E. Magnus Ohman, MB, FRCPI, FESC, FACC Professor of Cardiovascular Medicine Director, Program for...

E. Magnus Ohman, MB, FRCPI, FESC, FACCProfessor of Cardiovascular Medicine

Director, Program for Advanced Coronary DiseaseDuke University Medical CenterDuke Clinical Research Institute

Durham, North Carolina

Evidence-Based Medicine Therapies in ACS: From Principles to Practice

Conflict of interest:Research grants -

• Berlex, Sanofi-Aventis, Schering-Plough, The Medicine Company, Bristol Meyer Squibb, CVT

Therapeutics, and Eli LillyStock ownership -

• Medtronic, SavacorConsultant -

• Northpointe Domain, Liposcience, Abiomed, Datascope, and Inovise Medical

Evidence-Based Medicine Therapies in ACS; From Principles to Practice

Evidence-Based Medicine Therapies in ACS; From Principles to Practice

Changes in Health Care Systems: Moving From the 20th to the 21st Century

Changes in Health Care Systems: Moving From the 20th to the 21st Century

Provider-centered Price-driven Care decisions widely

varying Fragmented care Little quality

measurement Persistent escalating

costs

Provider-centered Price-driven Care decisions widely

varying Fragmented care Little quality

measurement Persistent escalating

costs

Patient-centered Value-driven Evidence-based care

Coordinated care Ubiquitous quality

measurement Overall cost decline

Patient-centered Value-driven Evidence-based care

Coordinated care Ubiquitous quality

measurement Overall cost decline

2020thth Century Century2020thth Century Century 2121stst Century Century2121stst Century Century

National Committee for Quality Health Care 2003National Committee for Quality Health Care 2003

Quality of Care Incorporated in the “Drugs for the Elderly” Medicare Bill Passed by Congress

in 2003

Quality of Care Incorporated in the “Drugs for the Elderly” Medicare Bill Passed by Congress

in 2003Program DescriptionPay for performance IOM to develop a strategy for

aligning quality and paymentHospital to report on Hospitals that report will get performance 0.4% larger payments

Changing MD’s practice MD that participate will get

higher pay

Improving access for Develop demonstrationchronic illness (CHF) programsIT provision Grants for electronic

prescribing

Program DescriptionPay for performance IOM to develop a strategy for

aligning quality and paymentHospital to report on Hospitals that report will get performance 0.4% larger payments

Changing MD’s practice MD that participate will get

higher pay

Improving access for Develop demonstrationchronic illness (CHF) programsIT provision Grants for electronic

prescribing

Improvement in Performance Scores

90%86%

64%

85%

70%

93% 90%

76%

91%

80%

0%

20%

40%

60%

80%

100%

AMI CABG CHF Joint Repl Pneumonia

Before After

Pilot trial of Medicare Population: 270 Hospitals – 400,000 PatientsPilot trial of Medicare Population: 270 Hospitals – 400,000 Patients

Source: Centers for Medicare and Medicaid ServicesSource: Centers for Medicare and Medicaid Services

1990 1992 1994 1996 1998 2000 20021990

ACC/AHAAMI

R. Gunnar

1994AHCPR/NHLBI

UA E. Braunwald

1996 1999 Rev Upd ACC/AHA AMI T. Ryan

2004 2007 Rev Upd

ACC/AHA STEMI E. Antman

2000 2002 2007 Rev Upd Rev

ACC/AHA UA/NSTEMI E. Braunwald J. Anderson

2004 2007

Figure 1. Evolution of Guidelines for Management of Patients with AMI

The first guideline published by the ACC/AHA described the management of patients with acute myocardial infarction (AMI). The subsequent three documents were the Agency for Healthcare and Quality/National Heart, Lung and Blood Institute sponsored guideline on management of unstable angina (UA), the revised/updated ACC/AHA guideline on AMI, and the revised/updated ACC/AHA guideline on unstable angina/non-ST segment myocardial infarction (UA/NSTEMI). The present guideline is a revision and deals strictly with the management of patients presenting with ST segment elevation myocardial infarction (STEMI). The names of the chairs of the writing committees for each of the guidelines are shown at the bottom of each box. Rev, Revised; Upd, Update

Evolution of Guidelines for ACS

CRUSADE National Quality Improvement CRUSADE National Quality Improvement InitiativeInitiative

Academic collaboration between cardiology and Academic collaboration between cardiology and emergency medicine specialties started in 2001emergency medicine specialties started in 2001

Multiple industry sponsorsMultiple industry sponsors Millennium-Schering PloughMillennium-Schering Plough Bristol-Myers-SquibbBristol-Myers-Squibb Sanofi-AventisSanofi-Aventis Merck-ScheringMerck-Schering PDL PharmaPDL Pharma

Goal: Improve adherence to ACC/AHA ACS Goal: Improve adherence to ACC/AHA ACS guidelines guidelines UA and NSTEMI UA and NSTEMI STEMI added in 2004 STEMI added in 2004

Goals for CRUSADE: Improve Adherence to ACC/AHA Guidelines for

Patients with Unstable Angina/Non-STEMI

Goals for CRUSADE: Improve Adherence to ACC/AHA Guidelines for

Patients with Unstable Angina/Non-STEMI

Aspirin Clopidogrel

Beta Blocker Heparin (UFH or

LMWH) GP IIb-IIIa Inhibitor

All receiving cath/PCI

Aspirin Clopidogrel

Beta Blocker Heparin (UFH or

LMWH) GP IIb-IIIa Inhibitor

All receiving cath/PCI

Aspirin Clopidogrel Beta Blocker ACE Inhibitor Statin/Lipid Lowering Smoking Cessation Cardiac

Rehabilitation

Aspirin Clopidogrel Beta Blocker ACE Inhibitor Statin/Lipid Lowering Smoking Cessation Cardiac

Rehabilitation

Acute TherapiesAcute TherapiesAcute TherapiesAcute Therapies Discharge TherapiesDischarge TherapiesDischarge TherapiesDischarge Therapies

Circulation, JACC 2002 - ACC/AHA Guidelines updateCirculation, JACC 2002 - ACC/AHA Guidelines updateCirculation, JACC 2002 - ACC/AHA Guidelines updateCirculation, JACC 2002 - ACC/AHA Guidelines update

Evaluating the Process of Care• An adherence score is applied to each patient. incorporating the components of process of care.• The score from each patient then combined for all patients at each hospital. Typical scores ranged from 50 to 95%.• All 400 hospital adherence scores then ranked in quartiles - best to worst.

Evaluating the Process of Care• An adherence score is applied to each patient. incorporating the components of process of care.• The score from each patient then combined for all patients at each hospital. Typical scores ranged from 50 to 95%.• All 400 hospital adherence scores then ranked in quartiles - best to worst.

Total sites = 568Total sites = 568(Active sites = 409)(Active sites = 409)

205,528 patients includedas of January 2007

AK(0)

WA(7)

OR(5)

CA(35)

ID(0)

NV(1)

MT(0)

WY(0)

CO(8)

NM(2)

ND(1)

SD(2)

NE (4)

KS(3)

OK(9)

TX(17)

MN(4)

IA(5)

MO(12)

AR(3)

LA(8)

WI(5) MI

(22)

MI

UT(1)

AZ(9)

HI (1)

IL(14)

IN(7)

KY(8)

TN(11)

MS(6)

AL(11)

GA(15)

FL(33)

SC(6)

NC(15)

VA(16)

OH(30)

WV(3)

PA(37)

NY(37)

MD (13)

ME(0)

VT (1)

NH (2)

NJ (10)

MA (11)

CT (8)

DE (3)

RI (1)

DC (1)

CRUSADE Site DistributionCRUSADE Site DistributionCRUSADE Site DistributionCRUSADE Site Distribution

AAcute cute

CCoronaryoronary

TTreatmentreatment and and IInterventionntervention

OOutcomes utcomes

NNetworketwork

National ACS Surveillance SystemNational ACS Surveillance System Assess characteristics, treatments, and Assess characteristics, treatments, and

outcomes of ACS patientsoutcomes of ACS patients Focuses on NSTEMI and STEMIFocuses on NSTEMI and STEMI

Optimize ACS management and outcomesOptimize ACS management and outcomes Implement evidence-based guideline Implement evidence-based guideline

recommendations in clinical practice recommendations in clinical practice

Improve quality and safety of ACS careImprove quality and safety of ACS care

Investigate novel QI methodsInvestigate novel QI methods

Follow Guidelines Adherence, Medication Dosing, Follow Guidelines Adherence, Medication Dosing, and Outcomes with the ACC-ACTIONand Outcomes with the ACC-ACTION Registry Registry

CRUSADE Lessons LearnedCRUSADE Lessons Learned Complex patient populationComplex patient population

Variations in use of medicationsVariations in use of medications

Disparities in use of invasive proceduresDisparities in use of invasive procedures

Rapid changes in revascularization Rapid changes in revascularization proceduresprocedures

Transfusions and bleeding are commonTransfusions and bleeding are common

Importance of proper medication dosingImportance of proper medication dosing

Comprehensive guidelines adherence saves Comprehensive guidelines adherence saves liveslives

Academic output critical to successAcademic output critical to success









89%

69%

54%

45%

12%

0%

20%

40%

60%

80%

100%

Cath Cath < 48 hr PCI PCI < 48 hr CABG

ACTION/CRUSADE: April, 2006 – May, 2007

CRUSADE CRUSADE ACTION – NSTEMI Patients ACTION – NSTEMI PatientsInvasive Procedures in Cath-Eligible Population*Invasive Procedures in Cath-Eligible Population*

* Excludes ~25% of patients with cath contraindications

Early Cath (<48h) Use by Risk StatusEarly Cath (<48h) Use by Risk Status

20253035404550556065707580

2002

Q1

2002

Q2

2002

Q3

2002

Q4

2003

Q1

2003

Q2

2003

Q3

2003

Q4

2004

Q1

2004

Q2

2004

Q3

2004

Q4

Low RiskMod RiskHigh Risk

26.626.632.232.2

53.553.5

63.263.2

64.164.1

75.575.5

18%18%

21%21%

- Tricoci et al AHA 2005- Tricoci et al AHA 2005

Procedure Use as a Function of AgeProcedure Use as a Function of Age

- Alexander, JACC 2005- Alexander, JACC 2005

Rates of Cardiac Catheterization According to Predictive Risk of Severe CAD (L-Main or 3

Vessel) in ACS Patients

Rates of Cardiac Catheterization According to Predictive Risk of Severe CAD (L-Main or 3

Vessel) in ACS Patients

72.179.1 75.3

64.2

53.644.7

0

25

50

75

100

<10% 10-19% 20-29% 30-39% 40-49% ≥50%

Expected Risk of SCAD

Cad

iac

Cat

hete

riza

tion

(%)

n = 97,004n = 97,004

- Cohen, et al AHA 2005- Cohen, et al AHA 2005

Risk – Treatment ParadoxRisk – Treatment Paradox

0

10

20

30

40

50

60

% o

f P

atie

nts

1 2 3 4 5 6 7 8 9 10

Cath PCI CABG

Cath, p=0.0002; PCI, p=0.03; CABG, p=0.01Cath, p=0.0002; PCI, p=0.03; CABG, p=0.01

24.624.6

53.653.6

38.038.0

5.45.4

16.016.0

5.85.8

GRACE Risk Score (Deciles)GRACE Risk Score (Deciles)GRACE Risk Score (Deciles)GRACE Risk Score (Deciles)

92.6

63.4

82.3

59.5

76

64.8

47.5

85.2

38.9

78.8

58.5

70.2

50.1

27.8

0

10

20

30

40

50

60

70

80

90

100

Aspirin Clopidogrel B-Blocker ACE-I Statin SmokingCessation

CardiacRehab

Early Cath No Early Cath

Discharge Medication Use by Invasive Care –Discharge Medication Use by Invasive Care –UA/NSTEMI Patients from CRUSADEUA/NSTEMI Patients from CRUSADE

Per

cen

tag

e U

seP

erce

nta

ge

Use

Bhatt DL, JAMA 2004;292:2096-104.









Independent Predictors of Early CathIndependent Predictors of Early Cath

Adjusted Odds RatioAdjusted Odds Ratio

110.50.5 1.51.5 22

Cardiology CareCardiology Care

Age (per 10 yrs)Age (per 10 yrs)

Prior CHFPrior CHF

Renal InsufficiencyRenal Insufficiency

Signs of CHFSigns of CHF

Caucasian RaceCaucasian Race

Female SexFemale Sex

Bhatt et al, JAMA 2004Bhatt et al, JAMA 2004

A Reduction in the Use of Medical Strategy Alone in ACS Patients After

Introduction of DES

A Reduction in the Use of Medical Strategy Alone in ACS Patients After

Introduction of DES

30

35

40

45

50

55

60

Med

ical T

hera

py, %

FDA approves DES

p<0.01

- Gogo et al, ACC 2006- Gogo et al, ACC 2006

More PCI for 3-Vessel CAD After Introduction of DES

More PCI for 3-Vessel CAD After Introduction of DES

35

40

45

50

55

60

65

Perc

ent

CABG PCI

FDA approves DES

p<0.01 for trend in CABG rates

35

40

45

50

55

60

65

Perc

ent

CABG PCI

FDA approves DES

p<0.01 for trend in CABG rates


Trends for DES Use for UA/NSTEMI – Trends for DES Use for UA/NSTEMI – CRUSADE to ACTION:CRUSADE to ACTION: July 2006 - March 2007July 2006 - March 2007

8981

72

0

10

20

30

40

50

60

70

80

90

100

Qtr 3 2006 Qtr 4 2006 Qtr 1 2007

% D

ES

am

on

g S

ten

t P

ts

The Use of Medical Therapy Alone in Patients The Use of Medical Therapy Alone in Patients With 3-Vessel CAD Has Been Constant Over TimeWith 3-Vessel CAD Has Been Constant Over Time

0

10

20

30

40

50

Perc

en

t

FDA approves DES

p=NS










Use of Blood Transfusions in CRUSADEUse of Blood Transfusions in CRUSADE

0

5

10

15

20

25

< 55 yrs 55-64 yrs 65-74 yrs > 75 yrs Men Women no CRI CRI

% R

BC T

rans

fusio

n

Yang X, JACC 2005;46:1490-5.









Excessive Dosing of Anticoagulants by Age

Excessive Dosing of Anticoagulants by Age

12.5

28.7

8.512.5

3733.1

16.5

38.5

64.5

0

10

20

30

40

50

60

70

LMW Heparin UF Heparin GP IIb/IIIa

% E

xces

sive

Do

se

< 65 yrs 65-75 yrs >75 yrs

12.5

28.7

8.512.5

3733.1

16.5

38.5

64.5

0

10

20

30

40

50

60

70

LMW Heparin UF Heparin GP IIb/IIIa

% E

xces

sive

Do

se

< 65 yrs 65-75 yrs >75 yrs

-- Alexander JAMA 2005;294:3108-3116

42% of patients got excess

Dosing Combinations and Transfusions: Heparin + GP IIb-IIIa Inhibitors*

Dosing Combinations and Transfusions: Heparin + GP IIb-IIIa Inhibitors*

4.1

9

18.5

02468

101214161820

Both Right 1 Excessive BothExcessive

% R

BC

Tra

ns

fus

ion

s

* Among patients receiving both Heparin (UFH or LMWH) and GP IIb-IIIa Inhibitors* Among patients receiving both Heparin (UFH or LMWH) and GP IIb-IIIa Inhibitors

-- Alexander JAMA 2005;294:3108-3116

8

6.7

4.4

10.4

8.8

13.3

0

2

4

6

8

10

12

14

UF Heparin LMWH GP IIb-IIIa

Recommended Excess

CRUSADE RBC Transfusions by Excess DosingCRUSADE RBC Transfusions by Excess DosingR

BC

Tra

nsf

usi

on

(%

)R

BC

Tra

nsf

usi

on

(%

)

Alexander KA, JAMA 2005;294:3108-16. Alexander KA, JAMA 2005;294:3108-16.

35.8

14.1

25.9

33.9

14.2

21.6

0

10

20

30

40

UF Heparin LMWH GP IIb-IIIa

Q4 2005 Q4 2006

Impact of Overdosing Reporting in CRUSADEImpact of Overdosing Reporting in CRUSADEO

verd

osi

ng

(%

)O

verd

osi

ng

(%

)









Link Between Overall ACC/AHA Guidelines Adherence and Mortality

Link Between Overall ACC/AHA Guidelines Adherence and Mortality

Peterson et al, ACC 2004Peterson et al, ACC 2004

5.95

5.16 4.97

4.16

5.074.63

4.17

6.33

0

1

2

3

4

5

6

7

<=25% 25 - 50% 50 - 75% >=75%

Hospital Composite Quality Quartiles

% I

n-H

osp

Mo

rtal

ity

Adjusted Unadjusted

5.95

5.16 4.97

4.16

5.074.63

4.17

6.33

0

1

2

3

4

5

6

7

<=25% 25 - 50% 50 - 75% >=75%

Hospital Composite Quality Quartiles

% I

n-H

osp

Mo

rtal

ity

Adjusted Unadjusted

Every 10% Every 10% in guidelines adherence in guidelines adherence 11% 11% in in mortalitymortality

Change in Mortality by Hospital Performance Improvement

Change in Mortality by Hospital Performance Improvement

-45-40-35-30-25-20-15-10

-505

% R

ela

tiv

e C

ha

ng

e in

Mo

rta

lity

Worsening N=78 No N=79 Modest N=79 Large N=79

-45-40-35-30-25-20-15-10

-505

% R

ela

tiv

e C

ha

ng

e in

Mo

rta

lity

Worsening N=78 No N=79 Modest N=79 Large N=79

Peterson et al, AHA 2004Peterson et al, AHA 2004

7.1%

4.9%

5.7%

4.3%

5.6%

4.9% 5.1%

4.1%

0%

1%

2%

3%

4%

5%

6%

7%

8%

1st 2nd 3rd 4rth

Hospital Mortality According to How Consistently Hospitals Follow Trial Evidence

Quartiles of Hospital Composite of Medication Core Measures

Granger Am J Med. 2005;118:858-65 Granger Am J Med. 2005;118:858-65

Proportion of Patients Receiving 100% of All Guidelines-Recommended

Therapies*

Proportion of Patients Receiving 100% of All Guidelines-Recommended

Therapies*

16%

30% 30%

21%

36% 34%31%

46% 47%

33%

48% 50%

0%

25%

50%

75%

100%

Overall 100% CorrectMedication

Acute 100% CorrectMedication

Discharge 100% CorrectMedication

Q1Q4Q8Q11

*In patients without contraindications*In patients without contraindications

Mehta et al, AHA 2005Mehta et al, AHA 2005

CRUSADE Lessons Learned: ConclusionsCRUSADE Lessons Learned: Conclusions

Disparities in use of invasive proceduresDisparities in use of invasive procedures The highest risk patients frequently do not The highest risk patients frequently do not

undergo an invasive management in ACSundergo an invasive management in ACS

Rapid changes in revascularization proceduresRapid changes in revascularization procedures Substantial changes in DES and CABG use Substantial changes in DES and CABG use

during the last year highlights physician during the last year highlights physician uncertainty on safetyuncertainty on safety


Importance of proper medication dosingImportance of proper medication dosing Appropriate dosing of therapies need to be Appropriate dosing of therapies need to be

emphasized before and after interventionsemphasized before and after interventions

Date post:	30-Dec-2015
Category:	Documents
Upload:	lesley-warren
View:	216 times
Download:	1 times

E. Magnus Ohman, MB, FRCPI, FESC, FACC Professor of Cardiovascular Medicine Director, Program for...

Documents