| 1. |
- Vallejo-Vaz, Antonio J., et al.
(författare)
-
Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)
- 2018
-
Ingår i: Atherosclerosis. - : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 277, s. 234-255
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in similar to 2/3 countries. Lipoprotein-apheresis is offered in similar to 60% countries, although access is limited. Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.
|
|
| 2. |
|
|
| 3. |
- Vallejo-Vaz, Antonio J., et al.
(författare)
-
Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration
- 2016
-
Ingår i: Atherosclerosis Supplements. - : ELSEVIER IRELAND LTD. - 1567-5688 .- 1878-5050. ; 22
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The potential for global collaborations to better inform public health policy regarding major non-hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. Methods: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. Conclusions: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients. (C) 2016 Elsevier Ireland Ltd.
|
|
| 4. |
- Raal, Frederick J., et al.
(författare)
-
PCSK9 Inhibitors : From Nature's Lessons to Clinical Utility
- 2020
-
Ingår i: Endocrine, Metabolic & Immune Disorders - Drug Targets. - : Bentham Science Publishers Ltd.. - 1871-5303 .- 2212-3873. ; 20:6, s. 840-854
-
Forskningsöversikt (refereegranskat)abstract
- Background: Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel class of non-statin lipid lowering therapy that reduce LDL-cholesterol by 50 - 6044,. PCSK9 inhibitors decrease LDL-cholesterol by preventing intracellular degradation of LDL receptors; subsequently, a greater number of LDL-receptors arc available on the cell surface to extract circulating LDL. Objective: To describe the origins of PCSK9 inhibitors and their current use in clinical practice. Methods: We performed a narrative review of the PCSK9 inhibitor class of drugs Results: Current data indicate that PCSK9 inhibitors effectively reduce LDL-cholesterol and are well tolerated and safe. PCSK9 inhibitors have also been shown to reduce cardiovascular event rates in patients with stable atherosclerotic cardiovascular disease and in patients with a recent (up to one year) acute coronary syndrome. Given the costs, chronicity of the treatment and the potential budget impact, PCSK9 inhibitors are often limited to patients with the highest absolute risk for major adverse cardiovascular events despite optimal treatment with high-intensity statin and ezetimibe. Conclusion: PCSK9 inhibitors have a favorable safety, efficacy and tolerability profile. Post marketing safety surveillance and real-world studies are needed to further support the long-term safety profile of this class of medicine.
|
|
| 5. |
- Chiang, Chern-En, et al.
(författare)
-
Suboptimal Control of Lipid Levels : Results from 29 Countries Participating in the Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS)
- 2016
-
Ingår i: Journal of Atherosclerosis and Thrombosis. - : Japan Atherosclerosis Society. - 1880-3873 .- 1340-3478. ; 23:5, s. 567-587
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Five multicentre, cross-sectional Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS) were conducted in 29 countries across Asia, Western Europe, Eastern Europe, the Middle East, and Africa. The surveys assessed the current use and efficacy of lipid-lowering drugs (LLDs) worldwide and identified possible patient and physician characteristics associated with failure to attain low-density lipoprotein cholesterol (LDL-C) goals. The aim of this analysis was to consolidate the global results from these surveys. Methods: The surveys involved patients aged >= 18 years who had been prescribed LLDs for at least 3 months without dose changes for at least 6 weeks. A single visit was scheduled for data collection, including fasting plasma lipid and glucose levels. Cardiovascular risk profile and LDL-C goal attainment were assessed according to the 2004 updated US National Cholesterol Education Program Adult Treatment Panel III guidelines. Results: In total, 35 121 patients (mean age: 60.4 years) were included, and 90.3% had been prescribed statin monotherapy. Overall, only 49.4% of patients reached their recommended LDL-C level. LDL-C goals were attained in 54.8% (5084/9273) and 22.8% (3287/14 429) of patients were at high and very high cardiovascular risk, respectively. Factors associated with an increased likelihood of LDL-C goal attainment were lower baseline cardiovascular risk; presence of diabetes mellitus, hypertension, or history of cardiovascular disease; and treatment with simvastatin, atorvastatin, or rosuvastatin (vs. all other LLDs). Conclusion: LDL-C goal attainment in patients taking LLDs is suboptimal worldwide, particularly in patients at high and very high cardiovascular risk.
|
|
| 6. |
- Mach, François, et al.
(författare)
-
Adverse effects of statin therapy: perception vs. the evidence - focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract
- 2018
-
Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 39:27
-
Forskningsöversikt (refereegranskat)abstract
- To objectively appraise evidence for possible adverse effects of long-term statin therapy on glucose homeostasis, cognitive, renal and hepatic function, and risk for haemorrhagic stroke or cataract.A literature search covering 2000-2017 was performed. The Panel critically appraised the data and agreed by consensus on the categorization of reported adverse effects. Randomized controlled trials (RCTs) and genetic studies show that statin therapy is associated with a modest increase in the risk of new-onset diabetes mellitus (about one per thousand patient-years), generally defined by laboratory findings (glycated haemoglobin ≥6.5); this risk is significantly higher in the metabolic syndrome or prediabetes. Statin treatment does not adversely affect cognitive function, even at very low levels of low-density lipoprotein cholesterol and is not associated with clinically significant deterioration of renal function, or development of cataract. Transient increases in liver enzymes occur in 0.5-2% of patients taking statins but are not clinically relevant; idiosyncratic liver injury due to statins is very rare and causality difficult to prove. The evidence base does not support an increased risk of haemorrhagic stroke in individuals without cerebrovascular disease; a small increase in risk was suggested by the Stroke Prevention by Aggressive Reduction of Cholesterol Levels study in subjects with prior stroke but has not been confirmed in the substantive evidence base of RCTs, cohort studies and case-control studies.Long-term statin treatment is remarkably safe with a low risk of clinically relevant adverse effects as defined above; statin-associated muscle symptoms were discussed in a previous Consensus Statement. Importantly, the established cardiovascular benefits of statin therapy far outweigh the risk of adverse effects.
|
|
| 7. |
|
|
| 8. |
- Raal, Frederick J., et al.
(författare)
-
PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial
- 2015
-
Ingår i: The Lancet. - : Elsevier: Lancet. - 0140-6736 .- 1474-547X. ; 385:9965, s. 331-340
-
Tidskriftsartikel (refereegranskat)abstract
- Background Heterozygous familial hypercholesterolaemia is characterised by low cellular uptake of LDL cholesterol, increased plasma LDL cholesterol concentrations, and premature cardiovascular disease. Despite intensive statin therapy, with or without ezetimibe, many patients are unable to achieve recommended target levels of LDL cholesterol. We investigated the effect of PCSK9 inhibition with evolocumab (AMG 145) on LDL cholesterol in patients with this disorder. Methods This multicentre, randomised, double-blind, placebo-controlled trial was undertaken at 39 sites (most of which were specialised lipid clinics, mainly attached to academic institutions) in Australia, Asia, Europe, New Zealand, North America, and South Africa between Feb 7 and Dec 19,2013.331 eligible patients (18-80 years of age), who met clinical criteria for heterozygous familial hypercholesterolaemia and were on stable lipid-lowering therapy for at least 4 weeks, with a fasting LDL cholesterol concentration of 2.6 mmol/L or higher, were randomly allocated in a 2:2:1:1 ratio to receive subcutaneous evolocumab 140 mg every 2 weeks, evolocumab 420 mg monthly, or subcutaneous placebo every 2 weeks or monthly for 12 weeks. Randomisation was computer generated by the study sponsor, implemented by a computerised voice interactive system, and stratified by LDL cholesterol concentration at screening (higher or lower than 4.1 mmol/L) and by baseline ezetimibe use (yes/no). Patients, study personnel, investigators, and Amgen study staff were masked to treatment assignments within dosing frequency groups. The coprimary endpoints were percentage change from baseline in LDL cholesterol at week 12 and at the mean of weeks 10 and 12, analysed by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01763918. Findings Of 415 screened patients, 331 were eligible and were randomly assigned to the four treatment groups: evolocumab 140 mg every 2 weeks (n=111), evolocumab 420 mg monthly (n=110), placebo every 2 weeks (n=55), or placebo monthly (n=55). 329 patients received at least one dose of study drug. Compared with placebo, evolocumab at both dosing schedules led to a significant reduction in mean LDL cholesterol at week 12 (every-2-weeks dose: 59.2% reduction [95% CI 53.4-65.1], monthly dose: 61.3% reduction [53.6-69.0]; both pless than0.0001) and at the mean of weeks 10 and 12 (60.2% reduction [95% CI 54.5-65.8] and 65.6% reduction [59.8-71.3]; both pless than0.0001). Evolocumab was well tolerated, with rates of adverse events similar to placebo. The most common adverse events occurring more frequently in the evolocumab-treated patients than in the placebo groups were nasopharyngitis (in 19 patients [9%] vs five [5%] in the placebo group) and muscle-related adverse events (ten patients [5%] vs 1 [1%]). Interpretation In patients with heterozygous familial hypercholesterolaemia, evolocumab administered either 140 mg every 2 weeks or 420 mg monthly was well tolerated and yielded similar and rapid 60% reductions in LDL cholesterol compared with placebo.
|
|
| 9. |
- Wiegman, Albert, et al.
(författare)
-
Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment.
- 2015
-
Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 36, s. 2425-2437
-
Tidskriftsartikel (refereegranskat)abstract
- Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C ≥5 mmol/L (190 mg/dL), or an LDL-C ≥4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is ≥3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is <3.5 mmol/L (130 mg/dL) if >10 years, or ideally 50% reduction from baseline if 8-10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and adolescents with FH.
|
|
