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CVD Critical Pathways Group 2005 Teleconferences

This activity is supported by an educational grant from

the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership.

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August 10, 2005

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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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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.

Disclosure Statement

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Gregg C. Fonarow, MD, has served as a consultant

to and has received research support from

GlaxoSmithKline, Pfizer Inc., and Scios Inc. He has

also received honoraria from Merck & Co., Inc.

The team from Aurora Sinai Medical Center reports

no such relationships.  

Faculty Disclosure Statement

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Polling Question #1

What is your institution’s status in terms of establishing critical pathways for ACS?

1) ACS pathways are not in place

2) ACS pathways are in place, but not updated per current ACC/AHA UA/NSTEMI and STEMI Guidelines

3) ACS pathways are up-to-date, but not regularly implemented

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

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Cost-effectiveness of CVD Therapies: Which Therapies Provide Good Value?

Gregg C. Fonarow, MD

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Cost-effectiveness

The health economic evaluation of therapeutic and diagnostic strategies is of increasing importance

The use of incremental cost-effectiveness estimates provides a rationale for health economic allocation discussions and funding decisions

The cost per quality life-year gained is a commonly reported measurement in outcomes research

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Cost-effectiveness There is no absolute standard for at what level a

therapy is considered “cost-effective” and at what level a therapy is not “cost-effective”

Many consider therapies at or below $50,000 per quality adjusted life-year gained to be “cost-effective” relative to other accepted therapies such a hemodialysis. Above $100,000 per QALY gained, many consider as indicating the therapy is less attractive

A therapy that reduces total medical costs while adding QALY is described as cost dominant (less than $0)

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13 million individuals in the US with prevalent coronary disease 6 million individuals with prevalent cerebral vascular disease 5 million individuals with prevalent peripheral vascular disease

40 million office visits annually 5 million hospitalizations annually 226 billion dollars in direct costs in 2004 368 billion dollars in total costs in 2004

Average direct costs over a 5-year period

$ 51,211 MI $ 34,581 Unstable angina

$ 9,780 Sudden death$ 62,524 CABG$ 58,453 PTCA

Heart and Stroke Facts: 2004 Statistical Supplement, American Heart Association.

Cost of Atherosclerosis

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Reported C/E Ratios: Cardiovascular Interventions

$16,491/LYGEptifibatide for ACS7

$2080/LYGLisinopril post-AMI2

$32,678/LYGt-PA vs SK10

$5400-$32,000/LYGStatin8,9

$6318/LYGClopidogrel – CURE5

$5910/LYGClopidogrel – PCI-CURE4

$3685/LYGClopidogrel – CREDO3

$220/LYGSmoking cessation post-AMI1

C/E RatioIntervention

1. Krumholz HM, et al. J Am Coll Cardiol. 1993;22:1697-1702.2. Franzosi MG, et al. Pharmacoeconomics. 1998;13:337-346.3. Beinart S, et al. AHA Scientific Sessions; 2003.4. Mahoney EM, et. al. AHA Scientific Sessions; 2003.5. Weintraub WS, et al. AHA Scientific Sessions; 2003.

6. Mahoney EM, et al. JAMA. 2002;288:1851-1858. 7. Hillegass WB, et al. Pharmacoeconomics. 2001;19:41-55. 8. Tsevat J, et al. Am Heart J. 2001;141:727-734. 9. Johannesson M, et al. N Engl J Med. 1997;336:332-336.10. Mark DB, et al. N Engl J Med. 1995;332:1418-1424.

LYG = life-year gained.

Early invasive strategy6 $12,739/LYG

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Cause of DeathCause of DeathSimvastatinSimvastatin

(10,269) (10,269)Placebo Placebo (10,267)(10,267)

VascularCoronary 587 707Other vascular 194 230

ANY VASCULAR 781 (7.6%) 937 (9.1%)

NonvascularNeoplastic 359 345Respiratory 90 114Other medical 82 90Nonmedical 16 21

NONVASCULAR 547 (5.3%) 570 (5.6%)

ALL CAUSES 1328 (12.9%) 1507 (14.7%)

HPS Simvastatin: Cause-Specific MortalityRisk ratio and 95% CI

STATINBetter

PLACEBOBetter

17% SE 4reduction(2P<0.0001)

5% SE 6reduction (NS) 13% SE 4

reduction(2P<0.001)

0.6 0.8 1.0 1.2 1.40.4

Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22.Reprinted with permission from Elsevier Science.

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Cost-effectiveness of Simvastatin in Patients at Different Levels of Vascular Disease Risk:

British Heart Protection Study Purpose: Determine the range of cost-effectiveness

of statin therapy in persons ranging from intermediate to high vascular event risk

Methods: – 20,536 adults (aged 40-80 years) with vascular

disease or diabetes– Randomly assigned to 40 mg simvastatin daily

or placebo for an average of 5 years Results: Simvastatin use was associated with a

highly significant 22% (95% CI 16-27; P<.001) proportional reduction in hospitalization costs for all vascular events

Mihaylova B, et al. Lancet. 2005;365:1779-1785.

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Reductions in 5-Year Vascular Event Costs (and 95% CI) With Simvastatin Allocation

by Baseline Risk Subgroups

Reproduced with permission from Mihaylova B, et al. Lancet. 2005;365:1779-1785.

• Estimated absolute reductions in vascular event costs per person allocated simvastatin ranged from UK £847 (US $1524) in the highest-risk quintile to £264 ($475) in the lowest-risk quintile

• Mean excess cost of statin therapy among participants allocated simvastatin was £1497 ($2694)

US dollar figures computed at a conversion rate of $1.80 per British pound.MVE = major vascular event.

1500

1125

750

375

01(12%) 2(18%) 3(22%) 4(28%) 5(42%)

Risk subgroup (5-year MVE risk)

Co

st r

edu

ctio

ns

(£)

% o

f statin co

st (2001 p

rices)

100

75

50

25

0

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Discounted Incremental Costs, Effects, and Cost-effectiveness During 5-Year Mean

Follow-up by Risk Group and Overall

Adapted with permission from Mihaylova B, et al. Lancet. 2005;365:1779-1785.

US dollar figures computed at a conversion rate of $1.80 per British pound.

MVE Vascular deaths Cost perRisk Group Incremental avoided per Cost per avoided per vascular death

(5-year MVE risk) cost 1000 persons MVE avoided 1000 persons avoided

1 (12%) £1164/$2095 37 £31,100/$55,980 4 £296,300/$533,340

2 (18%) £1062/$1912 58 £18,300/$32,940 7 £147,800/$266,040

3 (22%) £987/$1777 80 £12,300/$22,140 13 £78,900/$142,020

4 (28%) £893/$1607 93 £9600/$17,280 18 £46,600/$89,280

5 (42%) £630/$1134 141 £4500/$8100 29 £21,400/$38,520

Overall £947/$1705 82 £11,600/$20,880 14 £66,600/$119,880

*Discounted at 3.5% per annum. MVE = major vascular event.

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Months of Follow-up

*In addition to other standard therapies.Adapted with permission from Yusuf S, et al. N Engl J Med. 2001;345:494-502.

CURE Primary End Point: MI/Stroke/CV Death

Clopidogrel + Aspirin*(n=6259)

Placebo + Aspirin*(n=6303)

P<.001N=12,562

3 6 90 12

20%Relative RiskReduction

0.12

0.14

0.10

0.06

0.08

0.00

0.04

0.02

Cu

mu

lati

ve H

aza

rd R

ate

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Long-term Cost-effectiveness of Clopidogrel in Patients With NSTEMI

Adapted with permission from Weintraub WS, et al. J Am Coll Cardiol. 2005;45:838-845.

*Based on Medicare costs and Framingham and Saskatchewan life expectancy estimates; N=12,562.

ICER = incremental cost-effectiveness ratio; LYG = life-year gained.

Cost-effectiveness of Clopidogrel*

∆ Cost ∆ Life-Years ICER % <50,000/LYG

No direct costs beyond trial period

Framingham Medicare

$442 0.0699 $6318 93.9%

Saskatchewan Medicare

$442 0.0682 $6475 97.7%

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27%Relative RiskReduction

Months30 6 9 12

0

5

15

10

De

ath

, MI,

or

Str

ok

e (

%)

P=.02

8.5%

11.5%

Clopidogreln=1053

Placebon=1063

Adapted with permission from Steinhubl SR, et al. JAMA. 2002;288:2411-2420.

CREDO Study: 1-Year Primary Outcome

NNT=33

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-

12 -

-

8 -

-

4 -

-

0 -

4.6

CREDO Study: Benefit of Clopidogrel in PCI Patients at Various Time Intervals

Rand. to 1 Year Rand. to Day 28 Day 29 to 1 Year

Co

mb

ined

En

dp

oin

t O

ccu

rren

ce (

%)

MI, Stroke, or Death – ITT Population

Clopidogrel*

Placebo*

37.4% RRRP=.04

19.7% RRRP=.21

26.9% RRRP=.02

*Plus aspirin and other standard therapies.†Steinhubl S, et al. JAMA. 2002;288:2411-2420. ‡Steinhubl S. 75th Scientific Sessions of the AHA; November 18, 2002; Chicago, Ill.

8.5†

11.5†

5.5‡

6.9‡

2.9‡

4.6‡

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Cost-effectiveness of Prolonged Clopidogrel Therapy After PCI

Adapted with permission from Cowper PA, et al. J Am Coll Cardiol. 2005;45:369-376.

Modeled Outcomes and Cost-effectiveness

N=3976.

Total Sample

Variable Clopidogrel No Clopidogrel

Total Cost* $3,715 $2,819Outcomes MI (1 month to 1 yr) 3.24% 5.80%Cost-effectiveness $/MI avoided $34,336 $/yr of life saved $15,696

*Between 1 and 12 months following PCI.

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Cost-effectiveness of Prolonged Clopidogrel Therapy After PCI

Adapted with permission from Cowper PA, et al. J Am Coll Cardiol. 2005;45:369-376.

N=3976.

Modeled Outcomes and Cost-effectiveness

High-Risk Subset Low-Risk Subset

No NoVariable Clopidogrel Clopidogrel Clopidogrel Clopidogrel

Total Cost* $4,082 $3,307 $3,311 $2,328Outcomes MI (1 month to 1 yr) 4.46% 8.0% 2.06% 3.70%Cost-effectiveness $/MI avoided $21,893 $59,939 $/yr of life saved $10,333 $26,568

*Between 1 and 12 months following PCI

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2159 low- to intermediate-risk patients undergoing elective PCI with stent placement

Abciximab +70 U/kg heparin

(n=1079)

Placebo + 140 U/kg heparin

(n=1080)

End Points:• Primary 30-day death/MI/urgent target-vessel revascularization

• Secondary30-day bleeding complications

ISAR-REACT: Trial Design

Clopidogrel*(600-mg loading dose)

Randomized

*In addition to aspirin.

Kastrati A, et al. N Engl J Med. 2004;350:232-238.

Clopidogrel 150 mg/d until discharge, then

75 mg/d for 4 wk*

Clopidogrel 150 mg/d until discharge, then

75 mg/d for 4 wk*

325-500 mg Aspirin

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ISAR-REACT Primary End Point: 30-Day Death/MI/UTVR

4.0% 4.0%

0%

2%

4%

6%

P = NS

Death/MI/UTVR

0.9%0.7%

0%

1%

2%

3%

4%

P = NS

UTVR

0.3% 0.3%

0%

1%

2%

3%

4%

P = NS

Death

Abciximab +Clopidogrel

Placebo + Clopidogrel Abciximab +

ClopidogrelPlacebo +

ClopidogrelAbciximab +Clopidogrel

Placebo +Clopidogrel

UTVR = urgent target-vessel revascularization.Adapted with permission from Kastrati A, et al. N Engl J Med. 2004;350:232-238.

% o

f P

atie

nts

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High Cost of Post-MI Heart Failure

Impact of Heart Failure on Cost of Managing Post-MI Patients

$31,426

$44,997

05,000

10,00015,00020,00025,00030,00035,00040,00045,000

Post-MI Patients Post-MI Patients WithHeart Failure

Mean Annual Cost of Management

50,000

$13,571 per year

for patients who

develop heart failure

Akhras KS, et al. Abstract presented at: Heart Failure Society of America 2003 Scientific Meeting; September 21-24, 2003; Las Vegas, Nev.

Do

llar

s

(n=5298)

(n=2345)

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Impact of Eplerenone on Relative Risk of Total Mortality Post-MI With LVD

Months Since Randomization

Cu

mu

lati

ve

Inci

den

ce (

%)

22

0

2

20

16

18

14

12

10

8

6

4

RR=.85 (95% CI, .75-.96) P=.008

Placebo (n=3,313)

Eplerenone (n=3,319)

3633302724211815129630

Pitt B, et al. N Engl J Med. 2003;348:1309-1321.

CI = confidence interval; RR = relative risk.

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Early Benefits of Eplerenone When Added to Standard Post-MI Patient Care

Pitt B, et al. N Engl J Med. 2003;348:1309-1321.

All CauseMortality

CardiovascularMortality

Sudden CardiacDeath

Heart FailureHospitalization

30 Days

-31 -32-37

-18

-50-45-40-35-30-25-20

-15-10-505

10

Re

lati

ve

Ris

k (

%)

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Cost-effectiveness of Eplerenone vs Placebo in MI Patients With LV Dysfunction and HF

Adapted with permission from Weintraub WS, et al. Circulation. 2005;111:1106-1113.

Cost-effectiveness of Eplerenone

N=6632.

∆ Cost, $ ∆ Effectiveness ICER, $ <50,000/LYG, %

No added costs resultingfrom life-years saved

Life-years Framingham 1391 0.1014 13,718 96.7 Saskatchewan 1391 0.0636 21,876 93.8 Worcester 1391 0.1337 10,402 98.8

LYG indicates life-years gained.

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Critical Pathways for UA/NSTEMIUnstable Angina/

Non–ST-elevation MI*

ASA, Clopidogrel, -blockers, ACEI, statinHeparin or LMWH

Conservative Strategy Invasive Strategy

DC Home or ETT Hour 8-12

Cath/PCI Hour (0-6)

D/C Home Hour 8-16 D/C Day Hour 18-24

+

Rest pain

Adapted from UCLA Clinical Pathway for ACS. Available at: www.med.ucla.edu/champ.

ECG + and/or Troponin +Troponin -

6-hr Troponin - / ECG -

ASA, clopidogrel, -blockers, ACEI, statin, omega 3, and exercise

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CHAMP Study: UCLA

Designed to determine whether physician/patient compliance with preventive therapies can be improved through a hospital-initiated program

Tracked initiation of aspirin, β-blocker, ACE inhibitor, statins

Used preprinted orders, guidelines, lectures, discharge forms

Population: patients with symptomatic atherosclerosis treated at university-associated teaching hospital

Methods: no specific algorithms used before CHAMP (1992-1993)

National guidelines (ACC/AHA, NCEP ATP I and ATP II) used in CHAMP (1994-1995)

Evaluation: treatment rates and clinical outcomes pre-CHAMP and CHAMP in patients hospitalized for AMI

Fonarow GC, Gawlinski A. Am J Cardiol. 2000;85(3A):10A-17A.

Cardiac Hospitalization Atherosclerosis Management Program

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0

5

10

15

CHAMP Study: Clinical Events for the First Year After Discharge for Acute MI

Fonarow GC, et al. Am J Cardiol. 2001;87:819-822.

Eve

nt R

a te

, %

RecurrentMI

HeartFailure

Hospitalization TotalMortality

Pre-CHAMP

Post-CHAMP

7.8

4.7

14.8

7.0

3.3* 2.6

7.6*

3.3*

* P<0.05

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256 AMI pts discharged in 92/93 pre-CHAMP compared to 302 pts in 94/95 post-CHAMPUCLA Med Center Accounting Model, total costs averaged over each pt dc; meds at AWP

Fonarow GC, et al. Am J Cardiol. 2001;87:819-822.

CHAMP: Economic Analysis

$4,176

$3,182

Pre-CHAMP Post-CHAMP$1,000

$10,000

Total Medical Cost Per Patient Discharged (1 year)

P<0.001

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86,735 AMI patients in NRMI IV treated between 7/00 and 3/01. ACC/AHA Class I therapy.Hospitals divided into quartiles to composites of quality.

Peterson ED. Circulation. 2002;106:II-722. Abstract.

Median Performance Lagging Hospitals Leading Hospitalson Care Processes (n=271) (n=271)

Aspirin <24 h 73% 93%β-blocker <24 h 50% 86%Reperfusion 50% 71%DC ACEI 40% 70%DC Lipid Therapy 58% 80%Smoking Advice 7% 65%

Mortality 17.6% 11.9%

Variation in Acute MI Care Quality in 1085 Hospitals and Its Association

With Mortality Rates

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Performance Matters!

Reprinted with permission from Peterson ED. Presented at: Annual Scientific Sessions of the AHA; November 17-20, 2002; Chicago, Ill.

Relationship Between Process and Outcome in CRUSADE

5.9

5.04.6

3.6

0

1

2

3

4

5

6

7

<65% 65%-75% 75%-80% >80%

Hospital Composite Adherence Quartiles

In-h

os

pit

al M

ort

alit

y (

%)

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Featured Institution

Aurora Sinai Medical Center

Milwaukee, Wisconsin

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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 Remarks

Gregg C. Fonarow, MD

Next program: Wednesday, September 14, 2005at 12:00 Noon Eastern Time (9:00 AM Pacific)

Topic: The CRUSADE National Quality Improvement Initiative: 2005 Update

Faculty: Christopher P. Cannon, MD