Acute Coronary Syndromes and
the Role of Critical Pathway
Christopher Cannon, M.D.
Brigham and Women’s Hospital
Boston
1
Aspirin and Thrombolysis in
Acute MI
% of Patients
15
35 Day Mortality
13.2
10.7
10.4
10
8.0
5
0
Placebo
Aspirin
ISIS-2. Lancet 1988; 2:349-60.
SK
Aspirin + SK
2
TIMI 2: Effect of Time to Treatment
% of Patients
10
8
6 Week Mortality
*P=0.05
6.2
5.2
6
3.7
4
2
1 hour faster
treatment
=
3.2* 10 lives saved
per 1000 patients
treated
0
3-4 h
2-3 h
1-2 h
TIMM, et al. Circulation. 1991;84:II-230.
<1 h
3
Improving Thrombolysis: t-PA vs. SK
% of Patients
TIMI 1:
Reperfusion
Occluded arteries
80
*P<0.001
60
62
0
SK
t-PA
Mortality
8
7.3
6
*P<0.001
6.3
4
40
20
GUSTO 1:
31
2
0
TIMI Study NEJM 1985;312:397-401. GUSTO Inv. NEJM 1993; 329:673-682.
Thrombolysis vs. Primary Angioplasty
30 Day Mortality
% of Patients
10
7.2
6.5
4.4
5
4.2
0
Thrombolysis
PTCA
t-PA
Stent + IIb/IIIa
Weaver WD, JAMA 1997; 278:2093-2098. Schomig A, N Engl J Med 2000; 343:385-91
5
Medical Treatment After MI
Mortality During Follow-up
12.0
11.5
10.7
8.2
8.1
10
6.1
5
at
in
St
ac
eb
o
Pl
AC
E
ac
eb
o
Pl
oc
ke
r
Bb
l
ac
eb
o
0
Pl
% of Patients
15
ISIS-1 Lancet 1986; 2:57-66; HOPE N Engl J Med 2000; 4S. Lancet 1994;
6
344:1383-1389.
ACUTE MI GUIDELINES 11/96
Drug Rx Peri MI: Meta-Analyses
Number
RR Death
p value
Beta blocker during MI
28,970
.87 (.77-.98)
0.02
Beta blocker post MI
24,298
.77 (.70-.84)
<0.001
ACEI during MI
100,963
.94 (.89-.98)
0.006
ACEI post MI if LV dysfxn
5,986
.78 (.70-.86)
<0.001
Nitrates during MI
81,908
.94 (.90-.99)
0.03
Ca++ blockers
20,342
1.04 (.95-1.14)
NS
Magnesium
61,860
1.02 (.96-1.08)
NS
Lidocaine
9,155
1.38 (.98-1.95)
NS
Class I Antiarrhythmics
6,300
1.21 (1.01-1.44)
0.04
NEJM 335:1662, 1996
UA/NSTEMI 9/00
Class I Recommendations
for Anti-Ischemic Therapy
Continuing Ischemia/Other Clinical High-Risk Features
• Bed rest + continuous
ECG monitoring
• 02 to maintain Sa02 >90%
• NTG IV
• -Blockers, oral
• Morphine IV for pain
• IABP if ischemia or BP
• ACEI for HTN or  LVEF
(possibly all patients)
(+IV if high risk)
Braunwald et al. J Am Coll Cardiol. 2000;36:970-1062.
8
UA/NSTEMI 9/00
Class I Recommendations for
Antithrombotic Therapy*
Definite ACS
With Continuing Ischemia
or Other High-Risk Features†
or Planned PCI
Likely/Definite
ACS
Possible
ACS
Aspirin
+
IV heparin
+
IV platelet
GP IIb/IIIa antagonist
Aspirin
+
Subcutaneous
LMWH
or
IV heparin
Aspirin
* Clinical data on the combination of LMWH and platelet GP IIb/IIIa antagonists are lacking.
Their combined use is not currently recommended.
† High-risk features were previously listed; others include diabetes, recent MI,
and elevated cardiac TnT or Tnl.
Braunwald et al. J Am Coll Cardiol. 2000;36:970-1062.
9
Class I Recommendations:
Early Invasive Strategy
1. Early invasive strategy in patients with UA/NSTEMI and any of the
following high-risk indicators:
a. Recurrent angina/ischemia at rest or with low-level activities
despite intensive anti-ischemic rx
b. Recurrent angina/ischemia with CHF symptoms, S3 gallop,
pulmonary edema, worsening rales, or new or worsening MR
c. High-risk findings on noninvasive stress testing
d. Depressed LV systolic function
e. Hemodynamic instability
f. Sustained VT
g. PCI within 6 months
h. Prior CABG
2. In the absence of these, either an early conservative or an early
invasive strategy in hospitalized patients without contraindications for
revascularization
Braunwald et al. J Am Coll Cardiol. 2000;36:970-1062.
10
UA/NSTEMI 9/00
Class I Recommendations:
Risk Factor Modification
1. Smoking cessation and achievement or
maintenance of optimal weight, daily exercise,
and diet
2. HMG-CoA reductase inhibitors for LDL >130
mg/dL
3. Lipid-lowering agent if LDL after diet is >100
mg/dL
4. Hypertension control to a blood pressure of
>130/85 mm Hg
5. Tight control of hyperglycemia in diabetes
Braunwald et al. J Am Coll Cardiol. 2000;36:970-1062.
11
GUARANTEE
Implementation of AHCPR Guidelines
for Unstable Angina in 1996:
Unfortunate Differences Between Women and Men
Results from the GUARANTEE Registry
GUARANTEE
Global Unstable Angina Registry
ANd Treatment Evaluation
6 Regions
 35 Hospitals
 2,948 Patients

GUARANTEE
Men
No. Pts
1788
Medical Management
Women
P value
1160
Adjuste
d
P value
On Admission
ASA (%)
84
Heparin (%) 66
B-blockers (%)53
80
60
49
0.018
0.001
0.039
0.016
0.080
0.086
At Discharge
ASA (or Warfarin)77
69
0.001
0.001
All of above (%) 31
24
0.001
0.007
GUARANTEE
Men
No. Pts
Cath (%)
PTCA (%)
CABG (%)
Catheterization /
Revascularization
Women
1788
53
1160
44
18
10
12
7%
P value
Adjuste
d
P value
0.001
0.001
0.002
0.004
0.017
0.001
0.15
0.16
0.53
0.05
In Pts Meeting AHCRP criteria
59
CABG (% done) 46
Cath (% done)
56
36
GUARANTEE
Medical Management
Age
Age <65 Age >65 P value
No. Pts
1638
1309
Adjuste
d
P value
On Admission
ASA (%)
83
Heparin (%) 64
B-blockers (%)50
81
62
52
0.17
0.25
0.46
0.24
0.19
0.68
At Discharge
ASA (or Warfarin)71
78
0.001
0.003
All of above (%) 28
28
0.92
0.60
GUARANTEE
Medical Management
Non-Q wave MI vs. Unstable Angina
UA
No. Pts
2600
NQWMI
P value
300
Adjuste
d
P value
On Admission
ASA (%)
82
Heparin (%) 61
B-blockers (%)49
87
85
63
0.031
0.001
0.001
0.069
0.001
0.001
At Discharge
ASA (or Warfarin)73
82
0.001
0.001
All of above (%) 26
45
0.001
0.001
GUARANTEE
TIMI III Registry
Pre Guideline
Men
No. Pts
Women
Post Guideline
Men
Women
1678
1640
1788
1160
82
63
41
77
50
35
84
66
53
80
60
49
On Admission
ASA
Heparin
B-blockers
Comparing Pre- to Post-:
P values :
ASA
Heparin
B-blocker
Men
0.30
0.13
0.001
Women
0.05
0.001
0.001
Stone PH et al. JAMA 1996;275:1104; Scirica 1999 AHJ
Aspirin within 24 hours
100
94%
% survival
80
78%
P = .002
60
40
Aspirin ( n = 189 )
20
No aspirin ( n = 33 )
0
0
8
16
24
32
Weeks post discharge
Giugliano RP,et al. Arch Intern Med 2000;160.
40
48
Heparin within 24 hours
93%
80
85%
P = .06
% survival
100
60
40
Heparin ( n = 181 )
20
No heparin ( n = 47 )
0
0
8
16
24
32
40
post
discharge
Giugliano RP,et al. ArchWeeks
Intern Med
2000;160.
48
Unadjusted One Year Survival
95%
Percent surviving
100
80
P = .0001
81%
60
40
Guideline ( n = 189 )
20
Not guideline ( n = 86 )
0
0
8
16
24
32
Weeks post discharge
Giugliano RP,et al. Arch Intern Med 2000;160.
40
48
NRMI-1:
NRMI-1:
Medical
Medical Therapy
Therapy In-hospital
In-hospital
Thrombolysis
No Thrombolysis
No. Pts
84477
156512
ASA (%)
84
63
Heparin (%)
97
56
IV nitro (%)
76
50
IV B-Blockers (%)
17
6
Oral B-Blockers (%)
36
29
Ca-Blockers (%)
29
42
Rogers WJ, et al. Circulation 1994;90:2103-2114.
NRMI-2: Distribution of Door-to-Needle
Times
N=84,423
>90 mins
12%
0-30 mins
34%
61-90 mins
14%
46-60 mins
15%
31-45 mins
25%
Cannon CP ACC 2000
40%
Baseline Characteristics
Door-to-needle time (mins)
No. Pts
0-30
28,176
31-60
61-90
33,635 11,531
Age (mean)
Female (%)
Non-white (%)
DM (%)
Prior MI (%)
Anterior (%)
61.2
26
13
16
16
32
63.5
34
14
20
19
34
13
88
4
1.7
HMO (%)
14
Urban Hosp
87
Pre-hosp ECG 7
Onset-door (hr) 1.4
>90
10,244
P value
65.1
39
16
23
21
37
65.7
42
19
27
21
41
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
12
87
3
1.9
11
86
3
2.0
<0.0001
0.0005
<0.0001
<0.0001
(Median)
24
MV Adjusted Odds of Death
NRMI-2: Thrombolysis
Door-to-Needle Time vs. Mortality
P=0.0001
1.4
P=0.01
P=NS
1.2
1.23
1.11
1.03
1
0.8
N=28,624
33,867
11,616
10,316
0.6
0-30
Cannon CP ACC 2000
31-60
61-90
Door-to-Needle Tim e (m inutes)
>90
MV Adjusted Odds of Death
NRMI-2: Primary PCI
Door-to-Balloon Time vs. Mortality
P=NS
2.2
P=NS
P=0.01 P=0.0007 P=0.0003
1.8
1.62
1.4
1.61
1.41
1.15
1.14
1
0.6
0.2
N=2,230
5,734
6,616
0-60
61-90
91-120
4,461
2,627
121-150 151-180
5,412
>180
Door-to-Balloon Tim e (m inutes)
Cannon CP, et al JAMA 2000;283:2941-2947.
NRMI-2: Primary PCI
Distribution of Door-to-Balloon times
N=27,080
30
24.4
% of Patients
25
21.2
20.0
20
16.5
15
10
9.7
8.2
5
0
0-60
61-90
91-120
121-150
151-180
Door-to-Balloon Time (minutes)
>180
US News and World Report
30-day mortality by hospital category*
30%
25%
20%
15%
10%
5%
0%
US News
Invasive
Non-invasive
Stars
* 25th, 50th and 75th percentile for each category
US News and World Report
Aspirin in ideal candidates
100%
80%
60%
40%
20%
0%
Top-ranked
Invasive
Non-invasive
29
US News and World Report
Beta-blockers in ideal candidates
100%
80%
60%
40%
20%
0%
Top-ranked
Invasive
Non-invasive
30
30-day Mortality
US News Top-ranked vs Other Hospitals
Odds ratio
1.1
1
0.9
0.8
0.7
Adjusted*
+ASA
Adjusted*
+BB
Adjusted*
+RPF
* Adjusted for patient, hospital and physician characteristics
Quality implications
– The lower mortality observed in “America’s Best
Hospitals” appear to be explained in part by their
higher use of aspirin and beta-blockers
– Any hospital can be one of “America’s Best” by
increasing their use of aspirin and beta-blockers
32
EUROASPIRE II
European Action on Secondary and Primary
Prevention through Intervention
to Reduce Events
Euro Heart Survey Programme
European Society of Cardiology-ESC
Wood et al. Lancet 2001; 357: 995-1001
 European Society of Cardiology ESC
Therapeutic control of total cholesterol
at interview
EUROASPIRE
% reaching goal* at interview among those using
lipid-lowering medication
by center
39
BEL/GHE
31
CZE/PP
70
FIN/KUO
44
FRA/LLRT
41
42
GER/MUNS
GRE/ATCI
48
HUN/BUD
55
IRE/DUB
49
ITA/TV
66
NET/ROT
49
POL/CRA
41
SLO/LJU
52
SPA/BAR
65
SWE/MAL
54
UK/HL
51
ALL
0
20
40
* total cholesterol < 5 mmol/l
60
80
100
 European Society of Cardiology ESC
EUROASPIRE
% aspirin/other anti-platelets
at interview
by center
90
88
BEL/GHE
CZE/PP
82
FIN/KUO
86
86
FRA/LLRT
GER/MUNS
92
GRE/ATCI
75
HUN/BUD
93
92
IRE/DUB
ITA/TV
81
NET/ROT
87
POL/CRA
82
SLO/LJU
86
SPA/BAR
92
SWE/MAL
81
UK/HL
86
ALL
0
20
40
60
80
100
Wood et al. Lancet 2001; 357: 995-1001
 European Society of Cardiology ESC
% beta-blockers at interview
by center
EUROASPIRE
77
BEL/GHE
74
CZE/PP
88
FIN/KUO
60
FRA/LLRT
68
GER/MUNS
55
GRE/ATCI
84
HUN/BUD
47
IRE/DUB
61
ITA/TV
48
NET/ROT
62
POL/CRA
66
SLO/LJU
47
SPA/BAR
64
SWE/MAL
44
UK/HL
63
ALL
0
20
40
60
80
100
Wood et al. Lancet 2001; 357: 995-1001
 European Society of Cardiology ESC
EUROASPIRE II
EUROASPIRE
Conclusions
 A high prevalence of unhealthy lifestyles,
modifiable risk factors and inadequate use of
prophylactic drug therapies is found in
coronary patients across Europe
 Considerable potential to raise the
standard of preventive cardiology exists
throughout Europe in order to reduce
coronary morbidity and mortality
Wood et al. Lancet 2001; 357: 995-1001
 European Society of Cardiology ESC
National Heart Attack
Alert Program (NHAAP)
CRITICAL PATHWAYS
FOR THE TREATMENT OF
PATIENTS WITH
ACUTE CORONARY SYNDROMES
Critical Pathways - Definitions
• Standardized protocols for care
• Strict definition
– Full list of all tasks, tracks variances
• Broader definition
– Includes clinical protocols (NHAAP
4D’s)
• Diagnostic pathways - Chest Pain Centers
• Treatment pathways - Thrombolysis
39
Goals of Critical Pathways
• Increase use of recommended medical therapies
(e.g., aspirin)
• Decrease use of unnecessary tests.
• Decrease hospital length of stay
• Increase participation in clinical research
• Improve patient care and decrease costs.
40
Need and Rationale for Critical
Pathways
• Underutilization of recommended
medications (e.g. Aspirin)
• Overutilization of procedures
• Length of stay, # ICU days
• Quality of care measures (door-to-drug,
door-to-balloon times)
41
Development And Implementation Of
Critical Pathways
• Identify problems ( practice variation)
• Identify working committee/task force to develop
path
• Distribute draft Critical Pathway to all personnel
and departments involved. Revise based on
approach.
• Implement pathway
• Collect and monitor data on pathway
performance.
• Modify the pathway as needed to further improve
performance.
42
Methods of Implementation of
Pathways
• Specific case manager for each Pt
– High compliance, high cost
• Standardized order sheets, Pocket guides
• “Championing” - Grand rounds
• Recent study -> similar improvements in
care with either formal or simpler pathways
(Holmboe, ES et al. Am J Med
1999;107:324-31.)
43
44
Goal: < 30 Minutes
NHAAP
Ann Emerg Med
1994;23:311-29.
45
N
R
M
I1
&
2
T
r
e
n
d
s
:D
o
o
r
t
o
D
r
u
g
(
t
P
A
)
I
n
t
e
r
v
a
l
A
l
lH
o
s
p
i
t
a
l
s
,t
P
A
t
r
e
a
t
e
d
P
a
t
i
e
n
t
s
(
N
=
2
4
1
,
7
5
7
)
Minut es
(median)
65
60
55
50
45
40
90-b
91-a
91-b
92-a
92-b
93-a
93-b
94-a
94-b
95-a
95-b
96-a
96-b
97-a
97-b
98-a
35
W. Rogers, personal communication
Speeding Time to Treatment: Brigham and
Women’s Hospital Acute MI Critical Pathway in ED
__:__
Door
Pt. with Chest Pain. ED Arrival Time
10 mins
__:__
Data
Obtain ECG. Assess for ST Elevation
10 mins
__:__
Decision
Assess for Contraindications to Thrombolysis:
Active Bleeding
Prior Stroke
Confirmed BP > 190/110
Major Surgery <2 Mos.
Other Major Illness (cancer, etc.)
10 mins
__:__
Drug
Door-to-Drug Time
Goal: <30 Mins
NO
YES
o
Mix and Give Thrombolytic:
Primary PCI:
Double-Bolus r-PA
1. Patient with high
stroke/bleeding risk
2.
Cardiogenic shock
3.
(All patients)
Cannon CP et al. J Thromb Thrombolysis 1994;1:27-34.
47
BWH Thrombolysis Critical Pathway:
Effect on Door-to-Drug times
Door-to-Drug Time
80
70
Minutes
60
50
40
30
20
10
0
Jun93
JulSep
93
Pre-
OctDec
93
JanMar
94
AprJun
94
Post-Pathway
JulSep
94
OctDec
94
JanMar
95
AprJun
95
JulSep
95
OctDec
95
Cannon CP, Clin Cardiol 1999;22:17-22
Door-to-Needle Time (Mins)
BWH Thrombolysis Critical Pathway: Initial
Experience
120
BEFORE
Women
Men
100
80
*P=0.013
60
40
20
0
Jun-Nov 20, 93
Nov 21, 93June 94
July 94- Dec 94 Jan 95- June 95
Cannon CP, et al. Clin Cardiol 1999;22:17-22
49
50
PAMI II: Early Discharge Critical Pathway for LowRisk MI Patients treated with Primary Angioplasty
6 month outcomes
Early D/C
(%)
Standard
(%)
P value
Death
MI
Unstable Angina
D/MI/UA/CHF/stroke
0.8
0.8
10.1
15.2
0.4
0.4
12.0
17.5
NS
NS
NS
NS
Length of stay (days)
Hospital Costs
4.2
$9,658
+ 5,287
7.1
$11,604
+ 6,125
p<0.001
p=0.002
BWH ED Checklist Orders for
UA/NSTEMI
UA/NSTEMI
Hx.
Good Story and/or
+ ECG, or + CKMB/TnI
Hx MI, PCI/CABG
Tests
•CBC, CMP, PT/PTT
CK-MB, TnI
•Lipid profile
Meds
•
ASA 325mg chew
•Metoprolol IV/PO
•Discuss with Cards B
- Heparin IV + IIb/IIIa
- Enoxaparin SQ
- Cath Lab
•NTG PRN
53
Hospital Lenght of Stay (Days)
Effect of Critical Pathway on
Median Length of Stay
6
5
5
5
4
4
4
3
3
3
3
2
2
Oct.
Nov.
Not On Path
On Path
2
1
0
Feb
(Pre)
July
Sept.
54
CHAMP Program to improve
Secondary Prevention
•
Jan 1992- Dec 1995 N=256 pre- and 302 post
Pre-CHAMP
D/C 1 yr
post-CHAMP
D/C 1 yr
ASA
78%
68%
92%
94%
B-blocker
12% 18%
61%
57%
ACE
4%
16%
56%
48%
Statin
6%
10%
86%
91%
LDL <100
6%
58%
Fonarow GC et al. Am J Cardiol 2001;87:819-822.
55
Conclusions
•
Critical pathways hold great promise to improve
– Quality of care,
– Clinical outcomes
– Cost-effectiveness
•
Initial studies show better quality of care and
suggest improved outcomes
56