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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

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nstemi

NSTEMI

Conservative vs Early Invasive Approach

“How early?”

coronary artery disease
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
slide3
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
ami cont
AMI, cont.
  • GUSTO IIb trial performed in the early 1990s
definitions
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
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
STEMI

Complete occlusion, reddish (fibrin-rich) thrombi

nstemi treatment
NSTEMI Treatment
  • Intense medical therapy
    • ASA
    • Plavix
    • IV heparin/ LMWH
    • BB
    • IV ntg for symptoms
    • IIB/IIIA inhibitor
    • Conservative vs Invasive approach
conservative 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
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
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
TIMI IIIB (Thrombolysis in MI Trial)*UA or NSTEMI <24 hrs of rest angina *Treated with heparin/ASA

Early Invasive(18-48 hrs)

N=740

Conservative*

N= 733

*High rate of cross-over to invasive group, 58 % at 1 yr

vanqwish
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%
slide15
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
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
tactics timi 18
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

rita 3
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)
slide21
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
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)
summary
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
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
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
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
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
Thanks
  • Fellow residents and friends
  • Faculty and Staff
  • Mark Wilson
  • Sarah and Samuel Leonard