NSTEMI

1
NSTEMI

• Conservative vs Early Invasive Approach
• How early?

2
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

3
AMI

• Continuum of disease Ranging from chronic
  stable angina to STEMI
• Two multicenter, international surveys published
  in 2002 - the Euro Heart Survey and the GRACE
  registry, 22K pts

4
AMI, cont.

• GUSTO IIb trial performed in the early 1990s

5
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

6
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)

7
STEMI
Complete occlusion, reddish (fibrin-rich) thrombi
8
NSTEMI Treatment

• Intense medical therapy
• ASA
• Plavix
• IV heparin/ LMWH
• BB
• IV ntg for symptoms
• IIB/IIIA inhibitor
• Conservative vs Invasive approach

9
Conservative Approach

• Asymptomatic pts are given several days to cool
  off and plaque stabilization to occur, IV meds
  are d/cd
• Exercise testing is performed
• Pts catheterized if symptoms persist, symptoms
  recur, or a positive stress test

10
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

11
Clinical Trials

• TIMI IIIB, 1995
• VANQUISH, 1998
• MATE, 1998
• FRISC II, 1999
• TACTICS-TIMI 18, 2001
• RITA 3, 2002
• VINO, 2002
• ISAR-COOL, 2003

12
TIMI IIIB (Thrombolysis in MI Trial) UA or
NSTEMI lt24 hrs of rest angina Treated with
heparin/ASA
Early Invasive(18-48 hrs) N740
Conservative N 733
High rate of cross-over to invasive group, 58
at 1 yr
13
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

14
VANQWISH
15
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

16
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

17
FRISC II cont.
18
FRISC II
19
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

6 months
20
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- Deathnonfatal MI (7.6 vs 8.3) and MI
  reduced (9.4 vs 14.1)

21
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

22
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)

23
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 ( gt 0.1 mm or gt0.05 mm) on the ECG
  in gt1 lead FRISC II, TACTICS-TIMI 18, and TIMI
  IIIB
• Agegt 65 TIMI IIIB

24
TIMI Risk Score

• Derived from several large cardiac databases
• Seven Variables
• Age gt65
• Presence of at least 3 risk factors for CHD
• Prior coronary stenosis gt50
• ST segment deviation
• 2 anginal episodes in last 24 hrs
• Elevated serum cardiac biomarkers
• Use of ASA in last 7 days

25
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 419.9
• Score 5 26.2
• Score 6/7 40.9

26
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

27
Time to intervention?

• ISAR-COOLlt6 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

28
Thanks

• Fellow residents and friends
• Faculty and Staff
• Mark Wilson
• Sarah and Samuel Leonard

29
(No Transcript)