Zoltán Kiss

Periodic limb movements in sleep are associated with stroke and cardiovascular risk factors in patients with renal failure

Periodic limb movements in sleep (PLMS) is prevalent among dialysed patients and is associated with increased risk of mortality. Our study aimed to determine the prevalence of this disease in a sample of transplanted and waiting‐list haemodialysed patients. One hundred transplanted and 50 waiting‐list patients underwent polysomnography. Moderate and severe diseases were defined as periodic limb movements in sleep index (PLMSI) higher than 15 and 25 events h−1, respectively. The 10‐year coronary heart disease risk was estimated for all patients using the Framingham Score. Moreover, the 10‐year estimated risk of stroke was calculated according to the modified version of the Framingham Stroke Risk Profile. PLMS was present in 27% of the transplanted and 42% of the waiting‐list group (P = 0.094); the proportion of severe disease was twice as high in waiting‐list versus transplanted patients (32 versus 16%, P = 0.024). Patients with severe disease had a higher 10‐year estimated risk of stroke in the transplanted group [10 (7–17) versus 5 (4–10); P = 0.002] and a higher 10‐year coronary heart disease risk in both the transplanted [18 (8–22) versus 7 (4–14); P = 0.002], and the waiting‐list groups [11 (5–18) versus 4 (1–9); P = 0.032]. In multivariable linear regression models the PLMSI was associated independently with the Framingham cardiovascular and cerebrovascular scores after adjusting for important covariables. Higher PLMSI is an independent predictor of higher cardiovascular and cerebrovascular risk score in patients with chronic kidney disease. Severe PLMS is less frequent in kidney transplant recipients compared to waiting‐list dialysis patients.

Discovery and basic pharmacology of erythropoiesis-stimulating agents (ESAs), including the hyperglycosylated ESA, darbepoetin alfa: an update of the rationale and clinical impact

Cloning of the human erythropoietin (EPO) gene and development of the first recombinant human erythropoietin (rHuEPO) drug were truly breakthroughs. This allowed a deeper understanding of the structure and pharmacology of rHuEpo, which in turn inspired the discovery and development of additional erythropoiesis-stimulating agents (ESAs). In vivo specific activity and serum half-life of rHuEPO are influenced by the amount and structure of the attached carbohydrate. Increased numbers of sialic acids on carbohydrate attached to rHuEPO correlated with a relative increase in in-vivo-specific activity and increased serum half-life. The effect of increasing the number of sialic-acid-containing carbohydrates on in-vivo-specific activity was explored. Initial research focused on solving the problem of how the protein backbone could be engineered so a cell would add more carbohydrate to it. Additional work resulted in darbepoetin alfa, a longer-acting molecule with two additional carbohydrate chains.

Persistence of initial oral antidiabetic treatment in patients with type 2 diabetes mellitus.

Summary Background Adequate persistence of oral antidiabetic treatment is highly important to achieve proper glycemic control in patients with type 2 diabetes. The aim of this study was to evaluate the persistence of initial treatment with metformin and/or sulphonylureas in patients with type 2 diabetes. Material/Methods The study was performed among diabetic patients (n=256,384) who were with newly prescribed oral antidiabetic drugs (metformin and/or sulphonylureas) between 2007 and 2009. For making comparison, patients with newly prescribed statin or clopidogrel therapy (with and without percutaneous coronary intervention) were investigated. The database of the Hungarian National Health Insurance Fund Administration was used. Results The 1-year persistence of initial treatment with metformin, sulphonylureas or metformin/sulphonylurea combination was 47.7%, 45.4% and 55.8%, respectively, which was significantly better than the persistence of statin therapy (26.3%) but worse than that of clopidogrel therapy in patients undergoing coronary intervention (73.2%). Within the sulphonylurea group there was a tendency of better persistence of treatment with the “modified-release” tablets at 12 months compared to the conventional sulphonylureas (47.8 vs. 42.2%). The persistence of therapy using metformin 1000 mg – 60 tablets was significantly better (60.4%) at 12 months than that of other forms of metformin therapy with lower doses and smaller boxes (with fewer tablets) analyzed together (47.7%). Conclusions The persistence of initial treatment with metformin and/or sulphonylureas is far from optimal. Better diabetic care and continuous patient education should be encouraged to achieve higher persistence of oral antidiabetic treatment in patients with type 2 diabetes.

Persistence with statin therapy in Hungary

Introduction Persistence with lipid-lowering drug therapy by cardiovascular patients in Hungary has not been studied previously. This study was designed to determine the rate with which Hungarian patients with hyperlipidemia persist in taking lipid-lowering agents, and to compare this with rates reported from other countries. Material and methods This was a retrospective study that utilized data from the Institutional Database of the National Health Insurance Fund to analyze persistence rates with statins and ezetimibe. The study included data for patients who started lipid-lowering therapy between January 1, 2007, and March 31, 2009. Variables included type of lipid-lowering therapy, year of therapy start, and patient age. Main outcome measures were medians of persistence in months, percentages of patients persisting in therapy for 6 and 12 months, and Kaplan-Meier persistence plots. Results The percentage of patients who persisted with overall statin therapy was 46% after 1 month, 40.3% after 2 months, 27% after 6 months, and 20.1% after 12 months. Persistence was slightly greater for statin therapy started during 2008 than during 2007. Older patients were more persistent with therapy than younger patients. Persistence with the combination of ezetimibe-statin therapy was greater than with statin or ezetimibe monotherapy. Conclusions Persistence with statin therapy by patients in Hungary was low compared with other countries. Low persistence may have negated potential clinical benefits of long-term statin therapy.

How can we further improve the LDL-cholesterol target level achievement rate based on the Hungarian MULTI GAP 2011 study results and considering the new European dyslipidemia guidelines?

Introduction Despite the continuous improvement of the quality of lipid lowering therapy the achievement of target values is still not satisfactory, mainly in the very high cardiovascular risk category patients, where the goal of low density lipoprotein cholesterol (LDL-C) is 1.80 mmol/l. Material and methods The trends in lipid lowering treatment of 17420 patients from different studies conducted between 2004 and 2010 were compared to that of 1626 patients of MULTI GAP (MULTI Goal Attainment Problem) 2011 treated by general practitioners (GPs) and specialists. Results In MULTI GAP 2011 the mean LDL-C level ± SD) of patients treated by GPs was found to be 2.87 ±1.01 mmol/l, the target value of 2.50 was achieved by 40% of them, in the specialists’ patients the mean LDL-C level proved to be 2.77 ±1.10 mmol/l and the achievement rate was 45%. In the 2.50 mmol/l achievement rate of GPs’ patients a satisfactory improvement was observed in the studied years, but the 1.80 mmol/l LDL-C goal in 2011 was attained only in 11% of very high risk cases. There was a linear correlation between the patient compliance estimated by the physicians and the LDL-C achievement rate. Conclusions As the number of very high risk category patients has been increased according to the new European dyslipidemia guidelines, growing attention needs to be placed on attainment of the 1.80 mmol/l LDL-C level. Based on the results of the MULTI GAP studies, improving patients’ adherence and the continuous training of physicians are necessary.

An attempt to make lipid-lowering therapy more effective in Hungary. The results of MULTI GAP 2010 and the PLUS Program.

Introduction The primary goal of lipid-lowering therapy is the attainment of low-density lipoprotein cholesterol (LDL-C) target levels. Material and methods The MULTI GAP (MULTI Goal Attainment Problem) 2010 is a part of surveys started a few years ago, in which the lipid results of 1540 patients treated by general practitioners (GPs) and specialists were measured. The data were compared to the results of similar studies involving 15,580 patients between 2004 and 2009. Results In 2010 the mean LDL-C level (± SD) of patients treated by GPs was found to be 3.01 ±1.0 mmol/l. The target of 2.50 mmol/l was achieved by 32%, with a mean LDL-C level of 2.84 ±1.0 mmol/l and an achievement rate of 39% in patients treated by specialists. The results of comparisons starting from 2004 showed a marked improvement every year in the beginning, but in the last 3 years stagnation was observed. In 2010 in addition to the MULTI GAP main study, a group of physicians took part in special training called the Plus Program. As a result of this, the LDL-C level was 0.18 mmol/l lower in 114 of the GPs’ patients (p = 0.088) and 0.27 mmol/l (p < 0.0001) lower in 313 of the specialists’ patients, with a significantly better, 42% (p = 0.045) and 50% (p = 0.001), goal attainment rate, respectively. Conclusions The 2010 MULTI GAP study shows that the quality of lipid-lowering therapy in Hungary seems to be in stagnation. The results of the PLUS Program suggest that continuous training of doctors is the key to further improvement.

A change of attitude in lipidology, achievement of target levels. What comes next?

One of the greatest challenges of cardiovascular prevention is to minimize the risk of cardiovascular events through the achievement of target lipid levels. Its importance is suggested by the comprehensive meta-analyses of large scale clinical trials and the therapeutic guidelines determining everyday clinical practice. The attainment of target levels is often emphasized, nevertheless, there is a gap between theory and practice. The authors compare the goal attainment rate based on Hungarian medical literature and their own data, and analyze the possibilities of further improvement. The CEL Program evaluated the achievement rate of target total cholesterol levels in more than 10 000 patients of general practitioners in 2004, 2005 and 2006, and the ratio increased from 12% to 30% within 3 years. According to the results of the Hungarian REALITY study the rate of patients achieving the target total cholesterol levels was 21% in 2004, and it increased to 27% during a 3-year period. To this very low improving rate also belongs the fact that in 2007, when only one fourth of patients were on target levels, 87% of general practitioners and 56% of specialists reconciled themselves to it and did not propose any modification in the therapy of patients not achieving the target levels. The surveys conducted at the department of internal medicine with cardiological profile of the county hospital in Gyula proved a considerable increase in the last 7 years in the administration of drugs improving the life expectancy of cardiovascular patients (aspirin, beta-blockers, ACE-inhibitors and statins) due to the widespread application of clinical guidelines and the special attention; nowadays the administration rate is above 90% in all four groups. Nevertheless, the rate of patients achieving the LDL-cholesterol goals was 37% in the high risk and 18% in the very high risk groups in December 2007 and January 2008. The fact that in the latter group only 21% of patients received combination therapy indicates that improving this ratio may be the next step. A greater emphasis should be placed on the achievement of target levels and regular revision of applied medical therapy, particularly in the high and very high risk patients as these groups can benefit the most from it.

Persistence to Treatment with Novel Antidiabetic Drugs (Dipeptidyl Peptidase-4 Inhibitors, Sodium-Glucose Co-Transporter-2 Inhibitors, and Glucagon-Like Peptide-1 Receptor Agonists) in People with Type 2 Diabetes: A Nationwide Cohort Study

IntroductionAdequate persistence to antidiabetic treatment is highly important to achieve proper glycemic control. In this study we evaluate the persistence to treatment with dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists in a nationwide cohort of patients with type 2 diabetes.MethodsUsing a central database in Hungary, we analyzed the persistence to the treatment with dipeptidyl peptidase-4 inhibitors (n = 59,900), sodium-glucose co-transporter-2 inhibitors (n = 26,052), and glucagon-like peptide-1 receptor agonists (n = 17,332) at treatment intensification between 2014 and 2016. We also compared the persistence of dipeptidyl peptidase-4 inhibitors (n = 9163) and sodium-glucose co-transporter-2 inhibitors (n = 1257) in initial therapy to that of metformin (n = 79,305) or sulfonylureas (n = 29,057). The rates of persistence to treatment and risk of non-persistence are reported.ResultsThe persistence rates of dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists at treatment intensification were 69.6%, 67.8%, and 66.3% at year 1 which decreased to 57.3%, 56.8%, and 52.1% by year 2, respectively. The risk of non-persistence was higher by 6.6% (95% CI 3.6–9.6) for sodium-glucose co-transporter-2 inhibitors and by 8.3% (95% CI 5.0–11.5) for glucagon-like peptide-1 receptor agonists as compared to dipeptidyl peptidase-4 inhibitors. Novel oral antidiabetic drugs in fixed versus free add-on combinations with metformin had higher persistence. The persistence to treatment with novel oral antidiabetic drugs in initial therapy was better (dipeptidyl peptidase-4 inhibitors, 59.6% and 47.6%; sodium-glucose co-transporter-2 inhibitors, 61.9% and 47.0%) than that of initial monotherapy with metformin (47.0% and 39.1%) or sulfonylureas (52.4% and 41.8%) at years 1 and 2, respectively.ConclusionAnalysis of persistence of treatment with novel glucose-lowering medications revealed differences between drug classes, favoring dipeptidyl peptidase-4 inhibitors vs. sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Persistence data of novel antihyperglycemic agents may be useful for guiding the decision at initiation of antidiabetic treatment.FundingHungarian Diabetes Association.Plain Language SummaryPlain language summary available for this article.

A 2-es típusú diabetes antihyperglykaemiás kezelésének alakulása Magyarországon 2001–2014 között – az Országos Egészségbiztosítási Pénztár adatbázis-elemzésének eredményei

In the last couple of years, significant developments in antidiabetic treatment have influenced the pharmacological treatment of type 2 diabetes mellitus (T2DM). The aim of this study was to analyze the changes in prescribing patterns of glucose-lowering drugs for T2DM patients in Hungary between 2001 and 2014. The number of patients with newly diagnosed T2DM decreased from 75,700 (2001) to 33,700 (2014), while prevalent T2DM cases continuously increased and plateaued in 2014 with a number of registered patients of 727,000. Sulfonylurea-monotherapy decreased from 64% to 35% while metformin-monotherapy increased from 19% to 42% in this period. The most frequently used drug at first treatment initiation was metformin (66%) and sulfonylurea (16%) as monotherapy in 2014. DPP4-inhibitors were newly administered in 20,362 cases while GLP1-mimetics were newly used by 4,996 patients in 2014. Five years later after initiating sulfonylurea therapy between 2010 and 2014, metformin was more frequently used as second drug (39%) than sulfonylurea in patients with previous metformin treatment (22.9%). The prescribing patterns of glucose-lowering drugs have changed over time in accordance with new guidelines. Further changes in prescribing habits can be expected in the near future. Orv Hetil. 2017; 158(20): 770-778.Absztrakt: A 2-es tipusu diabetes mellitus (2TDM) kezelese teren uj antidiabetikumok valtak elerhetőkke. A vizsgalat celja az volt, hogy felmerjuk a 2TDM gyogyszeres kezelesi szokasainak valtozasat 2001–2014 kozott. A vizsgalatot az Orszagos Egeszsegugyi Penztar adatbazisanak elemzesevel vegeztuk. Az ujonnan felismert 2TDM eves előfordulasa 75 700 esetről 33 700 esetre csokkent. A 2TDM prevalenciaja fokozatosan emelkedett, majd kesőbb stagnalo jellegűve valt (2014-ben 727 000 eset). A szulfonilurea-monoterapia gyakorisaga 64%-rol 35%-ra csokkent, a metformin-monoterapia gyakorisaga 19%-rol 42%-ra nőtt. Gyogyszeres kezeles szuksegessege eseten 2014-ben a metformin volt a leggyakrabban valasztott első keszitmeny (66%), ezt kovette a szulfonilureak valasztasa (16%). Első alkalommal DPP-4-gatlot 20 362 beteg, GLP-1-mimetikumot pedig 4996 beteg kapott 2014-ben. Ot evvel a szulfonilureakezeles megkezdese utan (2010–2014 kozott) metforminra gyakrabban volt szukseg masodik szerkent (39,0%), mint a szulfonilureara...

Szívinfarktust túlélt betegek terápiahűsége a másodlagos megelőzés szempontjából fontos gyógyszeres kezelésekhez

Absztrakt: Bevezetes es celkitűzes: A szerzők szivinfarktust tulelt betegek terapiahűseget (adherencia) vizsgaltak a masodlagos prevencio szempontjabol szoba jovő gyogyszerek eseten. Modszer: A Nemzeti Szivinfarktus Regiszterben 2013. januar 1. es 2014. december 31. kozott regisztralt szivinfarktusos betegek kozul azok kerultek a vizsgalt betegcsoportba, akik a heveny myocardialis infarctust tuleltek es a korhazi kezelest kovetően 180 napig nem volt ujabb esemenyuk. Ezen kriteriumoknak 14 843 beteg felelt meg, akiket egy evig kovettek. Vizsgaltak a sztatin, a beta-blokkolo, a thrombocytaaggregacio-gatlo, valamint az angiotenzinkonvertalo enzim/angiotenzinreceptor-blokkolo kezeleshez valo adherenciat. A „gyogyszerszedest” az Egeszsegbiztosito Penztar gyogyszer-finanszirozasi adatbazisa alapjan kovettek. Az adherenciat az indexesemenytől a vegpontig (vagy a cenzoralasig) eltelt idő es a kivaltott keszitmenyekkel valo ellatottsagi idő hanyadosakent hataroztak meg. Vegpontnak a halalt vagy az ujabb infarktus ...