Importance: Despite recent advances in treatment of severe aortic valve stenosis (AS), AS remains a life-threatening condition with no proven disease-modifying therapy. Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) have been implicated in the pathobiology of AS. The proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab reduces circulating LDL-C concentrations by 50% to 60% and Lp(a) by 20% to 30%. Objective: To determine whether evolocumab reduces the risk of AS events in patients with atherosclerotic cardiovascular disease. Interventions: Patients were randomized 1:1 to evolocumab or placebo. Design, Setting, and Participants: Exploratory analysis of the FOURIER trial, which enrolled 27 564 patients with stable atherosclerotic cardiovascular disease who were taking statin therapy at 1242 sites in 49 countries from February 2013 to November 2016. Patients were randomized to evolocumab or placebo and followed up for a median (interquartile range) of 2.2 (1.8-2.5) years. This post hoc analysis was performed from September 2019 to February 2020. Main Outcomes and Measures: Site-reported adverse events of new or worsening AS or aortic valve replacement (termed AS events). The adjusted risk of AS events was calculated with a multivariable model including concentrations of Lp(a) and LDL-C corrected for Lp(a) content, plus age, sex, diabetes, hypertension, current smoking, and estimated glomerular filtration rate. Evolocumab efficacy was tested using a Cox proportional hazards model. Results: Aortic stenosis events occurred in 63 patients (48 men [76%]; mean [SD] age, 69 [9] years) over a median of 2.2 years. Elevated Lp(a) concentration was associated with higher rates of AS events (adjusted hazard ratio [aHR], 1.55 [95% CI, 1.17-2.05] per SD; P = .002), including aortic valve replacement (aHR, 2.22 [95% CI, 1.38-3.58] per SD; P = .001), after multivariable adjustment. The corrected LDL-C concentration was not significantly associated with AS events (aHR, 1.23 [95% CI, 0.93-1.61] per SD; P = .14). The overall HR for AS events with evolocumab was 0.66 (95% CI, 0.40-1.09), with no apparent association in the first year (HR, 1.09 [95% CI, 0.48-2.47]) but an HR of 0.48 (95% CI, 0.25-0.93) after the first year of treatment. Conclusions and Relevance: In this exploratory analysis of the FOURIER trial, higher Lp(a) levels, but not Lp(a)-corrected LDL-C levels, were associated with a higher risk of subsequent AS events, including aortic valve replacement. Long-term therapy with evolocumab may reduce AS events, and this raises the possibility that specific pharmacologic lipid-lowering therapy could offer a means to prevent or slow the progression of AS. These exploratory findings merit further investigation with a dedicated randomized clinical trial. Trial Registration: ClinicalTrials.gov Identifier: NCT01764633.

• MeSH
• anticholesteremika terapeutické užití   MeSH
• aortální stenóza krev   farmakoterapie   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• LDL-cholesterol krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 antagonisté a inhibitory   MeSH
• rizikové faktory MeSH
• subtilisin terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

V roku 2007 prebehla medzinárodná štúdia NICS v dvoch susedných krajinách Európy (v Poľsku a na Slovensku), ktorá sledovala rizikových pacientov s metabolickým syndrómom podľa identického protokolu. Tým bolo možné neskoršie sledovanie bežnej klinickej praxe dvoch odlišných populácií a krajín. Štúdiu navrhlo Poľsko a Slovensko realizovalo štúdiu v našich podmienkach podľa identického protokolu. Sledovanou skupinou boli pacienti s metabolickým syndrómom, ktorý predstavuje v oboch krajinách značný zdravotný, spoločenský i ekonomický problém. Liečivom, ktoré bolo vybrané na sledovanie, bol kardiometabolický sartan - telmisartan v dávke 80 mg raz denne. Cieľom bolo vyhodnotiť jeho vplyv u pacientov s hypertenziou v podmienkach reálnej klinickej praxe s ohľadom na vybrané metabolické parametre a účinnosť liečby. Priemerný pokles hodnôt krvného tlaku po trojmesačnej liečbe telmisartanom 80 mg denne predstavoval o 29,4 mmHg systolického a 15,7 mmHg diastolického krvného tlaku. Došlo tiež k významnému poklesu hladín celkového cholesterolu, LDL-cholesterolu, triacylglycerolov, glykémie nalačno i k zlepšeniu kompenzácie diabetu hodnoteného parametrom HBA1C.

In the year 2007 the international study NICS was performed in two neighbor European countries (Poland and Slovakia) that followed patients at risk with metabolic syndrome with the identical protocol. Later on comparisons of two different populations and their clinical practice could be evaluated. This study was designed in Poland and Slovakia used the identical protocol in our own clinical practice conditions. Patients with metabolic syndrome which represents in both our countries a significant health and economical problem were included in the study group. Cardiome-tabolic sartan - telmisartan in the dose of 80 mg once daily was chosen as the evaluating study drug. Primary endpoint was to evaluate its effect on patients with hypertension in the conditions of real clinical practice with the interest on therapeutical effectiveness and chosen metabolic parameters.

• MeSH
• fibrinolýza fyziologie   MeSH
• Publikační typ
• přehledy MeSH