EARLY INVASIVE VERSUS INITIAL

CONSERVATIVE STRATEGIES IN
UA/NSTEMI
Dr. Mayuresh

 In patients with unstable angina and non-ST

elevation myocardial infarction (UA/NSTEMI) two
strategies are possible,
either a routine invasive strategy where all patients
undergo coronary angiography shortly after
admission and, if indicated, coronary
revascularization; or
a conservative strategy where medical therapy
alone is used initially, with selection of patients for
angiography based on clinical symptoms or
investigational evidence of persistent myocardial
ischemia.

 Evidence for early invasive versus

conservative strategy in
management of NSTEMI

Fragmin during Instability in Coronary

Artery Disease (FRISC-2) 1999
Patients within 48 h UA/NSTEMI
Early inv vs conserv & dalteparin vs placebo
3048 patients dalteparin for 57 d 2457 continued
dalteparin/placebo & received either inv or conserv rx
strategy
Meds: ASA, -blockers unless contraindicated
No death/MI @ 3 mo by dalteparin
Death/MI @ 6 mo, 1 y & 5 y for inv strategy
Benefit confined to men, nonsmokers, and patients with
factors
2 risk
Wallentin L, et al. Lancet 2000;356:916 (1-year results). Lagerqvist B, et al. J Am
Coll Cardiol 2001;38:418 (women vs men). Lagerqvist B, et al. Lancet
2006;368:9981004 (5-yr follow-up).
7

Treat Angina with Aggrastat and Determine

Cost of Therapy with an Invasive or
Conservative Strategy (TACTICS-TIMI-18) 2001
2,220 patients within 24 h UA/NSTEMI
Early inv or conserv (selective invasive) strategy
Meds: ASA, heparin and tirofiban
Death, MI, and rehosp for an ACS @ 6 mo for inv strategy
Benefit in medium and high-risk patients (TnT of >
0.01 ng/mL, ST-segment deviation, TIMI risk score > 3)
No high-risk features, outcomes similar
Death/MI @ 6 mo for older adults with early inv
strategy
Benefit of early inv strategy for high-risk women ( TnT);
low-risk women tended to have worse outcomes, incl
risk of major bleeding
M N Engl
8
J Med. 2001 Jun 21;344(25):1879-87.: ed 2001;344:187987.

Cannon CP, et al. N En

gl J

Third Randomized
Intervention Treatment of Angina
(RITA-3) 2002
1,810 moderate- high risk ACS patients
Early inv or conserv (ischemia-driven) within 48 hrs. strategy
Exclusions: CK-MB > 2X ULN @ randomization, new Q-waves,
MI w/in 1 mo, PCI w/in 1 y, any prior CABG
Death, MI, & refractory angina for inv strategy @ 4 months
Benefit driven primarily by in refractory angina
Death/MI @ 5 y for early inv arm
No benefit of early inv strategy in women
Lancet. 2002 Sep 7;360(9335):743-51
Lancet. 2005 Sep 10-16;366(9489):914-20

ISAR-COOL (Intracoronary Stenting with Antithrombotic

Regimen Cooling-Off) trial 2003
Prolonged (3 to 5 days) antithrombotic pretreatment
(Cooling-Off strategy) before intervention V/S early
intervention after pretreatment for less than 6 hours
Aspirin, clopidogrel , tirofiban , unfractionated heparin (UFH).
410 patients with symptoms of unstable angina plus either STsegment depression or elevation of cardiac troponin T levels.
By 30 days follow-up, the primary endpoint of death or large
MI occurred in 11.6% of patients randomized to delayed
catheterization versus 5.9% of those in the early angiography
group.
strategy of coolingoff for 3 to 5 days before angiography
does not improve outcome in this setting.
small sample size and the prolonged delay before
angiography in the medical pretreatment arm.

THE RIGHT TIMING

TIMACS STUDY, 2009
Early invasive management: angiography within 24
hours followed by PCI or CABG as appropriatev/s
delayed invasive strategy: angiography after 36
hours followed by PCI or CABG as appropriate.
3031 patients.
Superior outcome among patients managed by
early rather than delayed intervention in the setting
of UA/NSTEMI,
Refractory ischemia was reduced by an early
approach, as were the risks of death, MI, and stroke
among patients at the highest tertile of ischemic
risk as defined by the GRACE risk score

ABOARD TRIAL, 2009

To assess whether a more aggressive strategy of very early
intervention, analogous to the standard of primary PCI for STEMI, would
lead to improved outcomes in patients with nonST-elevation ACS.
To determine whether immediate intervention (primary PCI strategy)
is superior to delayed intervention (next day strategy) in patients with
moderate-to-high risk (TIMI score > 3) non-ST segment elevation ACS.

A primary PCI strategy in NSTE-ACS (compared with a rapid

intervention on the next day):352 pts
is feasible, but does not reduce the risk of MI (primary outcome)
is not associated with significant differences in other efficacy or
safety outcomes
does not benefit to a particular subgroup of patients
shortens significantly hospital stay

Recommendations for Initial Invasive Versus

Initial Conservative Strategies(2012)
Class I
1. An early invasive strategy (ie, diagnostic angiography with intent
to perform revascularization) is indicated in UA/NSTEMI patients
who have refractory angina or hemodynamic or electrical instability
(without serious comorbidities or contraindications to such
procedures). (Level of Evidence: B)
2. An early invasive strategy (ie, diagnostic angiography with intent
to perform revascularization) is indicated in initially stabilized
UA/NSTEMI patients (without serious comorbidities or
contraindications to such procedures) who have an elevated risk for
clinical events (Level of Evidence : A)

2007 recommendation remains current.

 Class IIa
1. It is reasonable to choose an early
invasive strategy (within 12 to 24
hours of admission) over a delayed
invasive strategy for initially stabilized
high-risk patients with UA/NSTEMI.*
For patients not at high risk, a delayed
invasive approach is also reasonable
(Level of Evidence: B)

 Class III: No Benefit

1. An early invasive strategy (ie, diagnostic angiography with intent
to perform revascularization) is not recommended in patients with
extensive comorbidities (eg, liver or pulmonary failure, cancer), in
whom the risks of revascularization and comorbid conditions are
likely to outweigh the benefits of revascularization. (Level of
Evidence: C)
2. An early invasive strategy (ie, diagnostic angiography with intent
to perform revascularization) is not recommended in patients with
acute chest pain and a low likelihood of ACS. (Level of Evidence: C)
3. An early invasive strategy (ie, diagnostic angiography with intent
to perform revascularization) should not be performed in patients
who will not consent to revascularization regardless of the findings.
(Level of Evidence: C)
2007 recommendation remains current.

CONCLUSIONS
These trials, taken together with earlier studies, do provide
support for a strategy of early angiography and intervention
to reduce ischemic complications in patients who have been
selected for an initial invasive strategy, particularly among
those at high risk (defined by a GRACE score 140), whereas a
more delayed approach is reasonable in low- to intermediate
risk patients.
The early time period in this context is considered to be
within the first 24 hours after hospital presentation, although
there is no evidence that incremental benefit is derived by
angiography and intervention performed within the first few
hours of hospital admission.
The advantage of early intervention was achieved in the
context of intensive background antithrombotic therapy.