CVD Critical Pathways Group 2006 Teleconferences

1
CVD Critical Pathways Group 2006 Teleconferences
July 12, 2006
This activity is supported by an educational
grant from the Bristol-Myers Squibb/Sanofi
Pharmaceuticals Partnership.
2
Faculty

• Christopher P. Cannon, MD
• Associate Professor of Medicine
• Harvard Medical School
• Senior Investigator, TIMI Study Group
• Associate Physician, Cardiovascular Division
• Brigham and Womens Hospital
• Boston, Massachusetts

3
Disclosure Statement

• The Network for Continuing Medical Education
  requires that CME faculty disclose, during the
  planning of an activity, the existence of any
  personal financial or other relationships they or
  their spouses/partners have with the commercial
  supporter of the activity or with the
  manufacturer of any commercial product or service
  discussed in the activity.

4
Faculty Disclosure Statement

• Christopher P. Cannon, MD, has received
  grant/research support from Merck Co., Inc.,
  AstraZeneca Pharmaceuticals PL, and
  Merck/Schering Plough Partnership. He has served
  as a consultant on scientific/advisory boards of
  AstraZeneca Pharmaceuticals PL, Bristol-Myers
  Squibb Company, GlaxoSmithKline, Merck Co.,
  Inc., Merck/Schering Plough Partnership, Pfizer
  Inc, sanofi-aventis, and Schering-Plough
  Corporation. He has received honoraria for CME
  lectures supported by AstraZeneca Pharmaceuticals
  LP, Bristol-Myers Squibb Company, Merck Co.,
  Inc., Millennium Pharmaceuticals, Inc., Pfizer
  Inc, sanofi-aventis, and Schering-Plough
  Corporation.
• The team from New York Presbyterian Hospital
  reports no such relationships.

5
Reducing Time to Treatment in STEMIWhy Do Some
Hospitals Succeed?
Christopher P. Cannon, MD
6
Polling Question 1

• Does your hospital utilize pre-hospital ECGs and
  pre-hospital fibrinolysis?
• No, neither pre-hospital ECGs or pre-hospital
  lysis are done
• Yes, pre-hospital ECGs are done, but
  pre-hospital lysis is not administered
• Yes, both pre-hospital ECGs and pre-hospital
  lysis are used when indicated

7
Determine Whether Fibrinolysis or PCI Is
Preferred
If presentation is ?3 hours and there is no delay
to an invasive strategy, there is no preference
for either strategy.

• However, fibrinolysis generally preferred when
• Invasive strategy not an option
• Vascular access difficulties
• No access to skilled PCI lab
• Delay to invasive strategy
• Prolonged transport
• Door-to-balloon time gt90 min
• gt1 hr vs fibrinolysis (fibrin-specific agent) now

Adapted with permission from Antman EM, et al. J
Am Coll Cardiol. 200444671-719. Photo courtesy
of ACC/AHA guidelines for STEMI slide set.
Available at http//www.acc.org/clinical/guidelin
es/stemi/slide_show/slide_show.htm. Accessed May
1, 2006.
8
Determine Whether Fibrinolysis or PCI Is
Preferred (cont.)
If presentation is lt 3 hours and there is no
delay to aninvasive strategy, there is no
preference for either strategy

• However, invasive strategy generally preferred
  when
• Skilled PCI lab is available with surgical backup
• Door-to-balloon time lt90 min
• High risk from STEMI
• Cardiogenic shock, Killip class III
• Contraindications to fibrinolysis, including
  increased risk of bleeding and ICH
• Late presentation
• gt3 hr from symptom onset
• Diagnosis of STEMI is in doubt

Adapted with permission from Antman EM, et al. J
Am Coll Cardiol. 200444671-719. Photo courtesy
of ACC/AHA guidelines for STEMI slide set.
Available at http//www.acc.org/clinical/guidelin
es/stemi/slide_show/slide_show.htm. Accessed May
1, 2006.
9
Options for Transport of Patients With STEMI and
Initial Reperfusion Treatment
Hospital fibrinolysis door-to-needle within
30 min
Not PCI capable
Call 9-1-1 Call fast

• EMS on-scene
• Encourage 12-lead ECGs
• Consider prehospital fibrinolytic if capable and
  EMS-to-needle within 30 min

EMS triage plan
Inter-hospital transfer
Onset of symptoms of STEMI
9-1-1 EMS dispatch
PCI capable
GOALS
5 min
8 min
EMS Transport
Patient
EMS
Prehospital fibrinolysis EMS-to-needle within 30
min
EMS transport EMS-to-balloon within 90
min Patient self-transport Hospital
door-to-balloon within 90 min
Dispatch 1 min
Golden hr 1st 60 min
Total ischemic time within 120 min
Adapted with permission from Antman EM, et al. J
Am Coll Cardiol. 200444671-719.
10
Reperfusion Therapy
Patient
Transport
In-hospital
Reperfusion
Goals
D-N ?30 min
5 min
?30 min
D-B ?90 min
Methods of speeding time to reperfusion

• Media campaign
• Patient education
• Greater use of 9-1-1

• MI protocol
• Critical pathway
• Quality improvement program

• Bolus lytics
• Dedicated PCI team

• Prehospital ECG and Rx, if possible

Adapted with permission from Antman EM, et al. J
Am Coll Cardiol. 200444671-719 and Cannon CP,
et al. J Thromb Thrombolysis. 1994127-34.
11
Mortality Reduction and Time SavingsWith
Prehospital Thrombolysis
Time to Treatment (mean)
Early Mortality
Prehospital lysis vs primary PCI. Morrison LJ,
et al. JAMA. 20002832686-2692. Antman EM, et
al. Available at http//www.acc.org/clinical/guid
elines/stemi/index.pdf.Accessed May 1, 2006.
12
ER-TIMI 19 Time Saved to First r-PA Bolus with
Prehospital Administration
DataMedian Times (Q1-Q3)
Ambulance arrival
ED arrival
In-hospital lytic
63 min (4889)
Control
Plt.0001
31 min (2437)
32 min saved
Prehosp
First r-PA bolus
r-PA reteplase
Adjusted for any effect of site and
interaction. Morrow DA, et al. J Am Coll Cardiol.
20024071-77.
13
Goal of Fibrinolytic Therapy AloneOpen Arteries
and Reduce Mortality
GUSTO-I (STK vs t-PA) Angiographic Investigators
Postlytic TIMI Flow Predicts Mortality
2 years
15.7
16
14
12
7.9
10
Patient Mortality ()
8
6
4
2
0
TIMI 3
TIMI 0,1,2
90 min TIMI Flow Postfibrinolytic
Ross AM, et al. Circulation. 1998971549-1556.
14
Advantages of Bolus Thrombolysis

• Ease of administration
• ? Door-to-needle time
• Allows for prehospital Rx
• Avoids medication errors
• In GUSTO-I 12 of patients had medication error
  (eg, infusion too fast, wrong dose)
• Mortality significantly higher if medication
  error (t-PA 5.5 correct dose vs 7.7 if
  medication error, Plt.001)

Cannon CP. Am J Cardiol. 20008517C-22C.
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Weight-adjusted Fibrinolytics May Lead to Dosing
Errors

• Marked variation in ability to assess weight1
• Different for each investigator
• Majority of estimations within 20 of patients
  actual weights
• Senior House Officer with least experience
  consistently overestimated (Plt.001)
• Weight-adjusted fibrinolytics2
• Overdose increased risk of ICH or bleeding
• Underdose subtherapeutic lytic activity
  (decreased patency rates)

1. Coe TR, et al. Anaesthesia. 199954582-598. 2.
Cannon CP. Am J Cardiol. 20008517C-22C.
16
Primary PCI vs Thrombolysis in STEMI
Quantitative Analysis (23 RCTs, N7739)
25
Short-term outcomes (46 wk)
Plt.0001
20
Plt.0001
15
Plt.0001
P.0002
PCI
Frequency ()
P.032
10
Thrombolytic therapy
5
Plt.0001
0
Death
Nonfatal MI
Recurrent Ischemia
Hemor- rhagic Stroke
Major Bleed
Death, Nonfatal Reinfarction, or Stroke
Adapted with permission from Keeley EC, et al.
Lancet. 200336113-20.
17
Early Presenting Patients Primary PCI vs
Fibrinolytics
Lytic (STK)
Prehosp t-PA
Transfer for PCI
20
PCI
10
15.3
P.058
P.47
8
15
5.9
5.7
Plt.02
6
30-d Mortality ()
30-d Mortality ()
10
7.4
7.3
3.7
6.0
4
2.2
5
2
0
0
lt3 hr (n551)
gt3 hr (n299)
lt2 hr (n460)
gt2 hr (n374)
CAPTIM
PRAGUE-2
Widimsky P, et al. Eur Heart J. 20032494-104.
Steg PG, et al. Circulation. 20031082851-2856.
18
STEMI Primary AngioplastyIncreasing
Door-to-Balloon Time vs MortalityNRMI
(19941998) 27,080 Patients
1.62
1.61
2.2
1.41
1.8
1.15
1.14
1.4
Multivariately Adjusted Odds of Death
1.0
1
P.0007
P.0003
P.01
0.8
0.6
060 (n2230)
6190 (n5734)
91120 (n6616)
121150 (n4461)
151180 (n2627)
gt180 (n5412)
Door-to-Balloon Time (min)
Adapted with permission from Cannon CP, et al.
JAMA. 20002832941-2947.
19
Time From Symptom Onset to Treatment Predicts
1-yr MortalityPrimary PCI
Relative Risk of 1-yr Mortality Increases by
7.5 for Each 30-min Delay
Y2.86 ( 1.46) .0045X1 .000043X2Plt.001
De Luca G, et al. Circulation. 20041091223-1225.
20
Mortality With 1 PCI vs Time Delay
15
Circle sizes sample size of individual
study Solid line weighted meta-regression
10
P.006
Absolute Risk Difference in Death ()
5
62 min
Favors PCI
0
Favors lysis
-5
0
20
40
60
80
100
PCI-Related Time Delay (Door-to-Balloon minus
Door-to-Needle)
For every 10-min delay to PCI 1 reduction in
mortality difference vs lytics. Nallamothu BK,
Bates ER. Am J Cardiol. 200392824-826.
21
NRMI Registry Relationship Between In-Hospital
Mortality and Door-to-Balloon Time
Mortality ( of Patients)
Door-to-Balloon Time
3.0
lt90 min
4.2
91-120 min
5.7
121-150 min
7.4
gt150 min
P for trend lt0.01
McNamara RL, et al. J Am Coll Cardiol.
2006472180-2186.
22
NRMI Registry In-Hospital Mortality and
Door-to-Balloon Time in Patients Stratified By
Symptom Onset-to-Door Time
10
9
8
Time of symptom onset to arrival lt 1 hour
7
6
Time of symptom onset to arrival gt 1 to 2 hours
In-hospital Mortality ()
5
Time of symptom onset to arrival gt 2 hours
4
3
2
1
0
lt90
gt90 120
gt120 150
gt150
Door-to-Balloon Time (Min.)
P for trend lt0.001 for each line
McNamara RL, et al. J Am Coll Cardiol.
2006472180-2186.
23
NRMI In-Hospital Mortality and Door-to-Balloon
Time in Patients Stratified By Risk Factor Status
12
10
8
In-hospital Mortality ()
6
No risk factor gt 1 risk factor
4
2
0
gt90 120
gt120 150
gt150
lt90
Door-to-Balloon Time (Min.)
P for trend lt0.001 for each line. Risk factors
include anterior/septal location, diabetes
mellitus, heart rate gt100 BPM, systolic BP lt 100
mg Hg.
McNamara RL, et al. J Am Coll Cardiol.
2006472180-2186.
24
NRMI No Significant Trend for Door-to-Needle
Times (P 0.956) or Door-to-Balloon Times(P
0.094) Between Jan 1999 and Dec 2002
McNamara RL, et al. J Am Coll Cardiol.
20064745-51.
25
Clinical Trials of Interhospital Transferfor PCI
vs Fibrinolysis
20
On-site fibrinolysis
Transfer for PCI
14
15
12.1
10
Mortality ()
10
8.5
8.4
7
6.7
6.8
6.7
6.5
5
0
LIMI1
PRAGUE-12
AIR-PAMI3
PRAGUE-24
DANAMI5
(n150)
(n200)
(n137)
(n850)
(n1129)
1. Vermeer F, et al. Heart . 199982426-431. 2.
Widimsky P, et al. Eur Heart J.
200021823-831. 3. Grines CL, et al. J Am Coll
Cardiol. 2002391713-1719. 4. Widimsky P, et
al. Eur Heart J. 20032494-104. 5. Andersen HR,
et al. N Engl J Med. 2003349733-742.
26
Transfer for Primary PCI vs Fibrinolysis
Importance of Time Trials vs Practice
Symptom-to-therapy in trials 1, 3, 5
door-to-therapy in trials 2, 4. Data available
in 82 of patients. Data provided by H.
Krumholz, MD (personal communication). Nallamothu
BK, et al. Circulation. 2005111761-767. Herrmann
HC, et al. Circulation. 2005111718-720.
27
STEMI Transfer for PCI NRMI (19992002) 4278
Patients
of Patients
Door-to-Balloon Time
4.2
lt90 min
16.2
lt2 hr
55.4
24 hr
28.4
gt4 hr
Nallamothu BK, et al. Circulation.
2005111761-767.
28
National Registry of Myocardial Infarction
(NRMI) Median Door-to-Balloon Times Eligible
Patients By Transfer Status 19942004
250
228 minutes
225
Transfer-in
200
175
162 min.
150
Minutes (Median)
Nontransfer-in
125
100
99 min.
111 minutes
75
50
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
Year of Discharge
NRMI Web site. http//www.nrmi.org/index.html.
Accessed November 1, 2005. Gibson CM. Am Heart
J. 2004148(5 suppl)S29-S33.Shavelle DM, et al.
Am J Cardiol. 2005961227-1232.
29
GAP Initiative Adherence Improves With Tool Use
Early Quality Indicators and Standard Admission
Orders
P.004
P.001
100
Preintervention
Postintervention
80
No tool use
Tool use
60
Quality Adherence ()
40
20
0
343
308
96
213
174
71
131
165
87
No. of Ideal Patients
ASA
ß-Blocker
LDL-C
Adapted with permission from Mehta RH, et al.
JAMA. 20022871269-1276.
30
GAP Initiative Changes in Mortality Before and
After GAP Project
45
P.004
40
35
30
25
P.001

20
P.017
Baseline
15
Post-GAP
10
5
0
In-hospital
30-d
1-yr
Mortality
Mortality
Mortality
Eagle KA, et al. J Am Coll Cardiol.
2005461242-1248.
31
EMS Reperfusion Checklist Evaluation of the
STEMI Patient
Has patient experienced chest discomfort for gt 15
min and lt 12 h?
Step 1
YES
NO
Are there contraindications to fibrinolysis? If
ANY of the following are CHECKED, fibrinolysis
MAY be contraindicated.
Step 2
? Yes ? No
Systolic BP greater than 180 mm Hg
? Yes ? No
Diastolic BP greater than 110 mm Hg
? Yes ? No
Right vs left arm systolic BP difference greater
than 15 mm Hg
? Yes ? No
History of structural central nervous system
disease
? Yes ? No
Significant closed head/facial trauma within the
previous 3 months
? Yes ? No
Recent (lt 6 wk) major trauma, surgery (including
laser eye surgery), GI/GU bleed
? Yes ? No
Bleeding or clotting problem or on blood
thinners
? Yes ? No
CPR greater than 10 min
? Yes ? No
Pregnant female
? Yes ? No
Serious systemic disease(eg, advanced/terminal
cancer, severe liver or kidney disease)
? Yes ? No
Step 3
Is patient at high risk such that PCI is
preferable?
? Yes ? No
Adapted from Antman EM, et al. Available at
http//www.acc.org/clinical/guidelines/stemi/index
.pdf.
Heart rate greater than or equal to 100 bpm
? Yes ? No
Pulmonary edema (rales greater than halfway
up)
? Yes ? No
Systolic BP less than 100 mm Hg
? Yes ? No
Systemic hypoperfusion (cool, clammy)
32
STEMI Critical Pathways
ST-ELEVATION MI (STEMI) EMERGENCY DEPARTMENT
ORDERS

• Actual WEIGHT____________ ? kg
• ? Estimated ? lbs
• ? Actual HEIGHT ____________ ? cm? Estimated
  ? ft

ALLERGIES
DO NOT USE THESE UNSAFE ABBREVIATIONS U and
IU should be unit, Ug should be mcg. QD
should be daily. QOD should be every other day.
BIW should be two times a week. TIW should be
three times a week, AU, AS, OS, and OD
should be written out in full. Correct Use of
Leading and Trailing Zeros Always Leading Never
Trailing. .1 should be 0.1 and 1.0 should be 1

• Initial Orders Check all that apply
• DIAGNOSTICS
• ? Stat EKG, obtain old EKG record ? Repeat
  stat EKG 60 minutes after initial bolus of
  retavase
• Start Acute Coronary Syndrome Lab Panel CMP,
  CBC/diff, PT/INR/aPTT, CK CK-MB (site
  specific), Troponin-I, Magnesium, hs-CRP,
  lipid profile (routine)
• Stat portable CXR ? Cardiac monitor and SaO2
  monitors ? Other _____________________________
  _________

ANTI-ISCHEMIC THERAPY ? Oxygen 2L/minute Nasal
Cannula (titrate to keep pulse oximetry
saturations gt 94) ? IV 0.9 NS ?
Intermittent Infusion Device ? KVO ____
ml/hour ? Opiate ________________________________
__ mg IV (suggest Morphine Sulfate)
Nitroglycerin Therapy (Hold if patient has taken
Sildenafil (Viagra) within 24 hours ? NTG
0.4mg SL every 5 minutes X 3 doses or until pain
relief or systolic BP lt 100 mm Hg ? NTG
paste _______________________inch(es) topically X
1 ? IV- start NTG infusion at 10
mcg/minute, then titrate as per pharmacy protocol
(use 100mg in 250 ml D5W
ANTI-THROMBOTIC THERAPY ? Aspirin 162 mg po (2
chewable 81 mg tablets)
Corbelli J, et al. Critical Pathways in
Cardiology. 2003271-87.
33
STEMI Critical Pathways
Reperfusion Therapy
Indications Chest pain lt12 hours, EKG
ST-elevations or new left bundle branch block

• Fibrinolysis Indications
• ?3-hr symptom onset
• Delay in PCI (door-to-balloon gt90 min)
• Contraindications to PCI poor arterial access,
  renal failure, dye allergy

• Assess for contraindications for fibrinolytic
  therapy
• History of hemorrhagic stroke at any time other
  stroke or cerebrovascular event within 1 year
• Known intracranial neoplasm
• Active internal bleeding
• Suspected aortic dissection (consider CT of
  chest)

? Reteplase (Retavase) 10 units IV bolus, repeat
10 units IV bolus at 30 minutes
HEPARIN THERAPY (administer simultaneously with
retavase) ? Unfractionated heparin ___units IV
bolus (1000 units/ml), then ___units/hour IV
infusion Note When using a fibrinolytic (eg,
reteplase) Use Cardiac Unfractionated Heparin
Nomogram on back of form

• Primary PCI Indications
• gt3-hr symptom onset
• Presence of cardiogenic shock, CHF,
  contraindications to fibrinolysis
• ? Stat cardiology consult/catheterization lab page

? Eptifibatide (Integrilin) _____ml IV bolus,
then ____ml/hr IV infusion (dosing nomogram on
back of form) (Dose adjustment based on serum
creatinine may be required.) ? Unfractionated
heparin _____ units IV bolus (1000 units/ml),
then ______units/hour IV infusion
34
Implementation of Guidelines Improves the
Standard of Care Vienna STEMI Registry

• ACC/AHA and ESC guidelines recommend PCI as
  preferred STEMI reperfusion strategy
• In Vienna, Austria, time from first medical
  contact to balloon often 120 minutes or more
• Vienna STEMI Registry was instituted to determine
  whether implementation of ACC/AHA and ESC
  guidelines improves in-hospital mortality from
  acute STEMI

Kalla K, et al. Circulation. 20061132398-2405.
35
Implementation of Guidelines Improves the
Standard of Care Vienna STEMI Registry

• A network was organized comprising Viennese
  Ambulance Systems and 5 high-volume
  interventional cardiology departments to
• Expand performance of primary PCI
• Use fastest available reperfusion strategy in
  STEMI of short duration (2-3 h from symptom
  onset)
• PCI
• pre-hospital thrombolytic therapy
• in-hospital thrombolytic therapy

Kalla K, et al. Circulation. 20061132398-2405.
36
Vienna STEMI Registry Reperfusion Strategies
Before and After Implementation of Guidelines
No reperfusion Reperfusion PPCI TT
90
80
70
60
50

40
30
20
10
0
Vienna 2002
Vienna 2003/2004
Kalla K, et al. Circulation. 20061132398-2405.
37
Vienna STEMI Registry Influence of Time to
Treatment on In-Hospital Mortality
28.6
30
PPCI TT
25
20

15
12.5
10.6
10
7.8
6.7
5.1
5
(90)
(140)
(407)
(123)
(120)
(14)
0
0-2 h
2-6 h
6-12 h
Numbers in parentheses represent patient numbers
in the different treatment groups.
Kalla K, et al. Circulation. 20061132398-2405.
38
Summary

• Rapid re-establishment of perfusion remains a
  primary goal in STEMI
• Expeditious primary PCI with adjunctive therapy
  by an experienced center is generally preferred
  over fibrinolysis (except if symptoms lt2 hr)
• Studies show that critical pathways interventions
  improve care and are associated with improved
  outcomes
• Participation in national data registries enables
  multidisciplinary hospital teams to monitor and
  refine critical pathways and improve outcomes

39
Questions and Answers
40
Featured Institution Columbia Presbyterian
HospitalNew York, NY
41
Polling Question 2
If you participated in a previous teleconference,
how much progress have you made since
then? (Please refer to the checklists on the next
3 slides.)

• We are currently on the same item
• We have since moved to the next checkbox on the
  checklist
• We have progressed by more than one item on the
  checklist
• ACS pathways are up-to-date and regularly
  followed

42
Progress ChecklistImmediate Goals
43
Progress ChecklistShort-term Goals/Activities
44
Progress ChecklistLong-term Goals/Activities
45
Question-and-Answer Session
46
Concluding RemarksChristopher P. Cannon,
MDNext Program 2006 AHA/ACC Secondary
Prevention GuidelinesWhat is New?Gregg C.
Fonarow, MDWednesday, August 16, 2006300 PM
Eastern Time (1200 Noon Pacific Time)