2 0 %
5%
1Glasgow MONICA
100
2s t a t i n s
20-30%
30-50%
30-40%
35%
( r e v a s c u l a r i z a t i o n )
(WOSCOS
4-S
CARE
LIPID
)
ATP-III
( H P S
CARDS )
( HPS
PROSPER
ASCOT-L ASCOT-L A
A L L H AT- L L A )
( PROVE IT )
LDL
100
mg/dL
70 mg/dL
Statins
(
ST
S T
)
Statins
statins
stains
( Acute coronary syndrome )
Statins
( Evidence-based medicine )
3
statins
4( pleiotropic effects )
5(1)
( regression )
(2)
(3)
C R P
(4)
(5)
statins
L D L - C
s t a t i n s
statins
64S study
7statins
statins
statins
2000
( ACC/AHA )
ST
8Nitroglycerin
-blockers ACE
statins
( 2000
)
A C S
4
statins
LDL
statins
statins
statins
CARE
pravastatin
placebo
2
9HPS
Simvastatin
2
10statins
11,
statins
( 2001 )
12( MITR study )
13Mayo Clinic
( 2000 )
GUSTO II
( 2001 )
14PRISM
statin
( 2002 )
15GRACE
( 2004 )
17AMI ( 2005 )
165 8
40,389
80
1222,683
14
5,528
statins
1 4 , 0 7 1
s t a t i n s
34%
( p<0.001 )
3 6 %
statin
64%
A M I
( German maximal individual therapy in AMI
re-gistry )
statins
131994-1998
6,067
s t a t i n s
1 5 %
15.2%
1999-2000
2,268
statins
76%
13.2%
statins
( p<0.001 )
Mayo Clinic 1993-1999
705
28%
statins
N o n S T
3 %
s t a t i n s
1 2 %
s t a t i n s
s t a t i n s
( p<0.01 )
Gusto IIb
1,460
1,460
statins
10,170
6
3.4%
1.5%
statins
( p<0.001 )
tirofiban
PRISM ( Platelet Receptor
Inhibition in Ischemic Syndrome Management )
tirofiban
heparin
2,152
300-325mg Aspirin
statins
151,616
1,249
s t a t i n s
3 7 9
statins
6
86
statins
3 0
statins
statins
55%
statins
3 . 2 4
s t a t i n s
7 2
Troponin T
7 2
statins
statins
statins
( SYMPHONY
2nd SYMPHONY )
37
931
12,365
39,52
s t a t i n s
3
s t a t i n s
8 , 4 1 3
statins
90
statins
0 . 5 8
( GRACE
Global Registry of Acute Coronary
E v e n t s )
1 4
9 4
1999
2002
19,537
statins
( 4,056
)
(
15,481
)
1 7statins
( 50% )
statins
ST
( 40% )
C K
statins
statins
50%
300,823
statins
1,118
24
statins ( 21,978
)
statins ( 126,128
)
statins ( 9,411
)
16statins
( 4-5% )
15%
16.5%
statins
statins
statins
s t a t i n s
18TNT study
15,432
open-labelled
10mg
80mg
atorvastatin
5 7 %
statins
6
wash-out
24
8
3 1
statins
statins
19statins
statins
statins
statins
( RCT, random controlled trial )
( double blind )
( placebo )
sta-tins
statin
ACS
1.Lipid-CAD (L-CAD)
202.Pravastatin Turkish
213.FLORIDA
( Fluvastatin on Risk Diminishing
After Acute Myocardial Infarction )
114.MIRACL ( Myocardial Ischemia Reduction
with Aggressive Cholesterol Lowering )
225.PRINCESS
236.A-Z study
Z phase
247.PROVE-IT trial
25L-CAD
40 mg pravastatin
cholestyramine
nicotinic acid
(
conven-tional )
126
(
LDL-C
136
260mg/dL
)
statins
20Pravastatin Turkish
150
40 mg
pravastatin
Trial
(P
)
MIRACL
Atorvastatin
24-96
16 weeks
No
3086
16 weeks
14.8% in
RR 0.84
(2001)
80 mg vs.
hours
Atorvastatin
(0.70-0.99)
Placebo
vs.17.4%
in Placebo
PRINCESS
Cerivastatin
48
48 hours
Cerivastatin,
3605
24 months
Up to
P=0.37
(2002)
0.4 mg or
hours
to 3 months
0.4 mg/d
4.5 months:
placebo
13% in
Cerivastatin
vs. 14%
in Placebo
A to Z, Z phase
Simvastatin
120 hours
120 hours
Simvastatin,
4497
24 months
14.4% in
P=0.14
(2004)
(40 mg/d
after
to 120 days
80 mg/d vs
Simvastatin
for 30 d then
hospitalization
20 mg/d
vs. 16.7%
80 mg/d)
in Placebo
vs usual care
for 120 d
PROVE IT-
Atorvastatin,
Within
2 years
No switch
4126
24 months
22.4% in
P=0.005
TIMI 22 (2004)
80 mg/d vs
10 days
atovastatin
pravastatin,
vs. 26.3%
statins
21statin
MIRACL
22(
)
3086
Non ST
2 4 - 9 6
8 0 m g
Atorvastatin
16
A t o r v a s t a t i n
14.8%
17.4% ( p<0.05 )
Atorvastatin
16%
statin
PRINCESS ( The Prevention
o f I s c h e m i c E v e n t s b y E a r l y Tr e a t m e n t o f
Cerivastatin study )
cerivastatin
ST
ST
3,605
cerivastatin
2 0 0 1
8
4 . 5
cerivastatin
cerivastatin
23A to Z
( Z
)
24s t a t i n
4497
statin
placebo
72
simvastatin ( 40mg )
statin
40mg
80mg
simvastatin
20mg
simvastatin
2
(
)
11%
( p=0.14 )
statins
2
PROVE-IT
( Pravastatin or
Atorvastatin Evaluation & Infarction Therapy
TIMI-22 )
pravas-tatin 40mg
atorvastatin 80mg
4 , 0 0 0
2 4 0 m g / d L
3 0
pravastatin
26.3%
atorvastatin
22.4%
16% ( p=0.005 )
3 0
A t o r v a s t a t i n
Pravastatin
statins
L D L
statins
( 2004 )
statins
26NSTE
class I
24-96
statins
L D L
1 0 0 m g / d L
Class IIa
statins
1.Braunwald E. Acute myocardial infarction--the value of being prepared. N Engl J Med 1996; 334: 51-2.
2.Tunstall-Pedoe H, Morrison C, Woodward M, Fitzpatrick B, Watt G. Sex differences in myocardial infarction and coronary deaths in the Scottish MONICA population of Glasgow 1985 to 1991. Presentation, diagnosis, treatment, and 28-day case fata-lity of 3991 events in men and 1551 events in women. Circulation 1996; 93: 1981-92.
3.Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program
Adult Treatment Panel III guidelines. Circulation 2004; 110: 227-39.
4.Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA 1998; 279: 1643-50.
5.Rosenson RS. Pluripotential mechanisms of cardioprotection with HMG-CoA reductase inhibitor therapy. Am J Cardiovasc Drugs 2001; 1: 411-20.
6.Robinson JG, Smith B, Maheshwari N, Schrott H. Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J Am Coll Cardiol 2005; 46: 1855-62. 7.Randomised trial of cholesterol lowering in 4444 patients with
coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-9.
8.Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guide-lines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol 2000; 36: 970-1062.
9.Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravas-tatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 1001-9. 10.Collins R, Armitage J, Parish S, Sleigh P, Peto R. MRC/BHF
Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003; 361: 2005-16.
11.Wright RS, Murphy JG, Bybee KA, Kopecky SL, LaBlanche JM. Statin lipid-lowering therapy for acute myocardial infarc-tion and unstable angina: efficacy and mechanism of benefit. Mayo Clin Proc 2002; 77: 1085-92.
12.Stenestrand U, Wallentin L. Early statin treatment following a-cute myocardial infarction and 1-year survival. JAMA 2001; 285: 430-6.
13.Zahn R, Schiele R, Schneider S, et al. Decreasing hospital mor-tality between 1994 and 1998 in patients with acute myocardial infarction treated with primary angioplasty but not in patients treated with intravenous thrombolysis. Results from the pooled data of the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Registry and the Myocardial Infarction Registry (MIR). J Am Coll Cardiol 2000; 36: 2064-71. 14.Aronow HD, Topol EJ, Roe MT, et al. Effect of lipid-lowering
therapy on early mortality after acute coronary syndromes: an observational study. Lancet 2001; 357: 1063-8.
15.Heeschen C, Hamm CW, Laufs U, Snapinn S, Bohm M, White HD. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation 2002; 105: 1446-52. 16.Fonarow GC, Wright RS, Spencer FA, et al. Effect of statin use
within the first 24 hours of admission for acute myocardial in-farction on early morbidity and mortality. Am J Cardiol 2005; 96: 611-6.
17.Spencer FA, Allegrone J, Goldberg RJ, et al. Association of statin therapy with outcomes of acute coronary syndromes: the GRACE study. Ann Intern Med 2004; 140: 857-66.
18.McGowan MP. There is no evidence for an increase in acute coronary syndromes after short-term abrupt discontinuation of statins in stable cardiac patients. Circulation 2004; 110: 2333-5.
19.Rothman KJ, Greenland S. Modern Epidemiology. 2nd ed. Philadelphia: Lippincott-Raven Publishers; 1998.
20.Arntz HR, Agrawal R, Wunderlich W, et al. Beneficial effects of pravastatin (+/-colestyramine/niacin) initiated immediately after a coronary event (the randomized Lipid-Coronary Artery Disease [L-CAD] Study). Am J Cardiol 2000; 86): 1293-8. 21.Kayikcioglu M, Can L, Kultursay H, Payzin S, Turkoglu C. Early
use of pravastatin in patients with acute myocardial infarction undergoing coronary angioplasty. Acta Cardiol 2002; 57: 295-302.
22.Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001; 285: 1711-8.
23.www.escardio.org/knowledge/OnlineLearning/slides/ESC_Co ngress_2004_Munich/R.S.Wright-FP1914 (accessed at Jan. 10, 2006)
24.de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004; 292: 1307-16.
25.Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syn-dromes. N Engl J Med 2004; 350: 1495-504.
26.Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guide-lines for the management of patients with ST-elevation my-ocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation 2004; 110: 588-636.
Updated Evidence on Lipid Lowering by Statins
on Prognosis of Acute Coronary Syndrome
Kuo-Liong Chien
Acute coronary syndrome is a medical emergency. Its clinical presentations as ST elevation myocardial in-farction (MI), non-ST elevation MI, or unstable angina, are related with high mortality. Evidence-based medicine showed lipid lowering effects by statins use can reduce cardiovascular events in primary and secondary clinical trial data. But the timing of statins in acute coronary syndrome was still arguable. It was unknown if early use of statin improved prognosis in acute coronary syndrome. This review focused on the recent evidences on the is-sues of statins use in acute coronary syndrome, including observational data and clinical trial data. ( J Intern Med Taiwan 2006; 17: 45-51 )
