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Lôïi ích cuûa phoøng ngöøa tieâ tien n phaù phatt bang baèng statin: Thaáy g gì q qua nghieâ g n cöùu JUPITER ? TS BS Hoà Huyønh Quang Trí Vieään Tim TP HCM


Caùc nghieân cöùu phoøng ngöøa tieân phaùt beänh tim maïch baèèng statin trong thaäp nieân 1990 N hi ân cöù Nghieâ öùu Beä B änh nhaâ h ân

LDL ban b ñaà ñ àu Ñieà Ñi àu trò t ò

K át quaûû Keá

WOSCOPS (1995)

6595 ngöôøi ñaøn ong, ñan oâng, tuoå tuoii 45-64

≥ 155 mg/dl (TB 192 mg/dl)

Pravastatin 40 mg/ngaø mg/ngay y (4,9 naêm)

↓ 31% NMCT hoaëc chet cheát do beänh maïch vaønh

AFCAPS/ TexCAPS (1998)

5608 ngöôø ngöôii ñaøn oâng (tuoåi 45-73), 997 phuï nöõ ((tuoåi p 55-73)

130-190 mg/dl Lovastatin (TB 150 40 mg/ngaøy mg/dl) (5,2 naêm)

↓ 37% NMCT / ñoät töû / ÑTN khoâng oån ñònh

TLTK TLTK: 1) N Engl J Med 1995;333:1301-1307 2) JAMA 1998;279:1615-1622


Ñaùnh giaù nguy cô tim maïch vaø ñieàu trò haï cholesterol theo NCEP ATP III


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Nhieàu ngöôøi coù cholesterol LDL < 130 mg/dl nhöng vaã van n bò cac caùc bieá bien n co coá maï mach ch vanh. vaønh Chæ döïa vaøo LDL ñeå phaân taàng nguy cô vaø choï h nñ ñoáái töôï töô ng cho h phoø h øng ngöø öøa ti tieâân phaù h ùt : khoâng phaûi laø tieáp caän toái öu.


Atherosclerosis is a chronic inflammatory disease with LDLLDL-C at the core Â&#x201E;

Libby P. J Intern Med. 2000;247:349-358.


Nguy cô tim maïch vaø caùc chæ ñieåm cuûa vieâm: Women’ss Health Study Women

Re elative Risk

5

CRP

4

TC/HDL--C TC/HDL

3

sICAM ICAM

SAA Cholesterol

2

IL--6 IL tHcy

1

HDL--C HDL

0 Q1

Q2

Q3

Q4

Quartile Qua t e of o Marker a e

(N Engl J Med 2000;342:836-843)

SAA: serum amyloid A sICAM: soluble intercellular adhesion molecule IL-6: interleukin-6


hs-CRP and CHD Risk: ARIC Study hs-CRP Level (mg/L) Average Ri A Risk k 1.0–3.0

High Hi h Ri Risk k >3.0

Model 1*

1 61 (1.21 1.61 (1 21–2 2.16) 16)

2 53 (1.88 2.53 (1 88–3 3.40) 40)

Model 2†

1.31 (0.96–1.80)

1.72 (1.24–2.39)

1.18 (0.71–1.96)

1.76 (1.01–3.03)

M d l 3† Model (LDL-C <130 mg/dl)‡

*Adjusted for age, sex, and race †Adjusted for age, sex, race, smoking, systolic BP, LDL-C, HDL-C, and diabetes ‡204 cases and 369 noncases Ballantyne CM et al. Circulation 2004;109:837-842.

Slide Source Lipids Online Slide Library www.lipidsonline.org


Nghieân cöùu JUPITER

((Justification f ffor the Use off Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) TNLS phaâ phan n nhom nhoùm ngau ngaãu nhien, nhieân mu muø ñoi, ñoâi ña trung taâ tam. m „ Muïc tieâu : Tìm hieåu lieäu ôû ngöôøi khoâng coù beänh tim maïch, coù LDL thaáp hôn ngöôõng caàn ñieàu trò vaø hsCRP cao, ñieàu trò baèng rosuvastatin coù ngaên ngöøa ñöôïc caùc bieán coá tim maïch naëng hay khoâng. „ Tieu Tieâu chuan chuaån choï chon n beänh : - Nam ≥ 50 tuoåi, nöõ ≥ 60 tuoåi - LDL < 130 mg/dl, g , TG < 500 mg/dl g - hsCRP ≥ 2 mg/l „


Keát quaû JUPITER : Taàn suaát doàn TCÑG chính

Placebo

Hazard Ratio 0.56 (95% CI 0.46-0.69) P < 0.00001

0.06

44%

0.04

Rosuvastatin 20 mg

NNT for 2y = 95 5y* = 25

0.00

0.02

Cum mulative Inc cidence

0.08

((NMCT,, ñoäät q quò, ò, ÑTN khoâng oån ñònh, ò , cheát do nguyeâ g y n nhaân tim maïïch,, taùi töôùi maùu)

0

1

2

4

Follow-up (years)

Number at Risk Rosuvastatin Placebo

3

8,901 8,901

8,631 8,621

8,412 8,353

6,540 6,508

*Extrapolated figure based on Altman and Andersen method

3,893 3,872

1,958 1,963

1,353 1,333

983 955

544 534

157 174

Ridker P et al. N Eng J Med 2008;359: 2195-2207


0.06

Keát quaû JUPITER : Tan Taàn suat suaát don doàn tö töû vong do moi moïi nguyen nguyeân nhaâ nhan n Placebo

20%

0.02

0.03

0.04

Rosuvastatin 20mg

0.00

0.01

Cum mulative Inc cidence

0.05

Hazard Ratio 0.80 (95% CI 0 0.67-0.97) 67-0 97) p=0.02

0 Number at Risk Rosuvastatin 8,901 Placebo 8,901

1

2

3

4

Follow-up (years) 8,847 8,852

8,787 8,775

6,999 6,987

4,312 4,319

2,268 2,295

1,602 1,614

1,192 1,196

683 684

227 246

Ridker P et al. N Eng J Med 2008;359: 2195-2207


Phaâ Phan n tích boå bo sung so soá lieäu cuû cua a JUPITER Lôiï ích cuûa rosuvastatin ñoái vôùi : ● Ngöôøi cao tuoåi ● Phuï nöõ ● Ngöôøi coù roái loaïn chöùc naêng thaän (eGFR < 60 ml/phuùt/1,73m2) „ AÛnh höôûng cuûa rosuvastatin treân nguy cô ñoät quò „ Muïc tieâu cuûûa ñieààu trò baèèng statin : caûû LDL laããn hsCRP „


Statin trong phoø phong ng ngöø ngöa a tieâ tien n phaù phatt ô ôû ngöôi ngöôøi cao tuoi tuoåi „ „

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Statin ít ñöôcï duøng cho ngöôø g i cao tuoåi. Tuoåi trung bình cuûa beänh nhaân trong WOSCOPS laø 55, trong AFCAPS/TexCAPS laø 58. Trong nghieân cöùu PROSPER ôû ngöôøi cao tuoååi (70(70-82 tuoååi), pravastatin giaûm 15% (p = 0,01) caùc bieán coá tim maïch naëng, tuy nhieâ nhien n trong phaâ phan n nhom nhoùm nhöõ nhöng ng ngöôi ngöôøi khoâ khong ng coù co tien tieàn sö söû beänh tim maïch (chieám 56% daân soá nghieân cöùu), möùc giaûm caùc bieán coá tim maïch khoâng coù yù nghóa thoáng keâ.


Tæ leä nöõ tham gia trong caùc nghieân cöùu phoø h øng ngöøøa tieâ ti ân phaù h ùt baè b èng statin t ti „ „ „

WOSCOPS: 0 AFCAPS/TexCAPS: 15% (997 /6605) JUPITER : 38,2% , ((6801 /17.802))


JUPITER â&#x20AC;&#x201C; Women Subgroup Data Rosuvastatin

Placebo

N (Rate*)

N (Rate*)

N=3426

N=3375

Primary endpoint**

39 (0.56)

Any MI

HR (95% CI)

P-value

70 (1.04)

0.54 (0.37-0.80)

0.002

10 (0.14)

18 (0.27)

0.54 (0.25-1.18)

0.11

Any stroke

18 (0.26)

23 (0.34)

0.77 (0.42-1.42)

0.40

Arterial revascularisation

8 (0.12)

29 (0.43)

0.27 (0.12-0.59)

0.0003

Arterial A i l revascularisation l i i or hospitalisation for unstable angina

8 (0.12) (0 12)

33 (0.49) (0 49)

0 24 (0.11-0.51) 0.24 (0 11 0 51)

<0.0001 0 0001

MI, stroke or CV death

36 (0.52)

48 (0.71)

0.73 (0.48-1.13)

0.16

N=5475

N=5526

Primary endpoint**

103 (0.88)

181 (1.54)

0.58 (0.45-0.73)

<0.0001

Any MI

21 (0.18)

50 (0.42)

0.42 (0.26-0.71)

0.006

Any stroke

15 (0.13)

41 (0.34)

0.37 (0.21-0.67)

0.0005

Arterial revascularisation

63 (0.54)

102 (0.86)

0.63 (0.46-0.86)

0.003

Arterial revascularisation or hospitalisation for unstable angina

68 (0.58)

110 (0.93)

0.63 (0.46-0.85)

0.002

MI, stroke or CV death

47 (0.40)

109 (0.92)

0.44 (0.31 (0.31-0.61) 0.61)

<0.0001

Women

Men

**Primary Endpoint: Time to first occurrence of a CV death, non fatal stroke, non-fatal MI, unstable angina or arterial revascularization Mora S et al. Circulation 2010; 120; 1069-1077

* Rates are per 100 person-years


Nguy cô tim maïch ôû ngöôøi beänh thaän maïn

(Harper CR. J Am Coll Cardiol 2008;51:2375-84)


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Trong nghieâ nghien n cöù cöu u WOSCOPS WOSCOPS, pravastatin khoâng giaûm nguy cô tim maïch ôû nhöõng ngöôøi beänh thaän man maïn.

(Circulation 2004;110:1557-1563)


45% (p = 0,002)


AÛnh höôûng cuûa statin treân nguy cô ñoät quò trong t caùùc nghieâ hi ân cöùùu phoø h øng ngöøøa ti tieâân phaù h ùt

(Circulation 2010;121:143-150)


(Lancet 2009;373:1175-1182)


TOÙ TOM M TAT TAÉT JUPITER chöùng toû : JU „ ÔÛ nam giôùi tuoåi ≥ 50 hoaëc nöõ giôùi tuoåi ≥ 60 khoâng coù tieàn söû beänh tim maïch, coù LDL < 130 mg/dl vaø hsCRP ≥ 2 mg/l, ñi àu tròò baè ñieà b èng rosuvastatin i keù k ùo daø d øi tuoååi thoï h vaøø ngaêên ngöøøa caùùc bieán coá tim maïch naëng. „ Lôi ôï ích c naø ay y khoâ o ng p phu uï tthuoä uoäc löù öaa tuoå tuo i (≥ (≥ 70 vs < 70), g giôù ôi tính (nam vs nöõ) vaø chöùc naêng thaän (GFR ≥ 60 ml/min/1,73 m2 vs GFR < 60 ml/min/1,73 m2). „ Nhöõ Nh ng ngöôøøi coùù döï d haä h äu toáát nhaá h át laø l ø nhöõ h ng ngöôøøi ñ ñaït ñ ñöôïc caûû 2 muïc tieâu LDL (< 70 mg/dl) vaø hsCRP (< 2 mg/l).


Cam Caûm ôn söï sö chu chuù yyù cua cuûa quyù quy ñaï ñaii bieu bieåu


4. Thay gi qua nghien cuu Jupiter