CHAPTER 56 – Unstable Angina and Non–ST Elevation

8/10/2019 CHAPTER 56 Unstable Angina and NonST Elevation

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CHAPTER 56 Unstable Angina andNon ST Elevation

Myocardial InfarctionPembimbing:dr. Nugroho Hadi S, Sp. PD, Sp. JP (K) FIHA

BRAUNWALD TEXTBOOK READING


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DEFINITION

UA/NSTEMI non ST 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), afterphysical exertion or emotional stress, and relieved on 5 -10minutes by rest or SL nitroglycerin

unstable angina : angina pectoris (or equivalent type of ischemicdiscomfort) 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


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Pathophysiology


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Thrombosis

Six sets of observations support thrombosis in thepathogenesis :

(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 ofplaque ulceration or irregularities suggesting a

ruptured plaque or thrombus;(5) the elevation of several serum markers of plateletactivity and fibrin formation; and

(6) the improvement in clinical outcome byantiplatelet and antithrombotic therapy.


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Platelet Activation and Aggregation


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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 (orpresumably new) ST- segment deviation (0.1mV). [9]

T wave changes are sensitive but not specific foracute ischemia unless they are marked (>0.3 mV)(Fig. 56-4).

Continuous ecg monitoring purposes: (1)identify arrhythmias and (2) identify recurrent ST-segment deviation indicative of ischemia


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Markers of Cardiac Necrosis

symptoms consistent with UA/NSTEMI+elevations of markers of myocardial necrosis NSTEMI.

Troponins more sensitive than CK-MB andassociated with a worse prognosis. [11]

false-positive troponin elevations but noepicardial stenoses at coronary angiography.[13]

Patients presenting with UA/NSTEMI whohad elevations of troponin but no apparentCAD on angiography had a significantlyworse prognosis than those who weretroponin negative without coronary disease


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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 stressechocardiography is slightly more sensitive than ecg stresstesting and has greater prognostic value

Exercise testing is generally recommended unless the patientcannot walk sufficiently pharmacologic stress testing


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Clinical Classification


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Risk Stratification

High-Risk Clinical Subgroups


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Risk Assessment by Electrocardiography independentpredictors of 1-year death or MI included LBBB, ST-segment deviation >0.05 Mv, and both P < 0.001. [9]

Risk Assessment by Cardiac Markers

Markers ofmyocyte necrosis(CKMB/troponin)

CRP White blood cellcount

myeloperoxidaseNatriuretic

peptide Creatinin

Glucose Thrombusprecursor protein


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Combined Risk Assessment Scores

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 24hours, ASA within prior

week, elevated cardiac

markers.

The Global Registryof Acute Coronary

Events (GRACE) increased mortality;

age

Killip

HR ST-segment

depression

signs of heart failure

lower SBP

cardiac arrest

creatinine /cardiacmarker. [44]

A risk score to predictmajor bleeding

CRUSADE registry

creatinineclearance,

women diabetics lower BP Higher HR


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Medical TherapyRelief of chest pain is an initial goal of treatment.

morphine sulfate by intravenous

NitratesContraindications: hypotension and the use of sildenafil or relatedphosphodiesterase type 5 inhibitors within 24 to 48 hours

Beta Blockersreducing subsequent MI or recurrent ischemia, reduce reinfarctionand ventricular fibrillation

initiated within the first 24 hours for patients with no: (1) signs ofheart failure, (2) low-output state, (3) increased risk for cardiogenicshock, or (4) relative CI(PR interval >0.24 second, 2-3-degree heartblock, active asthma, or reactive airway disease).

CCB

persistent ischemia despite nitrates and beta blockers,contraindications to beta blockers, and hypertension.


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Anti thrombotic therapy


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Aspirin (ASA)

Acetylates platelet cyclooxygenase 1(COX-1) blocking the synthesis andrelease of thromboxane A 2 decreasesplatelet aggregation and arterial thrombusformation.Irreversible

Contraindications: allergy, active bleeding,and a known platelet disorder


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ADP AntagonistsThienopyridinesprodrugs that are converted to active metabolites through oxidationby the hepatic cytochrome P-450 system [61] inhibit platelet aggregation by inhibiting irreversibly the binding ofadenosine diphosphate (ADP) to platelet P2Y 12 receptors andincrease bleeding time


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Clopidogrel

Initiation 75 mg daily platelet inhibition after 3 -5 days300 mg effective platelet inhibition within 4 -6 hours. [69] 600-mg loading dose achieves a steady-state level ofplatelet inhibition after just 2 hours

Nonresponders or hyporesponders to clopidogrel havebeen identified in several studies. [72-74]

Hyporesponsiveness more common among DM, obesity,

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


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Prasugrel generation of the prasugrelmetabolite is approximately 10 times asgreat as with clopidogrel administration,resulting in a roughly 10 times greaterpotency.

Ticagrelor whose active metabolites areirreversible platelet inhibitors, ticagrelor* isa reversible blocker of the P2Y 12 plateletreceptor that acts directly on the platelet


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Glycoprotein IIb/IIIa Inhibitors

These drugs block the final common pathway of plateletaggregation, 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 patientsundergoing PCI, and eptifibatide and tirofiban (small moleculeinhibitors).

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

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


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Anticoagulants

HeparinVariability effects from the heterogeneity of UFH andthe neutralization of heparin by circulating plasma factorsand 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 6hours until the target range is reached and every 12 to24 hours thereafter)

Adverse effects include bleeding, especially when APTTis elevated, and heparin-induced thrombocytopenia,which is more common with longer durations oftreatment


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Low-Molecular-Weight Heparininhibition of factors IIa and Xaadvantages over UFH:(1) greater anti factor Xa activity inhibits thrombin generation moreeffectively;

(2) induces a greater release of tissue factor pathway inhibitor , andit 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.


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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 ofanticoagulation, and do not cause thrombocytopenia

Direct ThrombinInhibitors

Among patients without a coronary stent but with another indicationfor warfarin, such as chronic atrial fibrillation or severe left

ventricular dysfunction, who are at high risk of systemicembolization, the combination of ASA and warfarin would bepreferable as the long-term antithrombotic strategy.

Oral Anticoagulation

rivaroxaban, apixabanFactor Xa

Inhibitors:

Thrombin potently stimulates platelets by activating PAR-1. Thethrombin receptor blocker Vorapaxar blocks this interaction

Protease-ActivatedReceptor (PAR-1)

Antagonists


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Prinzmetal Variant Angina

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

MechanismsThe original hypothesis: transient increases in coronary

vasomotor tone or vasospasm.reduction in nitric oxide productionEnhanced phospholipase C (PLC) activity.inflammatoryPolymorphisms of the alpha 2 presynaptic and the postsynapticbeta 2 receptor may also associate with PVA. [155]


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youngermany are often heavy cigarette smokers.The anginal pain is often extremely severe withsyncope related to atrioventricular block,asystole, or ventricular tachyarrhythmias.

ECG: episodic ST-segment elevation often withsevere chest pain, usually occurring at rest ;

multiple episodes of asymptomatic (silent) ST-segment elevation.Provocative Tests: Ergonovine; Acetylcholine


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Management

urged strongly to discontinue smokingThe mainstay of therapy is a calcium antagonistalone or in combination with a long-acting nitrateResponse to beta blockade in patients with PVAis variable.

Prazosin, a selective alpha-adrenergic receptorblocker, may also have value

ASA, increase the severity of ischemic episodesPVA because it inhibits biosynthesis coronaryvasodilator prostacyclin.CCB should be continued for at least 6 monthsafter successful revascularization in patients


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Guidelines UA/NSTEMI


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CHAPTER 56 – Unstable Angina and Non–ST Elevation

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