PURPOSE OF REVIEW: An evidence for lipid lowering therapy in heart failure is briefly summarized in this review. RECENT FINDINGS: Heart failure therapy is based on recent guidelines for diagnosis and treatment of acute and chronic heart failure. The question of the importance of hypolipidemic treatment in heart failure remains insufficiently answered. We still rely only on results of two randomized controlled trials that did not show significant benefit of statins on mortality in these patients. In contrast, some meta-analysis, prospective or retrospective cohorts, found some positive effects of this therapy. Recently, the role of inflammation and the possibility of its influence by hypolipidemics have been discussed. PCSK9 inhibitors, new lipid lowering drugs, are very effective in LDL-cholesterol lowering and atherosclerotic cardiovascular diseases prevention. The role of PCSK9 inhibitors in heart failure treatment is investigated. Based on current knowledge, hypolipidemics are not generally recommended in heart failure therapy, unless there is another indication for their use.
- Klíčová slova
- alirocumab,
- MeSH
- dospělí MeSH
- hyperlipoproteinemie typ II * farmakoterapie MeSH
- lidé MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 farmakologie terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Lipoprotein apheresis (LA) is a therapeutic option for patients with severe hypercholesterolemia who have persistently elevated LDL-C levels despite attempts at drug therapy. MicroRNAs (miRNAs), important posttranscriptional gene regulators, are involved in the pathogenesis of atherosclerosis. Our study aimed to monitor the dynamics of twenty preselected circulating miRNAs in patients under long-term apheresis treatment. Plasma samples from 12 FH patients (men = 50%, age = 55.3 ± 12.2 years; mean LA overall treatment time = 13.1 ± 7.8 years) were collected before each apheresis therapy every sixth month over the course of four years of treatment. Eight complete follow-up (FU) samples were measured in each patient. Dynamic changes in the relative quantity of 6 miRNAs (miR-92a, miR-21, miR-126, miR-122, miR-26a, and miR-185; all p < 0.04) during FU were identified. Overall apheresis treatment time influenced circulating miR-146a levels (p < 0.04). In LDLR mutation homozygotes (N = 5), compared to heterozygotes (N = 7), we found higher plasma levels of miR-181, miR-126, miR-155, and miR-92a (all p < 0.03). Treatment with PCSK9 inhibitors (N = 6) affected the plasma levels of 7 miRNAs (miR-126, miR-122, miR-26a, miR-155, miR-125a, miR-92a, and miR-27a; all p < 0.04). Long-term monitoring has shown that LA in patients with severe familial hypercholesterolemia influences plasma circulating miRNAs involved in endothelial dysfunction, cholesterol homeostasis, inflammation, and plaque development. The longer the treatment using LA, the better the miRNA milieu depicting the potential cardiovascular risk.
- MeSH
- cirkulující mikroRNA * genetika MeSH
- dospělí MeSH
- hyperlipoproteinemie typ II * genetika terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 genetika MeSH
- senioři MeSH
- separace krevních složek * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Elevated low-density lipoprotein (LDL) cholesterol levels lead to atherosclerosis and platelet hyperaggregability, both of which are known culprits of arterial thrombosis. Normalization of LDL cholesterol in familial hypercholesterolemia (FH) is not an easy task and frequently requires specific treatment, such as regularly performed lipid apheresis and/or novel drugs such as proprotein convertase subtilisin kexin 9 monoclonal antibodies (PCSK9Ab). Moreover, a high resistance rate to the first-line antiplatelet drug acetylsalicylic acid (ASA) stimulated research of novel antiplatelet drugs. 4-methylcatechol (4-MC), a known metabolite of several dietary flavonoids, may be a suitable candidate. The aim of this study was to analyse the antiplatelet effect of 4-MC in FH patients and to compare its impact on two FH treatment modalities via whole-blood impedance aggregometry. When compared to age-matched, generally healthy controls, the antiplatelet effect of 4-MC against collagen-induced aggregation was higher in FH patients. Apheresis itself improved the effect of 4-MC on platelet aggregation and blood from patients treated with this procedure and pretreated with 4-MC had lower platelet aggregability when compared to those solely treated with PCKS9Ab. Although this study had some inherent limitations, e.g., a low number of patients and possible impact of administered drugs, it confirmed the suitability of 4-MC as a promising antiplatelet agent and also demonstrated the effect of 4-MC in patients with a genetic metabolic disease for the first time.
- MeSH
- hyperlipoproteinemie typ II * farmakoterapie MeSH
- LDL-cholesterol MeSH
- lidé MeSH
- monoklonální protilátky farmakologie terapeutické užití MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 MeSH
- proproteinkonvertasy terapeutické užití MeSH
- separace krevních složek * metody MeSH
- subtilisin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cíle: Hodnocení dlouhodobého vlivu léčby rheoferézou na suchou formu věkem podmíněné makuární degenerace. Materiál a metody: Do hodnocení jsme zařadili 65 pacientů a do kontrolní skupiny 55 pacientů s minimální dobou sledování 60 měsíců. Základní léčba se skládala z 8 procedur rheoferézy, přídatná léčba (booster therapy) ze 2 rheoferéz za 1,5-2 roky po základní léčbě. Hodnotili jsme změny nejlépe korigované zrakové ostrosti, anatomických poměrů a elektrické aktivity sítnice, hematologické, biochemické a imunologické parametry. Výsledky: Léčba rheoferézou významně přispěla: 1) Ke stabilizaci nejlépe korigované zrakové ostrosti léčených pacientů, která se nejprve nevýznamně zvyšovala do 2 let sledování a následně jen mírně klesala. Naproti tomu v kontrolní skupině se zraková ostrost snižovala, do 4 let nevýznamně, poté již statisticky významně. 2) Ke zlepšení morfologického nálezu u 62,4 % léčených pacientů v porovnání se 7,5 % kontrol, naproti tomu k progresi onemocnění do 3. stadia (vlhká forma onemocnění nebo geografická atrofie) s významným poklesem zrakových funkcí došlo jen u 7,1 % léčených pacientů oproti 37,0 % kontrol. 3) K regresi, dokonce i k přiložení drúzového odchlípení retinálního pigmentového epitelu (DPED). Ke zmenšení plochy DPED u 80,4 % léčených pacientů, naproti tomu ke zvětšení plochy DPED u 47,1 % kontrol a rozvoji nového DPED jen u 2 očí léčených pacientů oproti 16 očím kontrol. 4) K udržení integrity vrstvy elipsoidů ve fovee u 68,2 % léčených pacientů, naproti tomu defektní elipsoidní vrstvu ve fovee jsme zaznamenali u 66,6 % kontrol. 5) Ke stabilizaci aktivity gangliových buněk, čípkového systému a aktivity centrální oblasti sítnice s excentricitou mezi 1,8° a 30° u léčených pacientů v porovnání s její alterací v kontrolní skupině projevující se zejména od 3,5 let sledování. 6) K statisticky významnému zlepšení rheologických ukazatelů, a tím ke zvýšení průtoku v mikrocirkulaci a pozitivnímu ovlivnění metabolizmu v sítnici. K pozitivnímu vlivu na klasickou, alternativní i lektinovou cestu aktivace komplementu, snížení hladiny PCSK9 (proprotein konvertáza subticilin kexin 9), a tím i hladiny LDL-cholesterolu a 7) Přídatná léčba 2 procedurami RHF (tzv. „booster therapy“) se zdá být bezpečnou a vhodnou metodou prodloužení fáze stabilizace, či dokonce zlepšení zrakové ostrosti, anatomického a funkčního nálezu. Závěr: Prokázali jsme pozitivní změny anatomických, funkčních i humorálních ukazatelů při léčbě VPMD rheoferézou. Jejich korelace skýtá reálnou možnost ohrožené nemocné vytipovat a řídit individualizovanou intenzitu rheoterapie. Metodika je účinná a bezpečná s nízkým procentem nezávažných vedlejších účinků.
Purpose: Evaluation of the long-term effect of rheopheresis treatment of dry form of age-related macular degeneration (AMD). Materials and Methods: The treatment group consisted of 65 patients and 55 patients in the control group, with a minimum follow-up period of 60 months. The basic treatment consisted of 8 rheopheresis procedures, and the additional treatment (booster therapy) of 2 rheopheresis procedures 1.5–2 years after the basic treatment. We evaluated changes in best corrected visual acuity, anatomical effect, electrical activity of the retina, haematological, biochemical and immunological parameters. Results: Rheopheresis treatment contributed significantly: 1) to stabilisation of best corrected visual acuity of the treated patients, which initially showed an insignificant increased during the 2-years follow-up period, and then slightly decreased. By contrast, visual acuity decreased in the control group, to an insignificant degree up to 4 years, then statistically significantly. 2) to an improvement of the morphological findings in 62.4% of treated patients compared to 7.5% in the control group, while disease progression to stage 3 (neovascular form of the disease or geographic atrophy) with a significant decrease of visual acuity occurred in only 7.1% of treated patients, versus 37.0% in the control group. 3) to regression, even to the attachment of drusenoid pigment epithelial detachment (DPED). To a reduction of the area of DPED in 80.4% of treated patients, in contrast with an steaincrease in the area of DPED in 47.1% of patients in the control group, and the development of new DPED in only 2 eyes of treated patients compared with 16 eyes of patients in the control group. 4) to a preservation of the integrity of the ellipsoid layer in the fovea in 68.2% of the treated patients, while by contrast we found a damaged ellipsoid layer in the fovea in 66.6% of the control patients. 5) to a stabilisation of the activity of ganglion cells, the pineal system and the activity of the central area of the retina, with eccentricity between 1.8° and 30° in the treated patients, compared to alteration in the control group manifested mainly after 3.5 years of the follow-up period. 6) to a statistically significant improvement in rheological parameters, thereby increasing flow in microcirculation and positively influencing the metabolism in the retina. Also to a positive effect on the classical, alternative and lectin pathway of complement activation, a reduction in the level of proprotein convertase subtilisin kexin 9 (PCSK9), and thus also the level of LDLcholesterol, and 7) Additional treatment with 2 RHF procedures (so-called "booster therapy") seems to be a safe and suitable method of prolonging the stabilisation phase, or even improving visual acuity, anatomical and functional findings. Conclusion: We demonstrated positive changes in anatomical, functional and humoral parameters upon rheopheresis treatment of AMD. Their correlation provides a real possibility to identify patients at risk and to manage an individualised regime of rheopheresis therapy. This method of treatment is effective and safe, with a low percentage of non-serious adverse effects.
- MeSH
- geografická atrofie patologie terapie MeSH
- lidé MeSH
- makulární degenerace patologie terapie MeSH
- plazmaferéza * metody škodlivé účinky MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 terapeutické užití MeSH
- retina patologie MeSH
- separace krevních složek metody škodlivé účinky MeSH
- výzkum MeSH
- Check Tag
- lidé MeSH
OBJECTIVES: The study aims to examine the extent to which the updated ACC/AHA management of blood cholesterol guideline (2018) is implemented in practice and to assess the value of the clinical pharmacist interventions in improving physicians' adherence the guidelines recommendations. METHODS: We utilized in this study an interventional before-after design. The study was conducted on 272 adult patients who visited the study site internal medicine clinics and were candidates for statin therapy based on the 2018 ACC/AHA guidelines for cholesterol management. Adherence to guideline recommendations was measured before and after clinical pharmacists' interventions by calculating the percentage of patients receiving statin therapy as per guideline recommendation, the type and intensity (moderate or high intensity) of statin therapy used, and the need for additional non-statin therapy. RESULTS: Adherence with guideline recommendations was significantly improved from 60.3% to 92.6% (X2 = 79.1, p = 0.0001) after clinical pharmacist interventions. Among patients who were on statin therapy, the percentage of those who were on proper statin intensity increased significantly from 47.6% to 94.4% (X2 = 72.5, p = 0.0001). The combination of statins with non-statin therapies such as ezetimibe and PCSK9 inhibitors increased from 8.5% to 30.6% (X2 = 95, p<0.0001) and from 0.0% to 1.6% (X2 = 6, p = 0.014), respectively. The use of other lipid-lowering agents was diminished from 14.6% to 3.2% (X2 = 19.2, p<0.0001). CONCLUSION: Collaboration between physicians and clinical pharmacists is a crucial strategy to improve patients' treatment and hence, achieve better health outcomes among patients suffering from dyslipidemia.
- MeSH
- cholesterol MeSH
- dodržování směrnic MeSH
- dospělí MeSH
- farmaceuti MeSH
- hypercholesterolemie * farmakoterapie chemicky indukované MeSH
- kardiologie * MeSH
- kardiovaskulární nemoci * MeSH
- lidé MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 MeSH
- statiny * terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Spojené státy americké MeSH
- Klíčová slova
- Inklisiran,
- MeSH
- dyslipidemie * farmakoterapie MeSH
- hodnocení léčiv metody MeSH
- klinická studie jako téma metody MeSH
- LDL-cholesterol účinky léků MeSH
- lidé MeSH
- malá interferující RNA farmakologie terapeutické užití MeSH
- náklady na léky MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 aplikace a dávkování farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- MeSH
- kardiovaskulární nemoci prevence a kontrola MeSH
- LDL-cholesterol * analýza účinky léků MeSH
- lidé MeSH
- malá interferující RNA * aplikace a dávkování farmakologie škodlivé účinky MeSH
- nežádoucí účinky léčiv epidemiologie MeSH
- PCSK9 inhibitory aplikace a dávkování farmakologie škodlivé účinky MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 analýza účinky léků MeSH
- statistika jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- klinické zkoušky, fáze II MeSH
- komentáře MeSH
- práce podpořená grantem MeSH
- souhrny MeSH
Statins are primary drugs in the treatment of hyperlipidemias. This group of drugs is known for its beneficial pleiotropic effects (e.g., reduction of inflammatory state). However, a growing body of evidence suggests its diabetogenic properties. The culpable mechanism is not completely understood and might be related to the damage to pancreatic beta cells. Therefore, we conceived an in vitro study to explore the impact of atorvastatin on pancreatic islet beta cells line (1.1.E7). We evaluated the influence on viability, insulin, low-density lipoprotein (LDL) receptor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression. A significant drop in mRNA for proinsulin and insulin expression was noted. Concurrently, a rise in LDL receptor at the protein level in cells exposed to atorvastatin was noted. Further experiments have shown that exenatide - belonging to glucagon-like peptide 1 (GLP-1) analogs that are used in a treatment of diabetes and known for its weight reducing properties - can alleviate the observed alterations. In this case, the mechanism of action of exenatide was dependent on a protein kinase A pathway. In conclusion, our results support the hypothesis that statin may have diabetogenic properties, which according to our study is related to reduced insulin expression. The concomitant use of GLP-1 receptor agonist seemed to successfully revert insulin expression.
- MeSH
- atorvastatin farmakologie metabolismus MeSH
- beta-buňky * MeSH
- exenatid farmakologie metabolismus MeSH
- inzulin metabolismus MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 metabolismus farmakologie MeSH
- proteinkinasy závislé na cyklickém AMP metabolismus farmakologie MeSH
- receptory LDL metabolismus MeSH
- sekrece inzulinu MeSH
- statiny * farmakologie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
