Kapilární elektroforéza (CZE) je alternativní metodou separace a semikvantitativního hodnocení sérových proteinů. Krátké sdělení se zabývá rutinním použitím multikapilárních systémů pro elektroforézu sérových bílkovin a dopadem výměny přístroje Paragon 2000 (Beckman-Coulter) za Capillarys 2 (Sebia) provázené změnou referenčních mezí. Dlouhodobé sledování cyklů externího hodnocení kvality dokládá plynulý přechod a srovnatelnost od elektroforézy na agarózovém nosiči k multikapilárním systémům. Výsledky jsou mezilaboratorně dobře srovnatelné, lze rovněž vyvodit závěr, že změny analytického systému pro rutinní elektroforézu sérových bílkovin v časovém intervalu dvou let nepřinesly komplikace ani v oblasti kvantitativního hodnocení gamapatií.
Capillary zone electrophoresis (CZE) is an alternative method for the separation and quantitative evaluation of serum proteins. CZE is very effective, quick and namely a precise method. Two specific automated multichannel (multicapillary) instruments are available, the Paragon 2000 (Beckman-Coulter) and the Capillarys 2 (Sebia), characterized by different number of assessed protein fractions are mentioned and newly tested reference intervals. Long-term observation of the cycles of external quality assurance (EQA) programs exemplifies smooth transition from agarose electrophoresis to multichannel capillary systems and comparability of analysis. The interlaboratory comparisons indicated good comparability of the results and conclusion may therefore be drawn that the changes in analytical systems for routine electrophoresis of serum proteins within the time interval of two years have not complicated the situation in the area of quantitative evaluation of gammapathies as well.
- MeSH
- Biomedical Research MeSH
- Electrophoresis, Capillary statistics & numerical data MeSH
- Blood Protein Electrophoresis methods statistics & numerical data MeSH
- Electrophoresis, Agar Gel statistics & numerical data MeSH
- Reference Standards MeSH
- Serum Globulins isolation & purification MeSH
- Serum Albumin isolation & purification MeSH
- Publication type
- Evaluation Study MeSH
- Geographicals
- Czech Republic MeSH
Studie PARAGON‑HF sledovala léčbu kombinací sakubitril/valsartan u nemocných se srdečním selháním se zachovanou ejekční frakcí (heart failure with preserved ejection fraction, HFpEF). Pacienti byli randomizováni k léčbě sakubitril/valsartanem, nebo valsartanem samotným. Terapie sakubitril/valsartanem nevedla u nemocných s chronickým HFpEF k signifikantnímu poklesu rizika hospitalizací pro srdeční selhání a ke snížení kardiovaskulární mortality, avšak trend k vyšší klinické účinnosti ve srovnání se samotným valsartanem se zdá být nepochybný.
PARAGON‑HF study evaluated the treatment with sacubitril/valsartan in patients with heart failure with preserved ejection fraction (HFpEF). Patients were randomised to treatment with sacubitril/valsartan or valsartan alone. The therapy with sacubitril/valsartan did not lead to significant decrease in risk of hospitalisations for heart failure and decrease in cardiovascular mortality in patients with chronic HfpEF. However, the trend towrds higher clinical efficacy in comparison with valsartan alone is unquestionable.
- Keywords
- sakubitril/valsartan, studie PARAGON-HF,
- MeSH
- Aminobutyrates therapeutic use MeSH
- Antihypertensive Agents therapeutic use MeSH
- Heart Failure, Diastolic drug therapy mortality MeSH
- Drug Combinations MeSH
- Humans MeSH
- Tetrazoles therapeutic use MeSH
- Valsartan therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Randomized Controlled Trial MeSH
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a global public health problem with important regional differences. We investigated these differences in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF), the largest and most inclusive global HFpEF trial. METHODS: We studied differences in clinical characteristics, outcomes, and treatment effects of sacubitril/valsartan in 4796 patients with HFpEF from the PARAGON-HF trial, grouped according to geographic region. RESULTS: Regional differences in patient characteristics and comorbidities were observed: patients from Western Europe were oldest (mean 75±7 years) with the highest prevalence of atrial fibrillation/flutter (36%); Central/Eastern European patients were youngest (mean 71±8 years) with the highest prevalence of coronary artery disease (50%); North American patients had the highest prevalence of obesity (65%) and diabetes (49%); Latin American patients were younger (73±9 years) and had a high prevalence of obesity (53%); and Asia-Pacific patients had a high prevalence of diabetes (44%), despite a low prevalence of obesity (26%). Rates of the primary composite end point of total hospitalizations for HF and death from cardiovascular causes were lower in patients from Central Europe (9 per 100 patient-years) and highest in patients from North America (28 per 100 patient-years), which was primarily driven by a greater number of total hospitalizations for HF. The effect of treatment with sacubitril-valsartan was not modified by region (interaction P>0.05). CONCLUSIONS: Among patients with HFpEF recruited worldwide in PARAGON-HF, there were important regional differences in clinical characteristics and outcomes, which may have implications for the design of future clinical trials. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.
- MeSH
- Aminobutyrates therapeutic use MeSH
- Angiotensin Receptor Antagonists therapeutic use MeSH
- Biphenyl Compounds therapeutic use MeSH
- Global Health * MeSH
- Double-Blind Method MeSH
- Drug Combinations MeSH
- Hospitalization statistics & numerical data MeSH
- Quality of Life MeSH
- Humans MeSH
- Neprilysin therapeutic use MeSH
- Risk Factors MeSH
- Aged MeSH
- Heart Failure drug therapy mortality physiopathology MeSH
- Stroke Volume * MeSH
- Valsartan therapeutic use MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. METHODS AND RESULTS: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. CONCLUSIONS: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.
- MeSH
- Mineralocorticoid Receptor Antagonists therapeutic use MeSH
- Angiotensin Receptor Antagonists therapeutic use MeSH
- Adrenergic beta-Antagonists therapeutic use MeSH
- Angiotensin II Type 1 Receptor Blockers therapeutic use MeSH
- Ventricular Function, Left drug effects MeSH
- Angiotensin-Converting Enzyme Inhibitors therapeutic use MeSH
- Clinical Trials as Topic MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Heart Failure drug therapy physiopathology MeSH
- Stroke Volume drug effects MeSH
- Valsartan therapeutic use MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Keywords
- PARAGON, sakubitril,
- MeSH
- Aminobutyrates administration & dosage MeSH
- Angiotensin Receptor Antagonists * administration & dosage MeSH
- Antihypertensive Agents administration & dosage MeSH
- Hospitalization statistics & numerical data MeSH
- Cardiovascular Diseases epidemiology mortality MeSH
- Drug Therapy, Combination methods MeSH
- Humans MeSH
- Kidney Diseases epidemiology MeSH
- Statistics as Topic MeSH
- Tetrazoles administration & dosage MeSH
- Valsartan administration & dosage MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Randomized Controlled Trial MeSH
Nový duální antagonista receptorů pro angiotenzin II (ARB) a neprilysinu (NEP) je dnes již schválen a registrován pro léčbu srdečního selhání. Filozofie léčby vychází s příznivých klinických účinků ARB a experimentálních účinků inhibice rozpadů vazoaktivních natriuretických peptidů. První velká klinická studie v léčbě hypertenze ukázala dostatečný hypotenzní účinek LCZ 696 a u srdečního selhání se zachovalou ejekční frakcí LCZ 696 významně snížil koncentraci NT-pro BNP. Klinická studie PARADIGM-HF u nemocných se sníženou ejekční frakcí a vysokými hodnotami natriuretických peptidů byla předčasně ukončena pro příznivý vliv LCZ696 ve srovnání s enalaprilem. Kardiovaskulární mortalita byla snížena o 20 %, první hospitalizace pro srdeční selhání o 21 %. V současnosti probíhá studie PARAGON-HF u srdečního selhání se zachovalou ejekční frakcí.
New dual antagonist of angiotensin II receptor (ARB) and neprilysin (NEP) is already aproved and registered for the treatment ofheart failure. The effect is due to favorite clinical effects of ARB and experimental effects of the inhibition of degradation of natriureticpeptides. The first big clinical trial in hypertension has shown a huge hypotensive effect and a clinical trial in heart failurewith preserved ejection fraction a decrease of NT-proBNP. Clinical trial PARADIGM-HF in patients with decreased ejection fractionand high natriuretric peptides was preliminary stopped due to a clear clinical benefit of LCZ696 if compared with enalapril. Thecardiovascular mortality was decreased by 20 %, the first hospitalisation for heart failure by 21 %. The PARAGON-HF clinical trialin patients with preserved ejection fraction is just running.
- MeSH
- Antihypertensive Agents pharmacology therapeutic use MeSH
- Angiotensin II Type 1 Receptor Blockers administration & dosage MeSH
- Enalapril administration & dosage MeSH
- Hypertension ethnology MeSH
- Angiotensin-Converting Enzyme Inhibitors administration & dosage MeSH
- Humans MeSH
- Natriuretic Peptides blood standards MeSH
- Neprilysin drug effects MeSH
- Primary Prevention MeSH
- Prospective Studies MeSH
- Randomized Controlled Trials as Topic MeSH
- Renin-Angiotensin System drug effects MeSH
- Secondary Prevention MeSH
- Heart Failure * diagnosis drug therapy mortality MeSH
- Check Tag
- Humans MeSH
Nový duální antagonista receptorů pro angiotenzin II (ARB) a neprilysinu s generickým názvem sacubitril-valsartan (dříve LZC 696 nebo také angiotenzin receptor blocker and neprilysin inhibitor – ARNI) byl jak experimentálně, tak klinicky ověřován pro hypertenzi a léčbu srdečního selhání. Filozofie léčby vychází z příznivých klinických účinků ARB a experimentálních účinků inhibice rozpadů vazodilatačních natriuretických peptidů. První klinická studie PARAMOUNT s LCZ696 v léčbě srdečního selhání se zachovalou ejekční frakcí prokázala významné snížení koncentrace NT-pro BNP. Další významná klinická studie PARADIGM-HF byla předčasně ukončena pro jasně příznivý vliv LCZ696 ve srovnání s enalaprilem, kdy o 20 % pokleslo riziko úmrtí a dalších kardiovaskulárních ukazatelů. V současnosti probíhá studie PARAGON-HF u srdečního selhání se zachovalou ejekční frakcí.
New dual antagonist for receptors for AII (ARB) and neprilysin, generic name sacubitril-valsartan (LZC696) or angiotensin receptor blocker and neprilysin inhibitor (ARNI), was experimentally and clinically tested for the treatment of hypertension and heart failure. The treatment draws on the positive clinical effects of ARB and experimentally proven effects of the inhibition of vasodilatating natriuretic peptide decomposition. In the PARAMOUNT study in patients with heart failure with preserved ejection fraction (HFpEF), LCZ696 reduced NT-pro BNP concentration to a greater extent than did valsartan at 12 weeks and was well tolerated. The PARADIGM-HF study was discontinued early, showing that LCZ696 was clearly superior to enalapril, with a 20% reduction of the risk of death and hospitalisation for heart failure. PARAGON-HF will assess the effect of LCZ696 on the outcomes concerning cardiovascular death and total – first and recurrent – HF hospitalisations in patients with HFpEF.
- MeSH
- Aminobutyrates therapeutic use MeSH
- Angiotensin Receptor Antagonists * therapeutic use MeSH
- Enalapril therapeutic use MeSH
- Drug Combinations * MeSH
- Humans MeSH
- Multicenter Studies as Topic MeSH
- Natriuretic Peptide, Brain blood MeSH
- Neprilysin antagonists & inhibitors MeSH
- Randomized Controlled Trials as Topic MeSH
- Heart Failure * drug therapy MeSH
- Tetrazoles therapeutic use MeSH
- Valsartan therapeutic use MeSH
- Check Tag
- Humans MeSH
Duální antagonista receptorů AT1 pro angiotenzin II (ARB) a neprilysinu s generickým názvem sacubitril‑valsartan (dříve LCZ696 nebo také angiotenzin receptor blocker and neprilysin inhibitor – ARNI) byl klinicky ověřován pro léčbu hypertenze a srdečního selhání. Mechanismus účinku je v blokádě receptorů AT1 valsartanem v kombinaci s blokádou rozpadů vazodilatačních natriuretických peptidů a tím intenzifikované vazodilatace. První klinická studie PARAMOUNT s LCZ696 v léčbě srdečního selhání se zachovalou ejekční frakcí prokázala významné snížení koncentrace NT‑proBNP. Klinická studie PARADIGM‑HF u nemocných se sníženou ejekční frakcí a vysokými hodnotami natriuretických peptidů byla předčasně ukončena pro příznivý vliv LCZ696 ve srovnání s enalaprilem jak na mortalitu, tak na hospitalizace. Kardiovaskulární mortalita byla snížena o 20 %, první hospitalizace pro srdeční selhání o 21 %. Probíhá studie PARAGON‑HF u srdečního selhání se zachovalou ejekční frakcí.
Dual antagonist of AT1 receptors for angiotensin II (ARB) and neprilysin, generic name sacubitril valsartan (formaly LCZ 696 or angiotensin receptor blocker and neprilysin inhibitor – ARNI) was clinicaly tested in the treatmet of hypertension and heart failure. The mechanism of action is in the blockade of AT1 receptros by valsartan in combination with decreased degradation of natriuretic peptides with increased vasodilatation. The first clinical trial PARAMOUNT with LCZ696 in the treatment of Heart failure patients with preserved ejection fraction has whown significant decrea-se of NT-proBNP concentrations. Clinical trial PARADIGM-HF in patients with decreased ejection fraction and high natriuretic peptides levels was fi-nished prematuraly for a positive effect of LCZ696 both on mortality and morbidity if compared with enalapril. Cardiovascular mortality was decreased by 20%, first hospitalisation for Heart failure by 21%. The PARAGON-HF study is testing the effect of sacubitril valsartan in patients with preserved ejection fraction.
- Keywords
- sacubitril-valsartan,
- MeSH
- Aminobutyrates administration & dosage pharmacology MeSH
- Antihypertensive Agents MeSH
- Angiotensin II Type 1 Receptor Blockers MeSH
- Drug Combinations MeSH
- Humans MeSH
- Heart Failure drug therapy MeSH
- Valsartan administration & dosage pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
