benjamin scirica, md mph investigator, timi study group
DESCRIPTION
Risk Stratification Based on Ischemia Detected on Continuous ECG Monitoring in Non-ST-elevation Acute Coronary Syndromes. Benjamin Scirica, MD MPH Investigator, TIMI Study Group Associate Physician, Brigham and Women’s Hospital Instructor in Medicine, Harvard Medical School. Disclosures. - PowerPoint PPT PresentationTRANSCRIPT
Risk Stratification Based on Ischemia Detected on Continuous ECG Monitoring
in Non-ST-elevation Acute Coronary Syndromes
Risk Stratification Based on Ischemia Detected on Continuous ECG Monitoring
in Non-ST-elevation Acute Coronary Syndromes
Benjamin Scirica, MD MPHBenjamin Scirica, MD MPHInvestigator, TIMI Study GroupInvestigator, TIMI Study Group
Associate Physician, Brigham and Women’s HospitalAssociate Physician, Brigham and Women’s Hospital
Instructor in Medicine, Harvard Medical SchoolInstructor in Medicine, Harvard Medical School
Disclosures
The TIMI Study Group has received research/grant The TIMI Study Group has received research/grant support in the past 2 years through the support in the past 2 years through the Brigham and Women’s Hospital from :Brigham and Women’s Hospital from :
AstraZenecaAstraZeneca
Bristol-Myers Squibb CompanyBristol-Myers Squibb Company
CV Therapeutics, Inc. CV Therapeutics, Inc.
Eli Lilly and CompanyEli Lilly and Company
Daiichi SankyoDaiichi Sankyo
GlaxoSmithKlineGlaxoSmithKlineMerck & Co., Inc.Merck & Co., Inc.Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc. Novartis PharmaceuticalsNovartis PharmaceuticalsNuvelo, Inc. Nuvelo, Inc. Ortho-Clinical Diagnostics, Inc. Ortho-Clinical Diagnostics, Inc. Pfizer Inc Pfizer Inc Sanofi-AventisSanofi-AventisSanofi-Synthelabo RechercheSanofi-Synthelabo RechercheSchering-Plough Research InstituteSchering-Plough Research Institute
Dr Scirica has received research support from:Dr Scirica has received research support from:
AstraZeneca AstraZeneca
Bristol-Myers SquibbBristol-Myers Squibb
CV Therapeutics, Inc. CV Therapeutics, Inc.
Daiichi SankyoDaiichi Sankyo
Novartis PharmaceuticalsNovartis PharmaceuticalsSanofi-AventisSanofi-Aventis
Dr Scirica is on the speaker’s bureau of:Dr Scirica is on the speaker’s bureau of:
Pfizer Inc Pfizer Inc
Dr Scirica has received honoraria for educational Dr Scirica has received honoraria for educational presentations/advisory boards from:presentations/advisory boards from:
CV Therapeutics, Inc. CV Therapeutics, Inc.
Novartis PharmaceuticalsNovartis Pharmaceuticals
ACUTE CORONARY SYNDROMESACUTE CORONARY SYNDROMESACUTE CORONARY SYNDROMESACUTE CORONARY SYNDROMES
NQWMIUA QwMI
Tn
CK-MB
ST-elevation ACSST-elevation ACSST-elevation ACSST-elevation ACSNon–ST-elevation ACSNon–ST-elevation ACSNon–ST-elevation ACSNon–ST-elevation ACS
UAUAUAUA NSTEMINSTEMINSTEMINSTEMI STEMISTEMISTEMISTEMI
Duration - 13.5 min
ST
dev
iati
on
fro
m b
asel
ine
Typical Episode of Ischemic ST-segment Depression
TIMI ECGCore Laboratory
TIMI CECG Core Lab ST Depression Analysis
Max ST dev.2.1 mm
Before Episode During IschemicEpisode
Definition of Ischemia
ST depression > 1 mm from baseline lasting > 1 min in
duration
Clinical Significance of Recurrent Ischemia in NSTEACS
9
1.53
16
0
5
10
15
20
MI Urgent Revasc
Inci
den
ce (
%)
(Gottlieb SO, et al. NEJM 314;1986
No Ischemia Ischemia
P<0.01P<0.001
N=37 N=33
P<0.001
N=37 N=33
(Jernberg, et al. JACC 1999)
FAST Study (n=630 pt)
P<0.001
Adj HR 5.7P<0.001
P<0.02
2.9 1.6
9.96.6
11.1
9.8
1.4
3.4
0
5
10
15
20
0 1 to 2 2 to 5 >5
Clinical Significance of Recurrent Ischemia in Non-STEMI ACS
1.5 1.6
5.63.66.3
9.9
0.13.2
0
5
10
15
20
0 1 to 2 2 to 5 >5
Meta-analysis of 995 patients from CAPTURE, PURSUIT, and FROST
Inci
den
ce (
%)
of D
ea
th a
nd D
eat
h/M
I
(Akkerhuis, et al. Eur Heart J 2001;22:1997)
DeathMI
5 Day 30 Day
P<0.001 P<0.001
Number of Events / 24hrs
N=724 N=137 N=63 N=71 N=724 N=137 N=63 N=71
UA/NSTEMIUA/NSTEMI(Moderate-High Risk)(Moderate-High Risk)
RanolazineRanolazineIV to POIV to PO
Placebo Placebo Matched IV/POMatched IV/PO
RANDOMIZE (1:1)RANDOMIZE (1:1)Double-blindDouble-blind
HolterHolterContinuous Continuous
7-day recording7-day recording
Long-term Follow-upLong-term Follow-up(Median 348 Days)(Median 348 Days)
Standard TherapyStandard Therapy
N = 6560N = 6560
Baseline CharacteristicsBaseline Characteristics
RANOLAZINE(n=3,162)
PLACEBO(n=3,189)
Age (yrs, median)Female (%)Prior MI (%)DM (%)Prior Revasc (%)TRS (%) Low (0-2) Moderate (3-4) High (>4)NSTEMI on admission (%)Cath during Index Event (%)
6436343426
2753205169
6434343427
2752215159
Holter Cohort6,351 pts (97% of entire trial)
ResultsResults
Clinical Correlates of IschemiaClinical Correlates of Ischemia
0.5 1 5
+ Ultra TnI 1.2 (0.99, 1.4)
BNP >80 pg/ml 1.4 (1.2, 1.7)
No Early Inv. Rx 1.1 (0.98, 1.3)
High TRS 2.6 (2.1, 3.3)
Mod TRS 1.5 (1.2, 1.8)
Low TRS 1.0 (referent)
Female 1.3 (1.1, 1.5)
Hazard Ratio
Adj HR (95% CI)Variable
No episodes [869 / 5095]1 to 2 episodes [156 / 590]> 2 episodes [191 / 648]
0 100 200 300 400 500
0
10
20
30
40
Days from randomization
CV
dea
th /
MI /
Rec
urr
ent
Isch
emia
(%
)
Primary endpoint according to number episodes of Primary endpoint according to number episodes of ischemia ischemia excludingexcluding events during first 7 days events during first 7 days
p<0.0001
Days from randomization
CV
dea
th (
%)
No episodes [173 / 5095]1 to 2 episodes [42 / 590]> 2 episodes [71 / 648]
0 100 200 300 400 500
0
5
10
15
CV death according to number episodes of CV death according to number episodes of ischemia ischemia excludingexcluding events during first 7 days events during first 7 days
p<0.0001
CV Death / MI / Severe Recurrent Ischemia CV Death / MI / Severe Recurrent Ischemia by TIMI Risk Score and Presence of Ischemia on CECGby TIMI Risk Score and Presence of Ischemia on CECG
11.1%
17.0%
24.5%
15.8%
29.8%
42.7%
0%
10%
20%
30%
40%
50%
Low (0-2) Moderate (3-4) High (5-7)
No Ischemia Ischemia
1657 259 638 3427582701
p=0.02
p<0.001
p<0.001
TIMI Risk Score Category
CV Death by TIMI Risk Score and CV Death by TIMI Risk Score and Presence of Ischemia on CECGPresence of Ischemia on CECG
1.6%3.3%
6.7%
2.7%
8.9%
16.1%
0%
5%
10%
15%
20%
Low (0-2) Moderate (3-4) High (5-7)
No Ischemia Ischemia
1657 259 638 3427582701
p=0.2
p<0.001
p<0.001
TIMI Risk Score Category
Days from randomization
CV
dea
th /
MI /
Rec
urr
ent
Isch
emia
(%
)
0 100 200 300 400 500
0
10
20
30
40
50
No episodes [611 / 3038]1 to 2 episodes [106 / 337]> 2 episodes [249 / 475]
Primary Endpoint by Occurrence of Ischemia Conservative Strategy
p<0.0001
No episodes [386 / 2142]1 to 2 episodes [83 / 272]> 2 episodes [63 / 191]
Primary Endpoint by Occurrence of Ischemia Early Invasive Strategy
0 100 200 300 400 500
0
10
20
30
40
Days from randomization
CV
dea
th /
MI /
Rec
urr
ent
Isch
emia
(%
)
p<0.0001
ConclusionsConclusions
Among a contemporary cohort of patients with Among a contemporary cohort of patients with NSTEACS, recurrent ischemia is commonNSTEACS, recurrent ischemia is common
Recurrent ischemia as detected on cECG is Recurrent ischemia as detected on cECG is strongly associated with death and recurrent MI in strongly associated with death and recurrent MI in the months after ACSthe months after ACS
Ischemia on cECG is a sensitive method to detect Ischemia on cECG is a sensitive method to detect myocardial perfusion after PCImyocardial perfusion after PCI
This relationship is consistent even in patients at This relationship is consistent even in patients at different clinical risk and in patients who undergo different clinical risk and in patients who undergo an early invasive management strategyan early invasive management strategy