1. Unstable angina Non-ST elevation MI
Xin Yang MB Bchir, MA(Cantab), MRCP(Lond)
2008
Zoll Firm Lecture Series

2. Zoll Firm Lecture Series
Definitions
UA: Angina pectoris or equivalent with at least one of the following:
occurs at rest or on minimal exertion.
severe and described as frank pain and of new onset.
a crescendo pattern.
NSTEMI: UA with evidence of myocardial necrosis on the basis of release of cardiac markers.
2008
Zoll Firm Lecture Series

3. Zoll Firm Lecture Series
Demographics
1.57 million hospital admission for ACS.
1.24 million were for NSTEMI/UA.
The incidence of NSTEMI/UA has progressively increased over the years.
This results from a combination of change in presentation, aggressive medical therapy as well as interventional therapy.
Circulation 2007; 115:69-171
2008
Zoll Firm Lecture Series

4. Zoll Firm Lecture Series
Pathophysiology
Almost all MIs result from atherosclerosis.
NSTEMI/UA typically results from disruption of atherosclerotic plaque leading to activation of thrombogenesis pathway with thrombus formation from platelet aggregates, fibrin and red blood cells.
Characteristically there is either incomplete occlusion of the epicardial vessel, good collateral support or spontaneous recanulation of complete occlusions.
Bear in mind that there’s abnormal perfusion in the non-culprite vessels as well during ACS as evident by the TIMI frame count or the TIMI perfusion score, likely secondary to a more diffuse vascular dysfunction secondary to various neurohormonal and paracrine mechanism.
2008
Zoll Firm Lecture Series

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Pathophysiology
2008
Zoll Firm Lecture Series
Nature Reviews Genetics 7, (March 2006)

6. Zoll Firm Lecture Series
Pathophysiology
Causes of MIs without atherosclerosis includes:
Arteritis
Trauma/Dissection/Spasm
Mural thickening with metabolic disease
Embolic event
Congenital coronary artery anomalies or intimal proliferative disease
Myocardial oxygen demand supply disproportion.
2008
Zoll Firm Lecture Series

7. Clinical Presentation
Symptoms of ischemia:
Angina pectoris.
Vagal symptoms.
Atypical symptoms.
Symptoms to consider other diagnoses: PE
Pericarditis
Aortic dissection
Peptic ulcer
Boerhaave syndrome.
Chest pain, radiation, levine sign, coldness, clamminess, sweatiness, nausea, vomiting, quarter of patients have no ischemic symptoms, indigestion, fatigue.
2008
Zoll Firm Lecture Series

8. Clinical Presentation
Symptoms of complication:
Heart failure
Cardiogenic shock.
Conduction dysfunction
Arrythmia.
Death
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Zoll Firm Lecture Series

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EKG Findings
No EKG changes.
ST segment depression.
T wave flattening.
T waves become more prominent, symmetrical, and pointed ("hyperacute"). Hyperacute T waves are most evident in the anterior chest leads and are more readily visible when an old electrocardiogram is available for comparison. These changes in T waves are usually present for only five to 30 minutes after the onset of the infarction and are followed by ST segment changes.
2008
Zoll Firm Lecture Series

10. Anderson, J. L. et al. J Am Coll Cardiol 2007;50:e1-e157
Algorithem
2008
Zoll Firm Lecture Series
Anderson, J. L. et al. J Am Coll Cardiol 2007;50:e1-e157

11. Anti-ischemic Therapy
Bed rest - I, C.
Supplement oxygen - I, B.
Sublingual NTG and IV NTG - I, C.
Oral beta blocker - I, B and IV beta blocker - IIa, B.
ACE-I/ARB given within 24h to those with pulmonary congestion or LVEF less than 40% in the absence of contraindications - I, A. Can be given in patients without the above - IIa, B.
1) signs of HF, 2) evidence of a low-output state, 3) increased risk* for cardiogenic shock, or 4) other relative contraindications to beta blockade (PR interval greater than 0.24 s, second or third degree heart block, active asthma, or reactive airway disease).
2008
Zoll Firm Lecture Series

12. Anti-platelet Therapy
Aspirin:
mg load - I, A.
mg daily for minimum 1month (BMS), 3 months (Cypher), 6 months (Taxus).
After which chronic therapy should be continued at mg daily.
Plavix:
mg load - I, A.
75mg daily for minimum 1month (BMS), 1 year (DES).
2008
Zoll Firm Lecture Series

13. Initial Conservative vs Invasive Strategy
High TIMI risk score (>3) or GRACE score.
Recurrent ischemia at rest on intensive therapy.
Elevated cardiac markers (TnT/TnI).
New or presumed new ST depression.
Signs or symtpoms of HF or new/worsening MR.
High risk findings from non-invasive testing.
Hemodynamic instability.
Sustained VT.
PCI within 6 months / prior CABG.
2008
Zoll Firm Lecture Series

14. Initial Conservative vs Invasive Strategy
Low TIMI risk score (≤ 3) or GRACE score.
Patient or physician preference in the absence of high risk features.
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TIMI Risk Score
Age 65 year or older.
At least 3 risk factors for CAD.
Prior coronary stenosis of 50% or more.
ST depression in EKG presentation.
At least 2 anginal events in the prior 24hours.
Use of aspirin in the prior 7 days.
Elevated serum cardiac biomarkers.
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Zoll Firm Lecture Series

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TIMI Risk Score
Risk Score: All cause mortality / MI / Revascularization: % % % % % %
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Zoll Firm Lecture Series

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GRACE score
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Zoll Firm Lecture Series
JAMA 2004;291:2727–33

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Relative Risk of All-Cause Mortality for Early Invasive vs Conservative Therapy at Mean F/U of 2 years
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Zoll Firm Lecture Series
Bavry AA, et al. J Am Coll Cardiol 2006;48:1319–1325. Reprinted with permission from Elsevier. CI = confidence interval; RR = relative risk.

19. Zoll Firm Lecture Series
Relative Risk of Recurrent Nonfatal MI for Early Invasive vs Conservative Therapy at Mean F/U of 2 years
2008
Zoll Firm Lecture Series
Bavry AA, et al. J Am Coll Cardiol 2006; 48:1319–1325. CI = confidence interval; RR = relative risk. Reprinted with permission from Elsevier.

20. Zoll Firm Lecture Series
Relative Risk of Recurrent UA Resulting in Rehosp for Early Invasive vs Conservative Therapy at Mean F/U of 13 months
2008
Zoll Firm Lecture Series
Bavry AA, et al. J Am Coll Cardiol 2006; 48:1319–1325. Reprinted with permission from Elsevier. CI = confidence interval; RR = relative risk; UA = unstable angina.

21. Early Invasive Strategy
Acceptable options:
Lovenox or UFH - I, A.
Bivalirudin or Fondaprinux - I, B.
Prior to Angiography,
initiate at least one (I, A) or both (IIa, B) of the following:
Plavix
IV GP IIb/IIIa inhibitor
Factors favoring administration of both agents including:
Delay to angiography/High risk features/Early recurrent ischemic discomfort.
Proceed to diagnostic angiography.
2008
Zoll Firm Lecture Series

22. Early Conservative Strategy
Acceptable options:
Lovenox or UFH - I, A
Fondaparinux - I, B
Lovenox or Fondaprinux are preferable - IIa, B
Initiate Clopidogrel – I, A
Consider adding IV eptifibatide or tirofiban – IIb, B.
Further risk stratification
2008
Zoll Firm Lecture Series

23. Early Conservative Strategy
Any subsequent events necessitating angiography? D
(Class I, LOE: A)
Yes No
(Class I,
LOE: B) L
Evaluate LVEF M
(Class IIa, LOE: B) N
EF 40% or less O
EF greater
than 40%
Stress Test
(Class I, LOE: B)
Recurrent symptoms, ischemia, heart failure, arrythmias
(Class IIa, LOE: B)
E-1
E-2
Proceed to Dx Angiography
Not Low Risk
Low Risk
(Class I, LOE: A)
(Class I, LOE: A) K
Cont ASA (Class I, LOE A)
Cont clopidogrel (Class I, LOE A) and ideally up to 1 yr (Class I, LOE B)
DC IV GP IIb/IIIa if started previously (Class I, LOE A)
DC ACT (Class I, LOE A)
2008
Zoll Firm Lecture Series

24. Anticoagulation Therapy
Bivalirudin:
LD: 0.1 mg/kg IV bolus,
MD: 0.25 mg/kg/h infusion.
Lovenox:
LD: 30mg IV bolus may be given.
MD: 1mg/kg/12H SC.
Heparin:
LD: 60 U/Kg IV bolus (max 4000U).
MD: 12 U/kg/h (max 1000 U/h), maintain ptt 50-70s.
2008
Zoll Firm Lecture Series

25. Anticoagulation Therapy
Integrilin:
LD: 180 mcg/kg IV bolus.
MD: 2 mcg/kg/min IV infusion and reduce by 50% with GFR < 50 ml/min.
2008
Zoll Firm Lecture Series

26. Long Term Medical Therapy
UA/NSTEMI Patient Groups at Discharge
Medical Therapy without Stent
Bare Metal Stent Group
Drug Eluting Stent Group
ASA 75 to 162 mg/d indefinitely (Class I, LOE: A)
&
Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B)
ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A)
&
Clopidogrel 75 mg/d for at least 1 month and up to 1 year
(Class I, LOE:B)
ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely
(Class I, LOE: A)
&
Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B)
Indication for Anticoagulation?
Yes No
Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B)
Continue with dual antiplatelet therapy as above
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157,
2008
Zoll Firm Lecture Series

27. Long Term Medical Therapy
Beta blockers are indicated for all patients recovering from NSTEMI/UA unless contraindicated - I, B.
ACE-I/ARB should be given and continued indefinitely for patients recovering from UA/NSTEMI with HF, LVEF < 40%, hypertension, or DM, unless contraindicated – I,A.
ACE-I/ARB are reasonable for patients recovering from UA/NSTEMI without LV dysfunction, HTN or DM – II, A.
2008
Zoll Firm Lecture Series

28. Long Term Medical Therapy
Statins in the absence of contraindications, regardless of baseline LDL-C and diet modification, should be given to post-UA/NSTEMI patients – I, A.
For patients with elevated LDL-C (≥ 100 mg per dL), cholesterol-lowering therapy should be initiated or intensified to achieve an LDL-C < 100 mg per dL.
Further titration to less than 70 mg per dL is reasonable – IIa, A.
HPS: 20,536 patients with CHD
Simvastatin (40 mg qd) vs placebo
↓ Total mortality by simvastatin
― ↓ Total CHD, total stroke, revascularization
― ↑ Benefit over time, irrespective of initial cholesterol level and in broad spectrum of patients (e.g., women, elderly & patients with diabetes)
Recommend: Statin in all patients at discharge regardless of baseline LDL-C (Class I, LO
Prove it – timi 22
4,162 patients within 10 d of ACS
40 mg pravastatin vs 80 mg atorvastatin daily
↓ All-cause death, MI, UA requiring hosp, revasc & 2 y by atorvastatin
― Median LDL-C ↓ (62 vs 95 mg/dL)
2008
Zoll Firm Lecture Series