1
11234
23456
123456ACE
1ACE 2
7 123
2004-2005
2006Guidelines for Secondary Prevention of Myocardial Infarction
(JCS 2006)
2006 11
2
2004-2005
2000 1
2006
secondary prevention
cardiac events
cardiovascular
eventsvascular events
2
total mortality:
end point
Yusuf 3 1985
8
Soriano 4
8
8
5
JAMIS Japanese Antiplatelets Myocardial
Infarction Study 29.9
6 1 475
7 ST 8
CCU 7
secondary prevention
JCS 2006
8
3 910
JAMIS
67
JAMP Japanese Angina and Myocardial Infarction
Prospectivestudy group11
17 8
ST ST
ST
ST Q
Q ST
812 ST
1315ST ST
ST ST
ST
Classification of RecommendationsLevel of Evidence
1990
16 3
a
a
b1996 17
19991220048
ab 4
1999
18
ABC 3
Level of Evidence
148
18
1
2
8
a b a
b
Benefit >>> Risk
a Benefit >> Risk
b Benefit Risk
Benefit Risk
1
3
1 Classification of Recommendations18
a
b
2 Level of Evidence 18
A A
B B
C C
4
2004-2005
14
ACE
ARB
1
percutaneous
coronary intervention PCI
coronary artery bypass graftingCABG 2
CABG PCI
1
1 3
120042005
1
ACE ARB
2
PCI* CABG
PCI*CABG
5
2000
1998
1999
1
3 a a
1 6g Body Mass Index118.5 24.9 kg/m2 1 30 ml 50 %
25 % 7 % -3 1 300 mg Body Mass Index118.524.9 kg/m2
Body Mass Index118.524.9kg/m2
HbA1c 6.5 %
1 30 34
50162 mg 300 mg
2
LDL
a
a
ACE ACE EF40 % ACE
a 10 /LVEF 40 %a dl-aa
EPS3
24
*1 Body Mass Index kgmm*2 *3 EPS electrophysiological study
6
2004-2005
1
a'
18
ABC 3
18
18
ab 4
Benefit=Riskb
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1
24
3
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7
1 1 6g A
2Body Mass IndexBMIkgm2
18.5-24.9 A
31 30 ml
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A
a
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2004 192003
WHOISH 202003
7 2114090 mmHg
14090 mmHg
13080 mmHg
1922
1921
5
192123
1
1 1112 g 13
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1980 INTERSALT 1990
INTERMAP 12 g 2527 20
282004
2000
1 7 g 6 g
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28
8 g 2527
1112 g 24271 6 g
1
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INTERSALT
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Ca Ca
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Mg
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1921
Body Mass IndexBMIkgm2
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BMI 23.5 25
2426
1BMI 12 mmHg
21
192133
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1921341 3060 ml
11
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353630 ml
1 30 ml 19213237
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341921
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3-3
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A
5Body Mass IndexBMIkgm2
18.5-24.9 A
LDL 100
mgdl HDL 130
mgdl 3839
HDL
HDL 40 mgdl
3839 150 mgdl
38
LDL
3642HDL
38394142
LDL
3839
INTERMAP 4050 25 %
2643
2425 %
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7 %
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2643
INTERMAP
1 450 mg
350 mg 26431 300 mg
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-3
4445
-3
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243
LDL
45
HDL
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INTERMAP
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46BMI 25
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9
Body Mass IndexBMIkgm2
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3839
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10 %
1 kg
47
3839
HbA1c 6.5 %
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b
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383948HbA1c
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47INTERMAP 4050
50 %56 % 26
62 % 59 % 24
11 30 34
A
2
B
3
C
a
*
C
p11 4
8
1
1982 May 52 6
2132 %
Oldridge 53
O'Connor 544000
2025 %
Taylor 55
Cochrane Library 48
8940
20 % 26 %
3
4
22
10
2004-2005
ACCAHA 8
1 30 3-4
anaerobic thresholdAT
AT
5070 % 4060 %
HRR 4060 % 72
AT
AT 73
Borg 11-13
74
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Borg
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75
7677
4
66
3
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11
5657
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1 30
19
LDL
HDL
5960Taylor
55 14.3 mgdl
20.4 mgdl
61
6264
The National Weight Control Registry65
10 % 1
66
6769
70
CRP
71
2
11
50 %
2
248081
80822579
55 %
75 % 82 25
%
1.53 0.81 2.27
82
83
Houston-Miller Taylor
84
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4
5
6
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8
C
192185
37 20-40
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LDL
8687
38 % 6678
79
HRR k
220
k0.40.6
1 A
2
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4
EF50 %
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EF=3149%
3 5 6METS
0.10.2mV ST
EF30 %
15 mmHg
0.2 mV ST
3344
12
2004-2005
1921636567
1
2 2
24
87
C
1520
% 88
89
9091
1
B
2
C
459296
75
75
97
150-162 mg
A
2300 mg
B
3
A
a
150 mg150
mg200 mg
B
2
B
3
INR 2.0
A
b
1
C
2
INR 2.8-4.2
B
3
C
55
66
11
13
2
Japanese Antiplatelets in Myocardial Infarction Study
JAMIS7 Japan Multicenter Investigation for
Cardiovascular Diseases-MochidaJMIC-M98
JAMIS
81 mg
2 300 mg
3 JMIC-M
300 mg
50 mg
B
5
COX
COX-1 A2TxA2
COX
8 10
1 3050 mg 710
TxA2
Antithrombotic Trialists' Collaboration
ATT2 12 18,788
27
13.5 %
17.0 % p0.0001 25 %
ATT
75-150 mg
81-162 mg
5 18 5
COX 81
ADP
PDE
AbciximabGPb/a Eptifibatide
Tirofiban
TxA2
K K
AT
AT Xa
Ximelagatran
14
2004-2005
81 mg
99
100
1960 1999 7
1011990
2004 10 10 5,938
102
INR2.0
56 %
1.9
INR2.0
44%54 %20 %
2.5
INR 2.84.2
2 7
0.20
0.18
0.16
0.14
0.12
0.10
0.08
0.06
0.04
0.02
0.00
Prob
ablil
ity o
f Rei
nfar
ctio
n
0 100 200 300 400 500 600 700 800 900Days after
Randomization
Controln 230
Aspirinn 250
P 0.0045Odds Ratio 0.271
3 7
0.280.260.240.220.200.180.160.140.120.100.080.060.040.020.00
Prob
ablil
ity o
f Car
diov
ascu
lar
Even
ts
0 100 200 300 400 500 600 700 800 900 1000Days after
Randomization
Controln 230
Trapidiln 243 P 0.0039Odds Ratio 0.496
15
103
1,083104
50 mg150 mg
200 mg
ADP P2Y12
ADP GP ba
17 8
CAPRIEclopidogrel versus aspirin in
patients at risk of ischemic events10519,815
75 mg
325 mg
16 4
3
1
2
2
91 5 5.5 %
108 3 2.8 %
106
736
59 734 59
18 2.4 %
8 1.1 %
PDE cAMP
48 % 29 %
107
subacute stent
thrombosisSAT
108
SAT 109
SAT 107
110
111
INR2.2-3.5 55 6
INR1.5-2.1
60 0p
16
2004-2005
0.0103112
1*
A
2
B
3
A
a
A
60
100 mmHg PR
0.24 2
C
*
1965 Snow113 91
454628
16 35 %
7 16 %
Gteborg Metoprolol
Trial114Norwegian Multicenter StudyTimolol115-
blocker Heart Attack TrialBHATPropranolol116
1985 Yusuf 3 50,000 65
20 %
1997 Soriano4
711999 Freemantle 117 82
20 %23 %
4172 %118
80 % 119 ST
8 ST
120 ST
14
1
5121127
3 10
1
Yusuf 3
65
20 %
1
Beta-blocker Pooling Project Research Group
BBPP 1 9 13,679
24 %
128
2 10 Soriano 4
22
17
1990 73
1970
RRrelative risk 95 % 95 %
CI95 % confidence intervals
1975 RR 1
95 % CI
1981 95 % CI 1
Soriano 4 1990 RR 0.8995
% CI0.840.93
Very early treatment
12 RR 0.9495 %
CI0.871.01early treatment12 72
0.9195 % CI0.811.01late treatment72
0.8095 % CI0.730.88
3
4
Gottlieb 129 Cooperative
Cardiovascular Project
2
201,752 34 % 40 %
20 % RR 0.68
95 % CI0.580.802049 % 0.6095 % CI
0.570.6350 % 0.6095 % CI0.570.63
Basu 130 151
EA 45 %
remodeling 6
2001 CAPRICORN
the Carvedilol Post-Infarct Survival Control in LV
Dysfunctionstudy131 40
% 1,959
12 %15 % 0.7795 % CI0.600.98
Gottlieb 129
10 %
5121127122
1986 2002 1,896
1,029 867
16.2
454.4 %566.5 %
ORodds ratio 0.66p0.0595
% CI0.440.99 4
Killip Forrester
wall motion indexWMI 12
11
3.6 %
6.8 %
p0.05OR 0.5195 % CI0.261.01
2.0 %1.5 % 123
2
2004 ACC
AHA ST 132
4 122
%
P0.05
4.4 %
6.5 %
451029
56867
10
5
0
18
2004-2005
Barron 133
Barron
3
7.5 %30.7 %
Chen
134
1
122
135136
14
A
B
B
A
124
6.9 % 13.6 %
102 118
302 5 1.7
% 444 22 5.0 %
p0.05
1 138 1 0.7 %
157 5 3.2 %
189 8 4.2
% 179 18 10.1 %
p0.05
80
137139
126127
139144
Kendall 145 BHAT 3
11.7 %
7.8 % 33 %
19.2 %9.9 %
48 % Viskin Barron146
Soumerai 137
122
6.2 % 8.3 %
3.7 %5.9 %
147148Hjalmarson Olsson149
310
122124
3.7 % 6.8 %
p0.05124
2.3 %4.4 %
20 1
5.0 % 55 35.5 %
122124
1090
455
The Japanese -blockers and Calcium
Antagonists Myocardial InfarctionJBCMIInvestigators121
6
19
121
JBCMI
6121
144ACCAHA 8
Gheorghiade 150
Gottlieb
41,814 3,819
22.1 %17.7 %
129
RR
0.6095 % CI0.570.630.6095 %
CI0.570.63 0.6095 % CI0.57
0.63Chafin 151
BHAT116
146Gheorghiade
Goldstein144
ST
134137140142144146151154
2004 ACCAHA 8
PR
0.24
3ancillary properties
1
intrinsic sympathomimetic activityISA
membrane stabilizing activityMSA
Prichard 155
6 Follow-up events121
Primary end points 78 72 0.3493
Cardiovascular death 9 6 0.3772
Nonfatal reinfarction 5 7 0.6977
Unstable angina pectoris* 60 58 0.5722
Unstable angina due to coronary spasm* 7 1 0.0271
Nonfatal stroke 4 1 0.1481
Other cardiovascular event
Heart failure* 23 6 0.0011
-blocker Group Ca Antagonist Group p Valuesn 545 n 545
* Requiring hospitalization.
20
2004-2005
Yusuf 3 MSA
ISA
ISA
Soriano 4
1
ISA ISA
1MSA
MSAlipophilicity
8
Freemantle 1171 ISA
1
1
OR 1.1095 % CI0.891.39ISA
OR 1.1995 % CI0.961.47
ISA ISA
1
ISA ISA
1p0.01ISAp0.01MSA
p0.01
125
1 ISAMSAPrichard
4
114
a gradual titration scheme
ACCAHA 132150
4
Yusuf 3
1
12
156
23 157
1990 ACCAHA 158
I 2
1996
81217indefinitely
a
30 122 40 123125
3040
30
40
r e b o u n d
phenomenon
LDL
A
a
HDL
B
33
21
LDL
LDL
HMG-CoA
LDL
LDL
LDL 100 mgdl
38
LDL 100 mgdl
159 LDL
The Scandinavian Simvastatin
Survival Study4SCholesterol and Recurrent Events
CAREThe Long-Term Intervention with Pravastatin in
Ischaemic DiseaseLIPIDHeart Protection StudyHPS
Treating to New TargetsTNT4S
160
CARE
240 mgdl
161CARE
LDL 125 mgdl
LIPID
218 mgdl166-271 mgdl
162LIPID LDL
135 mgdl
HPS
163HPS
LDL 100 mgdl
TNT
LDL 130
mgdl 10 mg 80
mg
16480 mg LDL
77 mgdl10 mg 101 mg
2.2 % 22 %
GOTGPT 80 mg
LDL
100 mgdl
LDL
70 mgdl 165
4
HDL
The Bezafibrate Infarction PreventionBIP
200 mgdl
166
167
HDL
Veterans
Administration-HDL Intervention TrialVA-HIT
22 %
168 HDL-
LDL
HDL
LDL
100 mgdl
22
2004-2005
17.11000
54.31000 169
2 Japanese
Utilization of Simvastatin TherapyJUST
170
Coronary Artery Regression StudyCARS171Prevention
of Coronary Sclerosis PCS 172 Atheroma
ATHEROMA173
171172
5 The Pravastatin
Coronary Artery Bypass
174
220 mgdl LDL
140 mgdl 150 mgdl
HDL
2 8
175176
4142177
LDL
178
178
179180
C
a
1
A
2
B
C
1993 FDA181
NTG
ISDNISMN
3
44
23
182
183
Rapaport184139
ISDN 10.2 % ISDN
25.6 % ISDN p0.05
GISSI-
3185 ISIS-4186
19,39458,050
GISSI-3NTG 6.5 % 6.9 %ISIS-
4ISMN 7.34 % 7.54 %
1996 ACCAHA 187
24-48
48
ACE
188190
V-HeFT 1191 A-HeFT192
1932004
ACCAHA 8
90 mmHg 50 bpm
Ishikawa 194
1,002
6.6 % 3.1 %
5Kanamasa
195197Nagao 198
Nakamura 199MSMI 200MDPIT 201
202
JAMI
continuous
dosingeccentric dosing
1
1 3
2 24
2
2
185186
203204
1
2052062
34
185186
24
2004-2005
194201
197
197203204
3
aBenefitRiskbBenefitRisk
BenefitRisk
2
b
b
12-14
90 mmHg 50 bpm
1
2
3
4
IONA Study Group207 1-3
1.6 5,126
2,561 20 mg 1 2
2,565
436 17.0 %
378 14.7 %
p0.027IONA Study 208
Ishii 209 PCI
5
a
1
B
b
1
A
2ST
55
25
38 %
2 INVEST. CONVINCE
219220
b 1. B
A
2004 4 ACCAHA ST
23 2000
10
JBCMIJapanese beta-Blockers and Calcium Antagonists
Myocardial Infarction 1,090
2
455
121
1993
2
1994 1 1
55
Yui J-MICB 1,650
ACE 3
221
B
1
A
2
B
2000
210213
Furberg
214216
ACTION
7,665
GITS
4.9
217
214216
100 mmHg
1,997
24
CAMELOT 218
26
2004-2005
40 %
2,500
12 4
JBCMI J-
MICB
J-MICB
38 %ACE 46.4 %
201222226Pahor
ACE
25 %
227
PRAISE
228
ALLHAT
2 2 9
CONVINCE
220
Q
201230236
237239 33,357
ALLHAT
229
CONVINCE
220
1
A
2 40 %
100 mmHg
ACE
A
a
1 24
ACE
1 40-50 %
A
5 5
Nocalcium
antagonists Nifedipine
Long-actingShort-acting
4.0 %
11.6 %
4.0 %
30755
17146
12
10
8
6
4
2
0
6150
Car
diac
eve
nts
%
Effects of short- and long-acting nifedipine oncardiac events in
patients with myocardialinfarction
ACE 66
ACE 1
27
2 A
2
B
b
1 B
2
B
ACE
ACE
1980
ACE
240241
ACE
RA
242
ACE RA
243 ACE
244
RA
245246247
248
ACE
1
ACE
The Survival and Ventricular
EnlargementSAVE n2,231249
40 % 316
150 mg
42 24
20 % 37 %
25 %
Acute Infarction Ramipril Efficacy TrialAIRE
n2,006250 310
15 5 mg
10 mg 23 % 17
%
Trandolapril Cardiac EvaluationTRACE n
1,749251 37
35 %
1 mg 4 4 mg
24 50
2530 %
ACE
2
Cooperative New Scandinavian Enalapril Survival Study
CONSENSUSn6,090252
24
1 6.3 %
7.2 %6 10.2 %
11.0 %
RRrelative risk
1.1095 % 95 % CI:confidence interval
0.931.29
3.4 % 4.3 % p
0.06
28
2004-2005
12
9050 mmHg 3 %
12 % p0.001
24 RA
ACE
24
ACE
Fourth International Study of
Infarct SurvivalISIS-4 n58,050186
24
5 7.69 %
7.19 % 7 3 %
6
89.47 % 90.13 %1
87.47 %88.01 %
1
4.8 %
10.0 %
01
ACE
ST ST
Gruppo Italiano per lo Studio della Sopravvivenza
nell' Infarto Miocardico-3GISSI-3n19,394185
24
RR
0.8895 % CI0.790.99
RR 0.9095 %
CI0.840.98
60 % 5
24
7.5 mg 60 mg
Survival of Myocardial InfarctionLong-term
EvaluationSMILE n1,556253 6
1 10 %
6ACE
SAVE
AIRE
TRACE
SMILE
CCS-1
Consensus-
GISSI-3
ISIS-4
3-16
3-10
3-7
24
36
24
24
24
228/111520.4 %170/100416.9 %304/87634.7 %
38/7724.9 %617/68149.1 %312/304410.2 %597/94356.3 %
2088/290287.2 %
275/111624.6 %222/98222.6 %369/87342.3 %
51/7846.5 %65/6829.6 %286/30469.4 %673/94607.1 %
2231/290227.7 %
42
15
48
15
1
6
6
1
%ACE
95 %
ACE
0.50 0.75 1.00 1.25 1.50 1.75
29
14 %
Chinese Cardiac Study:CCS-1
n13,634254 36
4 6.25 mg 37.5 mg
8.4 % vs. 4.9 %
0.5 %
3
ACE
55
9,2975,128 65 66
51.9 %
The Heart Outcomes Prevention Evaluation StudyHOPE
255 1
4.5 17.8 %
14.0 %
RR 0.7895 % CI0.700.86p0.001
65 % 8 mg
EUROPE
n13,655256 4.2
1
8 % 10 %
20 %
Ca
ACE
7 ACE 2005 7
1 3 37.575
150
1 12 18.7575 R
150
510 20
2.5
1 12 2575
100
1 12 3060
120
1 1 0.252
2
1 1 1 20
510
1 1 510
1 1 510
1
1 2.55
1 1 24
1 1 520
1 1 12
1 1 24 8
mg
30
2004-2005
ACE
Japanese Angina and Myocardial Infarction Prospective
studyJAMPn8885.8 11
ACE
ACE
5
ACE
257 ACE
258
3
Nifedipine retard
221259
260273
274276 ACE
2005
12 ACE
ACE
HOPE 255
ACE
ISIS-4186GISSI-3185
SMILE253CCS-1254
ACE 24
24-48
CONSENSUS-
II252
Yusuf 4-6
ACE
2 7 7H O P E 2 5 5
EUROPE256
ACE
ACE
ACE
RA
ACE
ACE
B
a
ACE
ACE B
b
ACE B
ACE A
Angiotensinreceptor blockerARB
2
31
ACE
RA
A RA
A 1AT1
278A
279
A RA
ACE
A
1
A
1997
12.5 mg 2550 mg
18.75 mg37.5150
mg Evaluation of Losartan
in the ElderlyELITE n72248 280
9.4 % 13.2
% 32 %p0.075
14
ELITE n3,152281 2
vs.
17.7 % vs.15.9 %8.2 % vs.6.4 %
2 % vs.1.8 %1.1 % vs.0.7 %
9.0 % vs. 7.3 %
9.7 % 14.7 % p
0.001
0.3 % vs.2.7 %
ELITE
A
ACE A
Randomized Evaluation of Strategies for Left Ventricular
DysfunctionRESOLVD282
43
Valsartan Heart Failure Trial
Val-HeFT n50,01023 283
ACE
ACE
3
Candesartan in Heart Failure-
Assessment of Reduction in Mortality and Morbidity
CHARM n759950-60 %284
38
16 %
CHARM Val-HeFT283
3 ARBACE
2
A
Optimal
Therapy in Myocardial Infarction with the Angiotensin
Antagonist LosartanOPTIMAAL n5,477285
Valsartan in Acute Myocardial Infarction TrialVALIANT
n14,500286 2
OPTIMAAL
32
2004-2005
12.5 mg
50 mg
37.5 mg 3 150 mg
2.7
18 % 16 % RR
1.1395 % CI:0.991.28p0.07
45 mg
287
2003 VALIANT
320 mg 150 mg
180 mg 150 mg
1
Val-HeFT283CHARM284
A ACE
AT2
288
A ACE
A
class effect
ACE
OPTIMAALVALIANT
A ACE
ACE
A
ARCH-
JAssessment of Response to Candesartan in Heart Failure
in Japann3006 289290
60 %
291
292
A ACE
293297
8 2005 10
1 1 2550
100
1 1 48 12
28
1 1 4080
160
1 1 2040
80
520 40
1 510
mg
33
A
258
A
ACE
ACE
ACE
A ACE
2005
A
A
23,400
ONTARGET 298 5.5
2008 1
A
A
ACE
ACE
A
B
a
C
b
B
B
299303
304305
AFFIRM 306
AFFIRM
705 306307
308309
a
1
A
210
2LVEF
40 % B
3
77
12
34
2004-2005
dl- B
4
C
b
dl-
B
dl-
A
310313 2
10
CAST
314315
304316320
BASIS320321
316
CAMIAT3211202
10 1 3
40 % EMIAT323
324325
326
EMIAT
1
40 % 5 327
40 %
40 %
CAMIAT322
dl
324328329
328333
CASCADE328
334
131335336
MUSTT337
a
1
A
3
35
2LVEF40 %
B
a
LVEF30 % A
b
LVEF31-40 %
B
1
C
2LVEF40 %
C
2
338339
AVID340
CASHCIDS341342
0.72
343344
LVEF35 %
MADIT345
MUSTT346349LVEF40 %
MADIT350351
LVEF30 %
20
30 % 1252
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332
20
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T
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2004-2005
JCS2002
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C
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24
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AMI
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38
2004-2005
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