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International Cardiovascular Disease Statistics 2005; AHA
Hypercoagulable states Life-style (e.g., Homocysteinaemia smoking, diet, Hyperlipidaemia lack of exercise) Insulin resistance Diabetes Obesity Hypertension Genetics Infection? Age
Atherosclerosis
Gender
American Heart Association. Heart and Stroke Facts: 1997 Statistical Supplement; Wolf. Stroke 1990;21(suppl 2):II4II-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.
1.Grundy SM et al. Circulation. 2004; 110: 22739. 2.Gordon DJ, Probstfield JL, Garrison JD et al. Circulation 1989; 79: 8-15. 3.Boden W. American Journal of Cardiology 2000; 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 Med 1999; 341:410-418
NC tien cu, ngau nhien, so sanh cheo (simvastatin vi gia dc). cac bien co tim mach cho oi tng co nguy c cao.
Muc tieu NC: Simvastatin co lam giam ty le t vong va Tieu ch chnh: Ty le t vong chung, Ty le cac bien co
Simvastatin 40 mg
Nguy c BMV
Simvastatin 40 mg
60
100
LDL-C (mg/dL)
TNT Trial
10,003 benh nhan benh M vanh on nh Tuoi 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
Atorvastatin 80 mg n=4,995
Atorvastatin 10 mg n=5,006
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 khong t vong . Theo doi 4.9 nam.
randomised to atorvastatin 80 mg/d (n = 4439), or simvastatin 20 mg/d (n = 4449), with a median follow-up of 4.8 years.
coronary event (coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitation).
11
IDEAL
Major coronary event in 463 on simvastatin (10.4%) and
411 on atorvastatin (9.3%) P = 0.07 (not significant); nonfatal MI in 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
12
PROVE-IT
The Pravastatin or Atorvastatin Evaluation and Infection Therapy trial (PROVE-IT/TIMI-22)
4162 Patients with acute coronary syndrome
13
reduction in nonfatal MI and CHD death beyond treatment with pravastatin 40 mg.
approximate additional 22% reduction in major CHD events in the atorvastatin group at 5 years.
14
Secondary Prevention
20
4S - Rx
LIPID - Pl 15 LIPID - Rx CARE - Rx HPS - Rx TNT Atv80 PROVE-IT Atv 5 TNT Atv10 PROVE-IT - Pra CARE - Pl HPS - Pl
10
0 40 (1.0) 60 (1.6) 80 (2.1) 100 (2.6) 120 (3.1) 140 (3.6) 160 (4.1) 180 (4.7) 200 (5.2)
MCAEs (%)
18 16
15.9
14
12 10 8 6 4 2 0
6.7
Rosuvastatin
Control
1.0 1.5 2.0 2.5 3.0 Years post randomization 703 (84.2) 686 (83.6) 666 (80.9) 642 (78.8) 647 (80.2) 610 (76.1)
3.5
4.0
MACE, major adverse cardiac event. Serruys PW. Presented at: ACC 51st Annual Scientific Session; March 20, 2002; Atlanta, GA.
A large number of clinical events occur in those with below average cholesterol levels
Total Cholesterol Distribution: CHD vs Non-CHD Population Framingham Heart Study26-Year Follow-up
No CHD
CHD
6.5
7.7
Nonfatal MI/CHD death* CHD death Nonfatal MI PCTA/CABG Stroke All cardiovascular deaths Total mortality#
31 28 31 37 11 32 22
* primary endpoint # study not powered to detect differences in this endpoint RRR relative risk reduction
Shepherd J et al. N Engl J Med 1995;333:13011307.
Years
AFCAPS/TexCAPS
6605 patients. Average TC and LDL-C levels (Mean TC 5.71
mmol/L, LDL-C 3.89 mmol/L, mean HDL-C level 0.94 mmol/L and median (SD) TG levels were 1.78 (0.86) mmol/L).
0.07
Cumulative incidence 0.06 0.05 0.04 0.03 0.02 0.01
placebo lovastatin
0.00
0.0 1 2 3 4 5 >5 Years of follow-up
Statin and Usual Care in Hypertensive Patients with Average Cholesterol Levels: ALLHAT-LLT
Number of events
Outcomes
All-cause mortality CVD deaths Non-CVD deaths Cause unknown Fatal CHD and nonfatal MI All stroke Heart failure
RR relative risk
pravastatin (n=5170)
631 295 302 34 380 209 243
RR
p-value
ALLHAT
Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C.
The results may be due to the modest differential in total cholesterol (9.6%) and LDL-C (16.7%) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention.
(Average cholesterol)
ASCOT-LLA: Anglo-Scandinavian Cardiac Outcomes Trial Lipid Lowering Arm - RESULTS continued Nonfatal MI and fatal CHD
Proportion of patients (%) 4
2 1
0 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Years after randomization
Atorvastatin
JUPITER - Objective
The primary objective: Long-term rosuvastatin 20 mg decreases the rate of first major cardiovascular events compared with placebo in patients with low to normal LDL-C + elevated CRP levels
No history of CAD men 50 yrs women 60 yrs LDL-C <130 mg/dL CRP 2.0 mg/L
Rosuvastatin 20 mg (n=8901)
Placebo
run-in
Placebo (n=8901)
Visit: Week:
1 6
2 4
3 0
4 13
6-monthly
Final
Lead-in/ eligibility
Randomisation
CAD=coronary artery disease; LDL-C=low-density lipoprotein cholesterol; CRP=C-reactive protein; HbA1c=glycated haemoglobin Ridker P et al. N Eng J Med 2008;359: 2195-2207
Placebo
44%
Cumulative Incidence
0.06
0.04
Rosuvastatin 20 mg
0.00 0
Number at Risk Rosuvastatin Placebo 8,901 8,901 8,631 8,621 8,412 8,353 6,540 6,508
0.02
Follow-up (years)
3,893 3,872 1,958 1,963 1,353 1,333 983 955 544 534 157 174
Nghin cu Phng nga th pht 1994 1996 1998 2002 2004 4S CARE LIPID HPS TNT
Thuc
S bnh nhn
1998
2003
AFCAPS/TexCAPS
ASCOT-LLA
Lovastatin
Atorvastatin
6,605
10,305
37%
36%
2005
JUPITER
Rosuvastatin
17,802
44%
Ket luan
Statin la thuoc hieu qua trong phong nga bien co M vanh 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