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1.
Am J Cardiol ; 152: 57-62, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34147211

RESUMO

Heterozygous familial hypercholesterolemia (HeFH) results in significant elevations in LDL-C and premature atherosclerotic cardiovascular disease (ASCVD). Current guidelines recommend add-on proprotein subtilisin/kexin type 9 inhibitor (PCSK9i) therapy for additional LDL-C lowering beyond statins. Data are sparse, however, regarding treatment patterns and barriers relating to PCSK9i in HeFH patients. We examined physician attitudes, use, and barriers for treatment in patients with HeFH. We surveyed 1,000 physicians (500 primary care providers [PCPs] and 500 cardiologists in the US regarding their preferred treatments, experience and barriers associated with using PCSK9is. Cardiologists compared to PCPs were more likely to rank a PCSK9i as most important for an HeFH patient needing additional LDL-C lowering (68.6% vs. 64.8%; p <0.05), as well as prescribing and having a patient on a PCSK9i. PCPs vs. cardiologists were less likely (odds ratio [OR] [95% confidence interval] = 0.46 [0.34-0.63]), private vs. academic practice more likely (OR = 1.53 [1.02-2.28]), and those who would prescribe a PCSK9i in an HeFH patient with (OR = 3.86 [2.57-5.78]) or without (OR = 1.96 [1.40-2.72]) ASCVD needing additional LDL-C reduction beyond a statin were more likely to actually prescribe a PCSK9i. Those practicing in an urban vs. rural setting were less likely (OR = 0.56 [0.34-0.93]), and those indicating they would prescribe a PCKS9i in an HeFH patient with (OR = 2.80 [1.74-4.49]) or without (OR = 1.43 [1.02-2.02]) ASCVD needing additional LDL-C lowering beyond a statin were more likely to face difficulty prescribing a PCSK9i (all p <0.05 to p <0.01). Greater physician education and assistance among both cardiologists and PCPs are needed to address the gaps in understanding and treatment regarding PCSK9is.


Assuntos
Anticolesterolemiantes/uso terapêutico , Cardiologistas , Custos de Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Preferência do Paciente , Médicos de Atenção Primária , Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Serino Proteinase/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Quimioterapia Combinada , Heterozigoto , Humanos , Hiperlipoproteinemia Tipo II/genética , Seguro Saúde , Autorização Prévia , Inquéritos e Questionários
2.
J. bras. econ. saúde (Impr.) ; 13(1): 14-20, Abril/2021.
Artigo em Inglês | LILACS, ECOS | ID: biblio-1252666

RESUMO

Objective: Familial hypercholesterolaemia is a hereditary disease characterized by very high levels of low-density lipoprotein cholesterol and an elevated risk of early-onset cardiovascular disorders. New drugs provide alternatives for the treatment of patients with homozygous familial hypercholesterolaemia. The study aims to explore a practical application of multiple-criteria decision analysis on prioritization of new and emerging technologies for familial hypercholesterolaemia. Methods: The decision model was constructed using the MACBETH method. There were three stages: structuring the problem, measuring the performance of alternatives, and building the model. The weights for alternatives and levels were obtained by indirect comparisons, which evaluated the attractiveness of the performance levels of the criteria using the swing weights technique. Results: The drugs lomitapide, ezetimibe, evolocumab, and mipomersen were selected as alternatives for decision-making. "Cardiovascular Death", "Stroke" and "Acute Myocardial Infarction" had the three most significant weights. The criteria with the lowest weights were "Comfort" and "LDL-C Reduction". The top-ranked technology was evolocumab, with an overall score of 59.87, followed by ezetimibe, with a score of 37.21. Conclusion: How to apply the result of a higher score in the actual decisionmaking process still requires further studies. The case in question showed that evolocumab has more performance benefits than other drugs but with a cost approximately 50 times higher


Objetivo: A hipercolesterolemia familiar é uma doença hereditária caracterizada por níveis muito elevados de lipoproteína de baixa densidade (LDL-colesterol) e um risco elevado de doenças cardiovasculares de início precoce. Novos medicamentos oferecem alternativas para o tratamento de pacientes com hipercolesterolemia familiar homozigótica. Esse estudo tem como objetivo explorar uma aplicação prática da análise de decisão multicritério na priorização de tecnologias novas e emergentes para hipercolesterolemia familiar. Métodos: O modelo de decisão foi construído usando o método MACBETH. Três etapas foram criadas: estruturação do problema, mensuração do desempenho das alternativas e construção do modelo. Os pesos para alternativas e níveis foram obtidos por comparações indiretas, que avaliaram a atratividade dos níveis de desempenho dos critérios usando a técnica de pesos de balanço. Resultados: Os medicamentos lomitapida, ezetimiba, evolocumabe e mipomersen foram selecionados como alternativas para a tomada de decisão. "Morte Cardiovascular", "Acidente vascular cerebral" e "Infarto Agudo do Miocárdio" tiveram os três pesos mais significativos. Os critérios com os menores pesos foram "Conforto" e "Redução do LDL-C". A tecnologia mais bem avaliada foi o evolocumabe, com pontuação geral de 59,87, seguido da ezetimiba, com pontuação de 37,21. Conclusão: Ainda são necessários estudos para determinar como aplicar o resultado de uma pontuação mais alta no processo de tomada de decisão. O caso em questão demonstrou que o evolocumabe tem benefícios mais significativos em relação aos outros medicamentos, mas com um custo cerca de 50 vezes maior


Assuntos
Avaliação da Tecnologia Biomédica , Tomada de Decisões , Hiperlipoproteinemia Tipo II
3.
Postgrad Med ; 133(2): 146-153, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32744105

RESUMO

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.


Assuntos
LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II , Hipolipemiantes/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/epidemiologia , Masculino , Conduta do Tratamento Medicamentoso/normas , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Prevalência , Turquia/epidemiologia
4.
Curr Atheroscler Rep ; 22(11): 64, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32870376

RESUMO

PURPOSE OF REVIEW: Statins are first-line therapy for lowering low-density lipoprotein (LDL) cholesterol in familial hypercholesterolemia (FH), particularly in heterozygous patients. We review advances and new questions on the use of statins in FH. RECENT FINDINGS: Cumulative evidence from registry data and sub-analyses of clinical trials mandates the value of statin therapy for prevention of atherosclerotic cardiovascular disease (ASCVD) in FH. Statins are safe in children and adolescents with FH, with longer term cardiovascular benefits. The potentially toxic effects of statins in pregnancy need to be considered, but no association has been reported in prospective cohort studies with birth defects. There is no rationale for discontinuation of statins in elderly FH unless indicated by adverse events. FH is undertreated, with > 80% of statin-treated FH patients failing to attain LDL cholesterol treatment targets. This may relate to adherence, tolerability, and genetic differences in statin responsiveness. Statin treatment from childhood may reduce the need for stringent cholesterol targets. Combination of statins with ezetimibe and PCSK9 inhibitors significantly improves the efficacy of treatment. Whether statin use could improve the clinical course of FH patients with COVID-19 and other respiratory infections remains an unsolved issue for future research. Statins are the mainstay for primary and secondary prevention of ASCVD in FH. Sustained long-term optimal statin treatment from an early age can effectively prevent ASCVD over decades of life. Despite their widespread use, statins merit further investigation in FH.


Assuntos
Infecções por Coronavirus/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hiperlipoproteinemia Tipo II , Conduta do Tratamento Medicamentoso , Pneumonia Viral/epidemiologia , Anticolesterolemiantes/classificação , Anticolesterolemiantes/farmacologia , Betacoronavirus , COVID-19 , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/epidemiologia , Pandemias , SARS-CoV-2
5.
Expert Opin Pharmacother ; 21(16): 1971-1974, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32749892

RESUMO

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.


Assuntos
Anticolesterolemiantes/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , RNA Interferente Pequeno/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/economia , LDL-Colesterol/sangue , Ensaios Clínicos como Assunto , Esquema de Medicação , Custos de Medicamentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/enzimologia , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/enzimologia , Adesão à Medicação , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/economia
6.
High Blood Press Cardiovasc Prev ; 27(4): 331-338, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32651891

RESUMO

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.


Assuntos
Anticolesterolemiantes/economia , Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Aterosclerose/economia , LDL-Colesterol/sangue , Custos de Medicamentos , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/economia , Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Serino Proteinase/economia , Inibidores de Serino Proteinase/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/efeitos adversos , Aterosclerose/sangue , Aterosclerose/diagnóstico , Biomarcadores/sangue , Regulação para Baixo , Feminino , Gastos em Saúde , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Seguro de Serviços Farmacêuticos/economia , Masculino , Pró-Proteína Convertase 9/metabolismo , Estudos Retrospectivos , Inibidores de Serino Proteinase/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
7.
Atherosclerosis ; 304: 1-8, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32526542

RESUMO

BACKGROUND AND AIMS: There are no studies that have specifically investigated the cost-effectiveness of cascade screening of children for heterozygous familial hypercholesterolemia (FH) and treatment of affected individuals with statins to prevent coronary heart disease (CHD). This study explores the cost-effectiveness of this strategy from the perspective of the Australian public healthcare system. METHODS: A lifetime Markov model with four health states (Alive without CHD, Alive with CHD, Dead from fatal CHD, and Dead from other causes) was developed to simulate the progression of ten-year-old children screened for FH and treated immediately with statins if found to have FH. The underlying prevalence of FH in this target population was assumed to be 56.8%, and the sensitivity and specificity of testing were 100%. The comparator was usual care, which assumed that subjects started statins spontaneously at a later point or when they experienced a cardiovascular event. The effect of reducing low-density lipoprotein cholesterol (LDL-C) on the risk of a first event at each age assumed that risk was proportional to total lifetime exposure and was implemented using Mendelian randomisation analysis data. Cost and other outcome data were sourced from published sources. Outcome of interests were costs in Australian dollars (AUD), life years gained (LYG) and quality-adjusted life years (QALYs) gained, as well as incremental cost-effectiveness ratios (ICERs) of costs per LYG and per QALY gained. All future costs and outcomes were discounted by 5% annually. RESULTS: Undiscounted results showed that compared with usual care, cascade screening of ten year-old children for FH and initiation of treatment of affected individuals saved 7.77 LYG and 7.53 QALYs per person over a lifetime. With 5% annual discounting, there were 0.97 LYG and 1.07 QALYs gained per person, at net reduction cost of -$1134. The cascade screening of ten-year-old children for FH and initiation of treatment compared to usual case was a cost saving approach. In 51.2% of iterations, screening and initiation with statin were cost saving and in 48.8% of iterations were cost-effective. In most of the one-way sensitivity and scenario analyses, the ICER stayed within the accepted Australian threshold. CONCLUSIONS: Compared to usual care, cascade screening of ten-year-old children for FH and treating affected individuals are likely to be cost saving.


Assuntos
Análise Custo-Benefício , Hiperlipoproteinemia Tipo II , Programas de Rastreamento/economia , Austrália/epidemiologia , Criança , LDL-Colesterol , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida
8.
Lipids Health Dis ; 19(1): 101, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32438925

RESUMO

BACKGROUND: Familial Hypercholesterolemia (FH) is a serious under-diagnosed disease characterized by raised low-density lipoprotein cholesterol (LDL-C) and premature coronary artery diseases (CAD). The scarcity of FH reported patients in Saudi Arabia indicates lack of FH awareness among physicians. OBJECTIVE: The goal of this research was to assess knowledge, awareness, and practice (KAP) about FH disorder among Saudi medical interns and to identify areas that need educational attention. METHODS: This cross-sectional study involved 170 Saudi medical interns (83 males and 87 females) from academic institutes in Jeddah, Saudi Arabia. The interns were asked to fill an online FH-KAP questionnaire. Total score for each separate domain measured by adding correct answers. RESULTS: Although, knowledge of FH definition (76.5%) and classical lipid profile (52.4%) were reasonable; knowledge on inheritance (43.5%), prevalence (12.4%) and CAD risks (7.1%) were poor. Knowledge score was significantly higher in female than male (7.5 ± 3 vs. 5.3 ± 2.6, P < 0.001). Regarding awareness, 54.1% were familiar with FH disorder, 50.6% with the presence of lipid clinic but only 16.5% were acquainted with guidelines. Furthermore, in the practice domain 82.9% selected statin as first line treatment and 62.9% chose routinely checking the rest of the family, while 15.3% chose ages 13-18 years to screen for hypercholesterolemia in patients with a positive family history of premature CAD. CONCLUSION: Substantial defects in FH-KAP among Saudi medical interns were found, emphasizing the importance of professional training. Extensive and constant medical education programs as early as an internship are required to close the gap in CAD prevention.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Hiperlipoproteinemia Tipo II/psicologia , Internato e Residência , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Arábia Saudita , Inquéritos e Questionários , Adulto Jovem
9.
Adv Ther ; 37(5): 1724-1736, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32200537

RESUMO

OBJECTIVE: Assess achievement of low-density lipoprotein cholesterol (LDL-C) targets in European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines. DESIGN: Systematic literature review. DATA SOURCES: Medline, EMBASE, Cumulated Index to Nursing and Allied Health Literature. ELIGIBILITY CRITERIA: Observational studies reporting LDL-C levels/target attainment, measured between 1 August 2006 to 31 August 2017, in European adults with established cardiovascular disease (CVD), diabetes with target organ damage, familial hypercholesterolaemia (FH) or 10-year risk of fatal CVD ≥ 5% (assessed by Systematic Coronary Risk Evaluation [SCORE]). DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted relevant studies and assessed study quality using the Risk of Bias for Non-Randomised Studies-Interventions (ROBINS-I) tool. Primary outcome was the proportion of patients achieving LDL-C targets in the 2011/2016 ESC/EAS guidelines. Where available, patient characteristics were presented as means weighted by sample size. The proportions of patients achieving LDL-C targets in the 5 years before and after publication of the 2011 guidelines were compared using a chi-square test. RESULTS: Across 81 eligible studies (303,534 patients), achievement of LDL-C < 1.8 mmol/L was poor among patients with established CVD (16%; range 9-56%) and at very high risk of CVD (SCORE ≥ 10% [18%; 14-25%]). In individuals with FH, SCORE 5-10%, or diabetes and target organ damage, LDL-C < 2.5 mmol/L was achieved by 15% (9-22%), 46% (21-55%) and 13% (6-34%), respectively. Comparing the 5 years before/after publication of the 2011 guidelines, target achievement increased significantly over time but remained suboptimal (LDL-C < 1.8, 22% versus 15%; LDL-C < 2.5, 68% versus 61%; both p < 0.001; established CVD group only). CONCLUSIONS: These data show suboptimal LDL-C control among European patients at high risk of CVD. Those at greatest overall risk (clinically established CVD or at least a 10% 10-year risk of fatal CVD) had the lowest achievement of 2011/2016 EAS/ESC LDL-C targets. With lower LDL-C targets advocated in 2019 ESC/EAS guidelines, this unmet need will increase. PROTOCOL REGISTRATION: PROSPERO registration number; CRD77844.


Assuntos
Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , LDL-Colesterol/normas , Hiperlipoproteinemia Tipo II/prevenção & controle , Hiperlipoproteinemia Tipo II/fisiopatologia , Conduta do Tratamento Medicamentoso/normas , Guias de Prática Clínica como Assunto/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente)/epidemiologia , Feminino , Humanos , Hiperlipoproteinemia Tipo II/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
JAMA Cardiol ; 5(2): 217-229, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31895433

RESUMO

Importance: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH. Observations: In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created. Conclusions and Relevance: By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well.


Assuntos
Hiperlipoproteinemia Tipo II/prevenção & controle , Efeitos Psicossociais da Doença , Saúde Global , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/terapia , Guias de Prática Clínica como Assunto , Saúde Pública
11.
Clin Genet ; 97(2): 257-263, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31571196

RESUMO

Familial hypercholesterolaemia (FH) is associated with increased risk of coronary artery disease (CAD); however, risk prediction and stratification remain a challenge. Genetic risk scores (GRS) may have utility in identifying FH patients at high CAD risk. The study included 811 patients attending the lipid disorders clinic at Royal Perth Hospital with mutation-positive (n = 251) and mutation-negative (n = 560) FH. Patients were genotyped for a GRS previously associated with CAD. Associations between the GRS, clinical characteristics, and CAD were assessed using regression analyses. The average age of patients was 49.6 years, and 44.1% were male. The GRS was associated with increased odds of a CAD event in mutation-positive [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 1.3-8.2; P = .009] and mutation-negative FH patients (OR = 1.8; 95% CI = 1.0-3.3; P = .039) after adjusting for established predictors of CAD risk. The GRS was associated with greater subclinical atherosclerosis as assessed by coronary artery calcium score (P = .039). A high GRS was associated with CAD defined clinically and angiographically in FH patients. High GRS patients may benefit from more intensive management including lifestyle modification and aggressive lipid-lowering therapy. Further assessment of the utility of the GRS requires investigation in prospective cohorts, including its role in influencing the management of FH patients in the clinic.


Assuntos
Aterosclerose/genética , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Hiperlipoproteinemia Tipo II/genética , Aterosclerose/complicações , Aterosclerose/epidemiologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de LDL/genética , Medição de Risco , Fatores de Risco
12.
QJM ; 113(6): 411-417, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883017

RESUMO

BACKGROUND: Familial hypercholesterolemia (FH) is an under-diagnosed condition. AIM: We applied standard laboratory criteria across a large longitudinal electronic medical record database to describe cross-sectional population with possible FH. METHODS: A cross-sectional study of Clalit Health Services members. Subjects who met the General Population MED-PED laboratory criteria, excluding: age <10 years, documentation of thyroid, liver, biliary or autoimmune diseases, a history of chronic kidney disease stage 3 or greater, the presence of urine protein >300 mg/l, HDL-C>80 mg/dl, active malignancy or pregnancy at the time of testing were considered possible FH. Demographic and clinical characteristics are described at time of diagnosis and at a single index date following diagnosis to estimate the burden on the healthcare system. The patient population is also compared to the general population. RESULTS: The study cohort included 12 494 subjects with out of over 4.5 million members of Clalit Health Services. The estimated prevalence of FH in Israel was found to be 1:285. These patients are notably positive for, and have a family history of, cardiovascular disease and risk factors. For most of them the LDL-C levels are not controlled, and only a quarter of them are medically treated. CONCLUSIONS: By using the modified MED-PED criteria in a large electronic database, patients with possible FH can be identified enabling early intervention and treatment.


Assuntos
Bases de Dados Factuais , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Adulto , LDL-Colesterol/sangue , Estudos de Coortes , Comorbidade , Estudos Transversais , Atenção à Saúde/organização & administração , Registros Eletrônicos de Saúde , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Classe Social , Adulto Jovem
13.
J Clin Lipidol ; 13(6): 970-978, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31767518

RESUMO

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.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Apolipoproteínas B/genética , Mutação com Ganho de Função/genética , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/genética , Pró-Proteína Convertase 9/genética , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/sangue , LDL-Colesterol/sangue , Humanos , Hiperlipoproteinemia Tipo II/sangue , Pessoa de Meia-Idade , Adulto Jovem
15.
Can J Cardiol ; 35(10): 1419.e1-1419.e4, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31521416

RESUMO

Homozygous familial hypercholesterolemia is caused by mutations in the low-density lipoprotein receptor gene. It is diagnosed in children or youth who present with extensive tendinous and cutaneous xanthomas and extreme elevation of low-density lipoprotein cholesterol. Untreated, premature coronary artery disease develops in the teenage years or earlier and survival to ages older than 30 years is rare. Herein we describe the clinical course of a patient with homozygous familial hypercholesterolemia treated according to the standards of care and experimental approaches. Despite aggressive therapies, atherosclerosis in all vascular beds progressed, leading to the patient's demise at age 59 years, highlighting the importance of early diagnosis and appropriate follow-up.


Assuntos
Hiperlipoproteinemia Tipo II , Efeitos Psicossociais da Doença , Evolução Fatal , Homozigoto , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/terapia , Masculino , Pessoa de Meia-Idade
16.
Turk Kardiyol Dern Ars ; 47(6): 476-486, 2019 Sep.
Artigo em Turco | MEDLINE | ID: mdl-31483296

RESUMO

OBJECTIVE: The aim of this retrospective study based on real-life data was to evaluate the lipid profile and demographic, clinical, and laboratory features of patients with acute coronary syndrome (ACS) at a tertiary center and to examine the mortality rate. METHODS: Information including endpoint data for at least 2 years following the index ACS event was retrieved from hospital records. Patients without sufficient follow-up data were called by phone. Modified Dutch Lipid Clinic Network criteria were used to identify the presence of familial hypercholesterolemia (FH). Factors affecting mortality in the 2-year follow-up period were evaluated using Cox regression analysis. RESULTS: A total of 985 ACS patients (215 females) between 21 and 93 years of age were included. The females were older and had a lower smoking rate than the males. In females, the history of obesity and hypertension, the diabetes rate, and the thyroid-stimulating hormone level were higher than those of the males. In 95.6% of the patients, lipid parameters were measured upon hospital admission. No significant difference in dyslipidemia frequency was observed between genders. The frequency of FH was 7.6%. The rate of lipid-lowering drug use was <20% at admission, >90% at discharge, and decreased to 50% in the follow-up period. The mortality rate was 3.8% in the in-hospital period and 8.1% during the 2 years of follow-up. CONCLUSION: The mortality rate in ACS patients was 3.8% in the in-hospital period and 8.1% in the 2-year follow-up period. The frequency of hypercholesterolemia was 89.5% and the rate of lipid-lowering drug use was insufficient. Secondary prevention after ACS was not adequately employed even at a tertiary center. The FH frequency was 7.6% and those with FH were observed to have ACS at a younger age than those without.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Hiperlipoproteinemia Tipo II/epidemiologia , Lipídeos/sangue , Síndrome Coronariana Aguda/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperlipoproteinemia Tipo II/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Adulto Jovem
17.
Atherosclerosis ; 287: 140-146, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31280039

RESUMO

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.


Assuntos
Custos de Cuidados de Saúde , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/economia , Hipolipemiantes/uso terapêutico , Pró-Proteína Convertase 9/antagonistas & inibidores , Análise Custo-Benefício , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Pró-Proteína Convertase 9/sangue
18.
J Clin Lipidol ; 13(4): 525-537, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281070
19.
J Am Heart Assoc ; 8(13): e011822, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31256702

RESUMO

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.


Assuntos
Custos de Cuidados de Saúde , Insuficiência Cardíaca/epidemiologia , Hiperlipoproteinemia Tipo II/epidemiologia , Mortalidade , Infarto do Miocárdio/epidemiologia , Idoso , Algoritmos , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Registros Eletrônicos de Saúde , Feminino , Insuficiência Cardíaca/economia , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/economia , Hipercolesterolemia/epidemiologia , Hipercolesterolemia/terapia , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/economia , Hiperlipoproteinemia Tipo II/terapia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/economia , Revascularização Miocárdica/estatística & dados numéricos , Países Baixos/epidemiologia , Razão de Chances , Prevalência , Acidente Vascular Cerebral/epidemiologia , Triglicerídeos/sangue , Doenças não Diagnosticadas/economia , Doenças não Diagnosticadas/epidemiologia
20.
Atherosclerosis ; 288: 33-41, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31319356

RESUMO

BACKGROUND AND AIMS: The prevalence of familial hypercholesterolemia (FH) is high among patients with stable coronary artery disease (CAD). However, data on FH on admission among patients with acute coronary syndrome (ACS) are still relatively scarce. Therefore, we aimed to assess the prevalence, lipid-lowering therapy and short- and long-term outcomes in patients with FH among ACS patients. METHODS AND RESULTS: The investigation was performed in a cohort of 19,781 consecutive patients from the TERCET Registry. There were 7319 patients admitted with ACS: 3085 due to STEMI, 2256 due to NSTEMI, and 1978 due to UA. The stable CAD group (n = 12,462) was considered the reference group. Based on the personal and familial history of premature cardiovascular disease and LDL cholesterol concentration, the Dutch Lipid Clinic Network (DLCN) algorithm was used for FH diagnosis. The overall occurrence of probable/definite FH and possible FH was 1.2% and 13.5% respectively. Among patients with ACS, 1.6% had probable/definite FH and 17.0% possible FH. The highest occurrence of FH was observed in the STEMI subgroup (20.6%). Patients with definite and probable FH had higher 30-day mortality than patients without FH (8.2% and 3.8% vs. 2.0%, respectively; p = 0.0052). No significant differences were observed between the FH groups in the 12-, 36- and 60-month follow-up. Propensity-score matching analysis showed that definite/probable FH patients had significantly higher all-cause mortality at 36- and 60-month follow-up in comparison to non-FH subjects (11.4% vs. 4.8% and 19.2% vs. 7.2%, respectively; p ≤ 0.021 for both). CONCLUSIONS: The prevalence of FH according to the DLCN criteria in the Polish very high-risk population is significantly higher in patients with ACS than in patients with sCAD. FH is a cause of increased all-cause mortality in the long-term follow-up.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Hiperlipoproteinemia Tipo II/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Idoso , Quimioterapia Combinada , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/mortalidade , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica , Polônia/epidemiologia , Prevalência , Prognóstico , Sistema de Registros , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Centros de Atenção Terciária , Fatores de Tempo
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