with homozygous FH had meaningful biochemical responses, with a reduction in the frequency of LA permitted in one patient and complete cessation in another. Four of seven patients with heterozygous FH were able to be managed without LA after commencing PCSK9 inhibitors. CONCLUSION: While PCSK9 inhibitors have reduced the need for LA, some patients with severe FH continue to require LA, and will require it for the foreseeable future. However, emerging therapies, including angiopoetin-like 3 inhibitors, may further reduce the need for LA.

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.

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.

Pharmacokinetic and pharmacodynamic assessment of alirocumab in patients with familial hypercholesterolemia associated with proprotein convertase subtilisin/kexin type 9 gain-of-function or apolipoprotein B loss-of-function mutations.

BACKGROUND: Familial hypercholesterolemia is characterized by high levels of low-density lipoprotein cholesterol (LDL-C), and causes of familial hypercholesterolemia include apolipoprotein B (APOB) loss-of-function mutations (LOFm) and proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutations (GOFm). OBJECTIVE: The aim of this study was to compare the pharmacokinetics and pharmacodynamics of alirocumab between patients with APOB LOFm vs PCSK9 GOFm. METHODS: Patients (6 APOB LOFm and 17 PCSK9 GOFm carriers) with LDL-C ≥70 mg/dL on maximally tolerated lipid-lowering therapies received alirocumab 150 mg at Weeks 0, 2, 4, and 6, placebo at Week 8, alirocumab at Week 10, placebo at Weeks 12 and 14, then completed a follow-up period at Week 22. RESULTS: At Week 8, mean ± standard error (SE) alirocumab concentration was lower in APOB LOFm carriers compared with PCSK9 GOFm carriers (12.12 ± 1.81 vs 16.74 ± 2.53 mg/L). APOB LOFm carriers had higher mean ± SE total PCSK9 (6.56 ± 0.73 mg/L) and lower mean ± SE free PCSK9 (0.025 ± 0.016 mg/L) at Week 8 compared with PCSK9 GOFm carriers (4.21 ± 0.35 and 0.11 ± 0.035 mg/L for total and free PCSK9, respectively). Despite this observed greater PCSK9 suppression, mean ± SE percent LDL-C reduction was lower in APOB LOFm (55.3 ± 1.0%) compared with PCSK9 GOFm carriers (73.1 ± 0.9%). Treatment-emergent adverse events occurred in 16 patients (94.1%) in the PCSK9 GOFm group and 5 patients (83.3%) in the APOB LOFm group. CONCLUSIONS: Overall, PCSK9 inhibition with alirocumab results in clinically meaningful reductions in LDL-C in both APOB LOFm and PCSK9 GOFm carriers, although reductions were greater in the PCSK9 GOFm carriers. The results indicate a possible underlying contributor to hypercholesterolemia other than PCSK9 in patients with APOB LOFm. CLINICAL TRIAL REGISTRATION: NCT01604824; clinicaltrials.gov.

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.

Treatment patterns and patient characteristics among early initiators of PCSK9 inhibitors.

PURPOSE: To describe patient characteristics and treatment patterns among early initiators of proprotein convertase subtilisin/kexin type nine inhibitors (PCSK9is) who initiated treatment within the first 6 months of market availability. PATIENTS AND METHODS: This retrospective cohort study used IQVIA's longitudinal open-source point-of-sale pharmacy claims database (LRx) and PharMetrics Plus (P+) health plan claims database to identify patients initiating a PCSK9i between January 1, 2016 and June 30, 2016. The index date was defined as the date of the first PCSK9i prescription (index claim) during the enrollment window; patients were followed for ≥6 months postindex. Patient characteristics including use of baseline lipid-lowering therapy (LLT) and measures such as persistence and adherence to PCSK9i therapy were evaluated with respect to health plan type (commercial vs Medicare). RESULTS: Overall, patients initiating PCSK9i (n=13,151) had a mean age of 66 years, and 51% were male. Approximately 67.4% of patients used some form of LLT (statin and/or ezetimibe) in the 24 months prior to initiating PCSK9i therapy. The proportion of patients covered by a commercial health plan (51.2%) was similar to that covered by Medicare (48.8%). Persistence on PCSK9i was marginally longer for patients with commercial insurance than Medicare (mean days on therapy 202.2 vs 198.5). Overall, 42.6% of patients discontinued their PCSK9i during the 180 days of follow-up. CONCLUSION: This study demonstrates that a large proportion of patients discontinue PCSK9i therapy at 30 and 90 days, which are the time frames for which many health plans require recertification to continue access to PCSK9i. Future studies looking at treatment patterns among patients who initiate PCSK9i therapy after the first 180 days once health plan formularies and utilization management criteria were finalized are needed to understand more comprehensively real-world PCSK9i usage patterns.

DIAgnosis and Management Of familial hypercholesterolemia in a Nationwide Design (DIAMOND-FH): Prevalence in Switzerland, clinical characteristics and the diagnostic value of clinical scores.

BACKGROUND AND AIMS: In Switzerland, the prevalence of familial hypercholesterolemia (FH) due to pathogenic apolipoprotein B-100 gene (APOB) variants was known, but not the prevalence of FH due to pathogenic low-density lipoprotein-receptor gene (LDLR) variants. Phenotypic differences (LDLR versus APOB) might affect the diagnostic value of the Dutch Lipid Clinic Network (DLCN) score and Simon Broome Diagnostic Criteria (SBDC). METHODS: A total of 2734 Swiss subjects were investigated, 2221 unselected subjects from three representative population surveys for estimation of the prevalence (LDLR variants), and 513 subjects from the DIAgnosis and Management Of familial hypercholesterolemia in a Nationwide Design (DIAMOND-FH) study for comparisons of phenotypic characteristics (LDLRversusAPOB variants), diagnostic values of clinical scores, and cardiovascular outcome. RESULTS: In 7 of 2221 individuals, FH (LDLR) was diagnosed (prevalence of FH due to LDLR variants: 1/317, prevalence of FH due to both LDLR and APOB variants: 1/125 to 1/135). In FH (APOB) patients under 35 years of age, mean total cholesterol (TC) was <8.5 mmoL/L but increased above 35. In FH (LDLR), TC was >8.5 mmoL/L in all age groups. This difference was crucial for the diagnosis of FH and resulted in a significantly lower sensitivity of clinical scores in FH (APOB) (DLCN: 13.8%, p < 0.0001; SBDC: 22.5%, p = 0.005). Thus, both scores were not useful for the definite diagnosis of FH due to APOB variants. Regarding the cardiovascular outcome, no differences (LDLR versus APOB) were found above 60 years. In countries with high percentages of FH due to APOB variants, cascade screening and molecular testing appear to be much more cost-effective.

Epidemiology of familial hypercholesterolaemia: Community and clinical.

Familial hypercholesterolaemia (FH) is a genetic disorder affecting the metabolism of low-density lipoprotein (LDL) particles, leading to high LDL-cholesterol levels maintained over time and higher risk of cardiovascular disease (CVD) early in life. Contemporary studies have challenged prior estimations of FH prevalence and suggest this condition to be more frequent than previously considered, with an overall prevalence rate of 1:200-300 individuals in the general population (1:160,000-300,000 for homozygous FH). However, prevalence of FH varies around the world. In part this is due to an artefact of approaches of detection and methods used to diagnose FH (e.g. lack of gold standard for diagnosis of FH, different criteria applied, availability of genetic testing). But also due to intrinsic characteristic of different populations, e.g. higher presence of founder effects or rates of consanguinity. Additionally, results from many regions are lacking and it is estimated that only a small percentage of subjects with FH would have been diagnosed overall. FH entails a significantly higher risk of CVD, reported to be higher than that estimated by conventional risk assessment tools for the general population. This risk is mainly driven by coronary heart disease. Despite this evidence, low rates of patients meet therapeutic targets for cardiovascular prevention, and implementation of therapy (high intensity statins, combination therapy) is needed. The introduction of novel lipid-lowering therapies may improve this situation. In the present review, we discuss the epidemiology of FH overall, with special attention to different aspects related to prevalence, cardiovascular risk and prognosis, and treatment of FH.

Knowledge, awareness and practice regarding familial hypercholesterolaemia among primary care physicians in Malaysia: The importance of professional training.

BACKGROUND AND AIMS: This study aimed to determine knowledge, awareness and practice (KAP) regarding familial hypercholesterolaemia (FH) among Malaysian primary care physicians (PCP), and to compare KAP between PCP with postgraduate qualification (PCP-PG-Qual) and PCP without PG qualification (PCP-noPG-Qual). METHODS: This was a cross-sectional study involving PCP with ≥1-year working experience in Malaysian primary care settings. An adapted and validated 25-item FH-KAP questionnaire was disseminated during primary care courses. Total score for each domain was calculated by summing-up the correct responses, converted into percentage scores. Normality distribution was examined and comparisons of mean/median percentage scores were made between the two groups of PCP. RESULTS: A total of 372 PCP completed the questionnaire. Regarding knowledge, 77.7% correctly defined FH. However, only 8.3% correctly identified coronary artery disease risk in untreated FH. The mean percentage knowledge score was significantly higher in PCP-PG-Qual compared to PCP-noPG-Qual (48.9, SD ±â€¯13.92 vs. 35.2, SD ±â€¯14.13), t(370) = 8.66, p < 0.001. Regarding awareness, 39% were aware of the NICE FH guideline and only 27.2% were aware of FH diagnostic criteria. The median percentage awareness score was significantly higher in PCP-PG-Qual compared to PCP-noPG-Qual (15.4, IqR ±â€¯23.08 vs. 7.7, IqR ±â€¯11.54), p = 0.013. Regarding practice, only 19.1% stratified FH patients as high risk irrespective of other risk factors. The mean percentage practice score was significantly higher in PCP-PG-Qual compared to PCP-noPG-Qual (52.4, SD ±â€¯12.92 vs. 42.7, SD ±â€¯16.63), t(370) = 9.65, p < 0.001. CONCLUSIONS: Substantial gaps in FH-KAP among Malaysian PCP were identified, with PCP-PG-Qual having better knowledge, awareness and practice than PCP-noPG-Qual, emphasising the importance of professional training and certification.

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.

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.

Assessment of arterial stiffness in patients with familial hypercholesterolemia.

BACKGROUND: Recently, the concept of severe familial hypercholesterolemia (FH) has been proposed to identify individuals at an extremely high risk of developing coronary artery disease (CAD) among patients with FH. Although the adverse effects of arterial stiffness have been proven in the general population, insufficient data exist regarding its clinical impact in patients with FH. OBJECTIVES: This study aimed to assess the association between arterial stiffness and CAD in patients with FH. METHODS: We examined 245 patients with FH (162 males; mean age, 46 ± 17 years) and brachial-ankle pulse wave velocity (baPWV) measurements. We assessed baseline characteristics including lipid profiles, other traditional risk factors, the presence of CAD, and the baPWV. RESULTS: Multivariable logistic analysis adjusted for age, sex, hypertension, diabetes, smoking, and low-density lipoprotein cholesterol revealed that the baPWV was independently associated with CAD (odds ratio [OR]: 1.25, 95% confidence interval: 1.10-1.41; P = .000372; per 100 cm/s). Moreover, considering the baPWV with other traditional risk factors improved the risk discrimination of CAD (C-statistics 0.736 vs 0.799; P = .006067). Compared with the reference group without hypertension and low baPWV, patients with hypertension and high baPWV had a significantly higher OR for CAD (OR: 18.68, 95% confidence interval: 6.62-60.62; P = 1.7 × 10-7). CONCLUSIONS: Arterial stiffness assessed by the baPWV was significantly associated with the presence of CAD in patients with FH. Such assessments are useful in the risk stratification of CAD and are independent of hypertension in patients with FH.

Prevalence and management of familial hypercholesterolemia in patients with coronary artery disease: The heredity survey.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low density lipoprotein cholesterol (LDL-C) predisposing to premature cardiovascular disease. Its prevalence varies and has been estimated around 1 in 200-500. The Heredity survey evaluated the prevalence of potential FH and the therapeutic approaches among patients with established coronary artery disease (CAD) or peripheral artery disease (PAD) in which it is less well documented. METHODS: Data were collected in patients admitted to programs of rehabilitation and secondary prevention in Italy. Potential FH was estimated using Dutch Lipid Clinic Network (DLCN) criteria. Potential FH was defined as having a total score≥6. RESULTS: Among the 1438 consecutive patients evaluated, the prevalence of potential FH was 3.7%. The prevalence was inversely related to age, with a putative prevalence of 1:10 in those with <55yrs of age (male) and <60yrs (female). Definite FH (DLCN score>8) had the highest percentages of patients after an ACS (75% vs 52.5% in the whole study population). At discharge, most patients were on high intensity statin therapy, but despite this, potential FH group still had a higher percentage of patients with LDL-C levels not at target and having a distance from the target higher than 50%. CONCLUSIONS: Among patients with established coronary heart disease, the prevalence of potential FH is higher than in the general population; the results suggest that a correct identification of potential FH, especially in younger patients, may help to better manage their high cardiovascular risk.

Health disparities among adult patients with a phenotypic diagnosis of familial hypercholesterolemia in the CASCADE-FH™ patient registry.

BACKGROUND AND AIMS: Most familial hypercholesterolemia (FH) patients remain undertreated, and it is unclear what role health disparities may play for FH patients in the US. We sought to describe sex and racial/ethnic disparities in a national registry of US FH patients. METHODS: We analyzed data from 3167 adults enrolled in the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE-FH) registry. Logistic regression was used to evaluate for disparities in LDL-C goals and statin use, with adjustments for covariates including age, cardiovascular risk factors, and statin intolerance. RESULTS: In adjusted analyses, women were less likely than men to achieve treated LDL-C of <100 mg/dL (OR 0.68, 95% CI, 0.57-0.82) or ≥50% reduction from pretreatment LDL-C (OR 0.79, 95% CI, 0.65-0.96). Women were less likely than men to receive statin therapy (OR, 0.60, 95% CI, 0.50-0.73) and less likely to receive a high-intensity statin (OR, 0.60, 95% CI, 0.49-0.72). LDL-C goal achievement also varied by race/ethnicity: compared with whites, Asians and blacks were less likely to achieve LDL-C levels <100 mg/dL (Asians, OR, 0.47, 95% CI, 0.24-0.94; blacks, OR, 0.49, 95% CI, 0.32-0.74) or ≥50% reduction from pretreatment LDL-C (Asians, OR 0.56, 95% CI, 0.32-0.98; blacks, OR 0.62, 95% CI, 0.43-0.90). CONCLUSIONS: In a contemporary US population of FH patients, we identified differences in LDL-C goal attainment and statin usage after stratifying the population by either sex or race/ethnicity. Our findings suggest that health disparities contribute to the undertreatment of US FH patients. Increased efforts are warranted to raise awareness of these disparities.