Purpose: We examined clinical characteristics and low-density lipoprotein cholesterol (LDL-C) lowering in patients initiating evolocumab in real-world practice in a Central and Eastern European (CEE) cohort from the pan-European HEYMANS study. Methods: Patients from Bulgaria, Czech Republic, and Slovakia were enrolled at initiation of evolocumab (baseline) as per local reimbursement criteria. Demographic/clinical characteristics, lipid-lowering therapy (LLT) and lipid values were collected from medical records for ≤6 months before baseline and ≤30 months after evolocumab initiation. Results: Overall, 333 patients were followed over a mean (SD) duration of 25.1 (7.5) months. At initiation of evolocumab, LDL-C levels were markedly elevated in all three countries, with a median (Q1, Q3) LDL-C of 5.2 (4.0, 6.6) mmol/L in Bulgaria, 4.5 (3.8, 5.8) mmol/L in the Czech Republic, and 4.7 (4.0, 5.6) mmol/L in Slovakia. Within the first three months of evolocumab treatment, LDL-C levels were reduced by a median of 61% in Bulgaria, 64% in the Czech Republic, and 53% in Slovakia. LDL-C levels remained low throughout the remaining period of observation. The 2019 ESC/EAS guideline-recommended risk-based LDL-C goals were attained by 46% of patients in Bulgaria, 59% in the Czech Republic, and 43% of patients in Slovakia. LDL-C goal attainment was higher in patients receiving a statin ± ezetimibe-based background therapy (Bulgaria: 55%, Czech Republic: 71%, Slovakia: 51%) compared to those receiving evolocumab alone (Bulgaria: 19%, Czech Republic: 49%, Slovakia: 34%). Conclusion: In the HEYMANS CEE cohort, patients initiated on evolocumab had baseline LDL-C levels approximately three-fold higher than guideline-recommended thresholds for PCSK9i initiation. Risk-based LDL-C goal attainment was highest in patients receiving high-intensity combination therapy. Lowering the LDL-C reimbursement threshold for PCSK9i initiation would allow more patients to receive combination therapy, thus improving LDL-C goal attainment. Trial registration: ClinicalTrials.gov (NCT02770131; registration date: 27 April 2016).
- MeSH
- anticholesteremika * škodlivé účinky MeSH
- LDL-cholesterol MeSH
- lidé MeSH
- statiny * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- východní Evropa MeSH
- MeSH
- anticholesteremika * škodlivé účinky terapeutické užití MeSH
- dyslipidemie * farmakoterapie MeSH
- játra účinky léků MeSH
- ledviny účinky léků MeSH
- lidé MeSH
- nemoci svalů chemicky indukované MeSH
- nežádoucí účinky léčiv MeSH
- statiny * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- MeSH
- anticholesteremika aplikace a dávkování ekonomika farmakologie klasifikace škodlivé účinky MeSH
- apolipoproteiny B analýza MeSH
- dyslipidemie * dietoterapie etiologie farmakoterapie prevence a kontrola terapie MeSH
- komplikace diabetu dietoterapie farmakoterapie prevence a kontrola terapie MeSH
- LDL-cholesterol analýza MeSH
- lidé MeSH
- lipoproteiny analýza MeSH
- potravní doplňky klasifikace MeSH
- riziko MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- rizikové faktory MeSH
- statiny aplikace a dávkování škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
AIMS: To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement. METHODS AND RESULTS: An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) LDL-C goal while receiving stabilized LLT; 2019 goal achievement was also assessed. Overall, 5888 patients (3000 primary and 2888 secondary prevention patients) were enrolled; 54% [95% confidence interval (CI) 52-56] achieved their risk-based 2016 goal and 33% (95% CI 32-35) achieved their risk-based 2019 goal. High-intensity statin monotherapy was used in 20% and 38% of very high-risk primary and secondary prevention patients, respectively. Corresponding 2016 goal attainment was 22% and 45% (17% and 22% for 2019 goals) for very high-risk primary and secondary prevention patients, respectively. Use of moderate-high-intensity statins in combination with ezetimibe (9%), or any LLT with PCSK9 inhibitors (1%), was low; corresponding 2016 and 2019 goal attainment was 53% and 20% (ezetimibe combination), and 67% and 58% (PCSK9i combination). CONCLUSION: Gaps between clinical guidelines and clinical practice for lipid management across Europe persist, which will be exacerbated by the 2019 guidelines. Even with optimized statins, greater utilization of non-statin LLT is likely needed to reduce these gaps for patients at highest risk.
- MeSH
- anticholesteremika * škodlivé účinky MeSH
- biologické markery MeSH
- dyslipidemie * farmakoterapie MeSH
- kardiovaskulární nemoci * diagnóza epidemiologie prevence a kontrola MeSH
- LDL-cholesterol MeSH
- lidé MeSH
- primární zdravotní péče MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- statiny * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
BACKGROUND AND AIMS: This European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients. METHODS: Evidence-based review. RESULTS: Statin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-high-risk patients with mild to moderately elevated TG levels (>2.3 and < 5.6 mmol/L [>200 and < 500 mg/dL) on a statin, treatment with either a fibrate or high-dose omega-3 fatty acids (icosapent ethyl) may be considered, weighing the benefit versus risks. Combination with fenofibrate may be considered for both macro- and microvascular benefits in patients with type 2 diabetes mellitus. CONCLUSIONS: This guidance aims to improve real-world use of guideline-recommended combination lipid modifying treatment.
- MeSH
- anticholesteremika * škodlivé účinky MeSH
- ateroskleróza * farmakoterapie prevence a kontrola MeSH
- diabetes mellitus 2. typu * MeSH
- LDL-cholesterol MeSH
- lidé MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 MeSH
- statiny * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), "lower is better for longer", and the recent data have strongly emphasized the need of also "the earlier the better". In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual's calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an 'Extremely High Risk' group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardiovascular risk in these patients.
- MeSH
- akutní koronární syndrom krev farmakoterapie MeSH
- anticholesteremika škodlivé účinky terapeutické užití MeSH
- ateroskleróza krev farmakoterapie MeSH
- ezetimib škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- lipidy krev MeSH
- management nemoci MeSH
- PCSK9 inhibitory škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Statiny jsou nejčastěji předepisované léky, účinné a s relativně nízkým výskytem nežádoucích vedlejších účinků. Mezi nežádoucími účinky léčby statiny (a i ezetimibem a PCSK9 inhibitory) je diskutováno i potenciální zvýšení rizika výskytu onemocnění diabetes mellitus 2. typu (DM2T). Zdá se, že rizikovým faktorem je zde primárně nízká hladina plazmatického cholesterolu. Již před čtvrt stoletím byl popsán nižší výskyt diabetu u pacientů s familiární hypercholesterolemií oproti běžné populaci. Vyšší výskyt DM2T byl u pacientů léčených statiny pozorován i v některých klinických studiích. Pomocí mendelovské randomizace bylo prokázáno, že zvýšení riziko vzniku DM2T je kauzálně způsobeno inhibicí aktivity reduktázy HMGCoA, jejíž aktivita je statiny blokována. Další geny, jejichž varianty byly využity jako "proxy" pro analýzu kauzality mezi snižováním cholesterolu a zvýšeným rizikem DM2T, jsou NPC1L1 (inhibitor vstřebávání cholesterolu ve střevě) a PCSK9 (protein řídící degradaci LDL-receptoru). I tyto studie ukázaly, že genetické varianty spojené s nižší hladinou cholesterolu jsou zároveň asociovány se zvýšeným rizikem rozvoje DM2T. Odhad rizik všech "civilizačních" onemocnění by měl být přísně individualizovaný a komplexní s pečlivým zvážením všech potenciálních nežádoucích účinků léčby (nejen) dyslipidemiky pro každého jedince.
Statins are the most commonly prescribed drugs, effective and with a low incidence of undesirable side effects. Among the undesirable side effects of statin therapy, the increased risk of type 2 diabetes (T2DM) is discussed. A quarter of century ago, a lower incidence of diabetes was observed in patients with familial hypercholesterolemia. Increased risk of T2DM in statin users has also been observed in some clinical trials. A Mendelian randomization study showed that the increased risk of developing T2DM has causality in the inhibition of HMGCoA reductase activity – activity, whose is blocked by statins. Other genes whose variants have been used as “proxies” to analyze the causality between lowering cholesterol and increasing the risk of T2DM are NPC1L1 (an inhibitor of intestinal cholesterol absorption) and PCSK9 (a protein that controls LDL-receptor degradation). Also here has been confirmed, that genetic variants associated with lower cholesterol levels are also associated with increased risk of T2DM. The risk assessment of the development of complex “civilization” noncommunicable diseases should be strictly individualized and comprehensive, with careful consideration of all potential undesirable side effects of (not only) dyslipidemic treatment for each individual.
- MeSH
- anticholesteremika * škodlivé účinky MeSH
- cholesterol analýza krev MeSH
- diabetes mellitus 2. typu * etiologie MeSH
- ezetimib škodlivé účinky MeSH
- hyperlipoproteinemie typ II genetika MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- statiny škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Hypolipidemic and cardioprotective effects of statins can be associated with the development of myopathies and new-onset type 2 diabetes. These adverse effects may be related to increased oxidative stress. The plant extract silymarin (SM) is known for its antioxidant and anti-inflammatory actions. We tested the hypothesis that the combination of atorvastatin (ATV) with SM could improve therapy efficacy and eliminate some negative effects of statin on hypertriglyceridemia-induced metabolic disorders. Hereditary hypertriglyceridemic rats were fed a standard diet for four weeks without supplementation; supplemented with ATV (5 mg/kg b. wt./day) or a combination of ATV with 1 % micronized SM (ATV+SM). ATV treatment elevated plasma levels of HDL-cholesterol (p<0.01), glucose and insulin and decreased triglycerides (p<0.001). The combination of ATV+SM led to a significant reduction in insulin, an improvement of glucose tolerance, and the hypolipidemic effect was enhanced compared to ATV alone. Furthermore, ATV supplementation increased skeletal muscle triglycerides but its combination with SM decreased triglycerides accumulation in the muscle (p<0.05) and the liver (p<0.01). In the liver, ATV+SM treatment increased the activities of antioxidant enzymes, glutathione and reduced lipid peroxidation (p<0.001). The combined administration of ATV with SM potentiated the hypolipidemic effect, reduced ectopic lipid accumulation, improved glucose metabolism, and increased antioxidant and anti-inflammatory actions. Our results show that SM increased the effectiveness of statin therapy in a hypertriglyceridemic rat model of metabolic syndrome.
- MeSH
- anticholesteremika škodlivé účinky MeSH
- antioxidancia farmakologie MeSH
- atorvastatin škodlivé účinky MeSH
- diabetes mellitus 2. typu chemicky indukované farmakoterapie patologie MeSH
- hypercholesterolemie krev MeSH
- hyperlipidemie farmakoterapie MeSH
- kombinovaná farmakoterapie MeSH
- krysa rodu rattus MeSH
- metabolický syndrom farmakoterapie genetika patologie MeSH
- modely nemocí na zvířatech MeSH
- oxidační stres účinky léků MeSH
- silymarin farmakologie MeSH
- triglyceridy krev MeSH
- zánět farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Projevy aterosklerózy jsou nejčastějším patogenetickým faktorem cévních chorob. V léčbě i prevenci arterosklerózy se používají statiny, fibráty a ezetimib. Statiny jsou inhibitory HMG-CoA reduktázy a blokují nejen syntézu cholesterolu, ale i syntézu dalších důležitých látek - např. koenzymu Q10. Z nežádoucích účinků statinů jsou nejčastější poruchy svalů, jen zcela zřídka poruchy nervosvalového přenosu a rovněž jsou popisovány změny periferního nervového systému (PNS). V současné době došlo k přehodnocení dřívějších epidemiologických údajů a výskyt periferní neuropatie (senzitivně motorické, axonální, s postižením vláken se závislostí na délce) je málo častý. Statiny však mají vliv na vznik senzitivní a autonomní ganglionopatie a rovněž na manifestaci ALS (amyotrofické laterální sklerózy).
Manifestation of artherosclerosis is the most frequent patogenetic factor. Statins, fibrates and ezetimib are used in prevention and therapy of arterosclerosis. Statins are inhibitors HMG-CoA reductasis and they are blocking not only cholesterol synthesis, but also synthesis of other important substances - e.g. coenzyme Q10. From the unwanted effects of statins the muscle disorders are the most frequent, neuromuscular junction disorders are rare and there are described peripheral nervous system disorders. Nowadays, the former epidemiological statistical data were reevaluated and occurence of peripheral statin-induced neuropathy (sensory-motor, axonal, with nerve fiber lesion according to the lenght) is not frequent. Statins have influence on development of sensory and autonomic ganglionopathy and also on ALS manifestation.
- MeSH
- amyotrofická laterální skleróza patofyziologie MeSH
- anticholesteremika škodlivé účinky MeSH
- lidé MeSH
- neuralgie chemicky indukované epidemiologie MeSH
- nežádoucí účinky léčiv MeSH
- periferní nervový systém účinky léků MeSH
- senzorická ganglia účinky léků MeSH
- statiny * farmakologie škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Hyperaktívny močový mechúr je častým problémom starších pacientov. Vo farmakoterapii sa najčastejšie používajú anticholinergiká. Vyznačujú sa veľmi dobrou účinnosťou, ale môžu zhoršovať kognitívne funkcie pacientov. Tento nežiaduci účinok závisí najmä od schopnosti anticholinergika prechádzať hematoencefalickou bariérou a viazať sa na muskarínové M1 receptory v centrálnom nervovom systéme. Prienik cez hematoencefalickú bariéru závisí od veľkosti molekuly, náboja, lipofility a od toho, či je anticholinergikum substrátom P‐glykoproteínu. Výsledky viacerých štúdií ukázali, že nevhodným liečivom hyperaktívneho mechúra u starších pacientov je oxybutynín, ktorý významne znižuje kognitívne funkcie. Naopak, trospium, solifenacín, darifenacín a fesoterodín nepreukázali významný vplyv na zníženie kognitívnych funkcií starších pacientov. Článek poskytuje prehľad farmakoterapeutických možností liečby hyperaktívneho močového mechúra na príklade staršej pacientky s vekom podmieneným poklesom kognitívnych funkcí.
Overactive bladder is common condition in elderly. Anticholinergic agents are the mainstay of pharmacological treatment of overactive bladder. They are effective but can decline the cognitive function. This adverse event depends on their ability to cross the blood - brain barrier and binding on muscarinic M1 receptors in central nervous system. Crossing of anticholinegics across the hematoencephalic barrier is dependent upon the molecular size, ionic charge, lipophilicity and if the anticholinergic is a P-glycoprotein substrate. Results of studies have shown the inappropriate anticholinergic agent to treat overactive bladder in elderly is oxybutynin, which frequently causes the cognitive impairment. On the contrary, trospium, solifenacin, darifenacin a fesoterodine have insignificant effect on cognitive functions in the elderly. The article provides an overview of pharmacotherapeutic options for treatment of overactive bladder on an example of elderly female patient with age-associated cognitive decline.
