strive teleconf presentation dec6 2006

CVD Critical Pathways Group2006 Teleconferences

This activity is supported by an educational grant from the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership.

December 6, 2006

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Faculty

Gregg C. Fonarow, MDEliot Corday Professor of Medicine

and Cardiovascular ScienceDirector, Ahmanson-UCLA Cardiomyopathy Center

UCLA Division of CardiologyUCLA Medical Center

Los Angeles, California

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Disclosure StatementThe 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.

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Faculty Disclosure Statement

Gregg C. Fonarow, MD, has served as a consultant to and has received research support and honoraria from Bristol-Myers Squibb Company, GlaxoSmithKline, Merck & Co., Inc., Pfizer Inc, sanofi-aventis, Schering-Plough Corporation, and Scios, Inc.

Deborah B. Diercks, MD, of the University of California, Davis Medical Center, has served as a consultant to sanofi-aventis, has received honoraria from Bristol-Myers Squibb Company, sanofi-aventis, and Scios Inc., and has received research support from Biosite Inc.

Highlights From the 2006 American Heart Association

Scientific Sessions

Gregg C. Fonarow, MD

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Polling Question #1

1. <90 minutes

2. 91-120 minutes

3. >120 minutes

What is the average door-to-balloon time at your institution?

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Highlights From the AHA 2006 Scientific SessionsNew Registries and Initiatives● NCDR-ACTION Registry: Combines the CRUSADE and NRMI registries

● Door to Balloon (D2B) Initiative: Joint program of AHA, ACC, and other health organizations to reduce door-to-balloon time

Time to Treatment—Recent Trials● Hospital Delays in Trials of Primary PCI and In-Hospital Fibrinolysis in AMI

Reperfusion for ST-Elevation Myocardial Infarction

● Long-term Outcome of Primary Percutaneous Coronary Interventions vs Prehospital and In-Hospital Thrombolysis for Patients With ST-Elevation Myocardial Infarction

● RIKS-HIA Registry: Register of Information and Knowledge about Swedish Heart Intensive Care Admissions

● Pooled Analysis of Randomized Trials of Primary PCI and In-Hospital Fibrinolysis in AMI

Other Recent Trials● OAT: Occluded Artery Trial● CHICAGO Study: Carotid Intima-Media Thickness in Atherosclerosis Using

Pioglitazone● APEX MI: Assessment of Pexelizumab in Acute Myocardial Infarction

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New Initiatives: NCDR-ACTION Registry; D2B Campaign

NCDR-ACTION Registry1

CRUSADE and NRMI registries to merge to form the National Cardiovascular Data Registry–Acute Coronary Treatment and Intervention Outcomes Network (NCDR-ACTION Registry)

Will be largest and most comprehensive national cardiovascular patient database ever developed

D2B Program2

Door to Balloon (D2B) Campaign—joint program of AHA, ACC, and other health organizations

Aims to increase percentage of AMI patients who receive primary angioplasty within 90 minutes of hospital presentation to 75%; current figures indicate only 35% do

D2B implementation kit contains 6 evidence-based strategies for reducing D2B times

1. ACC News Release. Available at http://www.acc.org/media/releases/highlights/2006/nov06/NCDR_Action.htm. Accessed November 16, 2006. 2. Heartwire. Available at: http://www.theheart.org/article/753305.do. Accessed November 16, 2006.

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*P<.05 for all.

Bradley EH, et al. N Engl J Med. 2006. November 13. [Epub ahead of print].

D2B: Strategies Associated With a Significant Reduction in Door-to-Balloon Time

Strategy Mean reduction in door-to-balloon time

(min)*

Having emergency medicine physicians activate the cath lab 8.2

Having a single call to a central page operator activate cath lab 13.8

Having the ED activate the cath lab while patient still en route 15.4

Expecting staff to arrive at cath lab within 20 minutes after page 19.3

Having an attending cardiologist always on site 14.6

Having staff in ED and cath lab use and receive real-time feedback 8.6

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NRMI 2,3,4

452,544 Reperfusion Eligible

STEMI Patients

1963 Hospitals

Transfer Out Patients

n=119,235

Missing Time Intervalsn=13,137

Did Not Receive PCIor Fibrinolytic Therapyas Initial Reperfusion

n=89,524

Study Population192,509 Patients

645 Hospitals

230,648 Patients1860 Hospitals

≥20 STEMI Patients Treated

Treatment of ≥10 Patients With Primary PCI and ≥10 Patients With Fibrinolytic Therapy

© CM Gibson 2006. Pinto DS, et al. Circulation. 2006;114:2019-2025.Adapted with permission from clinicaltrialresults.org.

Implications of Hospital Delays for Selection of Reperfusion Strategy in STEMI

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Mortality Increases With Increasing PCI-Related Delay


PCI-Related Delay (door-to-balloon–door-to-needle time) (min)

In-H

osp

ital

Mo

rtal

ity

(%)

For every 30-minute delay,mortality increases 10%

12

10

8

6

4

2

00 20 40 60 80 100 120 140 160 180 200

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Advantage of PCI Compared With Fibrinolyisis Decreases as PCI-Related Delay Increases


Od

ds

of

Dea

th W

ith

F

ibri

no

lysi

s

PCI-Related Delay (door-to-balloon–door-to-needle time) (min)

PC

I B

ett

er

Fib

rin

oly

sis

Be

tte

r

12

1.5

1.25

1.0

0.8

0.560 75 90 105 114 135 150 165 180

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Pre-hospital Delay (Min)

Age <65 years and Anterior Infarction

Age <65 years and Non-anterior

Infarction

Age ≥65 years and Anterior Infarction

Age ≥65 years and Non-anterior

Infarction

0-120 39 min

Met goal without transfer: 2.6%

Met goal with transfer:

3.6%

(n=19,517 pts; n=269 hospitals)

56 minMet goal without transfer:

20.2%


17.3%



94.1%


92.8%



99.8%


100.0%


121+ 50 min

Met goal without transfer: 7.9%


11.9%



89.1%


82.2%



98.1%


97.1%



100.0%


100.0%


Time at Which PCI Loses Superiority in Survival Over Fibrinolysis Varies by

Patient Risk


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RIKS-HIA Registry: Long-Term Outcome of Primary PCI vs Prehospital and In-Hospital

Thrombolysis for STEMI Register of Information and Knowledge about Swedish

Heart Intensive Care Admissions (RIKS-HIA): prospective, observational cohort study of 26,205 consecutive STEMI patients who received reperfusion therapy within 15 hours of onset

Patients treated between 1999 and 2004

7084 patients underwent primary PCI; 3078 received prehospital thrombolysis; 16,043 received in-hospital thrombolysis

Stenestrad U, et al. JAMA. 2006;296:1749-1756.

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RIKS-HIA Registry: Comparisons of Thrombolysis and Primary PCI


End point

In-hospital thrombolysis,

n=16,043

Prehospital thrombolysis, n=3078

Primary PCI, n=7084

Mortality at 7 days (%)Adjusted HR (95% CI)

8.81.00

5.90.90 (0.76–1.06)

3.50.61 (0.51–0.73)

Mortality at 30 days (%)Adjusted HR (95% CI)

11.41.00

7.60.87 (0.76–1.01)

4.90.61 (0.53–0.71)

Mortality at 1 year (%)Adjusted HR (95% CI)

15.91.00

10.30.84 (0.74–0.95)

7.60.66 (0.60–0.76)

In-hospital reinfarction (%)Adjusted HR (95% CI)

4.01.00

3.40.88 (0.68–1.14)

2.00.79 (0.70–0.88)

Readmission for MI in 1st year (%)Adjusted HR (95% CI)

9.61.00

9.01.02 (0.90–1.17)

4.80.61 (0.53–0.71)

Hospital stay for index event (days)Adjusted HR (95% CI)

61.00

50.83 (0.80–0.87)

40.68 (0.65–0.70)

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RIKS-HIA Registry: Time to Reperfusion: 30-Day and 1-Year Mortality

End pointIn-hospital

thrombolysis Prehospital

thrombolysisPrimary

PCI

30-day mortality (%)

Time to reperfusion <2 h 8.6 5.6 3.8

Time to reperfusion >2 h 11.4 8.9 4.5

1-year mortality (%)

Time to reperfusion <2 h 11.9 8.0 6.7

Time to reperfusion >2 h 16.3 11.8 7.3


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8892 7675 7519 74171155 1020 1004 9973592 3375 3344 3318

No. at RiskThrombolysis

Prehospital 3993 3571 3530 3490Posthospital 1155 1077 1066 1060

Primary PCI 979 936 928 916

Estimated Cumulative Mortality for Patients Receiving Reperfusion Treatment Within

≤2 or >2 Hours of Symptom Onset

Mortality curves calculated using Cox regression analysis including propensity score for primary PCI.

Reprinted with permission from Stenestrad U, et al. JAMA. 2006;296:1749-1756.

20

15

10

5

0 100 200 300 400Cu

mu

lati

ve M

ort

alit

y,

%

Days

Reperfusion >2 h

In-Hospital ThrombolysisPrehospital ThrombolysisPrimary Percutaneous Coronary Intervention (PCI)

20

15

10

5

0 100 200 300 400Cu

mu

lati

ve M

ort

alit

y,

%

Days

Reperfusion ≤2 h

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Pooled Analysis of Randomized Trials of Primary PCI and In-Hospital

Fibrinolysis in AMI

Pooled analysis of 22 randomized trials (N=6763) published between 1990 and 2002 that tested the efficacy of primary PCI vs fibrinolysis

Examined the extent to which time to treatment affects the clinical benefit of primary PCI vs in-hospital fibrinolysis

Primary end point: All-cause mortality at 30 days

Boersma E, et al. Eur Heart J. 2006;27:779-788.

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Pooled Analysis: Primary PCI vs In-Hospital Fibrinolysis

Reproduced with permission from Boersma E, et al. Eur Heart J. 2006;27:779-788.

30-day death in patients randomized to primary PCI compared with fibrinolysis according to presentation delay (left panel) and PCI-related delay (right panel)

Primary PCI was associated with significantly lower 30-day mortality relative to fibrinolysis, regardless of treatment delay

Presentation Number of 30-daydelay (h) patients death (%)

FL PPCI

0-1 747 6.0 4.7

>1-2 2000 6.2 4.2

>2-3 1712 7.3 5.1

>3-6 1640 9.5 5.6

>6-12 664 12.7 8.5

All patients 6763 7.9 5.3

PCI-related Number of 30-daydelay (min) patients death (%)

FL PPCI

0-35 1417 8.2 2.8

>35-50 1292 6.8 5.4

>50-62 1425 5.4 4.8

>62-79 1280 9.5 6.9

>79-120 1349 9.6 6.6

All patients 6763 7.9 5.30.63

(0.42, 0.84)

OR and 95% Cl

0.0 0.5 1.0 1.5PPCI better FL better

0.0 0.5 1.0 1.5PPCI better FL better

OR and 95% Cl

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Primary End Points: Death, MI, or NYHA class IV Heart Failure

PCI With Stentingn=1082

Medical TherapyMedical Therapyn=1084n=1084

2166 patients with angiography on day 3-28 post-MI with evidence of total occlusion of the infarct-related artery with poor or absent antegrade flow

(TIMI flow grade 0 or 1); and met a criterion for increased risk, defined as ejection fraction <50%, proximal occlusion of a major

epicardial vessel with a large risk region, or bothExclusions: NYHA class III or IV heart failure, shock, serum creatinine concentration >2.5 mg/dL,

angiographically significant left main or 3-vessel coronary artery disease, angina at rest, or severe ischemia on stress testing.

Randomized.

22% women, mean age 59 years, mean follow-up 3 years, mean EF 48% at baselineConcomitant medications: Aspirin, anticoagulation if indicated, ACE inhibitors, beta blockers,

and lipid-lowering therapy, unless contraindicated

Occluded Artery Trial (OAT): PCI vs Medical Therapy for Persistent Occlusion After MI

Hochman JS, et al. N Engl J Med. 2006. November 14. [Epub ahead of print].Adapted with permission from clinicaltrialresults.org.

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OAT: Baseline Characteristics of the Study Population

Characteristic PCI Group (n=1082)

Medical Therapy Group

(n=1084)

Age, y 58.6±10.8 58.7±11.1

Sex, no. (%)

Men

Women

845 (78)

237 (22)

845 (78)

239 (22)

History, no/total no (%)

Angina

MI

Cerebrovascular disease

Peripheral-vessel disease

Heart failure

PCI

CABG

Diabetes

236/1081 (22)

127/1082 (12)

46/1081 (4)

42/1081 (4)

26/1081 (2)

51/1081 (5)

5/1082 (0.5)

200/1082 (18)

252/1084 (23)

117/1084 (11)

32/1084 (3)

39/1082 (4)

24/1082 (2)

53/1084 (5)

4/1084 (0.4)

246/1084 (23)**P=.02.Hochman JS, et al. N Engl J Med. 2006. November 14. [Epub ahead of print].

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OAT: Baseline Characteristics of the Study Population

Characteristic PCI Group (n=1082)

Medical Therapy Group

(n=1084)

Current cigarette smoker, no/total no (%)

423/1082 (39) 427/1084 (39)

ST-segment elevation 700/1037 (68) 681/1039 (66)

ST-segment elevation or Q-wave or R-wave loss

939/1082 (87) 932/1084 (86)

Multivessel disease, no/total no (%)

192/1074 (18) 191/1075 (18)

Ejection Fraction*

Mean

<50%, no/total no(%)

<40%, no/total no (%)

47.4±11.3

597/1075 (56)

236/1075 (22)

48.0±11.0

554/1075 (52)

206/1075 (19)

*Investigators at the study site reported the ejection fraction if a left ventriculogram was not obtained.

Hochman JS, et al. N Engl J Med. 2006. November 14. [Epub ahead of print].

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Outcome PCI (%) Medical (%) HR 95% CI P

Death, MI, HF 17.2 15.6 1.16 0.92–1.45 .20

All MI 7.0 5.3 1.36 0.92–2.00 .13

Nonfatal MI 6.9 5.0 1.44 0.96–2.16 .08

NYHA class 4 HF 4.4 4.5 0.98 0.64–1.49 .92

Death 9.1 9.4 1.03 0.77–1.40 .83

OAT: Estimated 4-Year Cumulative Event Rates

Hochman JS, et al. N Engl J Med. 2006. November 14. [Epub ahead of print].

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CHICAGO: Effect of Pioglitazone vs Glimepiride on CIMT in Type 2 Diabetes

CIMT has been shown to highly correlate with risk of future CV events

CHICAGO: Carotid Intima-Media Thickness in Atherosclerosis Using Pioglitazone

Randomized, double-blind, comparator-controlled trial in 462 adults with type 2 diabetes; CIMT images captured by ultrasound

72-week treatment period (1-week follow-up)– 232 patients received pioglitazone 15-45 mg/d– 230 received glimepiride 1-4 mg/d

Main outcome measure: absolute change from baseline to final visit in mean posterior-wall CIMT

CIMT = carotid artery intima-media thickness.

Mazzone T, et al. JAMA. 2006. November 13. [Epub ahead of print].

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CHICAGO: Progression of Mean and Maximum CIMT at Week 72

Mean CIMT:

End Point Pioglitazone Glimepiride Difference(95% CI) P

Primary end point, mm

–0.001 +0.012 –0.013 (–0.024 to 0.002)

.02

Mazzone T, et al. JAMA. 2006. November 13. [Epub ahead of print].

Maximum CIMT:

End Point Pioglitazone Glimepiride Difference(95% CI) P

Progression of maximum CIMT, mm

+0.002 +0.026 –0.024(–0.042 to 0.006)

.008

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Armstrong PW. Presented at: American Heart Association 2006 Scientific Sessions; November 14, 2006.

APEX-AMI: Outcomes at 30 Days (Revised End Points and Time Frame)

End pointPexelizumab, n=2860 (%)

Placebo, n=2885 (%)

All-cause mortality* 4.06 3.92

Death, shock, or HF 8.99 9.19

*Primary end point, revised from 90-day all-cause mortality in original protocol. No significant differences.

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End point Pexelizumab, n=2860 (%)

Placebo, n=2885 (%)

All-cause mortality* 4.51 4.93

Incident heart failure 4.82 4.76

Cardiogenic shock 3.47 3.36

Reinfarction 2.39 3.04

Stroke 1.18 1.36

*Original primary end point, later revised to 30-day all-cause mortality. No significant differences.

Armstrong PW. Presented at: American Heart Association 2006 Scientific Sessions; November 14, 2006.

APEX-AMI: Outcomes at 90 Days

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Featured Institution

University of California, Davis Medical Center

Sacramento, California

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Polling Question #2

1. We are currently on the same item

2. We have since moved to the next checkbox on the checklist

3. We have progressed by more than one item on the checklist

4. ACS pathways are up-to-date and regularly followed

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.)

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Progress Checklist:Immediate Goals

Assemble team and set up meeting of working group

Develop draft pathways

Circulate pathways to all cardiology, ED, and CV nursing staff for comments

Circulate discharge plan and other tools to all cardiology, ED, and CV nursing staff for comments

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Progress Checklist:Short-term Goals/Activities

Finalize critical pathways

Launch critical pathways

Circulate memo

Grand rounds/conference: Cardiology/IM

Grand rounds/conference: Emergency Dept.

Grand rounds/conference: Nursing

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Progress Checklist:Long-term Goals/Activities

Monitor data: Which registry?

NRMI

AHA Get With the Guidelines

ACC National Cardiovascular Data Registry

CRUSADE

GRACE

REACH

Other

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Question-and-Answer Session

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Concluding RemarksGregg C. Fonarow, MD

Next Program

Christopher P. Cannon, MDWednesday, January 17, 2007

12:00 Noon Eastern Time (9:00 AM Pacific Time)

strive teleconf presentation dec6 2006

Health & Medicine