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[PMID]:29419393
[Au] Autor:Ford TJ; Rocchiccioli P
[Ad] Endereço:British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
[Ti] Título:A keen eye for risk.
[So] Source:BMJ;360:j5884, 2018 02 01.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Arco Senil/diagnóstico
Doenças da Córnea/diagnóstico
Doença da Artéria Coronariana/diagnóstico
Hiperlipoproteinemia Tipo II/diagnóstico
Receptores de LDL/genética
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/administração & dosagem
Anticorpos Monoclonais/uso terapêutico
Anticolesterolemiantes/administração & dosagem
Anticolesterolemiantes/uso terapêutico
Arco Senil/etiologia
Colesterol/sangue
Doenças da Córnea/etiologia
Doença da Artéria Coronariana/complicações
Doença da Artéria Coronariana/etiologia
Feminino
Seres Humanos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
Hiperlipoproteinemia Tipo II/sangue
Hiperlipoproteinemia Tipo II/tratamento farmacológico
Hiperlipoproteinemia Tipo II/genética
Injeções Subcutâneas
Meia-Idade
Mutação
Pró-Proteína Convertase 9/antagonistas & inibidores
Xantomatose/diagnóstico
Xantomatose/etiologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Anticholesteremic Agents); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Receptors, LDL); 97C5T2UQ7J (Cholesterol); EC 3.4.21.- (PCSK9 protein, human); EC 3.4.21.- (Proprotein Convertase 9); LKC0U3A8NJ (evolocumab)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180209
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.j5884


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[PMID]:28464141
[Au] Autor:Larkin I; Ang D; Steinhart J; Chao M; Patterson M; Sah S; Wu T; Schoenbaum M; Hutchins D; Brennan T; Loewenstein G
[Ad] Endereço:University of California, Los Angeles.
[Ti] Título:Association Between Academic Medical Center Pharmaceutical Detailing Policies and Physician Prescribing.
[So] Source:JAMA;317(17):1785-1795, 2017 May 02.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: In an effort to regulate physician conflicts of interest, some US academic medical centers (AMCs) enacted policies restricting pharmaceutical representative sales visits to physicians (known as detailing) between 2006 and 2012. Little is known about the effect of these policies on physician prescribing. Objective: To analyze the association between detailing policies enacted at AMCs and physician prescribing of actively detailed and not detailed drugs. Design, Setting, and Participants: The study used a difference-in-differences multivariable regression analysis to compare changes in prescribing by physicians before and after implementation of detailing policies at AMCs in 5 states (California, Illinois, Massachusetts, Pennsylvania, and New York) that made up the intervention group with changes in prescribing by a matched control group of similar physicians not subject to a detailing policy. Exposures: Academic medical center implementation of policies regulating pharmaceutical salesperson visits to attending physicians. Main Outcomes and Measures: The monthly within-drug class market share of prescriptions written by an individual physician for detailed and nondetailed drugs in 8 drug classes (lipid-lowering drugs, gastroesophageal reflux disease drugs, diabetes drugs, antihypertensive drugs, hypnotic drugs approved for the treatment of insomnia [sleep aids], attention-deficit/hyperactivity disorder drugs, antidepressant drugs, and antipsychotic drugs) comparing the 10- to 36-month period before implementation of the detailing policies with the 12- to 36-month period after implementation, depending on data availability. Results: The analysis included 16 121 483 prescriptions written between January 2006 and June 2012 by 2126 attending physicians at the 19 intervention group AMCs and by 24 593 matched control group physicians. The sample mean market share at the physician-drug-month level for detailed and nondetailed drugs prior to enactment of policies was 19.3% and 14.2%, respectively. Exposure to an AMC detailing policy was associated with a decrease in the market share of detailed drugs of 1.67 percentage points (95% CI, -2.18 to -1.18 percentage points; P < .001) and an increase in the market share of nondetailed drugs of 0.84 percentage points (95% CI, 0.54 to 1.14 percentage points; P < .001). Associations were statistically significant for 6 of 8 study drug classes for detailed drugs (lipid-lowering drugs, gastroesophageal reflux disease drugs, antihypertensive drugs, sleep aids, attention-deficit/hyperactivity disorder drugs, and antidepressant drugs) and for 9 of the 19 AMCs that implemented policies. Eleven of the 19 AMCs regulated salesperson gifts to physicians, restricted salesperson access to facilities, and incorporated explicit enforcement mechanisms. For 8 of these 11 AMCs, there was a significant change in prescribing. In contrast, there was a significant change at only 1 of 8 AMCs that did not enact policies in all 3 areas. Conclusions and Relevance: Implementation of policies at AMCs that restricted pharmaceutical detailing between 2006 and 2012 was associated with modest but significant reductions in prescribing of detailed drugs across 6 of 8 major drug classes; however, changes were not seen in all of the AMCs that enacted policies.
[Mh] Termos MeSH primário: Centros Médicos Acadêmicos/estatística & dados numéricos
Conflito de Interesses
Indústria Farmacêutica
Prescrições de Medicamentos/estatística & dados numéricos
Política Organizacional
Médicos/estatística & dados numéricos
Medicamentos sob Prescrição/uso terapêutico
[Mh] Termos MeSH secundário: Anticolesterolemiantes/uso terapêutico
Antidepressivos/uso terapêutico
Anti-Hipertensivos/uso terapêutico
Antipsicóticos/uso terapêutico
California
Fármacos Cardiovasculares/uso terapêutico
Seres Humanos
Hipnóticos e Sedativos/uso terapêutico
Hipoglicemiantes/uso terapêutico
Illinois
Relações Interprofissionais
Massachusetts
New York
Pennsylvania
Análise de Regressão
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Antidepressive Agents); 0 (Antihypertensive Agents); 0 (Antipsychotic Agents); 0 (Cardiovascular Agents); 0 (Hypnotics and Sedatives); 0 (Hypoglycemic Agents); 0 (Prescription Drugs)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.4039


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[PMID]:28460629
[Au] Autor:Reith C; Staplin N; Herrington WG; Stevens W; Emberson J; Haynes R; Mafham M; Armitage J; Cass A; Craig JC; Jiang L; Pedersen T; Baigent C; Landray MJ; SHARP Collaborative Group
[Ad] Endereço:Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, UK. christina.reith@ndph.ox.ac.uk.
[Ti] Título:Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection.
[So] Source:BMC Nephrol;18(1):147, 2017 May 01.
[Is] ISSN:1471-2369
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Reducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with chronic kidney disease (CKD), with no evidence of an excess risk of cancer or death from any non-vascular cause. However, non-randomized data have suggested that statin therapy may have effects (both adverse and beneficial) on particular non-vascular conditions that do not cause death. METHODS: The Study of Heart and Renal Protection (SHARP) randomized patients with CKD to simvastatin 20 mg plus ezetimibe 10 mg (simvastatin/ezetimibe) daily versus matching placebo. Participants were followed up at least 6 monthly and all post-randomization serious adverse events (SAEs) were recorded. This supplementary analysis reports the effects of treatment on non-vascular SAEs, overall, by system of disease, by baseline characteristics, and by duration of follow-up. RESULTS: During a median of 4.9 years follow-up, similar numbers of participants in the two groups experienced at least one non-vascular SAE (3551 [76.4%] simvastatin/ezetimibe vs 3537 [76.6%] placebo; risk ratio [RR] 0.99, 95% confidence interval [CI] 0.95-1.04). There was no good evidence of any significant effect of simvastatin/ezetimibe on SAEs attributed to any particular nonvascular disease system (of 43 comparisons, only 3 yielded an uncorrected p value < 0.05, of which the smallest was p = 0.02). The relative risk of any nonvascular SAE did not vary significantly among particular prognostic subgroups or by duration of follow-up. CONCLUSIONS: In the SHARP trial, allocation to simvastatin/ezetimibe combination therapy was not associated with any significant non-vascular hazard. TRIALS REGISTRATION: SHARP was retrospectively registered after the first participant was enrolled in 2003 at ISRCTN (ISRCTN54137607 on 31 January 2005: http://www.isrctn.com/ISRCTN54137607) and ClinicalTrials.gov (NCT00125593 on 29 July 2005: https://clinicaltrials.gov/ct2/show/NCT00125593).
[Mh] Termos MeSH primário: LDL-Colesterol/sangue
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade
Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem
Hipercolesterolemia/mortalidade
Hipercolesterolemia/prevenção & controle
Insuficiência Renal Crônica/mortalidade
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Anticolesterolemiantes/administração & dosagem
Causalidade
Comorbidade
Feminino
Seres Humanos
Hipercolesterolemia/sangue
Incidência
Internacionalidade
Masculino
Meia-Idade
Fatores de Risco
Taxa de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Cholesterol, LDL); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1186/s12882-017-0545-2


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[PMID]:29275230
[Au] Autor:Hermánková E; Zák A; Poláková L; Hobzová R; Hromádka R; Sirc J
[Ad] Endereço:Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq. 2, CZ-162 06 Prague, Czech Republic. Electronic address: hermankova@imc.cas.cz.
[Ti] Título:Polymeric bile acid sequestrants: Review of design, in vitro binding activities, and hypocholesterolemic effects.
[So] Source:Eur J Med Chem;144:300-317, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Polymeric bile acid sequestrants (BAS) have recently attracted much attention as lipid-lowering agents. These non-absorbable materials specifically bind bile acids (BAs) in the intestine, preventing bile acid (BA) reabsorption into the blood through enterohepatic circulation. Therefore, it is important to understand the structure-property relationships between the polymer sequestrant and its ability to bind specific BAs molecules. In this review, we describe pleiotropic effects of bile acids, and we focus on BAS with various molecular architectures that result in different mechanisms of BA sequestration. Here, we present 1) amphiphilic polymers based on poly(meth)acrylates, poly(meth)acrylamides, polyalkylamines and polyallylamines containing quaternary ammonium groups, 2) cyclodextrins, and 3) BAS prepared via molecular imprinting methods. The synthetic approaches leading to individual BAS preparation, as well as results of their in vitro BA binding activities and in vivo lipid-lowering activities, are discussed.
[Mh] Termos MeSH primário: Anticolesterolemiantes/farmacologia
Ácidos e Sais Biliares/farmacologia
Desenho de Drogas
Hipercolesterolemia/tratamento farmacológico
Polímeros/farmacologia
[Mh] Termos MeSH secundário: Animais
Anticolesterolemiantes/síntese química
Anticolesterolemiantes/química
Ácidos e Sais Biliares/síntese química
Ácidos e Sais Biliares/química
Sítios de Ligação/efeitos dos fármacos
Seres Humanos
Estrutura Molecular
Polímeros/síntese química
Polímeros/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Bile Acids and Salts); 0 (Polymers)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171225
[St] Status:MEDLINE


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[PMID]:29384846
[Au] Autor:Wang L; Guo MJ; Gao Q; Yang JF; Yang L; Pang XL; Jiang XJ
[Ad] Endereço:College of Nursing.
[Ti] Título:The effects of probiotics on total cholesterol: A meta-analysis of randomized controlled trials.
[So] Source:Medicine (Baltimore);97(5):e9679, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Probiotics supplements provide a new nonpharmacological alternative to reduce cardiovascular risk factors. The impact of probiotics on the reduction of total cholesterol (TC) remains controversial. We conducted a meta-analysis to showcase the most updated and comprehensive evaluation of the studies. METHODS: Randomized controlled trials (RCTs) were searched from electronic databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang database dating from January 2007 to January 2017. The curative effects of probiotics on the reduction of TC were assessed using mean difference (MD), as well as their 95% confidence interval (CI). RevMan software (version 5.3) was used to carry out this meta-analysis. RESULTS: Thirty-two RCTs including 1971 patients met the inclusion criteria. Results of this analysis showed that compared with the control group serum TC was significantly reduced in probiotics group [MD = -13.27, 95% CI (-16.74 to 9.80), P < .05]. In addition, specific strains also significantly reduced serum TC, L acidophilus and B lactis [MD = -8.30, 95% CI (-10.44, -6.15), P < .05]; VSL#3 [MD = -11.04, 95% CI (-19.61, -2.48), P < .05]; L plantarum t ≤ 6 weeks: [MD = -1.56, 95% CI (-6.97, -3.86), P < .05] or t > 6 weeks: [MD = -22.18, 95% CI (-28.73, -15.63), P < .05]. Subgroup analysis indicated that the difference of baseline TC, probiotics forms and intervention duration might have a significant impact on the results. However, strains and doses of probiotics had no significant influence on curative effects. CONCLUSION: Available evidence indicates that probiotics supplements can significantly reduce serum TC. Furthermore, higher baseline TC, longer intervention time, and probiotics in capsules form might contribute to a better curative effect.
[Mh] Termos MeSH primário: Anticolesterolemiantes/uso terapêutico
Colesterol/sangue
Probióticos/uso terapêutico
[Mh] Termos MeSH secundário: Seres Humanos
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 97C5T2UQ7J (Cholesterol)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009679


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[PMID]:28450174
[Au] Autor:Ribeiro NQ; Costa MC; Magalhães TFF; Carneiro HCS; Oliveira LV; Fontes ACL; Santos JRA; Ferreira GF; Araujo GRS; Alves V; Frases S; Paixão TA; de Resende Stoianoff MA; Santos DA
[Ad] Endereço:Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
[Ti] Título:Atorvastatin as a promising anticryptococcal agent.
[So] Source:Int J Antimicrob Agents;49(6):695-702, 2017 Jun.
[Is] ISSN:1872-7913
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cryptococcosis caused by Cryptococcus gattii leads to pneumonia and meningoencephalitis, and has a high mortality rate worldwide due to the inadequacy of available therapy and increasing drug resistance. There is a need to develop effective treatments, and drug repositioning is an interesting alternative to achieve new strategies to treat cryptococcosis. Atorvastatin (ATO), a statin currently used to treat hypercholesterolaemia, was tested in this study as an adjuvant to control infections caused by C. gattii. Several aspects of the effect of ATO on the host and the yeast were evaluated, with particular focus on the association of ATO with fluconazole (FLC), which (i) reduced ergosterol content in the cell membrane and altered properties of the polysaccharide capsule of C. gattii; (ii) increased the production of reactive oxygen species by macrophages; and (iii) reduced yeast phagocytosis and the intracellular proliferation rate. In an animal model, infected mice treated with ATO + FLC showed increased survival, improved clinical condition, and reduced fungal burden in the lungs and brain. This study is the first to perform in vivo tests with ATO + FLC for the treatment of cryptococcosis. The results suggest that ATO may be an important adjuvant for the treatment of cryptococcosis.
[Mh] Termos MeSH primário: Anticolesterolemiantes/uso terapêutico
Antifúngicos/uso terapêutico
Atorvastatina Cálcica/uso terapêutico
Criptococose/tratamento farmacológico
Cryptococcus gattii/efeitos dos fármacos
Reposicionamento de Medicamentos
[Mh] Termos MeSH secundário: Animais
Anticolesterolemiantes/farmacologia
Antifúngicos/farmacologia
Atorvastatina Cálcica/farmacologia
Criptococose/microbiologia
Modelos Animais de Doenças
Quimioterapia Combinada/métodos
Fluconazol/farmacologia
Fluconazol/uso terapêutico
Masculino
Camundongos Endogâmicos C57BL
Análise de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Antifungal Agents); 48A5M73Z4Q (Atorvastatin Calcium); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:28465323
[Au] Autor:Walker ME; Souza PR; Colas RA; Dalli J
[Ad] Endereço:Lipid Mediator Unit, Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
[Ti] Título:13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis.
[So] Source:FASEB J;31(8):3636-3648, 2017 08.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rheumatoid arthritis is an inflammatory condition characterized by overzealous inflammation that leads to joint damage and is associated with an increased incidence of cardiovascular disease. Statins are frontline therapeutics for patients with cardiovascular disease and exert beneficial actions in rheumatoid arthritis. The mechanism that mediates the beneficial actions of statins in rheumatoid arthritis remains of interest. In the present study, we found that the administration of 2 clinically relevant statins-atorvastatin (0.2 mg/kg) or pravastatin (0.2 mg/kg)-to mice during inflammatory arthritis up-regulated systemic and tissue amounts of a novel family of proresolving mediators, termed 13-series resolvins (RvTs), and significantly reduced joint disease. Of note, administration of simvastatin (0.2 mg/kg) did not significantly up-regulate RvTs or reduce joint inflammation. We also found that atorvastatin and pravastatin each reduced systemic leukocyte activation, including platelet-monocyte aggregates (∼25-60%). These statins decreased neutrophil trafficking to the joint as well as joint monocyte and macrophage numbers. Atorvastatin and pravastatin produced significant reductions (∼30-50%) in expression of CD11b and major histocompatibility complex class II on both monocytes and monocyte-derived macrophages in joints. Administration of an inhibitor to cyclooxygenase-2, the initiating enzyme in the RvT pathway, reversed the protective actions of these statins on both joint and systemic inflammation. Together, these findings provide evidence for the role of RvTs in mediating the protective actions of atorvastatin and pravastatin in reducing local and vascular inflammation, and suggest that RvTs may be useful in measuring the anti-inflammatory actions of statins.-Walker, M. E., Souza, P. R., Colas, R. A., Dalli, J. 13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis.
[Mh] Termos MeSH primário: Anticolesterolemiantes/uso terapêutico
Artrite/tratamento farmacológico
Atorvastatina Cálcica/uso terapêutico
Ácidos Docosa-Hexaenoicos/metabolismo
Inflamação/tratamento farmacológico
Pravastatina/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Artrite/induzido quimicamente
Artrite/metabolismo
Inflamação/induzido quimicamente
Inflamação/metabolismo
Leucócitos/efeitos dos fármacos
Leucócitos/fisiologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 25167-62-8 (Docosahexaenoic Acids); 48A5M73Z4Q (Atorvastatin Calcium); KXO2KT9N0G (Pravastatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201700268


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[PMID]:29241886
[Au] Autor:Cheng WH; Gaudette É; Goldman DP
[Ad] Endereço:Schaeffer Center for Health Policy and Economics, University of Southern California Price School and School of Pharmacy, Los Angeles, CA, USA. Electronic address: weihanch@usc.edu.
[Ti] Título:PCSK9 Inhibitors Show Value for Patients and the US Health Care System.
[So] Source:Value Health;20(10):1270-1278, 2017 12.
[Is] ISSN:1524-4733
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved by the US Food and Drug Administration (FDA) as cholesterol-lowering therapies for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease. OBJECTIVES: To estimate the long-term health and economic value of PCSK9 inhibitors for Americans (51 years and older). METHODS: We conducted simulations using the Future Elderly Model, an established dynamic microsimulation model to project the lifetime outcomes for the US population aged 51 years and older. Health effects estimates and confidence intervals from published meta-analysis studies were used to project changes in life expectancy, quality-adjusted life-years, and lifetime medical spending resulting from the use of PCSK9 inhibitors. We considered two treatment scenarios: 1) current FDA eligibility and 2) an extended eligibility scenario that includes patients with no pre-existing cardiovascular disease but at high risk. We assumed that the price of PCSK9 inhibitors was discounted by 35% in the first 12 years and by 57% thereafter, with gradual uptake of the drug in eligible populations. RESULTS: Use of PCSK9 inhibitors by individuals covered by current FDA approval would extend life expectancy at the age of 51 years by an estimated 1.1 years and would yield a lifetime net value of $5800 per person. If use was extended to those at high risk for cardiovascular disease, PCSK9 inhibitors would generate a lifetime net benefit of $14,100 per person. CONCLUSIONS: Expanded access to PCSK9 inhibitors would offer positive long-term net value for patients and the US health care system at the current discounted prices.
[Mh] Termos MeSH primário: Anticolesterolemiantes/uso terapêutico
Aterosclerose/tratamento farmacológico
Simulação por Computador
Hiperlipoproteinemia Tipo II/tratamento farmacológico
Pró-Proteína Convertase 9/antagonistas & inibidores
[Mh] Termos MeSH secundário: Idoso
Anticolesterolemiantes/economia
Anticolesterolemiantes/farmacologia
Aterosclerose/economia
Análise Custo-Benefício
Assistência à Saúde/economia
Aprovação de Drogas
Definição da Elegibilidade
Seres Humanos
Hiperlipoproteinemia Tipo II/economia
Expectativa de Vida
Meia-Idade
Anos de Vida Ajustados por Qualidade de Vida
Estados Unidos
United States Food and Drug Administration
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Anticholesteremic Agents); EC 3.4.21.- (PCSK9 protein, human); EC 3.4.21.- (Proprotein Convertase 9)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


  9 / 14527 MEDLINE  
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[PMID]:29172973
[Au] Autor:Menzin J; Aggarwal J; Boatman B; Yu J; Stern K; Harrison DJ; Patel JG
[Ad] Endereço:1 Boston Health Economics, Waltham, Massachusetts.
[Ti] Título:Ezetimibe Use and LDL-C Goal Achievement: A Retrospective Database Analysis of Patients with Clinical Atherosclerotic Cardiovascular Disease or Probable Heterozygous Familial Hypercholesterolemia.
[So] Source:J Manag Care Spec Pharm;23(12):1270-1276, 2017 Dec.
[Is] ISSN:2376-1032
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ezetimibe is recommended by clinical practice guidelines as a second-line therapy for lowering low-density lipoprotein cholesterol (LDL-C) levels, but little is known about its use and effectiveness in real-world populations. OBJECTIVE: To understand the real-world impact of adding or switching to ezetimibe on LDL-C goal achievement in patients with clinical atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH). METHODS: Patients aged ≥ 18 years with an LDL-C measurement available between January 1, 2013, and June 30, 2014, were identified using the Inovalon MORE database; this included commercial, health insurance exchange, Medicare Advantage, and managed Medicaid patients. The index date was the date of the first LDL-C measurement. Patients were required to have evidence of clinical ASCVD or probable HeFH based on ICD-9-CM codes and ≥ 1 outpatient pharmacy claim for a statin in the 1-year pre-index period, as well as continuous medical and pharmacy coverage for 1 year pre- and post-index. Patients who added ezetimibe to existing statin therapy or switched to ezetimibe within 90 days post-index LDL-C measurement were identified in order to replicate the typical time a clinician takes to assess the use of ezetimibe. The primary outcome was the proportion of patients who met the LDL-C goal of < 70 mg/dL within the follow-up period. LDL-C goal achievement was evaluated by baseline LDL-C level groupings: < 70 mg/dL, 70-99 mg/dL, 100-129 mg/dL, or ≥ 130 mg/dL; and across 4 patient diagnosis categories: all patients, ASCVD only, probable HeFH only, and ASCVD and probable HeFH. Descriptive analyses were reported. Categorical variables were summarized as the number of and corresponding percentage of patients. Continuous variables were presented as the mean and SD of the number of observations and median and range where appropriate. RESULTS: Of 125,330 patients who met selection criteria, mean age was 70.1 (SD = 9.9) years and mean LDL-C baseline was 90.7 (SD = 34.0) mg/dL. Over one half of patients (70%) were receiving statin therapy. Within the post-index time frame, 1.05% (n = 1,309) of patients added or switched to ezetimibe. Of these, 26% achieved LDL-C goal during the 90-day follow-up (59.5% did not achieve goal and 14.4% did not have a follow-up lab value). Therapeutic targets were reached by 30% of patients with baseline LDL-C levels of 70-99 mg/dL; 14% of those with baseline LDL-C of 100-129 mg/dL; and 7% of those with baseline LDL-C of ≥ 130 mg/dL. Achievement of LDL-C goals also varied by baseline diagnosis category. CONCLUSIONS: The addition of or switch to ezetimibe therapy was associated with a relatively small percentage of LDL-C goal achievement (< 70 mg/dL) in patients with clinical ASCVD and/or HeFH, even among patients with baseline LDL-C between 70 and 99 mg/dL. To provide superior individualized care for patients with hyperlipidemia, there is a potential role for newer therapies in lipid lowering, such as PCSK9 inhibitors, in appropriate high-risk populations. DISCLOSURES: This study was sponsored by Amgen. Menzin, Yu, and Stern are employees of Boston Health Economics, which was contracted by Amgen to perform this study. Aggarwal is a former employee of Boston Health Economics. Boatman, Patel, and Harrison are employees and stockholders of Amgen. Study concept and design were contributed by Menzin, Aggarwal, Harrison, and Patel. Aggarwal, Stern, and Yu collected the data. Data interpretation was performed by Aggarwal, Harrison, Patel, and Boatman. The manuscript was written and revised primarily by Aggarwal, with assistance from the other authors.
[Mh] Termos MeSH primário: Anticolesterolemiantes/uso terapêutico
Aterosclerose/tratamento farmacológico
Ezetimiba/uso terapêutico
Hiperlipoproteinemia Tipo II/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Anticolesterolemiantes/administração & dosagem
LDL-Colesterol/sangue
Quimioterapia Combinada
Ezetimiba/administração & dosagem
Feminino
Seguimentos
Seres Humanos
Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem
Masculino
Meia-Idade
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Cholesterol, LDL); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); EOR26LQQ24 (Ezetimibe)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.18553/jmcp.2017.16414


  10 / 14527 MEDLINE  
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[PMID]:28455295
[Au] Autor:Lønnebakken MT; De Simone G; Saeed S; Boman K; Rossebø AB; Bahlmann E; Gohlke-Bärwolf C; Gerdts E
[Ad] Endereço:Department of Clinical Science, University of Bergen, Bergen, Norway.
[Ti] Título:Impact of stroke volume on cardiovascular risk during progression of aortic valve stenosis.
[So] Source:Heart;103(18):1443-1448, 2017 09.
[Is] ISSN:1468-201X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: In severe aortic valve stenosis (AS), low left ventricular (LV) stroke volume has been associated with increased cardiovascular (CV) mortality, but this association has not been explored during progression of AS in a large prospective study. METHODS: In 1671 patients from the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study, the association of stroke volume indexed for body surface area (SVI) with major CV events during a median of 4.3-year follow-up was assessed in Cox and time-varying Cox regression analyses. Low SVI was defined as <35 mL/m . RESULTS: Peak aortic jet velocity in the total study population was 3.1 ±0.7 m/s. Low SVI was found in 23% at baseline and associated with higher age, body mass index (BMI), heart rate and global LV load, and with lower mean aortic gradient, aortic valve area index, energy loss index, LV mass and ejection fraction and more often inconsistent AS grading (all p<0.05). A 5 mL/m lower SVI at baseline was associated with higher HRs of major CV events (n=544) (HR 1.09, 95% CI 1.05 to 1.13, p<0.001) and higher total mortality (n=147) (HR 1.08, 95% CI 1.01 to 1.16, p=0.038), independent of age, sex, atrial fibrillation, mean aortic gradient, LV ejection fraction, LV mass, BMI and study treatment. Adjusting for the same covariates, low SVI at baseline and in-study low SVI were also associated with increased rate of major CV events. CONCLUSION: In patients with AS in the SEAS study, lower baseline SVI was associated with higher HR of major CV events and total mortality independent of major confounders. TRIAL REGISTRATION NUMBER: NCT00092677: Results.
[Mh] Termos MeSH primário: Estenose da Valva Aórtica/fisiopatologia
Ezetimiba/uso terapêutico
Sinvastatina/uso terapêutico
Volume Sistólico/fisiologia
[Mh] Termos MeSH secundário: Idoso
Anticolesterolemiantes/uso terapêutico
Estenose da Valva Aórtica/tratamento farmacológico
Estenose da Valva Aórtica/mortalidade
Progressão da Doença
Método Duplo-Cego
Quimioterapia Combinada
Ecocardiografia
Feminino
Alemanha/epidemiologia
Seres Humanos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
Masculino
Noruega/epidemiologia
Prognóstico
Estudos Prospectivos
Fatores de Risco
Taxa de Sobrevida/tendências
Suécia/epidemiologia
Função Ventricular Esquerda/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); AGG2FN16EV (Simvastatin); EOR26LQQ24 (Ezetimibe)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180126
[Lr] Data última revisão:
180126
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170430
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1136/heartjnl-2016-310917



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