Transcript Evidence-Based Medicine Therapies in ACS

Evidence-Based Medicine Therapies in ACS:
From Principles to Practice
E. Magnus Ohman, MB, FRCPI, FESC, FACC
Professor of Cardiovascular Medicine
Director, Program for Advanced Coronary Disease
Duke University Medical Center
Duke 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 Lilly
Stock ownership • Medtronic, Savacor
Consultant • Northpointe Domain, Liposcience, Abiomed,
Datascope, and Inovise Medical
Changes in Health Care Systems:
Moving From the 20th to the 21st Century
21st Century
20th Century
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Provider-centered
Price-driven
Care decisions widely
varying
Fragmented care
Little quality
measurement
Persistent escalating
costs
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Patient-centered
Value-driven
Evidence-based care
Coordinated care
Ubiquitous quality
measurement
Overall cost decline
National Committee for Quality Health Care 2003
Quality of Care Incorporated in the “Drugs
for the Elderly” Medicare Bill Passed by
Congress in 2003
Program
Pay for performance
Description
IOM to develop a strategy for
aligning quality and payment
Hospital 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
chronic illness (CHF)
IT provision
Develop demonstration
programs
Grants for electronic
prescribing
Improvement in Performance Scores
Pilot trial of Medicare Population: 270 Hospitals – 400,000 Patients
100%
Before
90%
93%
86%
After
91%
90%
85%
80%
76%
80%
70%
64%
60%
40%
20%
0%
AMI
CABG
CHF
Joint Repl
Pneumonia
Source: Centers for Medicare and Medicaid Services
Evolution of Guidelines for ACS
1990 1992 1994 1996 1998 2000 2002 2004 2007
1990
ACC/AHA
AMI
R. Gunnar
1994
AHCPR/NHLBI
UA
E. Braunwald
1996
1999
Rev
Upd
ACC/AHA AMI
T. Ryan
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/nonST 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
2000 2002
2007
Rev
Upd
Rev
ACC/AHA UA/NSTEMI
E. Braunwald
J. Anderson
2004
2007
Rev
Upd
ACC/AHA STEMI
E. Antman
CRUSADE National Quality Improvement
Initiative

Academic collaboration between cardiology and
emergency medicine specialties started in 2001

Multiple industry sponsors






Millennium-Schering Plough
Bristol-Myers-Squibb
Sanofi-Aventis
Merck-Schering
PDL Pharma
Goal: Improve adherence to ACC/AHA ACS
guidelines
 UA and NSTEMI  STEMI added in 2004
Goals for CRUSADE:
Improve Adherence to ACC/AHA Guidelines for
Patients with Unstable Angina/Non-STEMI
Acute Therapies
Discharge Therapies

Aspirin
 Clopidogrel
 Clopidogrel
 Beta Blocker
Evaluating the Process
ofBlocker
Care
 Beta
• An
adherence
score
to each
patient.
 Heparin
(UFH
or is applied
 ACE
Inhibitor
incorporating
process of care.
LMWH) the components ofStatin/Lipid
Lowering
• The
score
from
each patient then combined for all
 GP
IIb-IIIa
Inhibitor
 Smoking
Cessation
patients
at
each
hospital.
Typical
scores
ranged
from
 All receiving cath/PCI
 Cardiac
50 to 95%.
Rehabilitation
• All 400 hospital adherence scores
then ranked in
quartiles - best to worst.

Aspirin
Circulation, JACC 2002 - ACC/AHA Guidelines update
CRUSADE Site Distribution
Total sites = 568
(Active sites = 409)
WA
(7)
VT (1)
MT
(0)
OR
(5)
MI
CA
(35)
AZ
(9)
MI
(22)
IA
(5)
NE
(4)
CO
(8)
NY
(37)
WI
(5)
WY
(0)
UT
(1)
NH (2)
MN
(4)
SD
(2)
ID
(0)
NV
(1)
ND
(1)
ME
(0)
IL
(14)
OK
(9)
AR
(3)
AL
(11)
RI (1)
CT (8)
NJ (10)
DE (3)
WV
(3)
VA
(16)
MD (13)
DC (1)
NC
(15)
TN
(11)
MS
(6)
TX
(17)
OH
(30)
KY
(8)
MO
(12)
KS
(3)
NM
(2)
IN
(7)
PA
(37)
MA (11)
SC
(6)
GA
(15)
LA
(8)
FL
(33)
AK
(0)
HI (1)
205,528 patients included
as of January 2007
Follow Guidelines Adherence, Medication Dosing,
and Outcomes with the ACC-ACTION Registry
Acute
Coronary
Treatment

National ACS Surveillance System
 Assess characteristics, treatments, and
outcomes of ACS patients
 Focuses on NSTEMI and STEMI
and

Optimize ACS management and outcomes
 Implement evidence-based guideline
recommendations in clinical practice

Improve quality and safety of ACS care

Investigate novel QI methods
Intervention
Outcomes
Network
CRUSADE Lessons Learned

Complex patient population

Variations in use of medications

Disparities in use of invasive procedures

Rapid changes in revascularization
procedures

Transfusions and bleeding are common

Importance of proper medication dosing

Comprehensive guidelines adherence saves
lives

Academic output critical to success
CRUSADE Lessons Learned

Complex patient population

Variations in use of medications

Disparities in use of invasive procedures

Rapid changes in revascularization
procedures

Transfusions and bleeding are common

Importance of proper medication dosing

Comprehensive guidelines adherence saves
lives

Academic output critical to success
CRUSADE  ACTION – NSTEMI Patients
Invasive Procedures in Cath-Eligible Population*
100%
89%
80%
69%
60%
54%
45%
40%
20%
12%
0%
Cath
Cath < 48 hr
PCI
PCI < 48 hr
CABG
* Excludes ~25% of patients with cath contraindications
ACTION/CRUSADE: April, 2006 – May, 2007
Early Cath (<48h) Use by Risk Status
75.5
18%
64.1
63.2
53.5
32.2
26.6
21%
20
02
Q
20 1
02
Q
20 2
02
Q
20 3
02
Q
20 4
03
Q
20 1
03
Q
20 2
03
Q
20 3
03
Q
20 4
04
Q
20 1
04
Q
20 2
04
Q
20 3
04
Q
4
80
75
70
65
60
55
50
45
40
35
30
25
20
Low Risk
Mod Risk
High Risk
- Tricoci et al AHA 2005
Procedure Use as a Function of Age
- Alexander, JACC 2005
Rates of Cardiac Catheterization
According to Predictive Risk of Severe
CAD (L-Main or 3 Vessel) in ACS Patients
Cadiac Catheterization (%)
100
79.1
75
75.3
72.1
64.2
53.6
44.7
50
25
0
<10%
10-19%
20-29%
30-39%
40-49%
Expected Risk of SCAD
≥50%
n = 97,004
- Cohen, et al AHA 2005
Risk – Treatment Paradox
60
Cath
PCI
CABG
Cath, p=0.0002; PCI, p=0.03; CABG, p=0.01
53.6
50
% of Patients
40
38.0
30
24.6
20
16.0
10
5.8
5.4
0
1
2
3
4
5
6
7
8
GRACE Risk Score (Deciles)
9
10
Discharge Medication Use by Invasive Care –
UA/NSTEMI Patients from CRUSADE
Early Cath
Percentage Use
100
90
No Early Cath
92.6
85.2
80
70
82.3
78.8
76
70.2
64.8
63.4
60
50
40
30
20
59.5 58.5
50.1
47.5
38.9
27.8
10
0
Aspirin
Clopidogrel B-Blocker
ACE-I
Statin
Smoking
Cessation
Cardiac
Rehab
Bhatt DL, JAMA 2004;292:2096-104.
CRUSADE Lessons Learned

Complex patient population

Variations in use of medications

Disparities in use of invasive procedures

Rapid changes in revascularization
procedures

Transfusions and bleeding are common

Importance of proper medication dosing

Comprehensive guidelines adherence saves
lives

Academic output critical to success
Independent Predictors of Early Cath
Cardiology Care
Age (per 10 yrs)
Prior CHF
Renal Insufficiency
Signs of CHF
Caucasian Race
Female Sex
0.5
1
1.5
2
Adjusted Odds Ratio
Bhatt et al, JAMA 2004
A Reduction in the Use of Medical
Strategy Alone in ACS Patients After
Introduction of DES
55
50
45
p<0.01
40
35
FDA approves DES
05
20
04
20
03
20
02
30
20
Medical Therapy, %
60
- Gogo et al, ACC 2006
More PCI for 3-Vessel CAD After
Introduction of DES
65
PCI
p<0.01 for trend in CABG rates
55
50
45
40
FDA approves DES
20
05
20
04
20
03
35
20
02
Percent
60
CABG
- Gogo et al, ACC 2006
% DES among Stent Pts
Trends for DES Use for UA/NSTEMI –
CRUSADE to ACTION: July 2006 - March 2007
100
90
89
81
80
72
70
60
50
40
30
20
10
0
Qtr 3 2006
Qtr 4 2006
Qtr 1 2007
The Use of Medical Therapy Alone in Patients
With 3-Vessel CAD Has Been Constant Over Time
50
30
20
p=NS
10
FDA approves DES
05
20
04
20
03
20
02
0
20
Percent
40
- Gogo et al, ACC 2006
CRUSADE Lessons Learned

Complex patient population

Variations in use of medications

Disparities in use of invasive procedures

Rapid changes in revascularization
procedures

Transfusions and bleeding are common

Importance of proper medication dosing

Comprehensive guidelines adherence saves
lives

Academic output critical to success
Use of Blood Transfusions in CRUSADE
% RBC Transfusion
25
20
15
10
5
0
< 55 yrs 55-64 yrs 65-74 yrs > 75 yrs
Men
Women
no CRI
CRI
Yang X, JACC 2005;46:1490-5.
CRUSADE Lessons Learned

Complex patient population

Variations in use of medications

Disparities in use of invasive procedures

Rapid changes in revascularization
procedures

Transfusions and bleeding are common

Importance of proper medication dosing

Comprehensive guidelines adherence saves
lives

Academic output critical to success
70
% Excessive Dose
60
Excessive Dosing of
Anticoagulants by Age
64.5
42% of patients got excess
50
37 38.5
40
28.7
30
20
33.1
12.5 12.5
16.5
8.5
10
0
LMW Heparin
< 65 yrs
UF Heparin
65-75 yrs
-- Alexander JAMA 2005;294:3108-3116
GP IIb/IIIa
>75 yrs
% RBC Transfusions
Dosing Combinations and Transfusions:
Heparin + GP IIb-IIIa Inhibitors*
20
18
16
14
12
10
8
6
4
2
0
18.5
9
4.1
Both Right
1 Excessive
Both
Excessive
* Among patients receiving both Heparin (UFH or LMWH) and GP IIb-IIIa Inhibitors
-- Alexander JAMA 2005;294:3108-3116
CRUSADE RBC Transfusions by Excess Dosing
Recommended
Excess
13.3
RBC Transfusion (%)
14
12
10.4
10
8.8
8
8
6.7
6
4.4
4
2
0
UF Heparin
LMWH
GP IIb-IIIa
Alexander KA, JAMA 2005;294:3108-16.
Impact of Overdosing Reporting in CRUSADE
Q4 2005
Overdosing (%)
40
35.8
Q4 2006
33.9
30
25.9
21.6
20
14.1 14.2
10
0
UF Heparin
LMWH
GP IIb-IIIa
CRUSADE Lessons Learned

Complex patient population

Variations in use of medications

Disparities in use of invasive procedures

Rapid changes in revascularization
procedures

Transfusions and bleeding are common

Importance of proper medication dosing

Comprehensive guidelines adherence saves
lives

Academic output critical to success
Link Between Overall ACC/AHA
Guidelines Adherence and
Mortality
% In-Hosp Mortality
7
6
5.95
6.33
5.16 5.07
5
4.97
4.63
4.16 4.17
4
3
2
1
Every 10%  in guidelines adherence  11%  in
mortality
0
<=25%
25 - 50%
50 - 75%
>=75%
Hospital Composite Quality Quartiles
Adjusted
Unadjusted
Peterson et al, ACC 2004
% Relative Change in Mortality
Change in Mortality by
Hospital Performance Improvement
5
0
-5
-10
-15
-20
-25
-30
-35
-40
-45
Worsening N=78
No N=79
Modest N=79
Large N=79
Peterson et al, AHA 2004
Hospital Mortality According to How
Consistently Hospitals Follow Trial Evidence
8%
7.1%
7%
6%
5.7%
5.6%
4.9% 4.9%
5%
5.1%
4.3%
4.1%
4%
3%
2%
1%
0%
1st
2nd
3rd
4rth
Quartiles of Hospital Composite of Medication Core Measures
Granger Am J Med. 2005;118:858-65
100%
Proportion of Patients Receiving
100% of All GuidelinesRecommended Therapies*
Q1
Q4
Q8
Q11
75%
46% 48%
50%
31%
25%
33%
47%
36%
30%
50%
34%
30%
21%
16%
0%
Overall 100% Correct
Medication
Acute 100% Correct
Medication
Discharge 100% Correct
Medication
*In patients without contraindications
Mehta et al, AHA 2005
CRUSADE Lessons Learned: Conclusions

Disparities in use of invasive procedures
 The highest risk patients frequently do not
undergo an invasive management in ACS

Rapid changes in revascularization procedures
 Substantial changes in DES and CABG use
during the last year highlights physician
uncertainty on safety

Transfusions and bleeding are common

Importance of proper medication dosing
 Appropriate dosing of therapies need to be
emphasized before and after interventions