This presentation is the property of its rightful owner.
Sponsored Links
1 / 101

临床调脂治疗的若干进展 厦门大学附属第一医院 厦门市心血管病研究所 李卫华 PowerPoint PPT Presentation


  • 75 Views
  • Uploaded on
  • Presentation posted in: General

临床调脂治疗的若干进展 厦门大学附属第一医院 厦门市心血管病研究所 李卫华. 2011 年欧洲血脂异常处理指南明确指出,降低 LDL-C 是调脂治疗的首要靶标。 对缺血性 CVD 、 DM 、 CKD 患者, LDL-C 应< 1.8mmol/L ,但达标率低。 家族性高胆固醇血症患者需更严格 LDL-C 目标值,但大剂量强效他汀亦难达标。 大剂量他汀的副作用. 生理学研究提示: LDL-C 为 0.52 ~ 0.78mmol/L 已能保证人体代谢需要。 Meta 分析表明,高危心血管病患者 LDL-C 水平降至 0.78mmol/L ,仍可减少心血管终点事件。

Download Presentation

临床调脂治疗的若干进展 厦门大学附属第一医院 厦门市心血管病研究所 李卫华

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


6977068


6977068

  • 2011LDL-C

  • CVDDMCKD LDL-C1.8mmol/L

  • LDL-C


6977068

  • LDL-C0.520.78mmol/L

  • MetaLDL-C0.78mmol/L

  • LDL-C


6977068

9

PCSK9


6977068

PCSK9(SREBP)LDLLDL-RALDL-C


6977068

PCSK9LDL-CPCSK9LDL-C28%1588%(2%)


6977068

HMG CoAPSK9PCSK9LDL-C


6977068

PCSK9LDL-CIIPCSK9


6977068

  • AMG145

  • SAR236553

  • RN316


6977068

  • AMG145IgG2 PCSK9LDL-R

  • II

    MENDEL

    LAPLACE-TIMI57

    GAUSS

    RUTHERRORD


6977068

  • MENDEL

    411TCAMG145

    12

    241 LDL-C3.7% 4.5%;

    (10mg/d): LDL-C14.7% ;


6977068

AMG145(21:

70mg 105mg 140mg

LDL-C 41.0% 43.9% 50.9%

AMG145(41:

280mg 350mg 420mg

LDL-C 39.0% 43.2% 48.0%


6977068


6977068

  • LAPLACE-TIMI57

    II

    631TCAMG145


6977068

  • 12

    AMG145(21:

    70mg 105mg 140mg

    LDL-C 41.8% 60.2% 66.1%

    AMG145(41:

    280mg 350mg 420mg

    LDL-C 41.8% 50.0% 50.3%


6977068

  • 284AMG14590%LDL-C1.82mmol/L

  • LDL-CAMG145


6977068

  • AMG145


6977068

  • GAUSS

    160TCAMG145

    12

    (10mg/d): LDL-C14.8% ;


6977068

AMG145(41:

280mg 350mg 420mg

LDL-C 40.8% 42.6% 52.7%

+AMG145(450mg)

LDL-C 63%


6977068

  • RUTHERRORD

    168TCAMG145

    90%65% 12


6977068

AMG145(41:

350mg 420mg

LDL-C 42.7% 55.2%

LDL-C2.60mmol/L):

70% 90%

LDL-C1.82mmol/L):

44% 65%


6977068

  • AMG145

  • SAR236553

  • RN316


6977068

SAR236553PCSK9

9210mg/d7LDL-C 2.60mmol/LSAR23655321150mg10mg80mg80mg


6977068

12

SAR+ SAR+

80mg 10mg 80mg

LDL-C 17.3% 66.2.2% 73.2%

LDL-C2.60mmol/L):

52% 100% 100%

LDL-C1.82mmol/L):

17% 90% 90%


6977068

  • REGN727/SAR236553

    JamesMcKenney [ACC2012]


6977068

ODYSSEY

1.8ACSLDL-C21SAR23655375mg


6977068

  • AMG145

  • SAR236553

  • RN316


6977068

RN316PCSK9

RN316


6977068

  • 41RN316 3mg/kg6mg/kg12LDL-C46% ~56%HDL-C7% ~10% RN316


6977068

HDL-C


6977068

HDL-CHDL-C(HDL-C1mg/dl2%3%)HDL-C


6977068

  • (CETP)


6977068

(CETP)


6977068

CETP

  • Torcetrapib

  • Dalcetrapib

  • Evacetrapib

  • Anacetrapib


6977068

CETP


6977068

CETP

CETPHDL-C30%-150%


Illuminate

ILLUMINATE

Torcetrapib

  • 15000

  • (LDLC)<100 mgdl

  • Torcetrapib (60mg+)(+)


6977068

  • 550Torcetrapib(HDL-C72.1LDLC24.9)25400%


Illuminate1

ILLUMINATE

  • ILLUMINATEHDLTorcetrapib


6977068

  • TorcetrapibCETPCETP


Dal outcomes

dal-OUTCOMES

  • CETPDalcetrapib 600mg

  • 1587145

  • N Engl J Med.2012,367:2089


6977068

  • 312012.5)

  • DalcetrapibLDL-CHDL-C30%

  • DalcetrapibDalcetrapib8.3%8.0%

  • HDL-CHDL-CDalcetrapibHDL-C


6977068


6977068

  • Dalcetrapib0.6mmHgLDL-C1.82mmol/LLDL-CHDLCETPHDLdal-OUTCOMESILLUMINATEDalcetrapib


6977068

CETP

IIEvacetrapib AnacetrapibRAASHDLLDL-CVLDL-CDalcetrapib


6977068

CETP

  • DEFINE

    Anacetrapib31625HDL140%LDL40%

  • REVEAL

    Anacetrapib3300002017

  • ACCELERATE

    Evacetrapib31623LDL-C

  • 3


6977068

  • anacetrapibevacetrapib

  • anacetrapib


6977068


Aim high

AIM-HIGH

3414SAP HDL-C40mg/dl

4080mg/d(10mg/dLDL-C1.04 2.08mmolg/L1.5 2.0g/d

32

18


Hps2 thrive

HPS2-THRIVE

  • 25673

    (10000)

  • 40mg+

    40mg+Tredaptive(2g

    +laropiprant40mg

  • 3.9


6977068

  • HDL-C 6mg/dl44mg/dl 14%

  • LDL-C63mg/dl

  • :15.0% 14.5%


6977068

  • 2/3Tredaptive

  • 0.5%

  • 25.4%16.6%

  • 3Tredaptive


6977068

  • HDL-C

  • Lancet.2012,380:57214HDL-CSNP

  • J Clin Endocrinol Metab.2012,97:E248 LCAT S208THDL-C


6977068

DAL-OUTCOME


6977068

MESA

  • MESA

    HDL-CHDL

    HDLHDL-CIMT

    J Am Coll Cardiol. 2012.7.11


6977068

  • 1.LDLLDL

    2.,LDL

    3.


Hdl c

HDL-C

ABCG1ABCA1;

Apo A I;

LCATHDL.

:

X ABCG1ABCA1;

miR-33 miR-33HDLmiR-33HDL-C

Apo A I

LCATLCAT


Hdl c1

HDL-C

  • CSL112

  • GSK1292263


6977068

CSL112

CSL2012ACCA-ICSL11236:,,,CSL112


6977068

GSK1292263

GSK1292263G119GPR119GSK1292263HDL-C30%LDL-C20%~36%60%C40%


6977068

  • HDL-C

  • HDLHDL-CHDL

  • HDL-CHDL-C


6977068


6977068


West of scotland coronary prevention study woscops

West of Scotland Coronary Prevention StudyWOSCOPS

5

2999


6977068

13

9114049%

25541


2012 2 28 fda

2012228FDA

3

2.

3.

http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm


6977068

FDA

(HbA1c)FDA

http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm


6977068

FDA

1. Sattar N, et al. Lancet 2010; 375(9716):735-742. 2. Rajpathak SN, et al. Diabetes Care 2009; 32(10):1924-1929.

3. Mills EJ, et al. QJM 2011; 104:109-124. 4. Culver AL, et al. Arch Intern Med 2012; 172(2):144-152.

5. Ridker PM, et al. N Engl J Med 2008; 359(21):2195-2207. 6. Sukhija R, et al. J Investig Med. 2009;57:495-499.

7. Sabatine MS, et al. Circulation 2004; 110(Suppl I):S834. 8. Koh KK, et al. J Am Coll Cardiol 2010; 55:1209-1216.

9. Thongtang N, et al. Am J Cardiol 2011; 107:387-392.


6977068

Wang

8412

33648

7.2


6977068

15%

18%

39%

,,


Press 2011

Press(2011)

1996

1000125 TNTIDEALA to ZPROVE-IT SEARCH


6977068

327524.9

12%16%


Tnt ideal

TNTIDEAL

80mg4>5.6mmol/L>1.70 mmol/L,>30kg/m2


6977068

0~180mg

2~4


6977068

Ma

16027

3.5


6977068


6977068


6977068

HMGCoA


6977068


6977068


6977068


6977068

  • MIN6MIN6ATPMIN6Kir6.2Cav1.2GLUT22


6977068

    • HbA1C


6977068


  • Login