SECTION 2 ​CARDIOVASCULAR DISORDERS ​ 5

Edited by Terry L. Schwinghammer

R

Acute Coronary Syndromes

ETPAH​
​ cute coronary syndromes ​(ACSs) include all syndromes compatible with acute
C​• A

• ​myocardial and ACSs supply.

are classified ischemia resulting according from to electrocardiographic imbalance between myocardial (ECG) changes oxygen into
demand (1)
ST-segment-elevation (STE) myocardial infarction (MI) or (2) non–ST-segment- elevation (NSTE) ACS, which includes NSTE MI
and unstable angina (UA).
PATHOPHYSIOLOGY
• • ​development Endothelial The cause of dysfunction, ACS of atherosclerotic in more inflammation, than coronary 90% of patients
and artery formation plaques.
is rupture, of fatty fissuring, streaks or contribute erosion of to
an
unstable atheromatous plaque. A clot forms on top of the ruptured plaque. Exposure of collagen and tissue factor induces platelet

adhesion and activation, which promote release of adenosine diphosphate (ADP) and thromboxane A​2 ​from platelets produc- ing
​
vasoconstriction and platelet activation. A change in the conformation of the gly-
• ​coprotein to Simultaneously, each other (GP) through IIb/IIIa activation fibrinogen surface of the receptors bridges.
extrinsic of coagulation platelets occurs cascade that occurs cross-links as a result platelets of
exposure of blood to the thrombogenic lipid core and endothelium, which are rich
• ​in cross-linked Ventricular tissue factor. remodeling platelets, This leads and occurs to trapped formation after red MI blood of and
a fibrin is cells.
characterized clot composed by left of ventricular fibrin strands,
dila-
• ​tion Complications and reduced of pumping MI include function, cardiogenic leading shock, to cardiac heart failure failure.
(HF), valvular dysfunc-
tion, arrhythmias, pericarditis, stroke secondary to left ventricular (LV) thrombus embolization, venous thromboembolism, and LV
free-wall rupture.
CLINICAL PRESENTATION
• ​Predominant symptom is midline anterior chest discomfort (usually at rest), severe new-onset angina, or increasing angina that
lasts at least 20 minutes. Discomfort may
• ​radiate symptoms No specific to the may features shoulder, include indicate down nausea, ACS the vomiting, left on arm,
physical diaphoresis, to the examination. back, or and to shortness the However, jaw. Accompanying
of patients breath.
with
ACS may present with signs of acute HF or arrhythmias.
DIAGNOSIS
• ​Obtain 12-lead ECG within 10 minutes of presentation. Key findings indicating myocardial ischemia or MI are STE, ST-segment
depression, and T-wave inversion. Appearance of a new left bundle-branch block with chest discomfort is highly spe- cific for acute
MI. Some patients with myocardial ischemia have no ECG changes,
• ​so should Biochemical biochemical be assessed.
markers markers of myocardial and other risk cell factors death are for important coronary for artery confirming disease diagno-
(CAD)
sis of acute MI. Diagnosis is confirmed with detection of rise and/or fall of cardiac ​37
SECTION 2 | Cardiovascular Disorders
biomarkers (cardiac troponin preferred) with at least one value above the 99th per- centile of the upper reference limit and at least
one of the following: (1) symptoms of ischemia; (2) new significant ST-segment–T-wave changes or new left bundle- branch block;
(3) pathological Q waves; or (4) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.
Typically, a blood sample is
• ​obtained patients Patient symptoms, into once low, in the medium, past emergency medical or high department, history, risk of
ECG, death, then and MI, 6 to biomarkers or 9 likelihood hours later.
are of used failing to stratify
phar- macotherapy and needing urgent coronary angiography and percutaneous coronary intervention (PCI).
TREATMENT
• ​Goals of Treatment: Short-term goals include: (1) early restoration of blood flow to the infarct-related artery to prevent infarct
expansion (in the case of MI) or prevent complete occlusion and MI (in UA), (2) prevention of death and other complications, (3)
prevention of coronary artery reocclusion, (4) relief of ischemic chest discomfort, and (5) resolution of ST-segment and T-wave
changes on ECG. Long-term goals include control of cardiovascular (CV) risk factors, prevention of additional CV events, and
improvement in quality of life. ​GENERAL APPROACH
• ​General measures include hospital admission, oxygen if saturation is low, continuous multilead ST-segment monitoring for
arrhythmias and ischemia, frequent measure- ment of vital signs, bedrest for 12 hours in hemodynamically stable patients, use of
• ​stool blood Obtain softeners cell serum count to potassium, avoid (CBC) Valsalva and magnesium, coagulation maneuver,
glucose, tests; and pain and and relief.
fasting creatinine; lipid baseline panel. Draw complete lipid panel within the first 24 hours of hospitalization because values for
cholesterol (an
• • ​acute It Patients is important phase with reactant) STE to triage MI may are and be at treat high falsely patients risk low of after
death, according that so period.
initiate to their immediate risk category efforts (​Fig. ​to ​5–1​). rees- tablish coronary perfusion and adjunctive pharmacotherapy.
NONPHARMACOLOGIC THERAPY
• ​For patients with STE MI presenting within 12 hours of symptom onset, the reperfu- sion treatment of choice is early reperfusion
with primary PCI of the infarct artery
• ​within with For patients either 90 minutes PCI with or NSTE coronary of first ACS, medical artery practice bypass contact.
guidelines graft (CABG) recommend surgery coronary revascularization angiography as early treatment for high-risk patients; such
an approach may also be considered for patients not at high risk. ​EARLY PHARMACOTHERAPY FOR STE MI (FIG. 5–2)
• ​In addition to reperfusion therapy, American College of Cardiology Foundation/ American Heart Association (ACCF/AHA)
guidelines recommend that all patients with STE MI and without contraindications should receive within the first day of
hospitalization and preferably in the emergency department: (1) intranasal oxygen (if oxygen saturation is low), (2) sublingual (SL)

nitroglycerin (NTG), (3) aspirin, (4) a P2Y​12 p

​ latelet inhibitor, (5) and anticoagulation with bivalirudin, unfractionated

• ​heparin Give Administer IV (UFH), β-blockers a GP or IIb/IIIa enoxaparin.

and IV inhibitor NTG to select with UFH patients. to patients Initiate oral undergoing β-blockers primary the first PCI.
day in patients without cardiogenic shock. Administer morphine to patients with refrac- tory angina as an analgesic and venodilator
that lowers preload. Start an angiotensin- converting enzyme (ACE) inhibitor within 24 hours in patients who have either anterior
wall MI or LVEF of 40% or less and no contraindications. 38
Acute Coronary Syndromes | CHAPTER 5
Ischemic chest discomfort symptoms, lasting at least 20 min;
suspect acute coronary syndrome
Obtain and interpret a 12-lead ECG within 10 min
ST-segment elevation No ST-segment elevation
ST-segment depression T-wave inversion No ECG changes
Initiate reperfusion therapy in appropriate candidates (fibrinolysis or primary PCI)
a​ b,c
Risk stratification​ ; multilead continuous ST-segment monitoring; obtain serial troponin and CK MB​
Obtain serial troponin and CK MB as confirmatory; results not needed before reperfusion therapy is initiated; multilead continuous ST-segment monitoring
Initiate pharmacotherapy for non-ST-segment elevation ACS based on patient risk
Low-risk Moderate- and high-risk
Initiate adjunctive ST-segment elevation ACS pharmacotherapy
Stress test to evaluate likelihood of CAD
Negative stress test
Diagnosis of noncardiac chest pain syndrome
Positive stress test
Coronary angiography with ​“Negative”: Below the myocardial infarction decision limit. ​revascularization ​(ACS, acute (​ PCI or ​coronary
CABG)
 FIGURE 5–1. ​Evaluation of the acute coronary syndrome patient. ​a​As described in textbook Table 7-1. ​b​“Positive”: Above the

myocardial infarction decision limit. ​c ​syndrome; CABG, coronary artery bypass graft; CAD, coronary artery disease; CK MB,
creatine kinase myocardial band; ECG, electrocardiogram; PCI, percutaneous coronary intervention. (Modified with permission from
Spinler SA. Evolution of antithrombotic therapy used in acute coronary syndromes. In: Richardson MM, Chant C, Cheng JWM, et al,
eds. ​Pharmacotherapy Self-Assessment Program. Book 1: Cardiology, 7th ed. ​Lenexa, KS: American College of Clinical Pharmacy;
2010.)
Fibrinolytic Therapy
• ​A fibrinolytic agent is indicated in patients with STE MI presenting within 12 hours
• ​of tiguous It is the not onset ECG necessary of leads chest and to discomfort obtain are unable the who to results undergo have
of at least biochemical primary 1 mm PCI of markers within STE in 120 two before minutes or more initiating
of
con-
• ​medical onset Absolute to patients contact. contraindications with Limit ongoing use of to fibrinolytic fibrinolytics ischemia.
therapy between include: 12 and (1) 24 history hours after of hemorrhagic
symptom
fibrinolytic therapy.
stroke (at any time), (2) ischemic stroke within 3 months, (3) active internal bleeding, (4) known intracranial neoplasm, (5) known

structural cerebrovascular lesion, (6) ​39

SECTION 2 | Cardiovascular Disorders

ST-segment elevation myocardial infarction

d​ d
Oxygen (if O​2 ​saturation <90%) SL
​ NTG, aspirin, morphine sulfate​ , IV NTG​
sis for select patients; for secondary PCI during hospitalization, administer bivalirudine​e
n​c ​or fondaparinux (plus UFH) with optional GP llb/Illa inhibitor at time of PCI​f

Symptoms δ to 12 h

Clopidogrel, statin
or ticagrelor ​
Reperfusion therapy
s >12 h Clopidogrel, prasugrel,

Bivalirudin​e ​alone or unfractionated heparin with GP llb/Illa receptor inhibitor

ed patients) or IV and SC fondaparinux​d

High-intensity statin

Primary PCI Fibrinolysis

®​-Blocker, ACE inhibitor (or ARB), eplerenone (or spironolactone)​d

FIGURE 5–2. ​Initial pharmacotherapy for ST-segment elevation myocardial infarction. a​​ For at least 48 hours. b​​ See textbook Table 24–2 for dosing
and specific types of patients who should not receive enoxaparin. ​c​For the duration of hospitaliza- tion, up to 8 days. ​d​For select patients, see textbook
Table 24–2. e​​ If pretreated with UFH, stop UFH infusion for 30 minutes prior to administration of bivalirudin (bolus plus infusion). f​ ​Increased risk of major
bleeding and ICH if a GP IIb/IIIa inhibitor is added to an anticoagulant for PCI following fibrinolysis, especially in the elderly; weigh risk ver- sus benefit
(ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CABG, coronary artery bypass graft surgery; GP, glycoprotein; NTG,
nitroglycerin; PCI, percutaneous coronary intervention; SC, subcutaneous; SL, sublingual; UFH, unfraction- ated heparin.) (Modified with permission
from Spinler SA. Evolution of antithrombotic therapy used in acute coronary syndromes. In: Richardson MM, Chant C. Cheng JWM, et al, eds.
Pharmacotherapy Self-Assessment Program​. 7th ed. Book 1: ​Cardiology.​ Lenexa, KS: American College of Clinical Pharmacy; 2010.)

40
Acute Coronary Syndromes | CHAPTER 5
suspected aortic dissection, and (7) significant closed head or facial trauma within 3
• • ​months. non–fibrin-specific time A Treat fibrin-specific they eligible Primary present patients PCI agent to agent the is as
emergency preferred (alteplase, soon streptokinase.
as possible, in reteplase, department, these but situations.
or preferably with tenecteplase) one within of the is 30 following preferred minutes regimens: from over the the

✓ ​Alteplase: ​15 mg IV bolus followed by 0.75 mg/kg infusion (maximum 50 mg) over ​30 minutes, followed by 0.5 mg/kg infusion

(maximum 35 mg) over 60 minutes ​✓ R

​ eteplase: (maximum
​ ​ dose
10 ​ ​units 100
​ ​IV mg)
​ ​over 2 minutes, followed 30 minutes later

​ units IV over ​A single 2

with another ✓ ​Tenecteplase: 10 ​ minutes ​IV bolus dose given over 5 seconds based on patient
weight: 30 mg if less than 60 kg; 35 mg if 60 to 69.9 kg; 40 mg if 70 to 79.9 kg; ​✓ ​Streptokinase: ​45 mg if 80 to ​1.5 ​89.9 ​million ​kg;

and ​units 50
​ mg ​in 50 if​ 90 ​mL kg
​ ​of or
​ ​normal greater
​ ​saline or 5% dextrose in water

• ​effects. Intracranial IV over The 60 risk hemorrhage minutes

of ICH is higher (ICH) with and fibrin-specific major bleeding agents are than the with most streptokinase. serious side
However, the risk of systemic bleeding other than ICH is higher with streptokinase than with fibrin-specific agents. ​Aspirin
• ​Administer ​aspirin ​to all patients without contraindications within 24 hours before or after hospital arrival. It provides additional
mortality benefit in patients with STE
• ​ACS be In patients chewed when given experiencing and swallowed with fibrinolytic an as ACS, soon therapy.
non–enteric-coated as possible after the aspirin, onset of 160 symptoms to 325 mg, or should imme- diately after presentation to
the emergency department regardless of the reperfusion strategy being considered. Patients undergoing PCI not previously taking
aspirin
• ​should continued A daily receive maintenance indefinitely. 325 mg dose Because non–enteric-coated of 75 of to increased 162
mg aspirin.
is bleeding recommended risk in thereafter patients receiving and should aspi- be

• ​rin Discontinue plus a P2Yother ​12 i​ nhibitor, nonsteroidal

​ ​low-dose anti-inflammatory
​ ​aspirin (81 mg drugs
​ ​daily) (NSAIDs)
​ ​is

preferred ​and cyclooxygenase-2 ​following PCI.

(COX-2) selective inhibitors at the time of STE MI due to increased risk of death,
• ​reinfarction, patients The most about frequent HF, the and risk side myocardial of GI effects bleeding.
of rupture.
aspirin include dyspepsia and nausea. Inform

Platelet P2Y​12 ​Inhibitors

• ​Clopidogrel​, ​prasugrel​, and ​ticagrelor ​block a subtype of ADP receptor (the P2Y​12 ​receptor) on platelets, preventing binding of
ADP to the receptor and subsequent ​• ​expression A
​ P2Y​12 ​receptor of platelet inhibitor GP IIb/IIIa in addition receptors, to reducing

aspirin is platelet recommended aggregation. for all patients ​with STE MI. For patients undergoing primary PCI, give clopidogrel,
prasugrel, or ticagrelor, in addition to aspirin, to prevent subacute stent thrombosis and longer-
• ​term The recommended CV events.
duration of P2Y​12 ​inhibitors for a patient undergoing PCI (either ​STE MI or NSTE ACS) is at least 12 months for patients receiving
either a bare metal
• ​or If CABG drug-eluting surgery stent.
is planned, withhold clopidogrel and ticagrelor for 5 days, and prasugrel at least 7 days, to reduce risk of postoperative bleeding,
unless the need for
• ​revascularization ing ​Clopidogrel: ​a fibrinolytic 300 mg outweighs or oral who loading do the not bleeding dose receive followed
risk.
reperfusion by 75 mg therapy. orally Avoid daily in loading patients dose receiv- in patients aged 75 years or more. A 600-mg oral

loading dose is recommended before pri- mary PCI, except that 300 mg should be given if within 24 hours of fibrinolytic therapy. ​41
SECTION 2 | Cardiovascular Disorders
• ​Prasugrel: ​60 mg oral loading dose followed by 10 mg orally once daily for patients
• • ​weighing orally and ​Ticagrelor: ​The diarrhea, most twice 60 frequent 180 daily.
kg (2%–5% mg (132 side oral lb) of effects loading or patients). more.
of dose clopidogrel Thrombotic in patients and thrombocytopenic undergoing prasugrel include PCI, followed purpura nausea, by
vomiting,
(TTP)
90 mg
has been reported rarely with clopidogrel. Ticagrelor is associated with nausea (4%),
• ​diarrhea once In patients daily (3%), with during dyspnea STE hospitalization MI (14%), receiving and, and fibrinolysis, rarely, up
to ventricular 28 days early reduces therapy pauses mortality with and bradyarrhythmias. clopidogrel and reinfarc-
75 mg
tion without increasing risk of major bleeding. In adults younger than 75 years receiv-
• ​ing For fibrinolytics, patients with the STE first MI dose who of do clopidogrel not undergo can reperfusion be a 300-mg therapy
loading with dose.

either pri- mary PCI or fibrinolysis, clopidogrel is the preferred P2Y​12 ​inhibitor added to aspirin and
​ should be continued for at least
14 days (and up to 1 year). Ticagrelor may also be an option in medically managed patients with ACS.
Glycoprotein IIb/IIIa Receptor Inhibitors
• ​GP IIb/IIIa receptor inhibitors block the final common pathway of platelet aggrega- tion, namely cross-linking of platelets by
fibrinogen bridges between the GP IIb and
• ​IIIa administered Abciximab receptors (IV in on patients or the intracoronary platelet with surface.
STE administration), MI undergoing primary eptifibatide, PCI or who tirofiban are treated may with be
UFH. Do not administer GP IIb/IIIa inhibitors to patients with STE MI who will not
• • • • ​be lowed 2 ​Abciximab: Eptifibatide: Tirofiban: ​Routine mcg/kg/min undergoing by use 0.125 25 0.25 of 180 mcg/kg for
PCI.
a mcg/kg/min mg/kg GP mcg/kg 18 IIb/IIIa to IV IV 24 bolus, IV hours bolus bolus, receptor (maximum then given after repeated
0.15 inhibitor PCI.
10 10 mcg/kg/min to mcg/min) in 60 is 10 minutes not minutes, recommended up for before to 12 18 followed hours.
to the 24 start hours in by patients of infusion after PCI, PCI. who fol-
of
have received fibrinolytics or in those receiving bivalirudin because of increased
• ​bleeding patients Bleeding with risk.
is the a history most significant of hemorrhagic adverse stroke effect. or recent Do not ischemic use GP stroke. IIb/IIIa Risk
inhibitors of bleed- in
ing is increased in patients with chronic kidney disease; reduce the dose of eptifiba- tide and tirofiban in renal impairment. An
immune-mediated thrombocytopenia occurs in approximately 5% of patients with abciximab and fewer than 1% of patients
receiving eptifibatide or tirofiban.
Anticoagulants
• ​Either ​UFH ​or ​bivalirudin ​is preferred for patients undergoing primary PCI,
• ​whereas tor UFH is planned initial for dose fibrinolysis, and for 70 primary to 100 either U/kg PCI UFH, is IV 50 bolus ​enoxaparin​,
to 70 if units/kg no GP or ​fondaparinux ​IIb/IIIa IV bolus inhibitor if a may GP is IIb/IIIa be planned; used.
inhibi- give
• ​supplemental lowed UFH initial by constant dose IV bolus with IV infusion fibrinolytics doses to of maintain 12 is U/kg/h 60 U/kg
the (maximum target IV bolus activated (maximum 1000 clotting U/h). 4000 Adjust time units), (ACT).
the UFH fol-
infusion dose frequently to maintain a target activated partial thromboplastin time (aPTT) of 1.5 to 2 times control (50–70 seconds).
Measure the first aPTT at 3 hours in patients with STE ACS who are treated with fibrinolytics and at 4 to 6 hours in

• ​patients [ClEnoxaparin ​cr​] ≥30 ​not ​mL/min) ​receiving dose is ​or ​1 mg/kg thrombolytics ​24 hours ​subcutaneous ​if impaired ​or
undergoing (SC) ​renal ​every ​function ​primary 12 hours ​(Cl​PCI.

cr ​15–29 (creatinine
​ ​mL/min). clearance
​

For patients
​ with STE MI receiving fibrinolytics, enoxaparin 30 mg IV bolus is followed ​immediately by 1 mg/kg SC every 12 hours if

younger than 75 years. In patients

42
Acute Coronary Syndromes | CHAPTER 5
75 years and older, give enoxaparin 0.75 mg/kg SC every 12 hours. Continue enoxa-
• ​parin kg/h Bivalirudin infusion. throughout dose Discontinue for hospitalization PCI in at STE the MI or end up is of 0.75 to PCI 8
days.
mg/kg or continue IV bolus, at 0.25 followed mg/kg/h by if 1.75 prolonged
mg/
• • ​anticoagulation hospital procedure. Fondaparinux For is necessary.
day 2.
dose is 2.5 mg IV bolus followed by 2.5 mg SC once daily starting on
patients In undergoing patients receiving PCI, discontinue an anticoagulant anticoagulation plus a fibrinolytic, immediately continue
after UFH
the
for a minimum of 48 hours and enoxaparin and fondaparinux for the duration of hospitalization, up to 8 days. In patients who do not
undergo reperfusion therapy, anticoagulant therapy may be administered for up to 48 hours for UFH or for the duration of
hospitalization for enoxaparin or fondaparinux. ​β-Adrenergic Blockers
• ​If no contraindications, administer a β-blocker early (within the first 24 hours) and
• ​continue Benefits indefinitely. result from heart rate, myocardial blockade of contractility, βand ​1 ​receptors in the myocardium,

which reduces
BP, thereby decreasing myocardial oxygen demand. Reduced heart rate increases diastolic time, thus improving ventricular fill-

• • ​ing lar ✓ β-Blockers Usual ​Metoprolol: arrhythmias.

​
and doses coronary reduce of ​5 ​β-blockers, ​mg artery
​ risk ​by slow ​for perfusion.

recurrent with ​(over target

​ ​1–2 ischemia,
​ resting ​minutes) heart
​ infarct ​IV rate
​ ​bolus, size,
​ of ​repeated 50
​ reinfarction, to 60
beats/min:

every and
​ ​5 minutes ventricu-
​
for total initial dose of 15 mg. If a conservative regimen is desired, reduce initial doses to 1 to 2 mg. Follow in 1 to 2 hours by 25 to

50 mg orally every 6 hours. If ​✓ ​Propranolol: appropriate,

​ ​0.5 initial
​ ​to 1 IV
​ ​mg therapy
​ ​slow IV may
​ ​push, ​be omitted. ​followed in 1

to 2 hours by 40 to 80 mg ✓ ​Atenolol: orally

​ every ​5 mg 6
​ to ​IV 8
​ ​dose, hours.
​ ​followed If
​ appropriate, ​5 minutes the
​ initial ​later by

IV ​a therapy
​ ​second 5 ​may ​mg ​be ​IV ​omitted. ​dose, then
50 to 100 mg orally once daily beginning 1 to 2 hours after the IV dose. The initial
• ​cardia, The IV most therapy and serious heart may block. side be omitted.
effects Initial acute early in administration ACS include of hypotension, β-blockers is acute not appropriate HF, brady-
for patients presenting with acute HF but may be attempted in most patients before
• ​discharge indefinitely Continue after β-blockers in patients treatment for with of at LV acute least systolic 3 HF.
years dysfunction in patients and with LVEF normal of 40% LV or function less.
and
Statins
• ​Administer a high-intensity statin, either ​atorvastatin ​80 mg or ​rosuvastatin ​40 mg, to all patients prior to PCI (regardless of prior
lipid-lowering therapy) to reduce the frequency of periprocedural MI following PCI. ​Nitrates
• ​NTG causes venodilation, which lowers preload and myocardial oxygen demand. In addition, arterial vasodilation may lower BP,
thereby reducing myocardial oxygen demand. Arterial dilation also relieves coronary artery vasospasm and improves
• ​myocardial Immediately blood upon flow presentation, and oxygenation.
administer one ​SL NTG ​tablet (0.4 mg) every
• ​5 dication ​Intravenous ​minutes and for ​NTG ​who up to is have three indicated persistent doses for to patients ischemia, relieve
with chest HF, an pain or ACS uncontrolled and who myocardial do not high have ischemia.
BP. a The contrain- usual dose is 5 to 10 mcg/min by continuous infusion, titrated up to 100 mcg/min until relief of symptoms or
limiting side effects (eg, headache or hypotension). Continue treatment for approximately 24 hours after ischemia is relieved.
43
SECTION 2 | Cardiovascular Disorders
• ​Oral nitrates play a limited role in ACS because clinical trials have failed to show a
• ​mortality ache, The most and benefit hypotension. significant for IV adverse Nitrates followed effects are by contraindicated oral
of nitrates nitrate include therapy in patients tachycardia, in acute who MI.
have flushing, taken head-
the oral phosphodiesterase-5 inhibitors sildenafil or vardenafil within the prior 24 hours or tadalafil within the prior 48 hours.
Calcium Channel Blockers
• ​After STE MI, calcium channel blockers (CCBs) are used for relief of ischemic symptoms in patients who have contraindications
to β-blockers. There is little clini- cal benefit beyond symptom relief, so avoid CCBs in acute management of all ACSs
• ​unless has A CCB LV there systolic that is lowers a dysfunction, clear heart symptomatic rate bradycardia, (diltiazem need or or
or verapamil) contraindication heart block. is In preferred those to β-blockers.
cases, unless either the patient

amlo- dipine or felodipine is preferred. Avoid nifedipine because it causes reflex sympa- thetic ​✓ ✓ ✓ ​Diltiazem: Verapamil:

Amlodipine: activation,
​ ​120 180 5 to tachycardia,
​ ​to to 10 360 480 mg mg mg orally sustained sustained and
​ ​once worsened
​

release release daily ​myocardial ischemia. ​orally once daily orally once daily ​EARLY PHARMACOTHERAPY FOR NSTE ACS
(FIG. 5–3)

• ​• Early
​ ​In absence pharmacotherapy
​ ​of contraindications, for
​ NSTE ​treat ACS
​ ​all is
​ ​patients similar
​ to ​in that
​ ​the for
​ ​emergency

STE ACS. ​department with ​intranasal oxygen ​(if oxygen saturation is low), ​SL NTG​, ​aspirin​, and an ​anticoagu-

• ​lant ​IIIa High-risk inhibitor (​UFH​, patients ​enoxaparin​, (optional should ​fondaparinux​, with proceed either to UFH early or
bivalirudin​).
or angiography enoxaparin but and should may receive be avoided a GP IIb/
with
• • ​bivalirudin).
Administer Give ​IV β-blockers ​a ​P2Y​12 ​and ​inhibitor ​IV NTG ​to all ​to select ​patients. ​patients. ​• • • I​ nitiate Give Fibrinolytic
morphine oral β-blockers ​therapy to patients is within never with administered the refractory first 24 hours angina, in NSTE in

patients as ACS. described without previously. cardiogenic shock. Aspirin

​
• ​Aspirin ​reduces risk of death or MI by approximately 50% compared with no anti- platelet therapy in patients with NSTE ACS.
Dosing of aspirin is the same as for STE ACS, and aspirin is continued indefinitely. ​Anticoagulants
• ​For patients treated by an early invasive approach with early coronary angiography
• • ​and ization), the If Continue an hospital PCI, initial enoxaparin, administer therapy conservative (or 8 days, for ​UFH​, UFH, at
whichever least strategy ​enoxaparin​, or 48 low-dose hours is is planned shorter) for or ​fondaparinux bivalirudin​.
UFH, (no for coronary until either the is enoxaparin recommended.
angiography patient is or discharged fondaparinux, or revascular-
from
and until the end of the PCI or angiography procedure (or up to 72 hours after PCI)
• ​for lowed For bivalirudin.
NSTE by a ACS, continuous the dose IV of infusion UFH is of 60 12 U/kg U/kg/h IV (maximum bolus (maximum 1000 U/h). 4000
Titrate units), the fol-

dose to maintain aPTT between 1.5 and 2 times control. ​P2Y​12 ​Inhibitors

• ​When an initial invasive strategy is selected, there are two initial options for dual antiplatelet therapy depending on choice of
P2Y​12 ​inhibitor: ​1. Aspirin plus early use of clopidogrel or ticagrelor (in the emergency department) ​2. Aspirin plus double-bolus dose

eptifibatide plus an eptifibatide infusion or high-

dose tirofiban bolus plus infusion administered at the time of PCI. 44
Early conservative strategy ​Medical management only planned
IV UFH, Subcut enoxaparin, Subcut fondaparinux​b
IV UFH, bivalirudin​c​, Subcut
d ​plus UFH administered at time of PCI

One of two options: (a) Either clopidogrel 600 mg or ticagrelor or (b) GP IIb/IIIa inhibitor
High-intensity statin
Recurrent ischemia, prior to PCI
heart failure, or arrhythmias Urgent angiography
Clopidogrel 300 mg or ticagrelor
No recurrent ischemia, heart failure, or arrhythmias

High-intensity statin ​Nonurgent angiography

Angiography
PCI
®-blocker, statin, ACE inhibitor (or ARB); and Discontinue anticoagulantIV ​f
NTG
PCI; consider prasugrel​e ​if clopidogrel/ticagrelor not previously given; discontinue anticoagulant; continue GP IIb/IIIa inhibitor per guidelines; discontinue NTG; continue statin and aspirin, add
®-blocker and ACE inhibitor (or ARB)

No or noncritical CAD; discontinue anticoagulant; treat CHD risk factors; if CAD, continue P2Y​12 ​inhibitor, aspirin, and ​statin; add ®-blocker and ACE inhibitor (or ARB)
CABG; continue/ change anticoagulant to UFH; discontinue clopidogrel/ticagrelor and GP IIb/IIIa inhibitor prior to surgery
No or noncritical CAD; Treat CHD risk factors; Continue clopidogrel/ ticagrelor, aspirin if CAD
Continue clopidogrel/ticagrelor; discontinue anticoagulant; continue GP IIb/IIIa inhibitor per guidelines; discontinue NTG; continue statin and aspirin; add ®-blocker and ACE inhibitor (or ARB)
Stress test
Positivefindings Negative findings
for ischemia for ischemia
Treat CHD risk factors
FIGURE 5–3. ​Initial pharmacotherapy for non–ST-segment elevation ACS. a​​ For selected patients. b​​ Preferred in patients at high
risk for bleeding. c​​ If pretreated with UFH, stop UFH infusion for 30 minutes prior to administration of bivalirudin bolus plus infusion.
d​
May require IV supplemental dose of enoxaparin. ​e​Do not use if prior history of stroke/TIA, age older than 75 years, or body weight
60 kg or less. f​​ SC enoxaparin or UFH can be continued at a lower dose for venous thromboembolism prophylaxis. (ACS, acute
coronary syndrome; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CABG, coronary artery bypass graft;
CAD, coronary artery disease; CHD, coronary heart disease; GP, glycoprotein; IV, intravenous; NSTE, non–ST-segment elevation;
NTG, nitroglycerin; PCI, percutaneous coronary intervention; SC, subcutaneous; SL, sublingual; STE MI, ST-segment-elevation
myocardial infarction; TIA, transient ischemic attack; UFH,

A​cuteCoronarySyndromes| CHAPTER5 ​4​5

Non–ST-segment elevation ACS
Oxygen (if O​2 saturation
​ less than 90%[0.90]) SL NTG, IV NTG ​a
Morphine sulfate Aspirin,
a

Early Invasive Strategy ​Early coronary angiography planned less than or equal to 12–24 hours from hospital presentation
Optional initiate GP IIb/IIIa inhibitor or switch anticoagulant to bivalirudin; administer additional loading dose of clopidogrel/ticagrelor prior to PCI
enoxaparin , or Subcut fondaparinux
unfractionated heparin.) (Modified with permission from Spinler SA, de Denus S. Acute coronary syndromes. In: Chisholm-Burns M,

Wells BG, Schwinghammer TL, ​Malone PM, Kolesar JM, DiPiro JT, eds. ​Pharmacotherapy Principles and Practice​. 3rd ed. New

York, NY: McGraw-Hill; 2013:133–167.)

SECTION 2 | Cardiovascular Disorders
• ​For subsequent antiplatelet therapy in patients undergoing PCI initially treated with regimen 1 above, a GP IIb/IIIa inhibitor
(abciximab, eptifibatide, or high-dose tirofi-
• ​ban) ticagrelor For patients can be can added, undergoing be started and then PCI within clopidogrel initially 1 hour treated after
continued PCI with and option with the low-dose 2, P2Yclopidogrel, ​12 ​inhibitor ASA.
​
prasugrel, ​continued
or

with low-dose aspirin. Following PCI, continue dual oral antiplatelet therapy for at ​• ​least can
​ For patients be ​12 administered
​

months. ​receiving in an addition initial conservative to aspirin. Continue strategy, dual either antiplatelet clopidogrel therapy or
ticagrelor
for at least 12 months. ​Glycoprotein IIb/IIIa Receptor Inhibitors

• ​The role of GP IIb/IIIa inhibitors in NSTE ACS is diminishing as P2Y​12 ​inhibitors are
• ​used angiography Routine earlier, administration and and bivalirudin PCI in of NSTE eptifibatide is often ACS selected does
(added not as reduce to the aspirin anticoagulant.
ischemic and clopidogrel) events and increases prior to
bleeding risk. Therefore, the two antiplatelet initial therapy options described in the
• ​previous routine For low-risk GP section IIb/IIIa patients are inhibitors preferred.
and a conservative because bleeding management risk exceeds strategy, the there benefit.
is no role for
Nitrates
• ​Administer SL NTG followed by IV NTG to patients with NSTE ACS and ongo- ing ischemia, HF, or uncontrolled high BP.
Continue IV NTG for approximately 24 hours after ischemia relief. ​β-Blockers
• ​In the absence of contraindications, administer oral β-blockers to all patients with NSTE ACS within 24 hours of hospital
admission. Benefits are assumed to be similar
• ​to 3 Continue years those in seen β-blockers patients in patients with indefinitely normal with STE LV in MI.
patients function.
with LVEF of 40% or less and for at least
Calcium Channel Blockers
• ​As described previously for STE ACS, CCBs should not be administered to most patients with ACS.
SECONDARY PREVENTION FOLLOWING MI
• ​Goals of Treatment: The long-term goals after MI are to: (1) control modifiable coronary heart disease (CHD) risk factors; (2)
prevent development of systolic HF; (3) prevent recurrent MI and stroke; (4) prevent death, including sudden cardiac death; and (5)
prevent stent thrombosis after PCI.
PHARMACOTHERAPY
• ​Start pharmacotherapy that has been proven to decrease mortality, HF, reinfarction
• ​or dications) After stroke, MI from and should stent either receive thrombosis STE indefinite MI or prior NSTE treatment to ACS,
hospital all with discharge patients aspirin (in for (or the secondary clopidogrel absence of prevention. if contrain- aspirin
contraindications), an ACE inhibitor, and a “high-intensity” statin for secondary
• ​tality, prevention Start ACE decrease inhibitors of death, reinfarction, stroke, and continue and or recurrent prevent indefinitely
HF. infarction.
Most in all patients patients with after CAD MI to (not reduce just those mor-
46
Acute Coronary Syndromes | CHAPTER 5
with ACS or HF) benefit from an ACE inhibitor. The dose should be low initially and

• ​titrated ​✓ ✓ ✓ cough
​ ​✓ ✓ An
​ ​Captopril: Enalapril: Lisinopril: Ramipril: Trandolapril: angiotensin
​ and to the a ​1.25 2.5 6.25

low ​2.5 dose

​ ​1 to receptor
​ ​to to LVEF
​ ​mg to 5 5 2.5 used
​ ​12.5 mg mg initially; mg and
​ ​initially; in
​ ​initially; mg blocker
​ ​initially; clinical
​
HF ​initially; target ​after ​target ​may ​target ​trials ​target dose ​MI:

​ ​dose dose if​ prescribed ​4 dose tolerated,

target be ​ ​mg dose 10 10 5 once mg to mg 50 20 twice mg twice for
​ ​daily
for ​mg patients
​ ​two example:
​ ​daily once daily or daily three or with
​ ​10 times mg ACE
​ ​once daily inhibitor
​ ​daily •​ ​✓ ​✓ tion
​ Continue

​ 40% a β-blocker ​40 or

Candesartan: Valsartan: of ​ less ​mg 4 to initially; and
​ ​8 mg for
​ indefinitely at ​initially; ​least ​target 3
​ ​dose

target years
​ in patients ​160 dose in
​ patients ​mg 32 with
​ ​twice mg without
​ LV ​once daily systolic
​ ​daily HF
​ or dysfunction an ejection
or frac- HF symptoms. A CCB can be used to prevent anginal symptoms in patients who cannot tolerate or have contraindications
to β-blockers but should not be used routinely in

• ​the Continue absence a P2Yof such ​12 ​inhibitor findings.

​

for at least 12 months for patients undergoing PCI and for patients
​ with NSTE ACS receiving a medical management strategy.
Continue clopi-
• ​dogrel or To spironolactone) reduce for at mortality, least 14 within days consider the in patients first a mineralocorticoid 7 days
with after STE MI MI in not receptor all undergoing patients antagonist already PCI.
(eplerenone receiving an ACE inhibitor (or ARB) and a β-blocker and have an LVEF of 40% or less and either
• • ​HF ​✓ ✓ ​priate nal All Prescribe ​Eplerenone: Spironolactone: ​symptoms symptoms patients targets a short-acting with based

25 when
​ or CAD ​mg diabetes
​ ​12.5 on
​ necessary. ​initially; mg ​should current SL mellitus. ​initially; NTG
​ ​target receive
​ practice

Chronic or lingual ​target The

​ ​dose dietary
​ guidelines.

drugs long-acting ​50 dose NTG

​ ​mg counseling
​ are ​25 once spray
​ ​to continued
​ nitrates ​50 daily for
​ ​mg and
​ all ​once have
​
indefinitely. patients a statin ​daily
not to to been reach relieve shown appro- angi-
to reduce CHD events after MI and are not used in ACS patients who have undergone revascularization unless the patient has
chronic stable angina or significant coronary
• ​stenosis (HTN), For all ACS dyslipidemia, that was patients, not revascularized.
treat obesity, and smoking, control modifiable and DM.
risk factors such as hypertension
EVALUATION OF THERAPEUTIC OUTCOMES
• ​Monitoring parameters for efficacy for both STE and NSTE ACS include: (1) relief of ischemic discomfort, (2) return of ECG
changes to baseline, and (3) absence or
• ​resolution used. Monitoring In general, of parameters HF the signs most and for common symptoms.
adverse adverse effects reactions are dependent from ACS on the therapies individual include
drugs
hypotension and bleeding.
See Chapter 7, Acute Coronary Syndromes, authored by Sarah A. Spinler and Simon De Denus, for a more detailed discussion of
this topic.
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