V rokoch 2017 a 2018 boli publikované výsledky dvoch veľkých kardiovaskulárnych štúdií s inhibítormi pro-proteín konvertázy subtilizín-kexín typu 9 (PCSK9i), ktoré potvrdili klinické výhody ich použitia u pacientov s vysokým rizikom rozvoja kardiovaskulárnych ochorení podmienených aterosklerózou (Atherosclerosis-related Cardio-Vascular Disease - ASCVD). Súhrnná analýza výsledkov štúdie FOURIER (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk) s evolokumabom bola publikovaná v NEJM [1]. V marci 2018 po čas kongresu ACC (American College of Cardiology) v Orlande boli prezentované výsledky štúdie ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes after an Acute Coronary Syndrome during Treatment with Alirocumab) s alirokumabom [2,3]. Aj keď existuje množstvo otvorených otázok, výsledky obidvoch štúdií potvrdzujú, že ďalšie znižovanie LDL-cholesterolu (LDL-C) vedie k zníženiu reziduálneho rizika ASCVD u vysokorizikových pacientov a doslova menia hypotézu týkajúcu sa LDL-C "čím nižšie tým lepšie" na realitu a potrebu každodenného života. V klinickej praxi však pridanie PCSK9i musíme vždy dôkladne zvážiť. V sekundárnej prevencii v prvej línii ostáva intenzívna statínová liečba s ezetimibom súčasne so zmenou životného štýlu. PCSK9i pridávame pacientom, u ktorých pretrváva LDL-C ≥1,8 mmol/l.

In the years 2017 and 2018, the results of two large cardiovascular trials with inhibitors of pro-protein convertase subtilisin-kexin type 9 (PCSK9i) were published and confirmed the clinical benefits of their use in patients at high risk of developing atherosclerosis-related cardiovascular disease (ASCVD). A summary analysis of FOURIER (Evolutionary Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) study was published in NEJM [1]. In March 2018, during the ACC Congress in Orlando, the results of the ODYSSEY Outcomes Study (Assessment of Cardiovascular Outcomes after an Acute Coronary Syndrome during Treatment with Alirocumab) were presented [2,3]. Although there are a number of open questions, the results of the trials confirm that further reduction of LDL-C leads to a reduction in the residual risk of ASCVD in high-risk patients and changes the hypothesis on LDL-C "the lower is better" to reality and the need for everyday life. In clinical practice, however, we must always carefully consider adding PCSK9i. In secondary prevention in the first line intensive statin treatment with ezetimibe and lifestyle changes remains. PCSK9i is added to patients with LDL-C ≥ 1.8 mmol/l.

• Keywords
• studie FOURIER, studie ODYSSEY OUTCOMES,
• MeSH
• Ezetimibe administration & dosage   therapeutic use   MeSH
• Cardiovascular Diseases drug therapy   MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• PCSK9 Inhibitors MeSH
• Proprotein Convertase 9 administration & dosage   therapeutic use   MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH
• Check Tag
• Humans MeSH

Studie ODYSSEY Outcomes prokázala účinnost alirokumabu ve snížení koncentrace LDL cholesterolu (LDL‑C) a rovněž v poklesu kardiovaskulárního rizika a celkové mortality. Výsledky zatím nepublikované studie i její budoucí analýzy slibují posun v terapii zaměřené na redukci koncentrace LDL‑C a jsou dalším argumentem pro dostupnost inhibitorů PCSK9 v klinické praxi.

ODYSSEY Outcomes trial has proven alirocumab efficiency in lowering LDL cholesterol (LDL‑C) concentrations as well as in reduction of cardiovascular risk and all‑cause mortality. Results of the yet unpublished trial and its future analyses promise an advance in therapy focused on reduction of LDL‑C concentrations and represent another argument for the availability of PCSK9 inhibitors in clinical practice.

• MeSH
• American Heart Association MeSH
• Atherosclerosis drug therapy   complications   prevention & control   MeSH
• Drug Therapy methods   utilization   MeSH
• Drug Evaluation MeSH
• Congresses as Topic MeSH
• Cholesterol, LDL * isolation & purification   drug effects   MeSH
• Humans MeSH
• Antibodies, Monoclonal * administration & dosage   adverse effects   therapeutic use   MeSH
• PCSK9 Inhibitors MeSH
• Proprotein Convertase 9 * therapeutic use   drug effects   MeSH
• Randomized Controlled Trials as Topic classification   methods   utilization   MeSH
• Statistics as Topic MeSH
• Outcome and Process Assessment, Health Care MeSH
• Check Tag
• Humans MeSH

U nemocných, kteří prodělali akutní koronární syndrom (AKS), zůstává vysoké riziko další kardiovaskulární (KV) příhody i při využití všech opatření v rámci sekundární prevence. Studie ODYSSEY OUTCOMES testovala účinky inhibitoru proprotein konvertázy subtilizin kexin 9 (PCSK9) u pacientů po AKS, u nichž zůstávaly vyšší hodnoty cholesterolu i přes intenzivní statinovou léčbu (LDL-cholesterol/LDL-C > 1,8 mmol/l). Do studie bylo zařazeno 18 924 jedinců, kteří byli randomizováni k léčbě alirokumabem nebo dostávali placebo. Dávka alirokumabu byla zaslepeně upravována s cílem dosáhnout hodnoty LDL-C 0,6-1,3 mmol/l. Střední doba sledování byla 2,8 roku. Alirokumab významně snížil riziko další KV-příhody (primární složený cílový ukazatel: úmrtí pro ICHS, nefatální infarkt myokardu, ischemická cévní mozková příhoda, nestabilní angina pectoris) relativně o 15 %. Léčba alirokumabem byla spojena i s nižší celkovou mortalitou. Alirokumab snižoval nejen riziko první KV-příhody, ale i příhod následných. Účinky alirokumabu byly nejvýraznější v podskupinách s vyšší vstupní hodnotou LDL-C (> 2,6 mmol/l) a u nemocných, léčených alirokumabem déle než 3 roky. Léčba alirokumabem byla bezpečná, pouze ve srovnání s placebem byla lokální reakce v místě vpichu častějším nežádoucím účinkem po alirokumabu. Alirokumab po přidání k intenzivní statinové léčbě u nemocných s AKS významně snižoval riziko další KV-příhody a léčba alirokumabem byla spojena i s nižší celkovou mortalitou.

Patients after acute coronary syndrome (ACS) remain at high risk for other cardiovascular (CV) events even when all the measures within secondary prevention are used. The ODYSSEY OUTCOMES Trial tested the effects of proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9) in patients with ACS, who had higher cholesterol levels remaining despite high-dose statin therapy (LDL-cholesterol > 1.8 mmol/L). The study included 18,924 individuals who were randomized to receive alirocumab therapy or placebo. The dose of alirocumab was blindly adjusted to achieve an LDL-cholesterol value of 0.6-1.3 mmol/L. The median follow-up was 2.8 years. Alirocumab significantly reduced the risk of another CV event (primary composite endpoint death from coronary heart disease, non-fatal myocardial infarction, ischemic stroke, unstable angina) by 15%. Treatment with alirocumab was also associated with lower total mortality. Alirocumab not only reduced the risk of the first CV event, but also subsequent events. The effects of alirocumab were the most pronounced in subgroups with the highest initial LDL-cholesterol value (> 2.6 mmol/L) and in patients treated with alirocumab for more than 3 years. Treatment with alirocumab was safe, only a local reaction at the injection site was a more common adverse effect of alirocumab compared to placebo. In coclusion, alirocumab, when added to intensive statin therapy in patients with ACS, significantly reduced the risk of recurrent CV event, and treatment with alirocumab was associated with lower total mortality.

• Keywords
• alirocumab, studie ODYSSEY OUTCOMES,
• MeSH
• Anticholesteremic Agents therapeutic use   MeSH
• Hypercholesterolemia drug therapy   MeSH
• Cardiovascular Diseases * prevention & control   MeSH
• Cholesterol, LDL * blood   drug effects   MeSH
• Humans MeSH
• Antibodies, Monoclonal * therapeutic use   MeSH
• PCSK9 Inhibitors MeSH
• Proprotein Convertase 9 * therapeutic use   MeSH
• Randomized Controlled Trials as Topic MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH

Počet pacientov užívajúcich hypolipidemickú liečbu z roka na rok narastá. V celosvetovom meradle najčastejšie predpisovanými hypolipidemikami sú statíny, ktoré sa stali liekmi prvej línie, ako aj základným kameňom kombinovanej hypolipidemickej liečby. Suboptimálna adherencia ku hypolipidemickej liečbe je spojená so suboptimálnou kontrolou lipidového spektra, s nárastom kardiovaskulárnych ochorení a úmrtí, ako aj so zvyšujúcimi sa nákladmi na manažment liečby dyslipidémií a s ňou súvisiacich pridružených ochorení a komplikácií. Najčastejšou príčinou nonadherencie alebo prerušenia hypolipidemickej liečby býva svalová symptomatológia s následnou intoleranciou statínov, pre ktorú máme zadefinované presné postupy. Možnosťou pokračovania liečby je použitie kombinovanej hypolipidemickej liečby s použitím ezetimibu alebo kyseliny bempedoovej, prípadne ich fixných kombinácií. Recentne publikované predšpecifikované analýzy štúdie CLEAR-Outcomes dokázali, že kyselina bempedoová je účinná v redukcii ďalších (nasledujúcich) kardiovaskulárnych príhod, je účinná u pacientov s rôznymi stupňami poruchy tolerancie glukózy, bez zvýšenia rizika rozvoja novovzniknutého diabetes mellitus a môže byť bezpečne a efektívne použitá v kombinácii s ezetimibom u jedincov s intoleranciou statínov.

The number of patients using hypolipidemic treatment is increasing from year to year. On a global scale, the most frequently prescribed hypolipidemic drugs are statins, which have become first-line drugs as well as the cornerstone of combined hypolipidemic therapy. Suboptimal adherence to hypolipidemic treatment is associated with suboptimal control of the lipid spectrum, with an increase in cardiovascular disease and death, as well as with increasing costs for the management of dyslipidemia treatment and associated diseases and complications. The most common cause of non-adherence or interruption of hypolipidemic treatment is muscle symptomatology with subsequent statin intolerance, for which we have defined precise procedures. The possibility of continuing the treatment is the use of combined hypolipidemic treatment with the use of ezetimibe and/or bempedoic acid, or their fixed combinations. Recently published pre-specified analyzes of the CLEAR-Outcomes trial proved that bempedoic acid is effective in reducing further (subsequent) cardiovascular events, is effective in patients with various degrees of impaired glucose tolerance, without increasing the risk of developing new-onset diabetes mellitus and can be safely and effectively used in combination with ezetimibe in individuals with statin intolerance.

• Keywords
• studie CLEAR OUTCOMES, kyselina bempedoová,
• MeSH
• Dyslipidemias * drug therapy   MeSH
• Ezetimibe * administration & dosage   therapeutic use   MeSH
• Cardiovascular Diseases drug therapy   prevention & control   MeSH
• Drug Therapy, Combination MeSH
• Dicarboxylic Acids * administration & dosage   pharmacology   therapeutic use   MeSH
• Humans MeSH
• Randomized Controlled Trials as Topic MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage   therapeutic use   MeSH
• Check Tag
• Humans MeSH

• MeSH
• Lumbar Vertebrae innervation   pathology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Microsurgery methods   MeSH
• Adolescent MeSH
• Surveys and Questionnaires MeSH
• Aged MeSH
• Patient Satisfaction MeSH
• Intervertebral Disc Displacement surgery   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Review MeSH
• Comparative Study MeSH

Dotazník CORE-OM (Clinical Outcomes in Routine Evaluation - Outcome Measure) je široko používaný sebaposudzovací nástroj merania, ktorý bol speciálně vyvinutý na meranie efektu psychologickej/psychiatrickej liečby. Proces jeho adaptácie na podmienky slovenskej klinickej praxe opisujeme v troch štúdiách. V štúdii I. sa zameriavame na overenie vnútornej konzistencie slovenského překladu dotazníka CORE-OM, overenie konštruktovej validity a schopnosti diskriminovat medzi klinickým a neklinickým výberom. V štúdii II., v ktorej sme použili revidovánu verziu slovenského překladu dotazníka, prinášame deskriptívne data z klinického a neklinického výběru, zameriavame sa na odhad test-retestovej reliability a výpočet kritérií štatisticky a klinicky signifikantnej změny. Studia III. opisuje proces konsenzuálnej tvorby finálnej verzie slovenského překladu CORE-OM, za účasti jedného z autorov originálnej verzie. Slovenská verzia CORE-OM preukázala dobré psychometrické vlastnosti, je vysoko vnútorne konzistentná a dosahuje dostatočnú test-retestovú reliabilitu, koreluje s referenčnými nástrojmi merania a dostatočne diskriminuje medzi klinickým a neklinickým výberom. Vypočítané kritérium statisticky signifikantnej změny (index spolahlivej změny RCI) má hodnotu 0,57. Cut-off skóre, ktoré je ukazovateľom klinicky signifikantnej změny, má pre celok CORE-OM hodnotu pre mužov 1,05 a pre ženy 1,12. Slovenská verzia dotazníka CORE-OM je připravená pre klinické používanie, jej ďalšie vlastnosti ohladom merania terapeutickej změny sa ďalej skúmajú.

CORE-OM (Clinical Outcomes in Routine Evaluation - Outcome Measure) is a widely used self-rating measure, developed specifically for measuring outcome of psychological/psychiatric treatment. The process of its adaptation for the use in Slovak context is described in three studies. Study I. presents internal consistency coefficients of the Slovak version of CORE-OM, an assessment of the construct validity of the instrument as well as the comparison of clinical and non-clinical samples. In Study II., where we used a revised Slovak translation of CORE-OM, we are presenting the descriptive data of clinical and non-clinical samples, the test-retest reliability and the criteria of the statistically and clinically significant change. Study III describes a process of establishing the final version of the Slovak CORE-OM in collaboration with one of the authors of the original version. The Slovak version of CORE-OM has good psychometric properties, is highly internally consistent, and has sufficient test-retest reliability. It discriminates well between clinical and non-clinical samples. The criterion of statistical significant change (reliable change index - RCI) for all items of CORE-OM is 0, 57. The cut-off score is 1,05 for males and 1,12 for females respectively. The Slovak version of CORE-OM is ready to be used widely in clinical practice; further research on its properties is being conducted.

• MeSH
• Research Support as Topic MeSH
• Outcome Assessment, Health Care methods   statistics & numerical data   utilization   MeSH
• Data Interpretation, Statistical MeSH
• Humans MeSH
• Surveys and Questionnaires standards   utilization   MeSH
• Psychotherapeutic Processes MeSH
• Reproducibility of Results MeSH
• Self-Assessment MeSH
• Check Tag
• Humans MeSH
• Publication type
• Comparative Study MeSH

Pacienti s akútnym koronárnym syndrómom (AKS) i po optimálnej liečbe akútneho ochorenia a i pri optimálnej liečbe v rámci sekundárnej následnej prevencie majú naďalej vysoké kardiovaskulárne (KV) riziko morbidity a mortality. Intenzívnejšia liečba dyslipidémie, ďalšia redukcia sérového LDL-cholesterolu (LDL-c), by mala zlepšiť prognózu týchto pacientov, čo bola hypotéza tejto štúdie s liečbou alirokumabom (PCSK9 inhibítorom) vs. placebom pri ostatnej štandardnej liečbe. V štúdii bolo zaradených 18 924 pacientov randomizovaných k tejto liečbe v období 1-12 mesiacov po AKS. V ramene aktívnej liečby došlo k ďalšej redukcii sérového LDL-c (z úrovne 2,62 na úroveň 1,37 mmol/l, redukcia 54,7 %). Tento pokles LDL-c viedol k redukcii primárneho endpointu (koronárne úmrtie/nefatálny infarkt a cievna mozgová príhoda/hospitalizácia pre nestabilnú anginu pektoris) o 15 % (štatisticky významne - S), aj jeho komponenty boli významne priaznivo ovplyvnené a celková mortalita bola redukovaná tiež o 15 % (S). Benefit bol najvyšší v podskupine pacientov, ktorí do štúdie vstupovali s najvyššou sérovou hladinou LDL-c, t.j. ≥ 2,6 mmol/l - primárny endpoint bol tu redukovaný o 24 % (S) a KV mortalita o 31 % (S). Liečba bola bezpečná. Odkazom štúdie je významná redukcia výskytu KV príhod (mortality, nefatálnych infarktov myokardu i mozgových príhod, nestabilnej anginy pectoris) u chorých s AKS pomocou alirokumabu - pričom všetci pacienti mali výbornú štandardnú liečbu ochorenia, včítane použitia silných statínov vo vysokých dávkach. Najviac z liečby profitovali pacienti s najvyššou vstupnou sérovou hladinou LDL-c (≥ 2,6 mmol/l).

Patients suffering from acute coronary syndrome (ACS) have a very high cardiovascular (CV) risk of morbidity and mortality even with an optimal treatment of ACS and optimal secondary prevention treatment afterwards. A more intensive treatment of dyslipidaemia, with further reduction of serum LDL-cholesterol (LDL-c) levels, should improve prognosis of these patients - such was the hypothesis of this study with alirocumab (PCSK9 inhibitor) treatment vs. placebo treatment. There were 18,924 patients in this study, randomized for the above-mentioned treatment in the time period of 1-12 months after ACS. In the active arm treatment there was a further reduction of serum LDL-c level (from 2.62 to 1.37 mmol/l, reduction of 54.7%). This serum LDL-c reduction contributed to a reduction of the primary end-point (coronary mortality/nonfatal myocardial infarction and stroke/hospitalization for unstable angina pectoris) of 15% (significantly - S), and also to an improvement of the components of this end-point and 15% reduction of all-cause mortality (S). The best benefit was achieved in the subgroup of patients with the highest serum level of LDL-c ≥ 2.6 mmol/l - the primary end-point was reduced by 24% (S) and CV mortality by 31% (S). The treatment was safe. The output of this study is a great reduction of CV events (mortality, nonfatal myocardial infarctions and strokes, unstable angina pectoris) in patients with an ACS treated by alirocumab - all patients had an excellent standard treatment of the disease, including strong and high doses of statins. Patients with the highest basal serum LDL-c levels (≥ 2.6 mmol/l) profited most.

• Keywords
• alirokumab,
• MeSH
• Acute Coronary Syndrome diagnosis   drug therapy   prevention & control   MeSH
• Hypercholesterolemia diagnosis   drug therapy   MeSH
• Cardiovascular Diseases mortality   MeSH
• Cholesterol, LDL blood   adverse effects   drug effects   MeSH
• Humans MeSH
• Antibodies, Monoclonal therapeutic use   MeSH
• Placebos therapeutic use   MeSH
• Randomized Controlled Trials as Topic MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Multicenter Study MeSH

• MeSH
• Adult MeSH
• External Fixators MeSH
• Fracture Fixation methods   MeSH
• Tibial Fractures classification   therapy   MeSH
• Outcome Assessment, Health Care methods   statistics & numerical data   MeSH
• Internal Fixators MeSH
• Humans MeSH
• Fracture Fixation, Internal methods   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH

• MeSH
• Lumbar Vertebrae MeSH
• Diskectomy methods   MeSH
• Sciatica MeSH
• Humans MeSH
• Intervertebral Disc Displacement drug therapy   surgery   rehabilitation   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Randomized Controlled Trial MeSH

• Keywords
• studie ODYSSEY OUTCOMES, alirokumab,
• MeSH
• Acute Coronary Syndrome drug therapy   MeSH
• Myocardial Infarction drug therapy   mortality   therapy   MeSH
• Cardiovascular Diseases drug therapy   prevention & control   MeSH
• Congresses as Topic MeSH
• Humans MeSH
• Antibodies, Monoclonal therapeutic use   MeSH
• Placebos therapeutic use   MeSH
• Check Tag
• Humans MeSH