1. Acute Coronary Syndromes and the Role of Critical Pathway
Christopher Cannon, M.D.
Brigham and Women’s Hospital
Boston

2. Aspirin and Thrombolysis in Acute MI
35 Day Mortality
% of Patients
Placebo Aspirin SK Aspirin + SK
ISIS-2. Lancet 1988; 2:

3. TIMI 2: Effect of Time to Treatment
6 Week Mortality
*P=0.05
1 hour faster treatment
6.2
5.2
% of Patients =
3.7
3.2*
10 lives saved per 1000 patients treated
3-4 h
2-3 h
1-2 h
<1 h
TIMM, et al. Circulation. 1991;84:II-230.

4. Improving Thrombolysis: t-PA vs. SK
TIMI 1:
Reperfusion
Occluded arteries
GUSTO 1:
Mortality SK
t-PA 80
*P<0.001
*P<0.001
7.3 60
6.3 62
% of Patients 40 31 20
TIMI Study NEJM 1985;312:
GUSTO Inv. NEJM 1993; 329:

5. Thrombolysis vs. Primary Angioplasty
30 Day Mortality
% of Patients
Thrombolysis PTCA t-PA Stent + IIb/IIIa
Weaver WD, JAMA 1997; 278: Schomig A, N Engl J Med 2000; 343:385-91

6. Medical Treatment After MI
Mortality During Follow-up
% of Patients
ISIS-1 Lancet 1986; 2:57-66; HOPE N Engl J Med 2000; 4S. Lancet 1994; 344:

7. Drug Rx Peri MI: Meta-Analyses
4/22/2017 6:04:54 AM
ACUTE MI GUIDELINES 11/96
Drug Rx Peri MI: Meta-Analyses
Beta blocker during MI
Beta blocker post MI
ACEI during MI
ACEI post MI if LV dysfxn
Nitrates during MI
Ca++ blockers
Magnesium
Lidocaine
Class I Antiarrhythmics
Number
RR Death
p value
28,970
24,298
100,963
5,986
81,908
20,342
61,860
9,155
6,300
.87 ( )
.77 ( )
.94 ( )
.78 ( )
.94 ( )
1.04 ( )
1.02 ( )
1.38 ( )
1.21 ( )
0.02
<0.001
0.006
0.03 NS
0.04
NEJM 335:1662, 1996

8. Class I Recommendations for Anti-Ischemic Therapy
UA/NSTEMI 9/00
Continuing Ischemia/Other Clinical High-Risk Features
Bed rest + continuous ECG monitoring
02 to maintain Sa02 >90%
NTG IV
-Blockers, oral (+IV if high risk)
Morphine IV for pain
IABP if ischemia or BP
ACEI for HTN or  LVEF (possibly all patients)
Braunwald et al. J Am Coll Cardiol. 2000;36:

9. Class I Recommendations for Antithrombotic Therapy*
UA/NSTEMI 9/00
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:

10. 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:

11. Class I Recommendations: Risk Factor Modification
UA/NSTEMI 9/00
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:

12. GU ARANTEE Implementation of AHCPR Guidelines
4/22/2017 6:04:54 AM GU
ARANTEE
Implementation of AHCPR Guidelines
for Unstable Angina in 1996:
Unfortunate Differences Between Women and Men
Results from the GUARANTEE Registry

13. Global Unstable Angina Registry ANd Treatment Evaluation
4/22/2017 6:04:54 AM GU
ARANTEE
Global Unstable Angina Registry
ANd Treatment Evaluation
6 Regions
35 Hospitals
2,948 Patients

14. GU ARANTEE Medical Management No. Pts ASA (%) Heparin (%)
4/22/2017 6:04:54 AM GU
ARANTEE
Medical Management
No. Pts
On Admission
ASA (%)
Heparin (%)
B-blockers (%)
At Discharge
ASA (or Warfarin)
All of above (%)
1788 84 66 53 77 31
Men
1160 80 60 49 69 24
Women
0.018
0.001
0.039
P value
0.016
0.080
0.086
0.007
Adjusted
P value

15. GU ARANTEE Catheterization / Revascularization 1788 53 18 10 59 46 Men
4/22/2017 6:04:54 AM GU
ARANTEE
Catheterization / Revascularization
No. Pts
Cath (%)
PTCA (%)
CABG (%)
In Pts Meeting AHCRP criteria
Cath (% done)
CABG (% done)
1788 53 18 10 59 46
Men
1160 44 12 7% 56 36
Women
0.001
0.002
0.15
0.16
P value
0.004
0.017
0.53
0.05
Adjusted
P value

16. GU ARANTEE Age Medical Management No. Pts ASA (%) Heparin (%)
4/22/2017 6:04:54 AM GU
ARANTEE
Medical Management
Age
No. Pts
On Admission
ASA (%)
Heparin (%)
B-blockers (%)
At Discharge
ASA (or Warfarin)
All of above (%)
1638 83 64 50 71 28
Age <65
1309 81 62 52 78
Age >65
0.17
0.25
0.46
0.001
0.92
P value
0.24
0.19
0.68
0.003
0.60
Adjusted
P value

17. Non-Q wave MI vs. Unstable Angina
4/22/2017 6:04:54 AM GU
ARANTEE
Medical Management
Non-Q wave MI vs. Unstable Angina
No. Pts
On Admission
ASA (%)
Heparin (%)
B-blockers (%)
At Discharge
ASA (or Warfarin)
All of above (%)
2600 82 61 49 73 26 UA
300 87 85 63 45
NQWMI
0.031
0.001
P value
0.069
Adjusted
P value

18. Stone PH et al. JAMA 1996;275:1104; Scirica 1999 AHJGU
ARANTEE
TIMI III Registry
Pre Guideline
Post Guideline
No. Pts
On Admission
ASA
Heparin
B-blockers
1678 82 63 41
Men
1640 77 50 35
Women
1788 84 66 53
1160 80 60 49
Women
Comparing Pre- to Post-: Men Women
P values : ASA
Heparin
B-blocker
Stone PH et al. JAMA 1996;275:1104; Scirica 1999 AHJ

19. Giugliano RP,et al. Arch Intern Med 2000;160.
4/22/2017 6:04:54 AM
Aspirin within 24 hours
94%
78%
P = .002
% survival
Weeks post discharge
Giugliano RP,et al. Arch Intern Med 2000;160.

20. Giugliano RP,et al. Arch Intern Med 2000;160.
4/22/2017 6:04:54 AM
Heparin within 24 hours
93%
85%
P = .06
% survival
Weeks post discharge
Giugliano RP,et al. Arch Intern Med 2000;160.

21. Unadjusted One Year Survival
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Unadjusted One Year Survival
95%
P = .0001
81%
Percent surviving
Weeks post discharge
Giugliano RP,et al. Arch Intern Med 2000;160.

23. NRMI-2: Distribution of Door-to-Needle Times
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NRMI-2: Distribution of Door-to-Needle Times
N=84,423
40%
Cannon CP ACC 2000

24. Baseline Characteristics
Door-to-needle time (mins)
>90 P value
No. Pts , , , ,244
Age (mean) <0.0001
Female (%) <0.0001
Non-white (%) <0.0001
DM (%) <0.0001
Prior MI (%) <0.0001
Anterior (%) <0.0001
HMO (%) <0.0001
Urban Hosp
Pre-hosp ECG <0.0001
Onset-door (hr) <0.0001
(Median)

25. Door-to-Needle Time vs. Mortality
NRMI-2: Thrombolysis
Door-to-Needle Time vs. Mortality
P=0.0001
P=0.01
P=NS
1.23
1.11
1.03
N=28, , , ,316
Cannon CP ACC 2000

26. Door-to-Balloon Time vs. Mortality
NRMI-2: Primary PCI
Door-to-Balloon Time vs. Mortality
P=NS
P=NS
P=0.01
P=0.0007
P=0.0003
1.62
1.61
1.41
1.14
1.15
N=2, , , , ,627 5,412
Cannon CP, et al JAMA 2000;283:

27. Distribution of Door-to-Balloon times Door-to-Balloon Time (minutes)
4/22/2017 6:04:54 AM
NRMI-2: Primary PCI
Distribution of Door-to-Balloon times
N=27,080
Door-to-Balloon Time (minutes)

28. US News and World Report 30-day mortality by hospital category*
* 25th, 50th and 75th percentile for each category

29. US News and World Report Aspirin in ideal candidates

30. US News and World Report Beta-blockers in ideal candidates

31. 30-day Mortality US News Top-ranked vs Other Hospitals
Odds ratio
* Adjusted for patient, hospital and physician characteristics

32. 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

33. 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:
 European Society of Cardiology ESC

34. Therapeutic control of total cholesterol
at interview
EUROASPIRE
% reaching goal* at interview among those using lipid-lowering medication
by center
* total cholesterol < 5 mmol/l
 European Society of Cardiology ESC

35. % aspirin/other anti-platelets
at interview
EUROASPIRE
by center
Wood et al. Lancet 2001; 357:
 European Society of Cardiology ESC

36. % beta-blockers at interview
by center
EUROASPIRE
Wood et al. Lancet 2001; 357:
 European Society of Cardiology ESC

37. Conclusions EUROASPIRE II
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:
 European Society of Cardiology ESC

38. ACUTE CORONARY SYNDROMES
4/22/2017 6:04:54 AM
National Heart Attack
Alert Program (NHAAP)
CRITICAL PATHWAYS
FOR THE TREATMENT OF
PATIENTS WITH
ACUTE CORONARY SYNDROMES
I am very pleased to present an overview of the National Heart Attack Alert Program (NHAAP) and to highlight some of its history, educational recommendations, achievements, and future directions. (The speaker may wish to add a personal comment concerning his or her involvement with the program.)

39. 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

40. 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.

41. 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)

42. 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.

43. 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: )

45. Goal: < 30 Minutes
NHAAP
Ann Emerg Med
1994;23:

46. W. Rogers, personal communication
4/22/2017 6:04:54 AM
W. Rogers, personal communication

47. 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 NO
YES
_ _ : _ _
Drug
Mix and Give Thrombolytic:
Double-Bolus r-PA
Primary PCI:
1. Patient with high stroke/bleeding risk
Cardiogenic shock
(All patients) o
Door-to-Drug Time
Goal: <30 Mins
Cannon CP et al. J Thromb Thrombolysis 1994;1:27-34.

48. BWH Thrombolysis Critical Pathway: Effect on Door-to-Drug times
4/22/2017 6:04:54 AM
BWH Thrombolysis Critical Pathway:
Effect on Door-to-Drug times
Door-to-Drug Time
Pre- Post-Pathway
Cannon CP, Clin Cardiol 1999;22:17-22

49. BWH Thrombolysis Critical Pathway: Initial Experience
BEFORE
*P=0.013
Cannon CP, et al. Clin Cardiol 1999;22:17-22

51. 4/22/2017 6:04:54 AM
PAMI II: Early Discharge Critical Pathway for Low-Risk MI Patients treated with Primary Angioplasty
6 month outcomes Early D/C Standard P value
(%) (%)
Death NS
MI NS
Unstable Angina NS
D/MI/UA/CHF/stroke NS
Length of stay (days) p<0.001
Hospital Costs $9,658 $11,604 p=0.002
+ 5, ,125
slide 4

53. BWH ED Checklist Orders for 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

54. Effect of Critical Pathway on Median Length of Stay

55. CHAMP Program to improve Secondary Prevention
Jan Dec 1995 N=256 pre- and 302 post
Pre-CHAMP post-CHAMP D/C 1 yr 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:

56. 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