- Keywords
- Repatha,
- MeSH
- Plaque, Atherosclerotic drug therapy MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Cholesterol, LDL drug effects MeSH
- Humans MeSH
- Coronary Artery Disease * etiology drug therapy MeSH
- PCSK9 Inhibitors MeSH
- Proprotein Convertase 9 MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Controlled Clinical Trial MeSH
- Multicenter Study MeSH
Doporučené postupy pro management dyslipidemií EAS a ESC publikované v srpnu 2016 představují rozsáhlý referenční dokument shrnující vývoj za pět let od publikace jejich první verze v roce 2011. Reflektují poznání učiněné v mnoha oblastech – od diagnostiky a stratifikace kardiovaskulárního rizika, přes stanovení léčebných cílů, vedení terapie, až k problematice dyslipidemií ve vybraných specifických skupinách pacientů. Nevynechávají ani otázky nežádoucích účinků léčby či aktuální otázku adherence. Následující text připomíná vybrané pasáže z obsáhlého dokumentu se stručným komentářem.
The ESC/EAS guidelines for the management of dyslipidaemias published in August 2016 represent a large reference document summarizing the development over the five years since the first version was published in 2011. They reflect the knowledge achieved in many areas – from diagnosis and cardiovascular risk stratification to setting therapeutic goals and guiding management to the issue of dyslipidaemias in selected specific groups of patients. Also discussed are medication adverse effects or the current issue of adherence. The present article highlights selected sections from the comprehensive document by briefly commenting on them.
- Keywords
- ESC/EAS 2016, cílové hodnoty,
- MeSH
- Medication Adherence MeSH
- Cholesterol MeSH
- Fibric Acids therapeutic use MeSH
- Dyslipidemias * diagnosis prevention & control therapy MeSH
- Ezetimibe MeSH
- Cholesterol, HDL drug effects MeSH
- Risk Assessment trends MeSH
- Hypolipidemic Agents * adverse effects therapeutic use MeSH
- Cardiovascular Diseases complications prevention & control MeSH
- Drug Therapy, Combination MeSH
- Cholesterol, LDL drug effects MeSH
- Humans MeSH
- Fatty Acids MeSH
- Proprotein Convertase 9 therapeutic use MeSH
- Practice Guidelines as Topic * MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Příklady z historie i současnosti ukazují, jak se měnil pohled na hyperlipoproteinemie a dyslipidemie (HLP a DLP) ve druhé polovině 20. a na počátku 21. století. Cílem není podat komplexní přehled, naopak, na dílčích problémech dokumentujeme měnící se postavení a význam těchto poruch tukového metabolismu v klinické medicíně. Pozornost je věnována projevům v kardiologii a angiologii (v souvislosti s aterosklerózou), ale i v dalších oborech, jako je diabetologie, hepatologie či gastroenterologie (se zaměřením na pankreas). HLP a DLP se z oblasti výzkumu a biochemických laboratoří dostaly do centra zájmu především jako rizikové faktory aterosklerózy (AT). HLP a DLP jsou vnímány jako onemocnění masového výskytu, např. také ve spojení se složkami metabolického syndromu. Na druhé straně lze najít poruchy tukového metabolismu, jež splňují kritéria vzácných onemocnění – třeba familiární chylomikronemie (FCS) nebo homozygotní familiární hypercholesterolemie.
The examples from the history, as well as the recent view, clearly demonstrate a great change in the perception of hyperlipoprotienemias and dyslipidemias (HLP and DLP) at the end of 20th and at the beginning of 21st century. Our aim is not a complex overview about HLP and DLP. We just want to describe the changing position and importance of these diseases in clinical medicine. We will touch cardiology, angiology, but also diabetology, hepatology and gastroenterology (pancreas). HLP and DLP, which started as a research topic in laboratory became clinically interesting as risk factors of atherosclerosis. They are understood as epidemic occurrence diseases, also in connection with metabolic syndrome. However, some of them, e.g. familial chylomicronemia or homozygous familial hypercholesterolemia fulfill criteria of rare diseases.
- MeSH
- Atherosclerosis * MeSH
- Diabetes Mellitus, Type 2 MeSH
- Dyslipidemias history diagnosis therapy MeSH
- Hyperlipoproteinemia Type I diagnosis etiology therapy MeSH
- Hyperlipoproteinemia Type II diagnosis etiology therapy MeSH
- Hyperlipoproteinemias * history MeSH
- Hypolipidemic Agents classification therapeutic use MeSH
- Comorbidity MeSH
- Cholesterol, LDL blood MeSH
- Humans MeSH
- Metabolic Syndrome MeSH
- PCSK9 Inhibitors MeSH
- Proprotein Convertase 9 therapeutic use MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Dyslipidemias drug therapy MeSH
- Cholesterol, LDL drug effects MeSH
- Humans MeSH
- Antibodies, Monoclonal adverse effects therapeutic use MeSH
- Neurocognitive Disorders chemically induced prevention & control MeSH
- Proprotein Convertase 9 drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Clinical Study MeSH
- Newspaper Article MeSH
BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m2, -0·09 to 0·30). INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins. FUNDING: British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.
- MeSH
- Diabetes Mellitus, Type 2 blood diagnosis genetics MeSH
- Genetic Predisposition to Disease genetics MeSH
- Genetic Variation genetics MeSH
- Cohort Studies MeSH
- Blood Glucose metabolism MeSH
- Cholesterol, LDL blood genetics MeSH
- Humans MeSH
- Mendelian Randomization Analysis methods MeSH
- Proprotein Convertase 9 genetics MeSH
- Randomized Controlled Trials as Topic methods MeSH
- Case-Control Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Medication Adherence MeSH
- Anticholesteremic Agents therapeutic use MeSH
- Cholestyramine Resin adverse effects therapeutic use MeSH
- Fibric Acids pharmacology therapeutic use MeSH
- Dyslipidemias diagnosis drug therapy MeSH
- Drug Combinations MeSH
- Hypercholesterolemia drug therapy MeSH
- Hyperlipoproteinemia Type II diagnostic imaging drug therapy genetics MeSH
- Hypolipidemic Agents therapeutic use MeSH
- Ezetimibe, Simvastatin Drug Combination administration & dosage MeSH
- Humans MeSH
- PCSK9 Inhibitors MeSH
- Proprotein Convertase 9 economics MeSH
- Risk Factors MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage adverse effects MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Keywords
- evolokumab, evolocumab, alirokumab, alirocumab, studie FOURIER, anacetrapib,
- MeSH
- Anticholesteremic Agents therapeutic use MeSH
- Atherosclerosis drug therapy MeSH
- Fibric Acids therapeutic use MeSH
- Dyslipidemias * drug therapy MeSH
- Ezetimibe therapeutic use MeSH
- Hypercholesterolemia drug therapy MeSH
- Cardiovascular Diseases mortality prevention & control MeSH
- Cholesterol, LDL blood MeSH
- Humans MeSH
- Antibodies, Monoclonal therapeutic use MeSH
- Oxazolidinones therapeutic use MeSH
- PCSK9 Inhibitors MeSH
- Proprotein Convertase 9 MeSH
- Randomized Controlled Trials as Topic MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use MeSH
- Cholesterol Ester Transfer Proteins antagonists & inhibitors MeSH
- Check Tag
- Humans MeSH
Ke klinickému použití jsou schváleny léky zcela nové třídy hypolipidemik, tzv. inhibitory PCSK9. V mnoha zemích Evropské unie včetně např. Slovenska jsou tyto léky již dostupné pro klinickou praxi. V tomto sdělení se zaměříme na vůbec první megastudii s inhibitorem PCSK9 evolocumabem, studii FOURIER. Do studie FOURIER bylo zařazeno více než 27 500 nemocných s prokázaným KVO, kteří byli léčeni statiny a navzdory maximální tolerované hypolipidemické léčbě měli hodnoty LDL cholesterolu nad 1,8 mmol/l, případně non‑HDL cholesterolu nad 2,6 mmol/l. Současně měli další významný kardiovaskulární rizikový faktor. Užívali pak dále maximální statinovou (popř. s ezetimibem) hypolipidemickou léčbu v kombinaci s evelocumabem nebo s placebem. Výsledky studie byly jednoznačně pozitivní. Primární cílový ukazatel se snížil o 15 %, sekundární o 20 %. Oba výsledky byly statisticky významné. Nepřekvapí, že došlo k výraznému poklesu LDL cholesterolu o téměř 60 %. Léčba byla dobře tolerována a byla prakticky bez nežádoucích účinků. „Podstudií“ studie FOURIER byla studie EBBINGHAUS, která se zaměřila na vyšetřování neurokognitivních funkcí a neprokázala žádné nežádoucí účinky léčby. Čerstvě byly prezentovány výsledky subanalýzy, která prokazuje, že prospěch z léčby pokračuje až do dosud neuvěřitelných hodnot LDL cholesterolu pod 0,3 mmol/l při zachování bezpečnosti.
- Keywords
- studie FOURIER, inhibitory PCSK9, evolocumab,
- MeSH
- Anticholesteremic Agents therapeutic use MeSH
- Hypolipidemic Agents therapeutic use MeSH
- Cardiovascular Diseases * epidemiology mortality prevention & control MeSH
- Cholesterol, LDL drug effects MeSH
- Humans MeSH
- Antibodies, Monoclonal therapeutic use MeSH
- PCSK9 Inhibitors MeSH
- Proprotein Convertase 9 * MeSH
- Randomized Controlled Trials as Topic MeSH
- Secondary Prevention MeSH
- Check Tag
- Humans MeSH
- Keywords
- studie FOURIER, inhibitory PCSK9, evolocumab,
- MeSH
- Anticholesteremic Agents therapeutic use MeSH
- Hypolipidemic Agents therapeutic use MeSH
- Cardiovascular Diseases * epidemiology mortality prevention & control MeSH
- Cholesterol, LDL * drug effects MeSH
- Humans MeSH
- Antibodies, Monoclonal therapeutic use MeSH
- PCSK9 Inhibitors MeSH
- Proprotein Convertase 9 * MeSH
- Randomized Controlled Trials as Topic MeSH
- Secondary Prevention MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use MeSH
- Check Tag
- Humans MeSH
