• MeSH
• kardiovaskulární nemoci * MeSH
• nemoci cév MeSH
• výsledek terapie MeSH
• Publikační typ
• periodika MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• kardiologie

• MeSH
• adiponektin MeSH
• ateroskleróza MeSH
• diabetes mellitus 2. typu MeSH
• diabetes mellitus MeSH
• fixní kombinace léků MeSH
• hyperinzulinismus MeSH
• kardiovaskulární nemoci MeSH
• klinické lékařství MeSH
• thiazolidindiony terapeutické užití   MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• kardiologie
• angiologie
• diabetologie

Importance: Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. Objective: To evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and Participants: Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). Exposures: Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and Measures: Multivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). Results: Among 11 135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P < .001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and Relevance: In this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.

• MeSH
• ambulantní monitorování krevního tlaku * MeSH
• cirkadiánní rytmus MeSH
• dospělí MeSH
• hypertenze komplikace   diagnóza   mortalita   MeSH
• kardiovaskulární nemoci epidemiologie   etiologie   MeSH
• krevní tlak fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• měření krevního tlaku metody   MeSH
• proporcionální rizikové modely MeSH
• rizikové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

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.

• Klíčová slova
• studie FOURIER, studie ODYSSEY OUTCOMES,
• MeSH
• ezetimib aplikace a dávkování   terapeutické užití   MeSH
• kardiovaskulární nemoci farmakoterapie   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• PCSK9 inhibitory MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 aplikace a dávkování   terapeutické užití   MeSH
• statiny MeSH
• Check Tag
• lidé MeSH

Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R2 statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of <90 (normotension, n=6183), 90 to <92 (elevated MAP, n=909), 92 to <96 (stage-1 hypertension, n=1544), and ≥96 (stage-2 hypertension, n=2960) mm Hg yielded equivalent 10-year major adverse cardiovascular events risks as office MAP categorized using 2017 American thresholds for office SBP and DBP. Compared with 24-hour MAP normotension, hazard ratios were 0.96 (95% CI, 0.80-1.16), 1.32 (1.15-1.51), and 1.77 (1.59-1.97), for elevated and stage-1 and stage-2 hypertensive MAP. On top of 24-hour MAP, higher 24-hour SBP increased, whereas higher 24-hour DBP attenuated risk (P<0.001). Considering the 24-hour measurements, R2 statistics were similar for SBP (1.34) and MAP (1.28), lower for DBP than for MAP (0.47), and reduced to null, if the base model included SBP and DBP; if the ambulatory BP indexes were dichotomized according to the 2017 American guideline and the proposed 92 mm Hg for MAP, the R2 values were 0.71, 0.89, 0.32, and 0.10, respectively. In conclusion, the clinical application of 24-hour MAP thresholds in conjunction with SBP and DBP refines risk estimates.

• MeSH
• ambulantní monitorování krevního tlaku * MeSH
• dospělí MeSH
• hypertenze komplikace   MeSH
• kardiovaskulární nemoci etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• proporcionální rizikové modely MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• Klíčová slova
• empagliflozin, studie EMPEROR-Preserved,
• MeSH
• diastolické srdeční selhání * farmakoterapie   MeSH
• glifloziny * terapeutické užití   MeSH
• hospitalizace MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• srdeční selhání * farmakoterapie   MeSH
• Check Tag
• lidé MeSH

• Klíčová slova
• studie COLCOT,
• MeSH
• infarkt myokardu * farmakoterapie   MeSH
• kardiovaskulární nemoci prevence a kontrola   MeSH
• klinická studie jako téma MeSH
• kolchicin farmakologie   terapeutické užití   MeSH
• lidé MeSH
• Check Tag
• lidé 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.

• Klíčová slova
• alirocumab, studie ODYSSEY OUTCOMES,
• MeSH
• anticholesteremika terapeutické užití   MeSH
• hypercholesterolemie farmakoterapie   MeSH
• kardiovaskulární nemoci * prevence a kontrola   MeSH
• LDL-cholesterol * krev   účinky léků   MeSH
• lidé MeSH
• monoklonální protilátky * terapeutické užití   MeSH
• PCSK9 inhibitory MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 * terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Many patients with acute coronary syndrome have concurrent metabolic risk factors that affect risk of major adverse cardiovascular events (MACE). We aimed to assess the effects of the PCSK9 inhibitor alirocumab compared with placebo on MACE according to baseline metabolic risk factors. METHODS: We performed a post-hoc analysis of the ODYSSEY OUTCOMES trial, which was a multicentre, double-blind, randomised controlled trial done in 1315 hospitals and outpatient clinics in 57 countries. Patients aged 40 years or older with recent acute coronary syndrome (ie, in the past 1-12 months) and elevated concentrations of atherogenic lipoproteins, despite high-intensity or maximum-tolerated statin treatment, were eligible for enrolment. Between Nov 2, 2012, and Feb 9, 2017, patients were randomly assigned (1:1) to 75 mg alirocumab by subcutaneous injection every 2 weeks or matching placebo, beginning 1-12 months after acute coronary syndrome and were followed up for a median of 2·8 years (IQR 2·3-3·4). Patients and investigators were masked to group assignment and treatment dose adjustment. The primary outcome was a composite of death from coronary artery disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. Analysis of MACE according to an ordinal number of metabolic risk factors was done post hoc. Metabolic risk factors were defined as blood pressure of at least 130/85 mm Hg or treatment with antihypertensive medication, triglyceride concentration of at least 150 mg/dL, HDL cholesterol concentration less than 40 mg/dL for men and 50 mg/dL women, fasting plasma glucose concentration of at least 100 mg/dL or treatment with glucose-lowering medication, and BMI of at least 30 kg/m2. Risk of MACE and effect of alirocumab were assessed according to the number of metabolic risk factors. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. FINDINGS: Of 18 924 patients, 3882 (41%) of 9462 in the alirocumab group and 3859 (41%) of 9462 in the placebo group had three or more metabolic risk factors. In the placebo group, MACE incidence increased monotonically with each metabolic risk factor from 7·8% (no risk factors) to 19·6% (five risk factors; HR 1·18, 95% CI 1·13-1·24 per metabolic risk factor). Alirocumab decreased relative risk of MACE consistently across categories defined by the number of metabolic risk factors (pinteraction=0·77), but absolute risk reduction (aRR) increased with the number of metabolic risk factors (no risk factors aRR 0·7%, -1·81 to 3·29 vs five risk factors aRR 3·9%, -1·45 to 9·25; pinteraction<0·001). Similarly, when patients with diabetes were excluded, the incidence of MACE in the placebo group increased from 7·7% in patients with no metabolic risk factors to 14·6% in those with five metabolic risk factors and aRR with alirocumab increased from 0·91% in patients with no metabolic risk factors to 3·82% in those with five factors. Alirocumab was well tolerated in all subgroups defined by the presence of metabolic risk factors. INTERPRETATION: Accumulation of metabolic risk factors was associated with higher risk of MACE in patients with recent acute coronary syndrome. Alirocumab reduced MACE consistently, but aRR increased with number of metabolic risk factors. FUNDING: Sanofi and Regeneron Pharmaceuticals.

• MeSH
• akutní koronární syndrom * komplikace   farmakoterapie   epidemiologie   MeSH
• cévní mozková příhoda * MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• ischemie mozku * MeSH
• lidé MeSH
• PCSK9 inhibitory terapeutické užití   MeSH
• rizikové faktory MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

• Klíčová slova
• studie ODYSSEY OUTCOMES, alirokumab,
• MeSH
• akutní koronární syndrom farmakoterapie   MeSH
• infarkt myokardu farmakoterapie   mortalita   terapie   MeSH
• kardiovaskulární nemoci farmakoterapie   prevence a kontrola   MeSH
• kongresy jako téma MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• placebo terapeutické užití   MeSH
• Check Tag
• lidé MeSH