03.Pgs q Binh Bao Cao Bv Thong Nhat 2011

8/4/2019 03.Pgs q Binh Bao Cao Bv Thong Nhat 2011

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DEMA-CVN.COMGII THIU

GII THIU CC TAI NGHIN CU KHOAHC TI HI NGH NI KHOA TOANQUC TI THANH PH H CH MINH

THNG 7/ 2011

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Statin trong phng nga

bincngmch vnhPGS.TS Trng Quang Bnh

HYD TP HCM

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Ganh nang toan cau cua benh ly tim machNam 2002:

T vong do benh tim mach chiem 1/3 so t vong toan cau (17 trieu)80% ganh nang nay se e tren vai cua cac quoc gia co thu nhap thap entrung bnh

D tnh vao nam 2020:Benh M vanh va ot qu :nguyen nhan gay t vong va thng tat hang autren toan the giiT vong do benh tim mach se tang en 20 trieu

=> Cham soc y te cho benh tim mach rat hao ton

International Cardiovascular Disease Statistics 2005; AHADEMA-CVN.COM


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Risk Factors for Atherothrombosis

Atherosclerosis

Atherothrombotic Manifestations(MI, Ischemic Stroke, Vascular Death)

AgeObesity

Diabetes

Hyperlipidaemia

Hypercoagulable states

Hypertension

Genetics

Infection?

HomocysteinaemiaLife-style (e.g.,smoking, diet,lack of exercise)

Gender

American Heart Association. Heart and Stroke Facts: 1997 Statistical Supplement; Wolf. Stroke 1990;21(suppl 2):II-

4II-6; Laurila et al. Arterioscler Thromb Vasc Biol 1997;17:2910-2913; Grau et al. Stroke 1997;28:1724-1729;Graham et al. JAMA 1997;277:1775-1781; Brigden. Postgrad Med 1997;101(5):249-262.

Insulin resistanc

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Cholesterol and atherosclerosis

LDL-C is strongly associated with an increased riskof atherosclerosis and CVD events

HDL-C has a protective effect for the risk ofatherosclerosis and CHD.

1% decrease in LDL-Creduces CHD risk by 1%1

1% change in HDL-C

associated with 1-3%reduction in CHD risk2-5

1.Grundy SM et al. Circulation. 2004; 110: 22739.2.Gordon DJ, Probstfield JL, Garrison JD et al. Circulation1989; 79: 8-15.3.Boden W. American Journal of Cardiology2000; 86 (suppl): 19L-22L.

4.Manninen V, Elo O, Frick MH et al. JAMA 1988; 260:641-651.5.Rubins HB, Robins S, Collins D et al. N Engl J Med1999; 341:410-418


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Key Statin Trials andSpectrum of Risk

CHD/high cholesterol

CHD/average to high cholesterol

CHD/low to average cholesterol

MI/low to average cholesterol

MI/low to average cholesterol

CHD or diabetes/low to average cholesterol

CHD/low to average cholesterol

Diabetes + 1 other risk factor/low to average cholesterol

CHD or risk factors/average cholesterolno MI/high cholesterol

some CHD/average cholesterol

>3 risk factors/low to average cholesterol

No CHD/average cholesterol

No CHD/low to normal cholesterol

Increasingabsolute CHDrisk

4S

LIPID

PROVE-IT

CARE

IDEALHPS

TNTCARDS

PROSPER

WOSCOPS

ALLHAT-LLT

ASCOT-LLA

AFCAPS/TexCAPS

JUPITER

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7

Nghien cu 4S: m ng cho ATP III

Trc NC 4S, statin:

* Giam t vong do benh MV, cha giam t vong chung.

NC 4S (Scandinavian Simvastatin Survival Study), 1994:* Giam t vong do benh MV va t vong chung 30%.

NC 4S la NC au tien tra li chnh thc ve tac dung co

li cua statin trong ieu tr RLLP mau.

NC 4S co anh hng ln cho khuyen cao ATP III


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8

HPS = Heart Protection Study

NC tien cu, ngau nhien, so sanh cheo (simvastatin vi gia dc).

Muc tieu NC: Simvastatin co lam giam ty le t vong va cac bien

co tim mach cho oi tng co nguy c cao. Tieu ch chnh: Ty le t vong chung, Ty le cac bien co tim mach

gay t vong va khong gay t vong.

Thi gian theo doi trung bnh : 5 nam


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9

Heart Protection Study(Nghien cu keo dai 5 nam)

Nguy c BMV

100 LDL-C (mg/dL)

Simvastatin

40 mg

60

Giam 26% nguy c BMV

Giam 22% nguy c BMV

Simvastatin

40 mg

Heart Protection Study Collaborative Group.Lancet2002;360:722.


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Atorvastatin 80 mgn=4,995

Primary Endpoint: Bien co tim mach chnh : t vong do benh M vanh,NMCT khong t vong, ngng tim c hoi sc, ot qu gay t vong hoac khongt vong . Theo doi 4.9 nam.

TNT Trial

Atorvastatin 10 mgn=5,006

10,003 benh nhan benh M vanh on nhTuoi 35-75 , LDL t 130 - 250 mg/dL, triglyceride 600 mg/dL

19% la n, tuoi trung bnh 60.3

Tat ca c dung atorvastatin 10 mg trong 8 tuan au

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TNT Trial: Primary endpointPrimary Composite of CHD death, nonfatal MI, resuscitated

cardiac arrest, and fatal or nonfatal strokeHazard Ratio [HR]=0.78p


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IDEAL (Incremental Decrease in End PointsThrough Aggressive Lipid Lowering)

8888 patients, 80 years or less with prior MIrandomised to atorvastatin 80 mg/d (n = 4439), orsimvastatin 20 mg/d (n = 4449), with a median follow-

up of 4.8 years.

Primary endpoint was occurrence of a major coronary

event (coronary death, confirmed nonfatal acute MI, orcardiac arrest with resuscitation).


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13

IDEAL

Major coronary event in 463 on simvastatin (10.4%) and 411on atorvastatin (9.3%) P = 0.07 (not significant); nonfatal MIin 321 (7.2%) and 267 (6.0%) (P = 0.02).

No differences in cardiovascular or all-cause mortality.

Patients with MI may benefit from intensive lowering of LDL-Cwithout an increase in noncardiovascular mortality or otherserious adverse reactions.


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PROVE-ITThe Pravastatin or Atorvastatin Evaluation and

Infection Therapy trial (PROVE-IT/TIMI-22)

4162 Patients with acute coronary syndromewithin the preceeding 10 days.

Aggressive lipid-lowering using atorvastatin 80

mg/day versus using pravastatin 40 mg/day.


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PROVE-IT likely benefits

Atorvastatin 80 mg: additional 18%reduction in nonfatal MI and CHD deathbeyond treatment with pravastatin 40 mg.

Extrapolation of the event rate: approximateadditional 22% reduction in major CHD

events in the atorvastatin group at 5 years.


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On-Treatment LDL-C is Closely Related toCHD Events in Statin Trials

Rosenson RS. Exp Opin Emerg Drugs2004;9(2):269-279, LaRosa JC et al. N Engl J Med2005;352:1425-1435.

LDL-C achieved mg/dL (mmol/L)

4S - Rx

HPS - Pl

LIPID - Rx

4S - Pl

CARE - Rx

LIPID - Pl

CARE - Pl

HPS - Rx

0

5

10

15

20

25

30

40(1.0)

60(1.6)

80(2.1)

100(2.6)

120(3.1)

140(3.6)

160(4.1)

180(4.7)

Secondary PreventionRx - Statin therapyPl PlaceboPra pravastatinAtv - atorvastatin

200(5.2)

PROVE-IT - Pra

PROVE-IT Atv

TNT Atv10TNT Atv80

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6.7

15.9

0

2

4

6

8

10

12

14

16

18

Rosuvastatin Control

MCAEs (30 days)MCAEs (%)

P=0.002

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Why Is LIPS Unique?

In previous secondary prevention trials PCI in subpopulations only

multiple previous PCIs allowed

PCI in distant past allowed

LIPS is the first prospective secondaryprevention statin trial with cardiac outcomes

(time to first MACE) as the primary endpoint toexclusively study the post-PCI population

PCI, percutaneous coronary intervention; MACE, major adverse cardiac event.


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Primary Endpoint:MACE-Free Survival Time

Subjectsfree fromMACEs

(%)

070

80

90

100

0.0 0.5 1.5 2.5 3.5

Years post randomization

Placebo

Fluvastatin

2.0 3.0 4.01.0

Subjects at risk (% survival)

Fluvastatin 844 (100.0) 703 (84.2) 666 (80.9) 647 (80.2) 250 (78.3)Placebo 833 (100.0) 686 (83.6) 642 (78.8) 610 (76.1) 228 (72.6)

MACE, major adverse cardiac event.

Serruys PW. Presented at: ACC 51st Annual Scientific Session;March 20, 2002; Atlanta, GA.

Risk reduction = 22%

P=0.0127

A l b f li i l i h


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Total Cholesterol Distribution: CHD vs Non-CHD Population

Castelli WP.Atherosclerosis. 1996;124(suppl):S1-S9.1996 Reprinted with permission from Elsevier Science.

35% of CHD Occursin People withTC


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Key statin trials onPrimary prevention studies

WOSCOPS (1995)

AFCAPS/TexCAPS (1998)ALLHAT-LLA (2002)

ASCOT-LLA (2003)

JUPITER (2008)

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Cardiovascular Endpoints: WOSCOPSSubjects with No Previous MI but Raised Cholesterol

placebo(n=3293)

pravastatin(n=3302)

RRR(%)

p-value

Nonfatal MI/CHDdeath*

CHD death

Nonfatal MI

PCTA/CABG

StrokeAll cardiovascular

deaths

Total mortality#

248

52

204

80

5173

135

174

38

143

51

4650

106

31

28

31

37

1132

22


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Nonfatal MI and CHD Death: WOSCOPS

Shepherd J et al. N Engl J Med1995;333:13011307.

Years

0

1

2

4

6

8

10

12

2 3 4 5 6

pravastatin (n=3302)

placebo (n=3293)

31%relative

riskreductionp


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AFCAPS/TexCAPS

6605 patients.

Average TC and LDL-C levels (Mean TC 5.71mmol/L, LDL-C 3.89 mmol/L, mean HDL-C level 0.94 mmol/L andmedian (SD) TG levels were 1.78 (0.86) mmol/L).

Without clinically evident atheroscleroticcardiovascular disease

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Fatal/Nonfatal MI, Sudden Cardiac Death,Unstable Angina: AFCAPS/TexCAPS

Downs JR et al. JAMA 1998;279:16151622.

37%relative

riskreductionp5

0.07

54321

0.05

0.02

lovastatin

placebo


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Statin and Usual Care in HypertensivePatients with Average Cholesterol Levels:

ALLHAT-LLT

usual care(n=5185)

pravastatin(n=5170)

RR p-value

631

29530234

380

209

243

Outcomes

Number of events

All-cause mortality

CVD deathsNon-CVD deathsCause unknown

Fatal CHD andnonfatal MI

All stroke

Heart failure

641

30030239

421

231

248

0.99

0.991.010.88

0.91

0.91

0.99

0.88

0.910.920.58

0.16

0.31

0.89

ALLHAT Collaborative Research Group.JAMA 2002;288:29983007.

RR relative risk


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ALLHAT

Pravastatin did not reduce either all-causemortality or CHD significantly when compared withusual care in older participants with well-controlledhypertension and moderately elevated LDL-C.

The results may be due to the modest differentialin total cholesterol (9.6%) and LDL-C (16.7%)between pravastatin and usual care compared with

prior statin trials supporting cardiovascular diseaseprevention.


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Anglo-Scandinavian CardiacOutcomes Trial (ASCOT)

19,342 hypertensive patients (40-79 years withat least three other CV risk factors randomisedto one of two antihypertensive regimens.

(Hypertension but no CAD)

10,305 with TC of 6.5 mmol/L or lessrandomised to additional atorvastatin 10 mg orplacebo- ASCOT-LLA.

(Average cholesterol)DEMA-CVN.COM


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ASCOT-LLA: Anglo-Scandinavian Cardiac OutcomesTrial Lipid Lowering Arm

- RESULTS continued -

Years after randomization

Proportion ofpatients

(%)

00

0.5 1.0 1.5 2.0 2.5 3.0 3.5

1

2

3

4

Nonfatal MI and fatal CHD

Sever et al.Lancet2003;361:114958.

Placebo

Atorvastatin

HR=0.64

(95% CI=0.500.83)P=0.0005

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JUPITER - Objective

The primary objective:

Long-term rosuvastatin 20 mgdecreases the rate of first major

cardiovascular events comparedwith placebo in patients with low tonormal LDL-C + elevated CRP

levels

Ridker PM. Circulation2003; 108: 22922297


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JUPITER study design

Lipids

CRPTolerability

Lipids

CRPTolerability

HbA1C

Placebo

run-in

16

24

30

413 Final6-monthly

Visit:Week:

Randomisation Lipids

CRPTolerability

Rosuvastatin 20 mg (n=8901)

Placebo (n=8901)

Lead-in/

eligibility

No history of CAD

men 50 yrs

women 60 yrs

LDL-C


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Placebo

Rosuvastatin 20 mg

JUPITER - Primary EndpointTime to first occurrence of a CV death, non-fatal stroke, non-fatal

MI, unstable angina or arterial revascularization

Hazard Ratio 0.56(95% CI 0.46-0.69)P


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Nghin cu Thuc S bnh nhn

Phng nga th pht

1994 4S Simvastatin 4,444

1996 CARE Pravastatin 4,1591998 LIPID Pravastatin 9,014

2002 HPS Simvastatin 20,536

2004 TNT Atorvastatin 10,000

Phng nga tin pht

1995 WOSCOPS Pravastatin 6,595 31%

1998 AFCAPS/TexCAPS Lovastatin 6,605 37%

2003 ASCOT-LLA Atorvastatin 10,305 36%

2005 JUPITER Rosuvastatin 17,802 44%DEMA-CVN.COM


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Ket luanStatin la thuoc hieu qua trong phong nga bien co Mvanh hau nh tat ca cac dang lam sang cua benh.

iem noi bat trong nhng nam gan ay la phong nga

tien phat cho nhng oi tng nguy c benh M vanh

khong cao

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03.Pgs q Binh Bao Cao Bv Thong Nhat 2011

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