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Krónikus vesebetegek lipideltéréseinek kezelése

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Az előadások a következő témára: "Krónikus vesebetegek lipideltéréseinek kezelése"— Előadás másolata:

1 Krónikus vesebetegek lipideltéréseinek kezelése
Prof. Dr. Karádi István egyetemi tanár Semmelweis Egyetem III. számú Belgyógyászati Klinika

2 Krónikus vesebetegek lipideltéréseinek kezelése
Karádi István dr. Semmelweis Egyetem III.Sz. Belgyógyászati Klinika

3 Az előadást az MSD támogatta
Az előadást az MSD támogatta. Az itt közölt információk az előadó (eredményeit és) nézeteit tükrözik, melyek eltérhetnek az MSD álláspontjától. A megemlített termékek használatakor az érvényes alkalmazási előírás az irányadó.

4 CKD és CV rizikó CKD stádiumai és lipideltérések LDL csökkentő terápiák eredményei

5 CKD és CV rizikó – Terápiás irányelvek
ESC/EAS Dyslipidaemia Guideline (2011. augusztus) V. Magyar Kardiovaszkuláris Konszenzus Konferencia (2011. november 25.) Európai CV prevenciós ajánlás (2012. május 3.) A krónikus vesebetegek nagy/ igen nagy CV rizikóval rendelkeznek LDL-C célérték <2,5 mmol/l (nagy CV rizikó) <1,8 mmol/l (igen nagy CV rizikó)

6

7 V. Magyar Kardiovaszkuláris Konszenzus Konferencia Kockázatbesorolás

8 V. Magyar Kardiovaszkuláris Konszenzus Konferencia ajánlása - 2011
V. Magyar Kardiovaszkuláris Konszenzus Konferencia ajánlása november 25.

9

10 3.7.2 Chronic kidney disease
There is a quantitative association between decreased GFR and cardiovascular risk: patients with moderately decreased renal function (stage 3, GFR 30–59 mL/min/1.73 m2) have a two- to four-fold increased risk in comparison with persons free of CKD. The risk increases to four- to 10-fold in stage 4 (GFR 15– 29 mL/min/1.73 m2) and to 10- to 50-fold in stage 5 renal failure (end-stage) (GFR ,15 mL/min/ 1.73 m2 or dialysis).

11 CKD és CV rizikó CKD stádiumai és lipideltérések LDL csökkentő terápiák eredményei

12 Kockázati tényezők CKD-ben szenvedő betegeknél
Tradícionális kockázati tényezők Idősebb életkor Férfi nem Hipertónia Magasabb LDL koleszterin szint Alacsonyabb HDL koleszterin szint Cukorbetegség Dohányzás Testmozgás hiánya Menopauza Koronária betegség a családi kórtörténetben Bal kamra hipertrófia Fehér rassz Nem tradícionális kockázati tényezők Tényezők elsősorban vesebetegeknél Anémia Folyadéktúlterhelés Kóros ásványianyag-csere Elektrolit-háztartás felborulása Albuminuria Tényezők az általános populációban Lipoprotein(a) és Apo(a) izoformák és lipoprotein maradékok Homocisztein Oxidatív stress/gyulladás Alultápláltság Trombogén tényezők Alvászavarok Magas szimpatikus tónus Megváltozott nitrogén-oxid/endothelin egyensúly Shastri S et al. Am J Kidney Dis Jul 2. [Epub ahead of print]

13 Összkoleszterinszint az NHANES felmérés résztvevői között (Két CKD stádiumbeosztást használva)
(mmol/l) n=30 528 CKD Stage/ Category 1 CKD Stage/ Category 2 CKD Stage/ Category 3 CKD Stage/ Category 4 No CKD P<0.001 Am J Kidney Dis. 59(3): , 2012

14 Hypercholesterinaemia* prevalenciája a KEEP programban
% n= No CKD CKD Stage 4-5 CKD Stages 1-2 CKD Stage 3 *Hypercholesterinaemia definíciója: TC>5,2 mmol/l vagy lipidcsökkentő terápiában részesül P<0.001 Am J Kidney Dis. 59(3)(S2):S24-S33, 2012

15 Lipidparaméterek változása a CKD súlyosságától függően
Predialysis CKD (Stages 3-4) Nephrotic syndrome (Stages 3-4) Hemodialysis (Stage 5) Peritoneal dialysis (Stage 5) Total Cholesterol1 ↔ or ↑ LDL Cholesterol2 ↔ or ↓ Small dense LDL2 Triglycerides2 HDL Cholesterol2 ↓ or ↔ or ↑ Lipoprotein(a) 2 Lipase activity1 Apolipoprotein B1 Apolipoprotein AI1 1. Kwiterovich O. The Johns Hopkins Textbook of Dyslipidemia. (New York, NY: Wolters Kluwers/Lippincott Williams & Wilkins,2010), 134; adapted from Saland JM, et al. Pediatr Nephrol. 2007;22: and Saland JM, et al. Curr Opin Pediatr. 2002;14: ; 2. Tsimihodimos V et al. Am J Nephrol. 2008;28(6):958–973.

16 Normál lipoprotein metabolizmus
Kwan BCH, Lipoprotein Metabolism and Lipid Management in Chronic Kidney DiseaseJ Am Soc Nephrol 18: 1246–1261, 2007

17 Lipideltérések krónikus vesebetegségben
J R Soc Med 2000, 93:

18 Hypertrigliceridaemia kialakulása krónikus vesebetegségben
Kwan BCH, Lipoprotein Metabolism and Lipid Management in Chronic Kidney DiseaseJ Am Soc Nephrol 18: 1246–1261, 2007

19 Lipidrendellenességek gyakorisága vesebetegségben
Összkoleszterin > 6,2 mmol/l LDL-C > 3,3 mmol/l HDL-C < 0,9 mmol/l Triglicerid > 2,3 mmol/l Átlagpopuláció 20 % 40 % 15 % CKD + Nephrosis 90 % 85 % 50 % 60 % CKD 1-4 st. 30 % 10 % 35 % CKD-5 HD 45 % CKD-5 PD 25 % AURORA study (A study to evaluate the Use of Rosuvastatin in subjects On Regular hemodialysis: an Assessment of survival and cardiovascular events) Start Q1 2003 20 countries (North America, Europe, Australia) Approx 3000 male and female HD patients Ages years Irrespective of previous history of CV disease and baseline lipids Endpoints Total mortality Cardiovascular events Effects on lipoprotein fractions Inflammatory markers safety issues Mátyus J., Paragh Gy.: Metabolizmus. VIII. évfolyam, különlenyomat május 19 19

20 CKD és CV rizikó CKD stádiumai és lipideltérések LDL csökkentő terápiák eredményei

21 Lipidcsökkentés CV rizikó csökkentő hatása nem kifejezetten vesebeteg populációban igazolt (negatív CV anamnézis mellett is) Coronaria-események -29% (p<0,001) Cerebrovasc. események -14% (p=0,02) Thavendiranathan P, et al. Arch Intern Med. 2006;166:

22 Lipidcsökkentés vesebeteg populációban sztatinokkal – nem egyértelmű eredmény
MEGCÉLZOTT INDIKÁCIÓ VIZSGÁLAT N KEZELÉSEK Primer végpont (p) LDL↓, CRP↑, obes JUPITER 17802 Rosuva 20 vs. plac. -44%(0,00001) (metab. sy.) Ischemiás CORONA 5011 Rosuva 10 vs. plac. -8% (NS) szívelégtelenség Bármilyen eredetű GISSI-HF 4631 0-1% (NS) Diabet. nephropathia 4D 1255 Atorva 80 vs plac. dialízissel Nephropathia AURORA 2773 -4% (NS) SHARP 9438 Inegy 10/20 vs. plac. ??? dialízissel és dialízis nélkül Tünetmentes SALTIRE 102 NS aortabillentyű-stenosis SEAS 1873 Inegy 10/40 vs. plac. ASTRONOMER 272 Rosuva 40 vs. plac.

23 SHARP (Study of Heart and Renal Protection): Beválasztási kritériumok
Krónikus vesebetegek Emelkedett kreatininszint (nem dializált): Férfi: ≥150 µmol/l több alkalommal Nő: ≥130 µmol/l több alkalommal Dializált: haemodialysis vagy peritonealis dialysis Kor ≥40 év Negatív ISZB (nem volt infarktus v. revaszkularizáció) The SHARP study: patient characteristics Patients recruited to the SHARP study were aged ≥40 years without coronary heart disease (prior MI or coronary revascularization) and with evidence of CKD (creatinine ≥150 µmol/l [≥1.7 mg/dl] in men or ≥130 µmol/l [≥1.5 mg/dl] in women). The mean age of patients was 62 years and the majority (63%) were male. Baseline mean systolic and diastolic blood pressure was 139 mmHg and 79 mmHg, respectively. Diabetes was present in 22% of patients, 15% had vascular disease and 15% were current smokers.24 Of note, there were only moderate abnormalities in the lipid profile, with mean levels at baseline of:24 •         LDL cholesterol = 2.79 mmol/l (108 mg/dl) •         Total cholesterol = 4.89 mmol/l (189 mg/dl) •         HDL cholesterol = 1.11 mmol/l (43 mg/dl) •         Triglycerides = 2.33 mmol/l (206 mg/dl). Concomitant medication use reflected the reality of clinical practice, with widespread use of antihypertensive medication such as ACE inhibitors (35% of patients), angiotensin receptor blockers (23%), calcium-channel blockers (41%), beta-blockers (37%) and diuretics (42%). Furthermore, 22% of patients were receiving antiplatelet therapy and 30% vitamin K supplements.24 In contrast to the earlier AURORA and 4D studies, the majority (68%) of patients were not on dialysis on entry to the study. The mean eGFR among the non-dialysis patients was 27 ml/min/1.73m2 and proteinuria was present in 80% of these patients.24 Am Heart J 2010;160: e10

24 SHARP: Felépítés Am Heart J 2010;160:785-794.e10
The SHARP study  The SHARP study is the first prospective, randomized, placebo-controlled trial to provide conclusive evidence of the benefits of lipid-lowering therapy in reducing CV risk in patients with CKD. It is also the largest study of lipid-lowering therapy in CKD to date, with 9,438 patients randomized in a 4:4:1 ratio to combination therapy with ezetimibe/simvastatin 10/20 mg daily, placebo or simvastatin 20 mg daily alone. Patients in the simvastatin only arm were re-randomized after 1 year in a 1:1 ratio to either placebo or ezetimibe/simvastatin 10/20 mg daily,24 and followed up for ≥4 years.  The SHARP study population was more than three times larger than the previous trials of lipid-lowering therapy in CKD. SHARP also recruited a broad spectrum of patients, including both dialysis and non-dialysis patients, and patients at all stages of CKD.24 SHARP also had a precisely defined primary composite endpoint of major atherosclerotic events which included coronary death, MI, ischaemic stroke or any revascularization procedure. The primary endpoint focused on the atherosclerotic events that lipid-lowering therapy is most likely to impact, and excluded those such as haemorrhagic stroke where anti-atherosclerotic activity is likely to be of less benefit.  The SHARP study was, therefore, well-designed to answer the question of whether lipid-lowering therapy reduces CV risk in CKD and resolve the controversy generated by the generally neutral results in previous trials of statin therapy.24 Am Heart J 2010;160: e10

25 SHARP: Kiindulási betegadatok
Betegjellemzők Átlag (SD) or % Kor 62 (12) Férfi 63% Szisztolés vérnyomás (mm Hg) 139 (22) Diasztolés vérnyomás (mm Hg) 79 (13) Body mass index 27 (6) Dohányos 13% Vaszkuláris betegség 15% Diabetes mellitus 23% Csak a nem dializáltakra vonatkozólag (n=6247) eGFR (ml/min/1.73m2) 27 (13) Albuminuria 80% Am Heart J 2010;160: e10 25

26 SHARP: Kiindulási betegadatok
The SHARP study: patient characteristics Patients recruited to the SHARP study were aged ≥40 years without coronary heart disease (prior MI or coronary revascularization) and with evidence of CKD (creatinine ≥150 µmol/l [≥1.7 mg/dl] in men or ≥130 µmol/l [≥1.5 mg/dl] in women). The mean age of patients was 62 years and the majority (63%) were male. Baseline mean systolic and diastolic blood pressure was 139 mmHg and 79 mmHg, respectively. Diabetes was present in 22% of patients, 15% had vascular disease and 15% were current smokers.24 Of note, there were only moderate abnormalities in the lipid profile, with mean levels at baseline of:24 •         LDL cholesterol = 2.79 mmol/l (108 mg/dl) •         Total cholesterol = 4.89 mmol/l (189 mg/dl) •         HDL cholesterol = 1.11 mmol/l (43 mg/dl) •         Triglycerides = 2.33 mmol/l (206 mg/dl). Concomitant medication use reflected the reality of clinical practice, with widespread use of antihypertensive medication such as ACE inhibitors (35% of patients), angiotensin receptor blockers (23%), calcium-channel blockers (41%), beta-blockers (37%) and diuretics (42%). Furthermore, 22% of patients were receiving antiplatelet therapy and 30% vitamin K supplements.24 In contrast to the earlier AURORA and 4D studies, the majority (68%) of patients were not on dialysis on entry to the study. The mean eGFR among the non-dialysis patients was 27 ml/min/1.73m2 and proteinuria was present in 80% of these patients.24 Am Heart J 2010;160: e10

27 Elsődlegesen elemzett végpont
SHARP: Fő végpontok Elsődlegesen elemzett végpont Súlyos atheroszklerotikus események (koronária-halálozás, AMI, ischémiás stroke vagy bármilyen revaszkularizació) Egyéb végpontok Súlyos vaszkuláris események (kardiális halál, AMI, bámilyen stroke, vagy bármilyen revaszkularizació) Súlyos atheroszklerotikus események összetevői Fő vesekimenetel Végstádiumú veseelégtelenség kialakulása (dialízis vagy transzplantáció) a nem dializáltak között Am Heart J 2010;160: e10

28 SHARP: Lipidprofil alakulása
Kiindulási: LDL cholesterin = 2.79 mmol/l (108 mg/dl)  Total cholesterin = 4.89 mmol/l (189 mg/dl)  HDL cholesterin = 1.11 mmol/l (43 mg/dl)  Triglycerid = 2.33 mmol/l (206 mg/dl) 2,5 év után: Eze/simva Placebo Különbség Különbség p (%) (mmol/l) (mmol/l) The SHARP study: patient characteristics Patients recruited to the SHARP study were aged ≥40 years without coronary heart disease (prior MI or coronary revascularization) and with evidence of CKD (creatinine ≥150 µmol/l [≥1.7 mg/dl] in men or ≥130 µmol/l [≥1.5 mg/dl] in women). The mean age of patients was 62 years and the majority (63%) were male. Baseline mean systolic and diastolic blood pressure was 139 mmHg and 79 mmHg, respectively. Diabetes was present in 22% of patients, 15% had vascular disease and 15% were current smokers.24 Of note, there were only moderate abnormalities in the lipid profile, with mean levels at baseline of:24 •         LDL cholesterol = 2.79 mmol/l (108 mg/dl) •         Total cholesterol = 4.89 mmol/l (189 mg/dl) •         HDL cholesterol = 1.11 mmol/l (43 mg/dl) •         Triglycerides = 2.33 mmol/l (206 mg/dl). Concomitant medication use reflected the reality of clinical practice, with widespread use of antihypertensive medication such as ACE inhibitors (35% of patients), angiotensin receptor blockers (23%), calcium-channel blockers (41%), beta-blockers (37%) and diuretics (42%). Furthermore, 22% of patients were receiving antiplatelet therapy and 30% vitamin K supplements.24 In contrast to the earlier AURORA and 4D studies, the majority (68%) of patients were not on dialysis on entry to the study. The mean eGFR among the non-dialysis patients was 27 ml/min/1.73m2 and proteinuria was present in 80% of these patients.24 (mmol/l) (mmol/l) (mmol/l) (mg/dl) (mg/dl) Am Heart J 2010;160: e10;

29 SHARP: Súlyos atheroszklerotikus események
25 Risk ratio 0.83 (0.74 – 0.94) Logrank 2P=0.0022 20 Placebo 15 Eze/simv Súlyos atheroszklerotikus. események (%) 10 The SHARP study: reduction in the risk of atherosclerotic events with lipid-lowering therapy Treatment with the combination of ezetimibe/simvastatin significantly reduced the primary outcome of major atherosclerotic events over 5 years (17% reduction, P=0.0022). The reduction in major atherosclerotic events was consistent across all subgroups studied, including non-dialysis and dialysis patients (note that during the course of the study approximately one-third of non-dialysis patients progressed to dialysis, which may have acted as a confounding effect in comparing the responses to therapy of these two groups).16 Reduction in risk of major atherosclerotic events was associated with a 0.83 mmol/l (32 mg/dl) reduction in LDL cholesterol. At 1 year, the reduction in LDL cholesterol with ezetimibe/simvastatin was 0.44 mmol/l (17 mg/dl) greater than with simvastatin alone.16 Estimates based on a meta-analysis of statin trials in the general population suggest that for every 39 mg/dl (1 mmol/l) reduction in LDL-cholesterol, the risk of major vascular events is reduced by 25%.25 Therefore, the results of the SHARP trial indicate that lipid-lowering therapy with ezetimibe/simvastatin provides comparable benefits in patients with CKD to those seen with statins in the general population.16 5 1 2 3 4 5 Év Forrás:

30 SHARP: Súlyos vaszkuláris/ath.scler. események
Eze/simv Placebo Risk ratio & 95% CI (n=4650) (n=4620) Súlyos koronária esemény 213 (4.6%) 230 (5.0%) Nem haemorrhagiás stroke 131 (2.8%) 174 (3.8%) Bármilyen revaszkularizáció 284 (6.1%) 352 (7.6%) Súlyos atheroszkl. esemény 526 (11.3%) 619 (13.4%) 16.5% SE 5.4 csökkenés (p=0.0022) Egyéb szív eredetű halálozás 162 (3.5%) 182 (3.9%) Haemorrhágiás stroke 45 (1.0%) 37 (0.8%) Egyéb súlyos vaszk. esemény 207 (4.5%) 218 (4.7%) 5.4% SE 9.4 csökkenés (p=0.57) Súlyos vaszkuláris esemény 701 (15.1%) 814 (17.6%) 15.3% SE 4.7 (p=0.0012) The SHARP study: lipid-lowering therapy reduces CV risk in CKD The SHARP study protocol originally defined the primary outcome as major vascular events, which included non- coronary cardiac deaths and haemorrhagic strokes as well as major atherosclerotic events. While still blinded to the study results, however, the investigators decided to restrict the primary outcome to major atherosclerotic events only to remove the potential confounding effects of non-atherosclerotic events that are unlikely to be reduced by lipid-lowering therapy. Analysis of major vascular events (which includes both atherosclerotic and non-atherosclerotic events) revealed a highly significant (P=0.0012) reduction with ezetimibe/simvastatin treatment comparable in magnitude (15% relative risk reduction) to that for major atherosclerotic events alone.16 Rates of the individual components of major coronary events, non-haemorrhagic stroke, any revascularization and non-coronary cardiac death were all lower with ezetimibe/simvastatin than placebo. Haemorrhagic stroke rate was higher with ezetimibe/simvastatin although the difference was not significant.16 No improvement in renal outcomes was evident in the initial analyses of the SHARP trial. Approximately one third of patients not on dialysis progressed to ESRD, regardless of whether they received ezetimibe/simvastatin or placebo. Further analyses are ongoing to investigate the possible impact 0.6 0.8 1.0 1.2 1.4 Eze/simv jobb Placebo jobb Forrás:

31 Anyagcserebetegség: jobb tendencia
Koleszterinhatás: jobb tendencia Lancet 2011; 377: 2181–92; webappendix

32 Stroke-megelőzés koleszterincsökkentőkkel
Vizsgálat Hatóanyag ~RR (Ther%/Plac%) Placebokontrollos vizsgálatok nem vesebeteg populációban1 Sim 20-40 Sim 40 Ator 10 Rosu 20 Pra 40 Lov 20-40 0.7 0.75 0.5 0.9 1.0 0.6 0.8 Placebokontrollos vizsgálatok krónikus vesebeteg populációban1,2 1.1 1.4 0.8 AURORA 4D ALERT SHARP Rosu 10 Ator 10 Flu 80 Eze/Sim 10/20 1. Cholesterol Treatment Trialists’ (CTT) Collaboration. Effi cacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from participants in 26 randomised trials. Lancet 2010;376: (webappendix) 2. Baigent C, et al for the SHARP Investigators. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011;377:

33 SHARP: Rák incidencia Risk ratio 0.99 (0.87 – 1.13) Logrank 2P=0.89
25 20 Risk ratio 0.99 (0.87 – 1.13) Logrank 2P=0.89 15 Rák előfordulás (%) Eze/simv Placebo 10 The SHARP study: safety of lipid-lowering therapy in chronic kidney disease Ezetimibe/simvastatin was generally well tolerated and there was no evidence that treatment increased the risk of serious adverse events compared with placebo. The proportion of patients discontinuing treatment with ezetimibe/simvastatin was similar to placebo, with approximately one third of patients non-compliant in each study arm. In the majority of cases, non-compliance was not related to side effects.16 There have been concerns about the carcinogenic potential of ezetimibe, based on a single trial of intensive lipid–lowering with ezetimibe/simvastatin in aortic stenosis in which the incidence of cancer was increased compared with placebo (11.1% vs. 7.5%; P=0.01).26 However, pre–clinical studies have found no evidence that ezetimibe poses a carcinogenic hazard27 nor was a significant cancer risk observed in a meta-analysis of clinical studies with ezetimibe.28 In the SHARP study, there was no increase in the risk of cancer with ezetimibe/simvastatin. The incidence of cancer over 5 years was ~10% in both the ezetimibe/simvastatin and placebo arms, and the location and type of tumours were similarly distributed in the two study arms.16 The potential for myopathy is often a concern with statin therapy. A systematic review has concluded that ezetimibe does not itself cause myopathy or exacerbate statin- induced myopathy except, possibly, in rare cases.29 Reassuringly, in the SHARP study treatment with ezetimibe/simvastatin did not increase the incidence of myopathy compared with placebo. There was also no evidence of an increased risk of liver enzyme abnormalities or gallstones with the combination therapy.16 5 1 2 3 4 5 Év Forrás:

34 SHARP: Biztonsági adatok
Eze/simv (n=4650) Placebo (n=4620) Myopathia CK >10 x de ≤40 x NFH 17 (0.4%) 16 (0.3%) CK >40 x NFH 4 (0.1%) 5 (0.1%) Hepatitis 21 (0.5%) 18 (0.4%) Tartósan emelkedett transzamináz >3x NFH 30 (0.6%) 26 (0.6%) Epekő komplikációk 85 (1.8%) 76 (1.6%) Egyéb hospitalizácó epekő miatt Pancreatitis epekő nélkül 12 (0.3%) The SHARP study: safety of lipid-lowering therapy in chronic kidney disease Ezetimibe/simvastatin was generally well tolerated and there was no evidence that treatment increased the risk of serious adverse events compared with placebo. The proportion of patients discontinuing treatment with ezetimibe/simvastatin was similar to placebo, with approximately one third of patients non-compliant in each study arm. In the majority of cases, non-compliance was not related to side effects.16 There have been concerns about the carcinogenic potential of ezetimibe, based on a single trial of intensive lipid–lowering with ezetimibe/simvastatin in aortic stenosis in which the incidence of cancer was increased compared with placebo (11.1% vs. 7.5%; P=0.01).26 However, pre–clinical studies have found no evidence that ezetimibe poses a carcinogenic hazard27 nor was a significant cancer risk observed in a meta-analysis of clinical studies with ezetimibe.28 In the SHARP study, there was no increase in the risk of cancer with ezetimibe/simvastatin. The incidence of cancer over 5 years was ~10% in both the ezetimibe/simvastatin and placebo arms, and the location and type of tumours were similarly distributed in the two study arms.16 The potential for myopathy is often a concern with statin therapy. A systematic review has concluded that ezetimibe does not itself cause myopathy or exacerbate statin- induced myopathy except, possibly, in rare cases.29 Reassuringly, in the SHARP study treatment with ezetimibe/simvastatin did not increase the incidence of myopathy compared with placebo. There was also no evidence of an increased risk of liver enzyme abnormalities or gallstones with the combination therapy.16 Forrás: 34

35 Összefoglalás CKD = nagy/ igen nagy CV kockázat
LDL-C célérték: 2,5 mmol/l (nagy CV kockázat) 1,8 mmol/l (igen nagy CV kockázat) CKD 3-5 stádiumban a hypercholesterinaemia aránya meghaladja a 60%-ot Heterogén lipideltérések a CKD stádiumaitól függően CV rizikócsökkentés vesebetegségben: sztatinokkal nem egyértelmű SHARP: első vizsgálati bizonyíték, hogy az LDL-C csökkentő terápia (Inegy 10/20) csökkenti a súlyos atheroscleroticus események kockázatát krónikus vesebetegek körében (RRR -17%, p<0,001) Stroke-rizikócsökkentés vesebetegségben: sztatinokkal következetes, nem szignifikáns kockázatfokozódás SHARP: első vizsgálati bizonyíték, hogy az LDL-C csökkentő terápia (Inegy 10/20) csökkenti a stroke kockázatát krónikus vesebetegek körében (RRR -19%, p=0,04) A 4,9 éves utánkövetésben az Inegy 10/20 biztonságossága és tolerálhatósága a placebóval összevethető volt

36 Köszönöm a figyelmet !!

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