Background Although familial hypercholesterolemia (FH) confers a high risk of coronary artery disease, most patients are undiagnosed, and little is known about the efficiency of genetic cascade ...screening programs at national level. Objective The aim of the study was to estimate the cost-effectiveness of a national genetic cascade screening program in Spain. Methods An economic evaluation was performed using a decision tree analysis. The choice in the decision tree was between implementation of the national program for FH (NPFH) or keeping the usual clinical care. The NPFH detects FH patients through total cholesterol measurement at primary care level and use of genetic testing in index cases and relatives. The payer (National Health System) and social (including the productivity lost) perspectives were considered. The outcome variables were coronary events avoided, deaths avoided, and quality-adjusted life years (QALYs) gained. Results From the payer perspective, the application of the NPFH during 1 year prevents 847 coronary events and 203 deaths in the 9000 FH patients cohort during a 10-year follow-up, yielding an extra 767 QALYs, at a cost of €29,608 per QALY gained. From the social perspective, the NPFH is dominant over the control (the cost decreases and the effectiveness increases). The sensitivity analysis confirms the robustness of the findings. Conclusion The NPFH based on molecular testing is a cost-effective diagnostic and management strategy that supports government expenditure aimed at preventing coronary artery disease in FH patients in Spain. Implementation of such a strategy is likely to be also cost-effective in countries with similar developed healthcare systems.
Elevated lipoprotein(a) Lp(a) is independently associated with increased cardiovascular risk. However, treatment options for elevated Lp(a) are limited. Alirocumab, a monoclonal antibody to ...proprotein convertase subtilisin/kexin type 9, reduced low-density lipoprotein cholesterol (LDL-C) by up to 62% from baseline in phase 3 studies, with adverse event rates similar between alirocumab and controls. We evaluated the effect of alirocumab on serum Lp(a) using pooled data from the phase 3 ODYSSEY program: 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included. Eight studies evaluated alirocumab 75 mg every 2 weeks (Q2W), with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 (75/150 mg Q2W); the other 2 studies evaluated alirocumab 150-mg Q2W from the outset. Comparators were placebo or ezetimibe. Eight studies were conducted on a background of statins, and 2 studies were carried out with no statins. Alirocumab was associated with significant reductions in Lp(a), regardless of starting dose and use of concomitant statins. At week 24, reductions from baseline were 23% to 27% with alirocumab 75/150-mg Q2W and 29% with alirocumab 150-mg Q2W (all comparisons p <0.0001 vs controls). Reductions were sustained over 78 to 104 weeks. Lp(a) reductions with alirocumab were independent of race, gender, presence of familial hypercholesterolemia, baseline Lp(a), and LDL-C concentrations, or use of statins. In conclusion, in addition to marked reduction in LDL-C, alirocumab leads to a significant and sustained lowering of Lp(a).
Objectives This study sought to evaluate the efficacy and safety of subcutaneous evolocumab compared with oral ezetimibe in hypercholesterolemic patients who are unable to tolerate effective statin ...doses. Background Statin intolerance, which is predominantly due to muscle-related side effects, is reported in up to 10% to 20% of patients. Evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), demonstrated marked reductions in plasma low-density lipoprotein cholesterol (LDL-C) in a phase 2 study in statin-intolerant patients. Methods The GAUSS-2 (Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects) trial was a 12-week, double-blind study of randomized patients (2:2:1:1) to evolocumab 140 mg every two weeks (Q2W) or evolocumab 420 mg once monthly (QM) both with daily oral placebo or subcutaneous placebo Q2W or QM both with daily oral ezetimibe 10 mg. Co-primary endpoints were percent change from baseline in LDL-C at the mean of weeks 10 and 12, and at week 12. Results Three hundred seven patients (age 62 ± 10 years; LDL-C 193 ± 59 mg/dl) were randomized. Evolocumab reduced LDL-C from baseline by 53% to 56%, corresponding to treatment differences versus ezetimibe of 37% to 39% (p <0.001). Muscle adverse events occurred in 12% of evolocumab-treated patients and 23% of ezetimibe-treated patients. Treatment-emergent adverse events and laboratory abnormalities were comparable across treatment groups. Conclusions Robust efficacy combined with favorable tolerability makes evolocumab a promising therapy for addressing the largely unmet clinical need in high-risk patients with elevated cholesterol who are statin intolerant. (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2; NCT01763905 )
Highlights ► We address clinical challenges in the diagnosis and management of familial hypercholesterolemia patients ► We address the controversies in diagnosing homozygous FH ► We offer a clinical ...care pathway to identify and manage patients with varying phenotypic severity of FH ► We address the underdiagnosis and undertreatment of all FH patients ► We address genotyping and cascade screening in FH patients
Familial hypercholesterolemia (FH) significantly increases the risk of coronary heart disease. Most individuals are unaware they have the condition. In the Western Australian Pregnancy Cohort (Raine) ...Study, 1 in 267 adolescents were found to have FH. Universal cholesterol screening in childhood may offer the best strategy for diagnosing FH.
Familial hypercholesterolemia (FH), the most common and severe monogenic form of hypercholesterolemia, is an autosomal co-dominant disease characterized by an increased plasma low density lipoprotein ...(LDL)-cholesterol concentration and premature coronary heart disease (CHD). The clinical phenotype depends on the gene involved and severity of mutation (or mutations) present. Patients with homozygous or compound heterozygous FH have severe hypercholesterolemia (LDL-cholesterol >13 mmol/L) due to a gene dosing effect and without treatment have accelerated atherosclerotic CHD from birth, and frequently die of CHD before age 30. Cholesterol-lowering therapies have been shown to reduce both mortality and major adverse cardiovascular events in individuals with FH. Lipoprotein apheresis concomitant with lipid-lowering therapy is the treatment of choice for homozygous FH. This article describes the rationale and role of lipoprotein apheresis in the treatment of severe FH and outlines the recent advances in new pharmacotherapies for this condition.
Background Familial hypercholesterolemia (FH) is the most common dominantly inherited cause of premature coronary artery disease (CAD). However, the diagnosis of FH in patients who have premature CAD ...in hospital settings is under-recognized, this also represents a missed opportunity for screening their close family members and implementing primary prevention. Objective To investigate the point prevalence of FH in a coronary care unit (CCU) among patients with early-onset CAD. Methods The prevalence of FH, based on modified phenotypic Dutch Lipid Clinic Network Criteria, and the spectrum of associated CAD risk factors, were investigated in a CCU setting. Data were collected on 175 coronary care patients with onset of CAD at age <60 years. Results The prevalence of probable/definite FH was 14.3% (95% confidence interval, 9.0%–19.5%); 46.3% of the patients gave a family history of premature CAD and 20.6% had an untreated low-density lipoprotein cholesterol >5.0 mmol/L. Diabetes, hypertension, obesity, and smoking were common and equally prevalent in patients with and without FH. Conclusions FH is relatively frequent among patients with a history of early-onset CAD in the CCU. Every effort should be made to detect FH in these patients and to initiate cascade testing of available family members to prevent the development of CAD in those who may be unaware that they also have the condition.
Background Familial hypercholesterolemia (FH) imposes significant burden of premature coronary heart disease (CHD). Objective This study aimed to determine the cost-effectiveness of FH detection ...based on genetic testing, supplemented with the measurement of plasma low-density lipoprotein cholesterol concentration, and treatment with statins. Methods A Markov model with a 10-year time horizon was constructed to simulate the onset of first-ever CHD and death in close relatives of probands with genetically confirmed FH. The model comprised of 3 health states: “alive without CHD,” “alive with CHD,” and “dead.” Decision-analysis compared the clinical consequences and costs of cascade-screening vs no-screening from an Australian health care perspective. The annual risk of CHD and benefits of treatment was estimated from a cohort study. The underlying prevalence of FH, sensitivity, specificity, cost of screening, treatment, and clinic follow-up visits were derived from a cascade screening service for FH in Western Australia. An annual discount rate of 5% was applied to costs and benefits. Results The model estimated that screening for FH would reduce the 10-year incidence of CHD from 50.0% to 25.0% among people with FH. Of every 100 people screened, there was an overall gain of 24.95 life-years and 29.07 quality-adjusted life years (discounted). The incremental cost-effectiveness ratio was in Australian dollars, $4155 per years of life saved and $3565 per quality-adjusted life years gained. Conclusion This analysis within an Australian context, demonstrates that cascade screening for FH, using genetic testing supplemented with the measurement of plasma low-density lipoprotein cholesterol concentrations and treatment with statins, is a cost-effective means of preventing CHD in families at risk of FH.
Background Familial hypercholesterolemia (FH) is a dominantly inherited disorder characterized by high plasma cholesterol levels and a very high risk of early heart disease. The prevalence of FH is ...estimated to be at least 1:500, with at least 3.6 million individuals in the Asia-Pacific region. Objective To assess awareness, knowledge, and perception of FH among practicing physicians in Japan, South Korea, and Taiwan. Methods Physicians from 3 economically developed Asian countries were requested to anonymously complete a structured Internet-based survey regarding FH. This survey sought responses on the clinical description, inheritance, prevalence, cardiovascular disease risk, practices, and opinions on screening. Results Of 230 physicians surveyed, 47% were aware of the heritability, 27% of the prevalence, and 13% of the risk of cardiovascular disease relating to FH. The majority (70%) perceived themselves to have an above-moderate familiarity with FH. Primary care physicians (59%) and lipid specialists (41%) were perceived as the best providers for caring for FH, including cascade screening services, with a lesser role perceived for cardiologists, endocrinologists, and no significant role for nursing staff. Only 35% of physicians were aware of specialist clinical services for lipid disorders in their geographic area. Conclusion Extensive education and training programs are required to complement the implementation of region-specific models of care for FH in Asia. Further enhancement of existing lipid services and facilities are also warranted to optimise service models.
Abstract Purpose The purpose of this review was to outline the current and emerging therapeutic options for the treatment of hypertriglyceridemia, with an emphasis on emerging therapies. Methods A ...systematic literature search was conducted with the use of PubMed and Embase for articles on hypertriglyceridemia, with a focus on therapeutics, pharmacology, and management. Abstracts from recent international meetings were also reviewed for presentations of Phase I and II data on agents with triglyceride-lowering effects. A further review of the references identified from these articles was also performed. Findings Consistent with the multifactorial cause of hypertriglyceridemia, the therapeutic options are broad and numerous. This review explores the current and potential therapeutic options for treating hypertriglyceridemia and outlines the potential mechanisms of action. However, the mechanism of triglyceride reduction is complex, multifactorial, or not fully elucidated for some of these agents. The magnitude of triglyceride reduction and findings of outcome studies are described. Implications Management of hypertriglyceridemia is about to enter an exciting phase, with multiple emerging therapies in the final stages of development. However, caution is warranted, because studies of therapeutic agents over the previous decade have often not found cardiovascular outcome benefits despite encouraging effects on triglyceride concentrations.
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