Transcript Grand Rounds Series - Clinical Trial Results

Care of ST-Segment Elevation Patients:
Insights From NRMI
C. Michael Gibson, MS, MD
Associate Professor of Medicine
Harvard Medical School
Director, TIMI Data Coordinating Center
Brigham and Women’s Hospital
Associate Chief of Cardiology
Beth Israel Deaconess Medical Center
Boston, Massachusetts
NRMI: A Historical Overview
• Since 1990: 1600 hospitals, over
2.2 million patients
• Model registry for CQI: data
reporting, trend analysis, and
benchmarking
• Accepted performance
measurement system for
JCAHO ORYX non-core and
core measures; CMS Qnet
clinical data warehouse
• Over 70 published manuscripts and
over 120 abstracts presented at ACC,
AHA, ACEP, and outcomes research
meetings
• Referenced in AHA/ACC AMI
Management Guidelines
• Data used to generate and test
hypotheses for future research
NRMI As A CQI and Academic Success Story:
Improvement in Time to Treatment over 10 Years
NRMI
Delayed Door to Drug Times Associated with Mortality
Science
Delayed Door to Balloon Times Associated with Mortality
NRMI Data
Hospital Door to Drug Times Prolonged
Indentifies Problem
Door to Balloon Times Prolonged
NRMI Data
Indentifies Potential
Door to Data, Data to EKG, EKG to Decision, Decision to
Drug; Transfer Times
Sources of Problem
NRMI Data
Provides Ongoing
Feedback to Centers
Door to Drug Times Decrease by ½
Door to Balloon Times Decrease Among Transfer Pts
MV Adjusted Odds of Death
NRMI 2: Primary PCI Door-to-Balloon Time vs. Mortality
2.2
P=0.01
P=0.0007
P=0.0003
1.62
1.61
1.8
1.41
1.4
1.14
1
1.15
0.6
0.2
0-60
61-90
91-120
121-150
151-180
>180
n = 2,230
5,734
6,616
4,461
2,627
5,412
Door-to-Balloon Time (minutes)
Primary PCI for STEMI
Time to Reperfusion and 30 Day Mortality
6
CADILLAC
Zwolle
N= 2002
N= 1791
% Mortality
12
1994-2001
5
10
P=0.04 (< 3h v > 3 h)
4
8
3
2.3
2.2
2
1
9.6
P < 0.001
4
0.9
5.6
6
3.1
2.5
2
0
0
<3
3-6
>6
<2
Cox ACC ‘03 Abst 827-1
Time to Reperfusion (h)
2-4
4-6
>6
DeLuca ACC ‘03 Abst 827-3
MV adjusted odds of mortality
Odds for Mortality Associated with Longer Door-to-drug Time
P=0.0001
1.4
P=0.01
1.2
1.23
P=NS
1.11
1.03
1
n=28,624
n=33,867
n=11,616
n=10,316
31-60
61-90
>90
0.8
0-30
Cannon et al. JACC 2000 (Abstract, Suppl A)
Door to Drug Times
NRMI 1
Minutes (Median)
70
NRMI 2
NRMI 3
NRMI 4
60
60
50
40
32
30
20
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
Door to Balloon Times
NRMI 1
NRMI 2
NRMI 3
NRMI 4
Minutes (Median)
135
120
125
115
106
105
95
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
Door to Balloon Times By Subgroup
1994-2003; NRMI 2,3,4
135
135
135
Minutes (Median)
127
131
128
125
125
125
Off Hours
118
114
115
Females
65+ Years
105
95
108
115
111
114
115
111
105
105
103
103
< 65 Years
Males
95
95
On Hours
85
90
DANAMI-2: Primary Results
P=0.0003
16%
14%
Death / MI / Stroke (%)
P=0.048
P=0.002
16%
RRR
45%
12%
Non-Transfer Sites
Transfer Sites
Combined
16%
14%
RRR
40%
12%
12%
12%
9%
8%
8%
8%
8%
4%
4%
4%
0%
0%
0%
Lytic
Primary PCI
RRR
45%
Lytic
Primary PCI
7%
Lytic
Primary PCI
DANAMI-2: Results
8%
Death
Recurrent MI
Stroke
P=0.35
P<0.0001
P=0.15
7.6%
8%
6.6%
8%
6.3%
6%
6%
6%
4%
4%
4%
2%
2%
1.6%
2.0%
2%
1.1%
0%
0%
Lytic
Primary PCI
0%
Lytic
Primary PCI
Lytic
Primary PCI
Recent Primary PCI vs Fibrinolytic Trials
CAPTIM
DANAMI-2
C-PORT
PCAT
840
1,572
451
2,725
n
PCI
t-PA*
PCI
t-PA
PCI
t-PA
PCI
Lytic
Death
4.6%
3.7%
6.6%
7.6%
6.2%
7.1%
6.2%
8.2%
ReMI
1.7%
3.7%
1.6%
6.3%
5.3%
10.6%
4.8%
9.8%
Stroke
0%
1.0%
1.1%
2.0%
2.2%
4.0%
0.7%
1.9%
*Pre-hospital administration.
P<0.05: ReMI;death (PCAT only); stroke (PCAT only).
Grines C, et al. Am Heart J. 2003;145:47-57.
Recurrent MI During Index Hospitalization is
Associated with Higher Mortality at 2 Years
Kaplan-Meier survival estimates, by early reinfarction
1
No early reinfarction
10.1%, n=19,265
Early reinfarction
19.6%, n=836
0.75
Log-rank p<0.0001
0.5
0
0.5
1
Years
1.5
2
Gibson CM et al, JACC 2003
Risk of Recurrent MI Following Thrombolysis in 20,101 Patients
5
Risk of Recurrent MI (%)
4.5
4
3
2
1.6
1
0
No PCI
Gibson CM, et al. J Am Coll Cardiol. 2003. In press.
PCI
Kaplan-Meier survival estimates, by PCI
in 20,101 Patients
1
PCI
Survival
0.9
No PCI
Log rank p<0.0001
0.8
0.7
0
0.5
1
Years
1.5
2
Gibson CM et al, JACC 2003
Door to Balloon Times By Transfer Status, Primary PTCA Patients
NRMI 1
NRMI 2
NRMI 3
NRMI 4
Minutes (Median)
255
228
225
NRMI Transfer-In Patients
195
171
165
135
111
NRMI Non-Transfer-In Patients
110: DANAMI Transfer
100
105
90: DANAMI On Site
75
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
Door to Balloon Times <90 Minutes By Transfer Status, Primary
PTCA Patients
Percent of Patients
NRMI 1
NRMI 2
45
NRMI 3
NRMI 4
Non-Transfer-In Patients
39.1
40
35
33.6
30
25
20
15
10
5
Transfer-In Patients
3.8
5.3
0
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
Door to Balloon Times <90 Minutes
NRMI 1
NRMI 2
NRMI 3
NRMI 4
Percent of Patients
40
35
30
All Patients
29.4 %
25
20
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
34.5 %
PCI-Related Time Delay vs Mortality Benefit
in 22 Randomized Studies of PCI vs Fibrinolytic Therapy
15
23 RCTs
N= 7419
10
For every 10 min delay to PCI:
1 % reduction in Mortality Difference
Between PCI & Lysis
90 DB – 50 DN =
40 min delay
DANAMI: with
transfer
p=0.006
5
DANAMI: on site
PCI
110 DB – 50 DN =
60 min delay
0
“USA AMI” with
transfer:
-5
0
20
40
60
PCI-Related Time Delay (min)
80
100
171 DB – 32 DN =
139 min delay
Nallamothu and Bates, AJC 2003
DANAMI-2 : Rationale and Design
4278 Pts
Screened
Included
1572
37%
Main Reasons for Exclusion
Excluded
2706
63%
H R Andersen et al AHJ 146: 234, 2003
Inclusion Criteria Not Met
ECG
928 (34%)
Symp > 12 h
458 (17%)
Symp < 30 min
13 (0.5%)
Refused
Lytic Contraind.
PCI Contraind.
LBBB
Transport not
considered safe
FU not possible
Other
505
198
166
144
(19%)
(7%)
(6%)
(5%)
109 (4%)
97 (3.6%)
334 (12%)
Medications Received Within First 24 Hours
All Eligible Patients NRMI 1 – NRMI 4
90
80
70
Percent
60
Aspirin
All Trends: p ≤ 0.0001
50
40
Oral & IV Beta Blockers
ACE-Inhibitor
Other Antiplatelet
Antithrombin
30
20
10
0
94 95 96 97 98 99 00 01 02 03
Year
Newer Classes of Medications Received Within First 24 Hours
All Eligible Patients NRMI 3 – NRMI 4
40
35
30
Percent
25
Low Molecular
Weight Heparin
Statins
IV IIb/IIIa Inhibitor
Lipid Lowering
Agent
20
15
All Trends: p ≤ 0.0001
10
5
0
1998
1999
2000
2001
Half-Years Since January, 1998
2002
2003
Medications at Discharge
Eligible STEMI Patients NRMI 4
100
90
80
70
ACEI
ASA
BB
Statins
Other Lipid Lowering
60
50
40
30
20
10
0
6mo. 2000
2001
2002
Use of Thrombolytic Therapies in Eligible Patients
No RT (n=20,319)
RT (n=64,344)
Eligible patients, 31% (n=84,663)
24%
RT=reperfusion therapy
76%
Barron HV, et al. Circulation 1998
Use of Reperfusion Therapy
RT less likely
LBBB
No chest pain
Age >75
Prior CHF
Prior MI
Killip III
Women
Caucasian
Smoker
Pre-hospital ECG
Sx <3 hrs
RT more likely
RT=reperfusion therapy
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
Adapted from Barron HV, et al. Circulation 1998
In-hospital Mortality
Patients, %
20
14.8
15
10
18.9
17.9
9.3
7.9
10.5
5.7
5
0
All
eligible
RT
RT=reperfusion therapy
No RT
Women Women >65 yrs
RT
no RT
RT
>65 yrs
no RT
Adapted from Barron HV, et al. Circulation 1998
Hospital Mortality: Reperfusion Therapy
NRMI 1
9
NRMI 2
NRMI 3
NRMI 4
7.8 %
Percent
8
PPCI
7
6
5
4
5.2 %
IV Lytic
4.4 %
4.3 %
3
2
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
What’s Coming Up in NRMI?
• Cr
• TIMI Flow Grades
• Coated / non coated stents
• Vasodilators in primary PCI
• Defibrillator implantation and EFs
• ARBs
• Clopidogrel administration
Room For Improvement
• Improve door to balloon times
• Improve utilization of reperfusion therapy among
appropriate candidates
• Improve rates of beta blocker, ACE, lipid lowering and
smoking cessation strategies