他汀展望2008課件

1、他汀展望2008 中南大學(xué)湘雅二醫(yī)院 趙水平14年循證歷程彰顯他汀價值針對特定的高?；颊呷?，使他汀應(yīng)用范圍更廣泛 ACS，老年人，糖尿病，高血壓 不僅僅與安慰劑對照 與常規(guī)治療或活性藥物對照 早期研究與安慰劑相比，證實(shí)他汀可降低死亡率和心血管事件發(fā)生率19944S 1995WOSCOPS1996CARE1998AFCAPS/TexCAPSLIPID2001MIRACL2002HPSPROSPERALLHAT LLT2003ASCOT-LLA2004PROVE ITALLIANCECARDSA to Z2005TNTIDEAL 在已接受現(xiàn)代治療的穩(wěn)定型冠心病患者，證實(shí)了更積極的他汀治療能進(jìn)一步獲

2、益2006SPARCL證實(shí)了他汀在卒中二級預(yù)防的作用降LDL-C是他汀獲益的重要機(jī)制Kastelein JP. Atherosclerosis 1999;143(suppl1):S17S21.LaRosa JC, et al. N Engl J Med. 2005;352:1425-1435 3025201510502.3 (90)2.8 (110)3.4 (130)3.9 (150)4.4 (170)4.9 (190)5.4 (210)LDL-C,mmol/L(mg/dL)woscops-pwoscops-pASCOT-pTNT-pCARE-SLIPID-SHPS-PCARE-PLIPID-

3、P4S-SASCOT-SAFCAPS-SAFCAPS-P二級預(yù)防S=他汀治療P=安慰劑治療一級預(yù)防極低LDL-C水平患者應(yīng)用他汀可改善生存率Statin Use in Patients With Extremely Low Low-Density Lipoprotein Levels Is Associated With Improved SurvivalCirculation. 2007;116:613-618LDL-C60mg/dL的患者，他汀治療可改善生存率LDL-C60mg/dl (n=6,107)，其中CHD（43%）、DM（47%)平均隨訪時間： 2.01.4年Circulatio

4、n. 2007;116:613-618.1.9.8.7存活比例050010001500他汀非他汀P=0.001時間（天）未調(diào)整因素：HR: 0.81, 95% CI, 0.68 to 0.96因素調(diào)整后：HR: 0.65; 95% CI, 0.53 to 0.80Circulation. 2007;116:613-618.即使LDL-C40mg/dL的患者，應(yīng)用他汀也可改善生存率基線LDL-C（mg/dL）1210864040-4950-59P=0.24P=0.08420年死亡率(%)非他汀他汀P=0.03因素調(diào)整后，HR, 0.51; 95% CI, 0.33 to 0.79TNT-老年亞組

5、：豐富了老年高?；颊呤褂盟?qiáng)化治療的證據(jù)發(fā)表年限研究患者治療事件2002PROSPER70-82歲n=5,804普伐他汀40mgvs 安慰劑15%P=0.0142006CARDS老年亞組65-75歲,DMn=1,129阿托伐10mgvs 安慰劑38%P210 mg/dL報告時間: 2008年3月30日, ACC 2008ENHANCE:設(shè)計(jì)N Engl J Med 2008;358:1431-43.ENHANCE：基線LDL水平及治療后下降百分比依折麥布辛伐他汀辛伐他汀P值 基線LDL (mg/dL)319318NS治療2年后下降百分比 (%)5841 3.5年安慰劑瑞舒伐他汀 20 mg隨

6、機(jī)分組N=15000入組 4周入選患者15,000名男性(年齡不小于50歲)和女性 (年齡不小于60歲);無心肌梗死、卒中或動脈血運(yùn)重建的病史LDL-C (130 mg/dL 3.36 mmol/L)，但通過測定CRP升高 (=2.0 mg/L)判定炎癥反應(yīng)增加，有CHD風(fēng)險的受試者主要終點(diǎn)隨機(jī)分組后首次發(fā)生主要心血管事件的時間 (心血管死亡、卒中、心肌梗死、因不穩(wěn)定性心絞痛或動脈血運(yùn)重建住院)次要終點(diǎn) 包括評價全部死亡、非心血管死亡、發(fā)生2型糖尿病、靜脈血栓事件、骨折和耐受性JUPITER研究設(shè)計(jì)長期、隨機(jī)、雙盲、安慰劑對照、平行組、多國參與的研究由于治療組明顯優(yōu)于安慰劑已提前結(jié)束JUPIT

7、ER “現(xiàn)在，所有的他汀類藥物均顯示了心血管終點(diǎn)獲益這進(jìn)一步說明我們應(yīng)該重新將強(qiáng)他汀作為一線治療，而不是依折麥布。”“我們一直在使用一種沒有臨床終點(diǎn)研究的藥物我建議我的同事們除非萬不得已，不要使用Vytorin?！?(Dr Steve Nissen)從夢想到現(xiàn)實(shí)調(diào)脂治療-2007回顧調(diào)脂治療的主旋律-他汀類藥物 2008 ACC Highlights調(diào)脂治療-新探索Subgroup Analysis in Patients With and Without Chronic Kidney Disease TNT 研究-CKD亞組Shepherd J et al. J Am Coll Cardio

8、l. 2008;51:1448-1454. TNT Study Design: Treatment Assignment by CKD StatusAtorvastatin 10 mgOpen-label run-inScreening and wash-outAtorvastatin 10 mg (n=1505)Atorvastatin 80 mg (n=1602)Double-blind periodn=9656(patients with complete renal data)*Includes normal and mild renal impairment (Stage 2) pa

9、tientsPatients with CKD at baseline(MDRD eGFR 60 mL/min/1.73 m2)Atorvastatin 10 mg (n=3324)Atorvastatin 80 mg (n=3225)Patients with normal eGFR at baseline(MDRD eGFR 60 mL/min/1.73 m2*)BaselineCKD SubgroupShepherd J et al. J Am Coll Cardiol. 2008;51:1448-1454. 8 weeks1-8 weeksMedian follow-up = 5.0

10、yearsFinalScreen031224364860BaselineFinalScreen031224364860BaselineChanges in LDL-C By Treatment Group in Patients by Baseline CKD StatusPatients with CKDPatients with normal eGFRCKD SubgroupShepherd J et al. J Am Coll Cardiol. 2008;51:1448-1454. 0123456Time (years)0.200.100.050Proportion of patient

11、s with major cardiovascular event0.15Time to First Major Cardiovascular Event By TreatmentAtorvastatin 10 mg (n=3324)Atorvastatin 80 mg (n=3225)Normal eGFRRelative risk reduction = 15%(Absolute risk reduction = 1.4%)HR=0.85 (95% CI: 0.72, 1.00)P=.049CKDRelative risk reduction = 32%(Absolute risk red

12、uction = 4.1%)HR=0.68 (95% CI: 0.55, 0.84)P=.0003Atorvastatin 10 mg (n=1505)Atorvastatin 80 mg (n=1602)CKD SubgroupShepherd J et al. J Am Coll Cardiol. 2008;51:1448-1454. Major coronaryCerebrovascularPADCHF with hosp.All-cause mortalityAny coronaryAny CV eventAtorvastatin 80 mg betterAtorvastatin 10

13、 mg better24.9% 21.0%4.2% 3.4%2.2%2.2%4.8% 4.6%3.7% 4.1%6.8% 6.1%30.9% 26.6% Event rate (normal eGFR)10 mg80 mgSecondary Event Rates in Patients With Normal eGFR and Patients With CKD 10.4%6.9%6.9%4.6%7.4%7.6%5.6%3.1%7.5%7.0%28.6%22.2%38.1%30.5% Event rate (CKD)10 mg80 mg0.40.60.81.01.21.41.6CKD Sub

14、groupShepherd J et al. J Am Coll Cardiol. 2008;51:1448-1454. Clinical Implications for CKD in CHDWhen applied to the TNT study population, MDRD eGFR identified a high-risk group of patients with concomitant CKD and CHDIn this cohort, intensive lipid reduction with atorvastatin 80 mg significantly re

15、duced the risk of major CV events compared with atorvastatin 10 mgThe results of this analysis of the TNT study have implications for future CHD and CKD guidelines, and physicians may consider these results when managing patients with stable CHD and CKDCKD SubgroupShepherd J et al. J Am Coll Cardiol

16、. 2008;51:1448-1454. AURORA-終末期腎病Rosuvastatin in end stage renal disease morbidity studyObjective :To assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis.AURORARosuvastatin in end stage renal disease morbidity study目前不清楚何時公布結(jié)果，預(yù)計(jì)于2

17、009年ASCOT-LLA延展研究ASCOT-LLA延展研究ASCOT研究降脂分支在3.3年時提前結(jié)束 但降壓分支(BPLA)仍在進(jìn)行。原降脂分支中患者不論阿托伐他汀組患者還是安慰劑組患者均服用阿托伐他汀10mg/日，繼續(xù)進(jìn)行BPLA研究。這些患者在BPLA研究結(jié)束時，是什么情況呢？ASCOT-LLA延展研究:總膽固醇變化安慰劑阿托伐他汀4.04.44.85.25.61601701801902002100.01.02.03.04.05.0年 末次拜訪TCmmol/Lmg/dLLLA研究延長期Sever PS, et al. Eur Heart J. 2008;29:499-508ASCOT-L

18、LA延展研究:非致死性MI和致死性CHD安慰劑: 3.3年后阿伐他汀10mg阿托伐他汀事件累積發(fā)生率(%)5.04.03.02.01.00.00.01.02.03.04.05.0年LLA 延長期結(jié)束LLA研究結(jié)束154*100*163*249*事件數(shù)36% 降低HR = 0.64(p0.001)36% 降低HR = 0.64(p0.0001)Sever PS, et al. Eur Heart J. 2008;29:499-508ASCOT-LLA延長期研究:致死和非致死性腦卒中安慰劑: 3.3年后阿伐他汀10mg阿托伐他汀 10mg事件累積發(fā)生率(%)5.04.03.02.01.00.00.01.02.03.04.05.0年LLA延長期結(jié)束LLA研究結(jié)束121*89*166*212*事件數(shù)27%降低HR = 0.73(p=0.024)23% 降低HR = 0.77(p=0.013)Sever PS, et al. Eur Heart J. 2008;29:499-508ASCOT-LLA延展研究:全因死亡8.06.04.02.01.051341.02.03.04.05.0安慰劑: 3.3年后也用阿