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BRAUNWALD

CHAPTER 56
Unstable Angina and
NonST Elevation
Myocardial Infarction
Pembimbing:
dr. Nugroho Hadi S, Sp. PD, Sp. JP (K) FIHA

LOGO

DEFINITION
UA/NSTEMI nonST elevation acute coronary syndrome

(NSTE-ACS).[1,2]
from severe obstruction, but not total occlusion
Stable angina pectoris typically manifests as a deep, poorly
localized chest or arm discomfort (rarely described as pain), after
physical exertion or emotional stress, and relieved on 5 -10
minutes by rest or SL nitroglycerin

unstable angina : angina pectoris (or equivalent type of ischemic

discomfort) with at least one of three features:
(1) occurring at rest (or minimal exertion) and usually >20 minutes
(2) being severe and usually described as frank pain; or
(3) occurring with a crescendo pattern
2/3 unstable angina elevated cardiac serum markers: NSTEMI

Pathophysiology

Thrombosis
Six sets of observations support thrombosis in the
pathogenesis :
(1) thrombi in the coronary arteries,
(2) the demonstration in coronary atherectomy
(3) thrombus at coronary angioscopy;
(4) angiography, intravascular ultrasound, optical
coherence tomography, and CT angiography of
plaque ulceration or irregularities suggesting a
ruptured plaque or thrombus;
(5) the elevation of several serum markers of platelet
activity and fibrin formation; and
(6) the improvement in clinical outcome by
antiplatelet and antithrombotic therapy.

Platelet Activation and Aggregation

Clinical Presentation
Clinical Examination
ischemia involves a large fraction LV
Electrocardiography
ST depression (or transient ST elevation) and T
wave changes occur in up to 50% New (or
presumably new) ST-segment deviation (0.1
mV).[9]
T wave changes are sensitive but not specific for
acute ischemia unless they are marked (>0.3 mV)
(Fig. 56-4).
Continuous ecg monitoring purposes: (1)
identify arrhythmias and (2) identify recurrent STsegment deviation indicative of ischemia

Markers of Cardiac Necrosis

symptoms consistent with UA/NSTEMI+

elevations of markers of myocardial necrosis
NSTEMI.
Troponins more sensitive than CK-MB and
associated with a worse prognosis.[11]
false-positive troponin elevations but no
epicardial stenoses at coronary angiography
.[13]
Patients presenting with UA/NSTEMI who
had elevations of troponin but no apparent
CAD on angiography had a significantly
worse prognosis than those who were
troponin negative without coronary disease

 chest radiograph : pulmonary congestion or edema

total cholesterol and HDL levels fall 30-40% 24 hours after
UA/NSTEMI or STEMI measured at initial presentation.

Noninvasive Testing
purposes:
(1) diagnose the presence or absence of CAD
(2) evaluate residual ischemia after medical therapy;
(3) evaluate left ventricular function;
(4) in risk stratification

Stress myocardial perfusion imaging or stress

echocardiography is slightly more sensitive than ecg stress
testing and has greater prognostic value
Exercise testing is generally recommended unless the patient
cannot walk sufficiently pharmacologic stress testing

Clinical Classification

Risk Stratification

High-Risk Clinical Subgroups

 Risk Assessment by Electrocardiography independent

predictors of 1-year death or MI included LBBB, STsegment deviation >0.05 Mv, and both P < 0.001.[9]
Risk Assessment by Cardiac Markers
Markers of
myocyte necrosis
(CKMB/troponin)

CRP

White blood cell

count

myeloperoxidase

Natriuretic
peptide

Creatinin

Glucose

Thrombus
precursor protein

Combined Risk Assessment Scores

The Global Registry
of Acute Coronary
Events (GRACE)
increased mortality;

The TIMI risk score:

age >65 years,
>3 risk factors for
CAD,
documented CAD at
catheterization
ST deviation >0.5
mm,
>2 episodes of
angina in last 24
hours,
ASA within prior
week,
elevated cardiac
markers.

age
Killip
HR
ST-segment
depression
signs of heart failure
lower SBP
cardiac arrest
creatinine /cardiac
marker.[44]

A risk score to predict

major bleeding
CRUSADE registry
creatinine
clearance,
women
diabetics
lower BP
Higher HR

Medical Therapy
Relief of chest pain is an initial goal of treatment.
morphine sulfate by intravenous
Nitrates
Contraindications: hypotension and the use of sildenafil or related
phosphodiesterase type 5 inhibitors within 24 to 48 hours
Beta Blockers
reducing subsequent MI or recurrent ischemia, reduce reinfarction
and ventricular fibrillation
initiated within the first 24 hours for patients with no: (1) signs of
heart failure, (2) low-output state, (3) increased risk for cardiogenic
shock, or (4) relative CI(PR interval >0.24 second, 2-3-degree heart
block, active asthma, or reactive airway disease).
CCB
persistent ischemia despite nitrates and beta blockers,
contraindications to beta blockers, and hypertension.

Anti thrombotic therapy

Aspirin (ASA)

Acetylates platelet cyclooxygenase 1

(COX-1) blocking the synthesis and
release of thromboxane A2 decreases
platelet aggregation and arterial thrombus
formation.
Irreversible
Contraindications: allergy, active bleeding,
and a known platelet disorder

ADP Antagonists
Thienopyridines
prodrugs that are converted to active metabolites through oxidation
by the hepatic cytochrome P-450 system[61]
inhibit platelet aggregation by inhibiting irreversibly the binding of
adenosine diphosphate (ADP) to platelet P2Y12 receptors and
increase bleeding time

Clopidogrel
Initiation 75 mg daily platelet inhibition after 3 -5 days
300 mg effective platelet inhibition within 4 -6 hours.[69]
600-mg loading dose achieves a steady-state level of
platelet inhibition after just 2 hours
Nonresponders or hyporesponders to clopidogrel have
been identified in several studies.[72-74]

Hyporesponsiveness more common among DM, obesity,

advanced age, and a genetic polymorphism of the
cytochrome P-450 system 150 mg/daily; prasugrel 10
mg/day, or potentially by adding cilostazol

 Prasugrel generation of the prasugrel

metabolite is approximately 10 times as
great as with clopidogrel administration,
resulting in a roughly 10 times greater
potency.

Ticagrelorwhose active metabolites are

irreversible platelet inhibitors, ticagrelor* is
a reversible blocker of the P2Y12 platelet
receptor that acts directly on the platelet

Glycoprotein IIb/IIIa Inhibitors

These drugs block the final common pathway of platelet
aggregation, the fibrinogen-mediated cross-linkage of
interfere with platelet aggregation caused by all types of stimuli
(e.g., thrombin, ADP, collagen, serotonin).

abciximab, a monoclonal antibody, approved only in patients

undergoing PCI, and eptifibatide and tirofiban (small molecule
inhibitors).

Opinion is divided on the optimal timing of the administration of GP

IIb/IIIa inhibitors. Some advocate starting these drugs at the time of
presentation, whereas others reserve it for use during PCI. The
ACC/AHA Guidelines have indicated that either strategy is
acceptable.[2]

Anticoagulants
Heparin
Variability effects from the heterogeneity of UFH and
the neutralization of heparin by circulating plasma factors
and by proteins released by activated platelets.[99]
Monitoring : activated partial thromboplastin time (APTT)
is 50 to 70 seconds or 1.5 to 2.5 times control (every 6
hours until the target range is reached and every 12 to
24 hours thereafter)
Adverse effects include bleeding, especially when APTT
is elevated, and heparin-induced thrombocytopenia,
which is more common with longer durations of
treatment

Low-Molecular-Weight Heparin
inhibition of factors IIa and Xa
advantages over UFH:
(1) greater antifactor Xa activity inhibits thrombin generation more
effectively;
(2) induces a greater release of tissue factor pathway inhibitor , and
it is not neutralized by platelet factor 4[101];
(3) LMWH causes thrombocytopenia at a lower rate[100];
(4) the high bioavailability allows subcutaneous administration; and
(5) LMWH binds less avidly than UFH to plasma proteins and
therefore has a more consistent anticoagulant effect.

Monitoring of the level of anticoagulation is not necessary.

Direct Thrombin
Inhibitors

potential advantage over indirect thrombin inhibitors, (UFH, LMWH)

do not require antithrombin and can inhibit clot-bound thrombin,
do not interact with plasma proteins, provide a stable level of
anticoagulation, and do not cause thrombocytopenia

Oral
Anticoagulation

Among patients without a coronary stent but with another indication

for warfarin, such as chronic atrial fibrillation or severe left
ventricular dysfunction, who are at high risk of systemic
embolization, the combination of ASA and warfarin would be
preferable as the long-term antithrombotic strategy.

Factor Xa
Inhibitors:
Protease-Activated
Receptor (PAR-1)
Antagonists

rivaroxaban, apixaban

Thrombin potently stimulates platelets by activating PAR-1. The

thrombin receptor blocker Vorapaxar blocks this interaction

Prinzmetal Variant Angina

syndrome of ischemic pain that occurred at rest, accompanied by
ST-segment elevation.

Mechanisms
The original hypothesis: transient increases in coronary
vasomotor tone or vasospasm.
reduction in nitric oxide production
Enhanced phospholipase C (PLC) activity.
inflammatory
Polymorphisms of the alpha2 presynaptic and the postsynaptic
beta2 receptor may also associate with PVA.[155]

 younger
many are often heavy cigarette smokers.
The anginal pain is often extremely severe with
syncope related to atrioventricular block,
asystole, or ventricular tachyarrhythmias.
ECG: episodic ST-segment elevation often with
severe chest pain, usually occurring at rest ;
multiple episodes of asymptomatic (silent) STsegment elevation.
Provocative Tests: Ergonovine; Acetylcholine

Management

urged strongly to discontinue smoking

The mainstay of therapy is a calcium antagonist

alone or in combination with a long-acting nitrate

Response to beta blockade in patients with PVA
is variable.
Prazosin, a selective alpha-adrenergic receptor
blocker, may also have value
ASA, increase the severity of ischemic episodes
PVA because it inhibits biosynthesis coronary
vasodilator prostacyclin.
CCB should be continued for at least 6 months
after successful revascularization in patients

Guidelines UA/NSTEMI