NSTEMI

Conservative vs Early Invasive Approach

“How early?”
 Coronary Artery Disease
• In the United States, nearly 1.0 million
patients annually suffer from AMI
• Fatal event in approximately 1/3 of
patients
• About 50 percent of the deaths
associated with AMI occur within 1
hour of the event and are attributable to
arrhythmias, most often ventricular
fibrillation
 AMI
• Continuum of STEMI 30-33%
disease: Ranging
from chronic stable
angina to STEMI
• Two multicenter, NSTEMI 25%
international
surveys published
in 2002 - the Euro
Heart Survey and UA 38-42%
the GRACE registry,
22K pts
 AMI, cont.
• GUSTO IIb trial performed in the early
1990s
Mortality 30 day 6 months 1 year

STEMI 6% 8% 9.6%
NSTEMI 5.7% 8.8% 11.1%
UA 2.4% 5% 7%
 Definitions
• Stable angina pectoris = deep, poorly localized chest or arm
discomfort (rarely described as pain) that is reproducibly
associated with physical exertion or emotional stress and
relieved within 5 to 15 minutes by rest and/or sublingual
nitroglycerin.

• Unstable angina = angina pectoris (or equivalent type of

ischemic discomfort) with at least one of three features: (1) it
occurs at rest (or with minimal exertion) usually lasting more
than 20 minutes (if not interrupted by nitroglycerin); (2) it is
severe and described as frank pain and of new onset (i.e., within
1 month); and (3) it occurs with a crescendo pattern (i.e., more
severe, prolonged, or frequent than previously). With or without
ischemic ECG changes

• NSTEMI = UA with evidence of myocardial necrosis on the basis

of the release of cardiac markers
 Pathophysiology
• UA/NSTEMI- Plaque
rupture and coronary
thrombosis
compromise blood flow
• Infarct-related artery
not generally
completely occluded for
prolonged period
• Thrombi are grayish
white (platelet rich)
 STEMI
Complete occlusion, reddish (fibrin-rich) thrombi
 NSTEMI Treatment
• Intense medical therapy
– ASA
– Plavix
– IV heparin/ LMWH
– BB
– IV ntg for symptoms
– IIB/IIIA inhibitor
– Conservative vs Invasive approach
 Conservative Approach
• Asymptomatic pts are given several
days to “cool off” and plaque
stabilization to occur, IV meds are d/c’d
• Exercise testing is performed
• Pts catheterized if symptoms persist,
symptoms recur, or a positive stress
test
 Early Invasive Approach
• Intensive medical regimen with more
widespread use of plavix and IIB/IIIA
• Prompt catheterization with
subsequent revascularization
• Time to intervention 4-48 hrs
 Clinical Trials
• TIMI IIIB, 1995
• VANQUISH, 1998
• MATE, 1998
• FRISC II, 1999
• TACTICS-TIMI 18, 2001
• RITA 3, 2002
• VINO, 2002
• ISAR-COOL, 2003
TIMI IIIB (Thrombolysis in MI Trial)
*UA or NSTEMI <24 hrs of rest angina
*Treated with heparin/ASA
Early Invasive(18-48 hrs) Conservative*
N=740 N= 733

Death 2.4 2.5

Nonfatal MI 5.1 5.7
+ 6 wk ETT 8.6 10
Total 16.2 18.1 P=.33
Hospital days 10.2 10.9
Rehospitalization 7.8 14.1
within 6 wks
*High rate of cross-over to invasive group, 58 % at 1 yr
 VANQWISH
• 920 pts with NSTEMI, 97% men
• Early invasive w/in 72 hrs of last chest pain vs
conservative
• ASA, Heparin
• No benefit in invasive group (only 44% of pts)
• At discharge: Death or Nonfatal MI 7.8 vs 3.2,
• Trend present at 1 yr and not at 2 yr
• Subset analysis of invasive population which did
worse: Received thrombolysis, no ST segment
depression, w/out hx of MI
• Large percentage of cross-over, 33%
VANQWISH
 MATE
• 210 pts with ACS not eligible for
thrombolysis
• ASA, IV heparin
• Triage angiography within 24 hrs
• 58% revascularization vs 37% in
conservative group
• 45% reduction in in-hospital end-pts, due to
reduction in angina
• No significant difference in 21 mo endpts
 FRISC II
• 2457 pts with unstable coronary
disease, randomly assigned after 48
hrs to invasive or conservative
approach
• Intervention within 7 days
• LMWH Heparin/ASA/ +/-Dalteparin
 FRISC II cont.
Invasive Non-invasive Risk
(1222 pts) (1235 pts) Ratio

Death, MI,or 113 (9.4%) 148 (12.1%) .78

FRISC II
 TACTICS-TIMI 18
• 2220 pts UA/NSTEMI undergoing
invasive (4-48 hrs) or conservative
approach
• ASA, IV heparin, tirofiban
• Benefit only noted if positive Troponin
Invasive Conservative
Death, MI, 15.9 19.4
Rehosp for
ACS*
Death or 7.3 9.5
nonfatal MI*
*6 months
 RITA 3
• 1810 pts with NSTEMI randomized
within 48 hrs of initial chest pain
• Enoxaparin, ASA
• 4 months- Improved combined end pt
of death, nonfatal MI, or refractory
angina (9.6 vs 14.5) Results due to
angina reduction
• 1 year- Death+nonfatal MI (7.6 vs 8.3)
and MI reduced (9.4 vs 14.1)
 VINO
• 131 pts with NSTEMI within 24 hrs of
last chest pain
• ASA/ IV heparin/ Ticlopidine if stented
• Six month improvement in mortality
(3.1 vs 13.4%) death or reinfarction (6
vs 22% in conservative)
• Despite 40% of conservative pts
undergoing catheterization by then
 ISAR-COOL
• 410 pts with NSTEMI treated with Heparin,
ASA, Plavix, Tirofiban
• Early invasive (2.4 hrs) vs. delayed invasive
(86 hrs)
• Difference due to reduced events prior to
catheterization (0.5 vs 6.3)

Outcomes at Prolonged Early RRI NNH

30 d pretreatment intervention
Lg MI or 11.6% 5.9% 96% 18
death
 Summary
• Benefit in all but VANQWISH and TIMI-IIIB in
the early invasive group
• Advancements in anticoagulation and stents
could have some role
• Most benefit in moderate to high risk groups
– Elevated Troponin: FRISC II & TACTICS-TIMI 18
– ST depression ( > 0.1 mm or >0.05 mm) on the
ECG in >1 lead: FRISC II, TACTICS-TIMI 18, and
TIMI IIIB
– Age> 65: TIMI IIIB
 TIMI Risk Score
• Derived from several large cardiac databases
• Seven Variables:
– Age >65
– Presence of at least 3 risk factors for CHD
– Prior coronary stenosis >50%
– ST segment deviation
– 2 anginal episodes in last 24 hrs
– Elevated serum cardiac biomarkers
– Use of ASA in last 7 days
 TIMI Score
• Score correlated with increased numbers of
events at 14 days (all-cause mortality, new or
recurrent MI, severe recurrent ischemia
requiring revascularization)
Score 0/1= 4.7 %
Score 2= 8.3%
Score 3= 13.2%
Score 4=19.9%
Score 5= 26.2%
Score 6/7= 40.9%
 2002 ACC/AHA guidelines
• Class I indication to early invasive therapy in pts with UA/NSTEMI
plus:
– Recurrent angina/ischemia at rest or with low-level activity
despite intensive anti-ischemic tx
– Elevated Troponin I or T
– New or presumably new ST-segment depression
– Recurrent angina/ischemia with CHF sx, S3 gallop, pulmonary
edema, worsening rales, new or worsening mitral
regurgitation
– High-risk findings on non-invasive study
– Depressed LVSF
– Hemodynamic instability or angina at rest accompanied by
hypotension
– Sustained VT
– PCI within 6 months
– Prior CABG
 Time to intervention?
• ISAR-COOL<6 hrs compared with RITA
3 and TACTICS-TIMI 18 (4-48 hrs)
• Within “next working day” is probably
acceptable, less than 48 hrs
• Specialized centers of excellence for
treating ACS may be future in providing
best evidence-based care
 Thanks
• Fellow residents and friends
• Faculty and Staff
• Mark Wilson
• Sarah and Samuel Leonard