缺血性卒中和短暂性脑缺血发作的二级预防

缺血性卒中和短暂性脑缺血发作的二级预防

TIA 160 140 120 100 80 60 135

150 76.1 40 20 0 3 Stroke. 2006;37:63-68 World Health Organization. Atlas of Heart Disease and Stroke. http://www.who.int/cardiovascular_diseases/resources/atlas/en/

/10 200 165 200 150 100 50 165 77 51

0 3 n=1091 8.8 13.0 58.5 56.0

13.0 16.3 22.0 17.9 29.0 41.5 /TIATIA 20.0 16.9

21.0 0.0 10.0 20.0 30.0 40.0

50.0 60.0 70.0

TIA TIA 10mmHg, 49% 5mmHg, 46% TIA 7 RCT

TIA 140/TIA90mmHg 130/TIA80mmHg

1. 2. 3. 1mmol/TIAL 25% : 1. 2.

LDL-C LDL VLDL 1 2 /TIATIA 2010 TIA - TIA

TIA CE (I) (II)II)

(II) LDL-C LDL-C <2.1mmol/TIAL 80mg/TIAdl

>2.1mmol/L 80mg/dl >2.6mmol/L 100mg/dl SPARCL >40% <2.6mmol/TIAL 100mg/TIAdl

30-40% . 2008;47(10) CEA TIA - TIA

TIA CE (I) (II)II) (II)

LDL-C LDL-C <2.1mmol/TIAL 80mg/TIAdl >2.1mmol/L 80mg/dl

>2.6mmol/L 100mg/dl >40% <2.6mmol/TIAL 100mg/TIAdl 30-40% / . . 2007;46(1):81-8 TIA

LDL-C 2.6mmol/L(100mg/dL) LDL-C 2.6mmol/L(100mg/ dL) , /TIA / / / , LDL-C 2.07mmol/L(80mg/ dL) , - TIA , LDLC<80mg/dl LDL-C 40% Yes LDL-C No

LDL-C Because 1. 20 2. LDL-C 1.8-2.1mmol/TIAL 3. 4.

1. 14 90056 CTT LDL-C 1mmol/TIAL 2. HPS : 3. TNT : LDL-C 2.7mmol/TIAL 1..7mmol/TIAL

SPARCL /TIA 4-8 612 1 3

CK CK 5 CK CK 2010

IDF 2010 34400 47200 IGT http://www.diabetesatlas.org/content/global-burden 66% n=557 , 2008, 12:824-827. :77% n 216 Ivey FM, et al. Cerebrovasc Dis 2006;22:368371.

n=25 72h MRI NIHSS mSR Baird TA, et al. Stroke 2003, 34:22082214. 286 238 P 0.001 mRS mRS 0-1 % NIHSS NIHSS

P 0.001 Matz K, et al. Diabetes Care, 2006, 29:792-797. 286 238 P<0.001 Matz K, et al. Diabetes Care, 2006, 29:792-797. HbA1c 1mmol/TIAL HR UKPDS 597 UKPDS 66 HbA1c 1mmol/L 17%

37% P=0.0071 P=0.0144 Diabetes Care,2004, 27:201207. 2 1mmol/L HR 2 38 2h 1mmol/L 17% Diabetologia. 2008 July; 51(7): 11231126.

5 HR 2 Wilterdink JL, Easto JD. Arch Neurol, 1992, 49(8):857863. OGTT : (IFG) IGT) (DM)) IGT 50% IFG IGT

mmol/ L 7.0 6.1 IFG+IGT IFG 5.6 IGT 7.8 11.1

OGTT2 mmol/L ADA IFG 5.6mmol/L 6.1mmol/L American Diabetes Association. Diabetes Care, 2010, 33:S11-S61. . 2 2007 . , 2008, 88(18):1227-1245. 2 2007 . 2 2007 . , 2008, 88(18):1227-1245. /TIA -------- REACH R: Risk factors managements E: Early detection

A: All-sides glucose control C: Combination rationality H: Hypoglycemia prevention R 1 -- 2 <130/TIA80mmHg, ACEI or ARB SPARCL R

ADA LDL-C <70mg/TIAdl 1.8mmol/TIAL LDL-C 30%-40% E /TIATIA oral glucose tolerance test OGTT IGR 1998-2001 5,628 6.87% IGR 8.53%

OGTT 49% 75% IGR IFG IFG+IGT IGT IGR J WP.Diabetologia,2007 Feb;50(2):286-292. OGTT (%)

80 100 80 60 20 0 80 60 40

3513 (%) 25 5 100 2/3 OGTT 40

OGTT OGTT 20 0 OGTT

2 European Heart Journal (2004) 25, 18801890. Da-Yi Hu, et al. European Heart Journal 2006;27:2573-2579. OGTT OGTT 89% IGR 14% n=557 IFG IGT+IFG IGT OGTT OGTT

, 2008, 12:824-827. ESC/EASD OGTT CVD OGTT B 2

OGTT A European Heart Journal .2007 (28):88136. WHO/IDF OGTT OGTT IGT FPG 6.1-6.9mmol/Lmmol/L OGTT

Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia: Report of a WHO/IDF Consultation OGTT 0 30 60 120 180 1985 WHO OGTT 75g 2 World Health Organ Tech Rep Ser. 1985;727:1-113.

A HbA1c 1. 3 2. 3. HbA1c6.5%6.5% 2004 woerle 64% HbA1c<7% 94% HbA1c HbA1c C 1. 2.a-

3. 4.- 5. H 2.8mmol/Lmmol/L 3.9mmol/Lmmol/L 1. 2. 3. /TIA /TIA /TIA /TIA /TIA

TIA FPG FPG 7mmol/TIAL OGTT / /TIA 10mmom/ L 10mmom/L

8.3mmom/L FPG 7.0mmom/L 7.0mmom/L* OGTT + IGT

IFG * 2010 /TIA 2 50-325mg/TIAd 25mg 200mgbid

75mg/TIAd 75mg/TIAd 50-325mg/TIAd I A I A ADP GPIIb/TIAIIIa

- 2010 Lancet 13% ASA 1.Hankey GJ,et al. Lancet Neurol,2010; 9: 27384

24 RR 95 CI 0.75 (0.71-0.81) 25 0.62 (0.55-0.71) 38

0.62 (0.51-0.75) 38 0.62 (0.48-0.80) 38 0 2007 24 2004 0.5 1

79439 30 55 24 Long-term Aspirin Use and Mortality in Women ARCH INTERN MED/VOL 167, MAR 26, 2007 562 /TIA 1000 0 2 4 6

8 10 12 14 16 55,462 108 273mg/TIAday 37 He J, et al. JAMA 1998;280:19305 75-150mg/TIAd (%) ( mg/d) 500 1500 14.5

17.2 (%) 19 3 160 325 11.5 14.8 26 3 75 150 10.9 15.2 32 6

<75 17.3 19.4 13 8 12.9 16.0 23 2 0 ATC Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86.

0.5 1.0 1.5 2.0 P<.0001 CAPRIE: RRR 14.9% p=0.045 * (%)

12 10 RRR 8.7% 10.2% 8.8% p=0.043 8 6 5.8% 5.3% 4

2 0 ASA CAPRIE (n=19,099) MI (n=4496) *MI, ; 1.6 1. Ringleb PA et al. Stroke 2004; 35: 528532. + Relative Risk (95% CI) Caneschi*

0.64 (0.15-2.72) Guiraud-Chaumeil 0.27 (0.03-2.37) AICLA 0.98 (0.50-1.91) ACCSG 0.83 (0.55-1.26) ESPS-2 0.74 (0.60-0.91) ESPRIT 0.79 (0.61-1.01)

Summary 0.77 (0.67-0.89) Favours aspirin + dipyridamole 0.01 * Data for stroke alone endpoint only 0.03 0.10 0.32 Favours aspirin 1.00 3.50

Risk Ratio (95% CI) Verro et al. Stroke 2008; 39: 13581363. ASA+ ASA+ PRoFESS 2 <=10 <72h 15.0 39.6%

6.6% 140 120 15.0 100 6.8% 80 28.3% 60 40.0% 28.8%

1.8% 1.8% ( lacune) 52.0% 52.1% 2.0% 2.1% n

TOAST ASA+ER -DP 10181 10151 40 20 PRoFESS <72h 121 (18%) ASA+ER- DP(n=672) P=0.006 75mg(n=688)mg(n=688) 86 (12.5%

) 36 ( ) 3 0 90 15.4% 15.6% PRoFESS 1360 <72h NIHSS=2.8 + (ASA+ER-DP)30 ASA+ER-DP ASA+ER-DP 36 3

1.Bath PMW, et al.Stroke.2010;41 4 :732-8 2. Sacco RL, et al. N Engl J Med. 2008;359:1238-1251 ASA+ 75mg/dmg/d % * * 25mg/d0 ICH 128

N Engl J Med, 2008 359:1238-1251 5%-85% Alberts MJ, et al. Stroke. 2004;35:175-178 1. ESSEN 2. 3.

Essen Essen 2010 73 Essen3 Essen<3 74 4.2% 95%CI 3.0%-5.5% 7.4% 95%CI 4.9%-9.8% P=0.001

Weimar C, et al. Stroke 2010;41(3):487-93 REACH:ESSEN ESSEN3 70% 14.0 12.0 /TIA %

10.0 8.0 ESSEN<3 30% 6.0 4.0 2.0 0.0 0 1 2 3 4

5 6 >6 ESSEN REACH 15,605 /TIATIA ( ) 1 ESSEN Christian Weimar, et al. The Essen Stroke Risk Score Predicts Recurrent Cardiovascular Events. Stroke, 2009, 40:350-354. ESSEN3 CAPRIE ESSEN 12 75mg

325mg 10 8 6 /TIA 4 (%) 2 0 0 1 2

3 4 5 6 ESSEN CAPRIE 6431 ESSEN >6 ( 96 1.4%) - Diener HC, et al. Clopidogrel for the secondary prevention of stroke. Expert Opin Pharmacother, 2005,6(5):755-764. ESSEN ESSEN3 <3

ESSEN /TIA 25mg(n=688) 23 20 20 % 15mg(n=688) 0.584) 14 AUC

0.571 (0.559- 0.575 (0.5640.586) 12 10 5mg(n=688) 0 ESSEN<3( ) ESSEN 3- 9mmol/L( ) NSAIDs

530 1 CYP2C19*2 CYP2C19 PPI PPI P450 CYP 2CY19 PPI

PPI Maximum Platelet Aggregation Intensity Induced by ADP 5 M, after M, after 5 Days of Clopidogrel Repeated Dosing (Mean SEM) 100 MAI(%) Induced by ADP 5 M 90 Treatment: Clopidogrel Alone Clopidogrel + Omeprazole 80 mg

80 70 Estimates of treatment difference (90% CI) = 8.00 (4.71 to 11.28) 60 50 40 30 20 10 0 D1 D2 Pre-dose Pre-dose D5 T2

Time (in Day) D5 T4 D5 T6 Mean inhibition of platelet aggregation (IPA) was diminished by 47% (24 hours) and 30% (Day 5) when Plavix and omeprazole were administered together Data on file FDA2010 10 New PPI , PPI PPI CYP2C19

PPI CYP2C19 1 * 1000 60.1

60 61.4 40 18.3 20 12.6 3.5 10

Coronary heart disease prevention: insights from modelling incremental cost effectiveness BMJ 327;1264 ESSEN

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