initial therapy anti-ischemic and analgesic therapy anti-platelet therapy anti-coagulant therapy
TRANSCRIPT
Initial Therapy
• Anti-ischemic and Analgesic therapy• Anti-platelet therapy• Anti-coagulant therapy
Management of UA/NSTEMI• Management Before UA/NSTEMI and Onset of UA/NSTEMI• Initial Evaluation and Management of UA/NSTEMI• Early Hospital Care• Select Management Strategy:
Initial Invasive Versus Initial Conservative Strategy
• Initial Invasive Strategy• Initial Conservative Strategy• Revascularization and
Late Hospital Care• Coronary Revascularization• Late Hospital Care, Hospital Discharge and Post-Hospital Discharge Care• Long-Term Medical Therapy and Secondary Prevention• Special Groups
Important Points in Hospital Care
• Stress test before discharge for assessment of ischemia in initial conservative strategy. Must be free of resting ischemia or HF for 12-24h – Class I, C
• If not classified as low risk, angiography should be performed – Class I, A
• Fasting lipid panel within 24 hours – Class I, C• Statin regardless of baseline LDL-C pre-discharge• Echo or MUGA must be done if no plan for left
ventriculography by angiogram – Class I, B
Initial Conservative Strategy: Early Hospital Care (1)
• ASA; clopidogrel if intolerant (I, A)
• Anticoagulant therapy should be added to antiplatelet therapy as soon as possible after presentation (I, A)– Enoxaparin or UFH (I, A)– Fondaparinux (I, B)– Enoxaparin or fondaparinux preferable (IIa, B)
• Initiate clopidogrel, loading dose + maintenance dose (I, A)– Consider IV eptifibatide or tirofiban (IIb, B)
Initial Conservative Strategy: Early Hospital Care (2)
• If LVEF is < 0.40, it is reasonable to perform diagnostic angiography (IIa, B)
• A stress test should be performed for assessment of ischemia (I, B)– If the patient is classified as not as low risk,
diagnostic angiography should be performed (I, A)• Measurement of BNP or NT-pro-BNP may be considered to
supplement assessment of global risk in patients with suspected ACS (IIb, B)
Initial Conservative Strategy: Early Hospital Care (3)
• Beta blocker therapy– Initiate oral therapy within first 24 hr unless HF, low-output
state, increased risk for cardiogenic shock, or relative contraindications (I, B)
– IV therapy for high blood pressure without contraindications (IIa, B)
– IV therapy may be harmful with contraindications to beta blockade, signs of HF or low-output state, or other risk factors for cardiogenic shock (III, A)
Initial Conservative Strategy: Early Hospital Care (4)
• Lipid management– Fasting lipid profile within 24 hr (I, C)– Statin (in absence of contraindications) should be given regardless
of baseline LDL-C pre-discharge (I, A)
• ACE inhibitor (oral)– Within 24 hr with pulmonary congestion or LVEF 40, in absence of
hypotension (systolic blood pressure <100 mmHg or <30 mmHg below baseline) or known contraindications (I, A)
– ARB if ACE intolerant (I, A)– Can be useful without pulmonary congestion or LVEF < 0.40
(IIa, B)– No IV ACE-I in first 24 hr because of increased risk of hypotension
(III, B)
More Aggressive Long-Term Antiplatelet Therapy
• Medical therapy without stenting– ASA 75-162 mg/d indefinitely (I, A)
+ – clopidogrel 75 mg/d, at least 1 mo (I, A), ideally up to 1 yr (I, B)
• Bare metal stent– ASA 162-325 mg/d at least 1 mo, 75-162 mg/d indefinitely (I, A)
+ – clopidogrel 75 mg/d, at least 1 mo (I, A), ideally up to 1 yr (I, B)
• Drug-eluting stent– ASA 162-325 mg/d at least 3 (sirolimus)-6 (paclitaxel) mo, 75-162 mg/d
indefinitely (I, A) +
– clopidogrel 75 mg/d at least 1 yr (I, B)
Treatment
• Increases oxygen supply to ischemic tissue
• Start at 4L/min
• Use caution in COPD patients
• Oxygen• Aspirin• Beta-blocker• Nitroglycerin• Morphine• Heparins, DTIs• IIb/IIIa inhibitors• Plavix• ACE/ARB• Aldosterone Blockade• Statins
Anti-ischemic and Analgesic Therapy
• Bed/chair rest – Class I, C• O2 for SaO2 < 90%, respiratory distress, or
hypoxemia – Class I, B• NTG 0.4 mg sl q 5 min x 3 doses, then gtt for ongoing
ischemic discomfort – Class I, C• NTG iv within 48h for persistent ischemia, HF, or
HTN. Should not preclude use of BB – Class I, B• Oral BB therapy within 24h without 1) HF, 2) low
output, 3) risk of shock, 4) relative contraindications – Class I, B
Anti-ischemic and Analgesic Therapy
• CCB (nondihydropyridine) if contraindication for BB in the absence of contraindications – Class I, B
• ACE inhibitor for LVEF <0.40 and no hypotension (SBP <100 or <30 below baseline) – Class I, A
• ARB if intolerant to ACE inhibitor – Class I, A• NSAIDS should be discontinued – Class I, C
Anti-Platelet Therapy• ASA – started immediately and continued
indefinitely – Class I, A• Plavix – loading dose (300-600mg)* plus
maintenance 75 mg if ASA intolerant – Class I, A• If h/o GIB, PPI plus anti-platelet therapy – Class
I, B• GP IIB/IIIA therapy depends on strategy chosen
* Risk/benefit to higher loading dose regimens is yet to be determined
Anti-Coagulant Therapy
• Anticoagulant Therapy should be added to antiplatelet therapy as soon as possible after presentation
• Choice of anticoagulant depends on the strategy chosen (more on this later)
Anticoagulants and Antiplatelets – Initial Invasive Strategy
Recommendation Evidence
Enoxaparin, UFH (I, A), bivalirudin, or fondaparinux (I, B) ASAP
Enoxaparin: ESSENCE, TIMI IIB, SYNERGY, OASIS 5, ACUTE II, INTERACT, A to ZFondaparinux: OASIS 5Bivalirudin: ACUITY
Plavix or IIb/IIIa inhibitor prior to angiography* (I, A)
*Abciximab only if no delay to cath and PCI likely (I, B)
Plavix: CUREGPIIb/IIIa Inhibitor: ISAR-REACT-2 (abciximab), PURSUIT (ebtifbatide), PRISM PLUS (tirofiban)
Anticoagulants and Antiplatelets – Initial Conservative Strategy
Recommendation Evidence
Enoxaparin, UFH, (I, A) or Fondaparinux (I, B) ASAP
Fondaparinux if increased bleeding risk (I, B)
Enoxaparin: ESSENCE, TIMI 11B, A to Z, INTERACTFondaparinux: OASIS 5
Plavix (loading dose plus maintainence) ASAP, continued for 1 month, ideally up to 1 year (I, A)
CURE
etifibatide or tirofiban in addition to Plavix (IIb, B), but not abciximab (IIIA)
ARMYDA 2
Initial Invasive Strategy: Antiplatelet, Anticoagulant Therapy
• Initiate anticoagulant therapy as soon as possible after presentation (I, A)– Enoxaparin or UFH (I, A)– Bivalirudin or fondaparinux (I, B)
• Prior to angiography, initiate one (I, A) or both (IIa, B)– Clopidogrel– IV GP IIb/IIIa inhibitorUse both if:
• Delay to angiography• High risk features• Early recurrent ischemic symptoms
Molecular Structure
• Generic: clopidogrel bisulfate• Class: ADP-receptor antagonist• Molecular weight = 419.9
CLOPIDOGREL
ASA COX
ADP
ADP
C
GPllb/llla(Fibrinogen receptor)
Collagen thrombinTXA
2Activation
TXA2
COX (cyclo-oxygenase)ADP (adenosine diphosphate)TXA2 (thromboxane A2)
The active metabolite exerts its antiplatelet effect by noncompetitive inhibition of the platelet ADP
receptor subtype P2Y12
Clopidogrel: An
inactive prodrug requires in vivo conversion in the liver by the cytochrome P450 (CYP) 3A4 enzyme system
A prodrug that needs to be
metabolized by cytochrome P450 (CYP) to 2-oxo-clopidogrel, an intermediate metabolite that is further hydrolyzed to the active thiol metabolite of clopidogrel
The thienopyridine clopidogrel
The active metabolite irreversibly binds to the P2Y12 receptor
The major circulating metabolite of clopidogrel is a carboxylic acid derivate that completely lacks antiaggregatory activity
The thienopyridine clopidogrel
Absorption (oral): rapid
Not affected by food or
antacids
Metabolism: rapid and
extensive hepatic metabolism
Pharmacology of Clopidogrel
Half-life: 8 hours (but has an
irreversible effect on platelets,
with a lifespan of approximately
7–10 days)
Excretion: 50% in urine and 46%
in feces, after 5 days
Pharmacology of Clopidogrel
Side Effect Of Clopidogrel
•Rash, or manifestations of a hypersensitivity reaction to clopidogrel
Side Effect Of Clopidogrel
Management include:• Clopidogrel desensitization• Treatment with antihistamines and
corticosteroid cream• Switching to ticlopidine.
GP IIb/IIIa inhibitors
Several GP IIb/IIIa inhibitors exist:• abciximab (ReoPro)• eptifibatide (Integrilin)• tirofiban (Aggrastat)
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Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI
Medical Therapy without Stent
Bare Metal Stent Group
Drug Eluting Stent Group
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)
Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B)
Continue with dual antiplatelet therapy as
above
Yes
No
Indication for Anticoagulation?
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 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)
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence.
UA/NSTEMI Patient
Groups at Discharge
New
