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2. An 81-year-old African American man (weight 90 4. A 62-year-old man presents to the ED after sev-
kg) presents to the ED with chest pressure (10/10 eral hours of chest discomfort. His ECG reveals
on a pain scale). His ECG reveals ST-segment a 1- to 2-mm ST-segment elevation with positive
depression in the inferior leads. His medical his- troponins. He has also had increasing shortness of
tory is signi�cant for hypertension and chronic breath and lower-extremity swelling over the past
kidney disease. Pertinent laboratory results are tro- 2–3 weeks. His medical history is signi�cant for
ponin 5.8 ng/L, serum creatinine (SCr) 3.7 mg/dL, tobacco use for 40 years, chronic obstructive pul-
and estimated creatinine clearance (eCrCl) 20 mL/ monary disease, diabetes, and hypertension. His
minute. The patient has been given aspirin 325 blood pressure is 102/76 mm Hg and heart rate is
mg single dose; a nitroglycerin drip, initiated at 5 111 beats/minute. He has rales in both lungs and
mcg/minute, will be titrated to chest pain relief and 2–3+ pitting edema in his extremities. His echocar-
blood pressure. The patient consents for cardiac diogram reveals an ejection fraction (EF) of 25%.
catheterization after adequate hydration. Which After primary percutaneous coronary intervention
anticoagulation strategy is most appropriate to ini- (PCI), he is transferred to the cardiac intensive
tiate in this patient? care unit. Which best describes the acute use of
A. Intravenous heparin 4000-unit intravenous β-blocker therapy in this patient?
bolus, followed by a 1000-unit/hour continu- A. Give 12.5 mg of oral carvedilol within the �rst
ous infusion. 24 hours.
B. Enoxaparin 90 mg subcutaneously every 12 B. Give 5 mg of intravenous metoprolol at the
hours. bedside.
C. Fondaparinux 2.5 mg subcutaneously daily. C. Give 50 mg of oral metoprolol succinate at
D. Bivalirudin 67.5-mg bolus, followed by a 157- discharge.
mg/hour infusion. D. Give no β-blocker at this time.
3. A 56-year-old man presents to the hospital with 5. A 60-year-old man (weight 75 kg) presents to
the chief concern of chest pain that was unrelieved the ED with crushing substernal chest pain and
at home with sublingual nitroglycerin. His ECG ST-segment elevations on ECG. He has a medical
reveals ST-segment depression and T-wave inver- history of diabetes and a 40 pack-year history of
sion. Cardiac markers show an elevated troponin I. smoking. He is taken immediately to the catheter-
The cardiologist has requested that the patient go ization laboratory for primary PCI, and a drug-
to the cardiac catheterization laboratory for further eluting stent is placed in his left anterior descend-
evaluation. The patient has a history of coronary ing artery. In addition to aspirin, which regimen
artery disease (CAD) and had a myocardial infarc- would best maintain this patient’s stent patency?
tion (MI) about 6 months ago. During his previous A. Clopidogrel 300-mg LD, followed by 75 mg
hospitalization, he was con�rmed to have devel- daily for 12 months.
oped heparin-induced thrombocytopenia (HIT)
B. Prasugrel 60-mg LD, followed by 10 mg daily
after his platelet count (Plt) dropped to 40,000/
for 12 months.
mm3 and he had a positive ELISA (enzyme-linked
immunosorbent assay) upon serologic testing after C. Ticagrelor 180-mg LD, followed by 90 mg
his previous catheterization. Given this patient’s daily for 6 months.
diagnosis and history, which treatment regimen D. Clopidogrel 600-mg LD, followed by 75 mg
would be most appropriate during his cardiac daily for 6 months.
catheterization?
A. Abciximab. 6. A 60-year-old woman with New York Heart
Association (NYHA) class IV heart failure (HF)
B. Bivalirudin.
(heart failure with reduced ejection fraction
C. Enoxaparin. [HFrEF]) is admitted for increased shortness of
D. Tenecteplase. breath and dyspnea at rest. Her extremities appear
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well perfused, but she has 3+ pitting edema in her 9. A 52-year-old woman has a witnessed cardiac
lower extremities. Her vital signs include blood arrest in a shopping mall and is resuscitated with
pressure 125/70 mm Hg, heart rate 92 beats/ an automatic external de�brillator device. On elec-
minute, and oxygen saturation (SaO2) 89% on 100% trophysiologic study, she has inducible VT. Which
facemask. After initiating an intravenous diuretic, is most appropriate for reducing the secondary
which intravenous agent is best to rapidly treat this incidence of sudden cardiac death (SCD)?
patient’s pulmonary symptoms? A. Propafenone.
A. Dobutamine. B. Amiodarone.
B. Milrinone. C. Implantable cardioverter-de�brillator (ICD).
C. Nitroglycerin. D. Metoprolol.
D. Metoprolol.
10. The Sudden Cardiac Death in Heart Failure trial
7. A 75-year-old woman admitted for pneumonia has evaluated the ef�cacy of amiodarone or an ICD
a history of NYHA class III HFrEF (left ventric- versus placebo in preventing all-cause mortality
ular ejection fraction [LVEF] 25%) and several in ischemic and nonischemic patients with NYHA
non–ST-segment elevation myocardial infarctions class II and III HF. There was a 7.2% absolute risk
(NSTEMIs). She had an episode of sustained ven- reduction and a 23% relative risk reduction in all-
tricular tachycardia (VT) during this hospitaliza- cause mortality at 60 months with an ICD versus
tion. Her corrected QT (QTc) interval was 380 placebo. Which best shows the number of patients
milliseconds on the telemetry monitor, and her needed to treat with an ICD to prevent one death
serum potassium and magnesium were 4.6 mEq/L versus placebo?
and 2.2 mg/dL, respectively. Which intravenous A. 1.
agent is most appropriate for this patient’s ventric-
B. 4.
ular arrhythmias?
C. 14.
A. Procainamide.
D. 43.
B. Metoprolol.
C. Magnesium. 11. You are working on a review article about newer
D. Amiodarone. treatment strategies for hypertensive crises. You
want to ensure that you retrieve all relevant clin-
8. A 53-year-old woman is admitted to the hospital ical trials and related articles on your subject.
after the worst headache she has ever had. Her Which comprehensive database is most appropri-
medical history includes exertional asthma, poorly ate to search to ensure that you have not missed key
controlled hypertension, glaucoma, and hyper- articles?
lipidemia. She is nonadherent to her medications A. International Pharmaceutical Abstracts.
and has not taken her prescribed blood pressure
B. Iowa Drug Information Service.
medications for 4 days. Vital signs include blood
pressure 220/100 mm Hg and heart rate 65 beats/ C. Clin-Alert.
minute. She has retinal hemorrhaging on fundus- D. Excerpta Medica.
copic examination. Which is most appropriate for
this patient’s hypertensive emergency? 12. A physician on your team asks that you report an
A. Fenoldopam 0.1 mcg/kg/minute. adverse drug reaction (ADR) experienced by a
B. Nicardipine 5 mg/hour. patient taking nesiritide. The patient had severe
hypotension after the initial bolus dose of nesirit-
C. Labetalol 0.5 mg/minute.
ide, though his blood pressure was in the normal
D. Enalaprilat 0.625 mg intravenously every 6 range before therapy initiation. The hypotension
hours. led to reduced renal perfusion, resulting in oliguric
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A. De�nitions
1. Acute coronary syndrome (ACS) is a spectrum of conditions compatible with acute myocardial isch-
emia or infarction caused by an abrupt reduction in coronary blood ow (Figure 1).
2. This chapter will focus on the most common presentation of ACS (type 1 MI), as de�ned by the Fourth
Universal De�nition of Myocardial Infarction, which is caused by coronary thrombosis.
3 Atherogenic plaque rupture is the underlying pathophysiology for ACS, causing several prothrombotic
substances to be released, which results in platelet activation and aggregation and eventual thrombus
formation leading to partial or total occlusion of the coronary artery.
4. ACS can be divided into ST-segment elevation myocardial infarction (STEMI) and non–ST-segment
elevation acute coronary syndrome (NSTE-ACS).
a. STEMI
i. De�ned by characteristic symptoms of myocardial ischemia in association with persistent
ST-segment elevation on ECG with positive troponins
ii. STEMI is an indication for immediate coronary angiography to determine whether reperfu-
sion can be done (see section C in this section, “Decision for Invasive Management”).
b. NSTE-ACS
i. Suggested by the absence of persistent ST-segment elevation on ECG
ii. NSTE-ACS can be divided into unstable angina (UA) and NSTEMI according to whether car-
diac biomarkers of necrosis are present. UA and NSTEMI are closely related conditions whose
pathogenesis and clinical presentation are similar but vary in risk and severity.
iii. ECG abnormalities and elevated troponins in isolation are insuf�cient to make the diagnosis
and must be interpreted in the appropriate clinical context (Table 1).
iv. Optimal inhibition of thrombosis is paramount in ACS management.
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NSTE-ACS
STEMI
ST Depression
ST Elevation
STEMI
Trop (+)
UA NSTEMI
Trop (-) Trop (+)
Initiate immediate reperfusion
(PCI vs. �brinolysis)
Primary PCI within 90 minutes
Door to needle time of 30 minutes if PCI
Risk strati�cation
not available within 120 minutes
Multi-lead continuous ECG monitoring
Obtain serial troponin
“early invasive
approach”
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4. Patients with STEMI and NSTE-ACS should be treated with antiplatelet and anticoagulant therapy
(Tables 3–9).
a. Platelets are activated by several different mechanisms, only some of which can be inhibited by
medications.
b. Combination therapy with several antiplatelet agents plus a concomitant anticoagulant is the main-
stay of acute ACS management, which targets the underlying pathophysiology of thrombus forma-
tion in ACS.
c. The roles and combinations of antiplatelet therapies continue to be re�ned through clinical trials in
varying subsets of ACS presentation (Table 3).
d. In general, all patients receive aspirin and P2Y12 receptor antagonists, and a minority of patients
may bene�t from the addition of GP IIb/IIIa inhibition in the acute management of ACS.
e. Antiplatelet recommendations
i. Aspirin
(a) An irreversible cyclooxygenase-1 inhibitor blocking the formation of thromboxane A 2–
and thromboxane A 2–mediated platelet activation
(b) Given to all patients (class I)
(c) Established �rst-line therapy in ACS; reduces the incidence of recurrent MI and death
(d) LD is necessary for aspirin-naive patients; avoid enteric coated initially because of delayed
and reduced absorption.
(1) Dosing is 162–325 mg for patients at initial presentation of ACS (Table 4).
(2) Dosing is 81–325 mg for those who are undergoing PCI, depending on chronic aspirin
therapy regimen.
(e) Aspirin is given inde�nitely at a preferred dose of 81 mg after ACS with or without PCI
(class I).
(1) High dose (greater than 160 mg) is associated with more bleeding than lower dose
(less than 160 mg).
(2) High doses (greater than 160 mg) have not been shown to improve outcomes after
ACS more effectively than lower doses (less than 160 mg).
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(f) Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 receptor inhibitor is indicated for
all patients after ACS for at least 12 months (see D, “Long-term Management After ACS”).
The optimal aspirin dose in patients treated with DAPT appears to be 75–100 mg daily.
Table 4. Guideline Recommendations for Aspirin Therapy in ACS with or without PCIa
Guideline Recommendation Class/Grade
Initiate 162–325 mg of ASA before PCI; after PCI, give ASA inde�nitely I
• 2013 ACCF/AHA guideline for STEMI
Initiate 81–325 mg of non–enteric-coated ASA before PCI in patients already taking ASA; I
in patients not taking ASA, give 325 before PCI; after PCI, continue ASA inde�nitely
• 2014 NSTE-ACS guideline
• 2011 ACCF/AHA/SCAI guideline for PCI
81 mg of ASA preferred to higher maintenance doses IIa
• 2014 NSTE-ACS guideline IIa
• 2013 ACCF/AHA guideline for STEMI IIa
• 2011 ACCF/AHA/SCAI guideline for PCI
Class I = should be performed or administered; class IIa = reasonable to be performed or administered; class IIb = may be considered; class III
a
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Table 5. Guideline Recommendations for P2Y12 Inhibitor Therapy in ACS with or without PCI
Guideline Recommendation Class/Gradea
An LD of P2Y12 receptor inhibitor should be given before PCI. Options include: I
a. Clopidogrelb 600 mg followed by 75 mg daily; LOE B
b. PRA 60 mg followed by 10 mg daily; or LOE B
c. TIC 180 mg followed by 90 mg BID LOE B
• 2013 ACCF/AHA guideline for STEMI
• 2014 NSTE-ACS guideline
For patients with NSTE-ACS treated with an early invasive or ischemia-guided strategy: I
a. Clopidogrel 600 mg followed by 75 mg daily LOE B
b. TIC 180 mg followed by 90 mg BID LOE B
• 2014 NSTE-ACS guideline
For patients with NSTE-ACS treated with an early invasive or ischemia-guided strategy: IIa
It is reasonable to use TIC in preference to clopidogrel LOE B
• 2014 NSTE-ACS guideline
For patients with NSTE-ACS treated with PCI who are not at risk of bleeding complications: IIa
• It is reasonable to choose PRA over clopidogrel LOE B
• 2014 NSTE-ACS guideline
PRA should not be administered to patients with a history of TIA or stroke Class III
• 2014 NSTE-ACS guideline
• 2013 ACCF/AHA guideline for STEMI
a
Class I = should be performed or administered; class IIa = reasonable to be performed or administered; class IIb = may be considered; class III
= not to be administered or harmful.
Before PCI after �brinolytic therapy: 300-mg LD if within 24 hr of event; clopidogrel 600-mg LD if > 24 hr after event.
b
BID = twice daily; LOE = level of evidence; TIA = transient ischemic attack.
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(d) Pivotal trials comparing cangrelor with clopidogrel in ACS have not shown the superiority
of cangrelor; however, both the CHAMPION PHOENIX PCI and the PLATFORM trials
were discontinued prematurely.
(e) Cangrelor had better ef�cacy than post-PCI clopidogrel with increases in minor bleeding
(not major) (CHAMPION PHOENIX).
(f) Cangrelor treatment is associated with a risk of dyspnea.
(g) Cangrelor has not been studied in settings with preloaded clopidogrel or compared with
prasugrel or ticagrelor.
(h) Cangrelor has a potential use as a bridge therapy after discontinuation of oral P2Y12 inhib-
itors in high-risk patients undergoing coronary artery bypass grafting (CABG) (JAMA
2012;307:265-74).
(i) The onset of action of both clopidogrel and prasugrel is delayed when coadministered
with cangrelor, suggesting that cangrelor preferentially binds to the P2Y12 and prevents
irreversible inhibition with prasugrel and clopidogrel’s active metabolite. Therefore, clopi-
dogrel and prasugrel should not be initiated until termination of the cangrelor infusion. No
such drug interaction exists with ticagrelor.
(j) Expense and lack of evidence showing superiority to other P2Y12 inhibitors limit cangre-
lor’s use.
(k) Cangrelor has not been included in the ACS guidelines to date because FDA approval
occurred after guideline release.
iv. Intravenous GP IIb/IIIa inhibitors
(a) Intravenous GP IIb/IIIa receptor inhibitors can be added to aspirin with or without an oral
P2Y12 inhibitor for cardiovascular (CV) bene�t in select high-risk patients in the acute
management of ACS.
(b) Block the �nal common pathway of platelet aggregation; achieve 80% inhibition of ex
vivo platelet aggregation
(c) GP IIb/IIIa inhibition may be bene�cial in patients with high-risk features, particularly in
those inadequately pretreated with P2Y12 inhibition.
(d) Double-bolus epti�batide and high-dose bolus tiro�ban are class I options for the invasive
strategy (Table 7).
(e) GP IIb/IIIa inhibitors reduce the incidence of composite ischemic events, primarily
through decreasing documented MIs, but can increase the risk of bleeding.
(f) Most, but not all, data were gathered in the era before routine P2Y12 inhibitor use.
(g) Bene�t from adding GP IIb/IIIa inhibitors to aspirin therapy is greatest among those with
highest-risk features (elevated biomarkers, diabetes, undergoing revascularization) and in
those not receiving adequate pretreatment with clopidogrel or ticagrelor.
(h) It is reasonable (class IIa, 2014 NSTE-ACS guideline) to give GP IIb/IIIa inhibitors to
high-risk patients with NSTE-ACS treated with UFH and adequately pretreated with
clopidogrel or ticagrelor.
(i) Most studies combined GP IIb/IIIa inhibitors with UFH as the anticoagulant.
(j) Upstream administration (given before PCI) has not been shown superior to delayed
administration (given at time of PCI).
(1) Upstream administration is noninferior to delayed timing for reducing ischemic
events.
(2) Signi�cantly higher bleeding rates occur in those receiving upstream GP IIb/IIIa
inhibitors than in those receiving delayed administration.
(3) Bolus-only GP IIb/IIIa inhibitor administration has been adopted in clinical practice
but not in the practice guidelines.
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f. Anticoagulant recommendations
i. An anticoagulant should be administered to all patients with ACS in addition to antiplatelet
therapy to reduce the risk of intracoronary and catheter thrombus formation (Tables 8 and 9),
irrespective of initial treatment strategy.
ii. Use of anticoagulants is typically concentrated in the procedural setting, though use may con-
tinue for a �nite period after the procedure.
iii. Selection and use among agents may depend on ACS presentation, timing or dose of prepro-
cedural antiplatelet medication, clot burden during procedure, and estimated risk of bleeding
during procedure.
iv. Anticoagulants increase the risk of bleeding and will require some type of monitoring for
agent-speci�c risks.
Fondaparinux should not be used as the sole anticoagulant to support PCI. Give additional anticoagulant during revascularization if fondaparinux
d
was initially chosen as the anticoagulant strategy. Fondaparinux is given a class I recommendation in the 2014 NSTE-ACS guidelines (for an
ischemia-guided strategy) and a class III or harmful recommendation in the 2011 PCI and 2013 STEMI guidelines when PCI is indicated.
PPCI = primary percutaneous coronary intervention; SC = subcutaneous(ly).
g. Anticoagulant agents
i. UFH
(a) Exerts its effects as an indirect thrombin inhibitor on �brin-bound clots
(b) Given as an intravenous bolus with or without infusion and adjusted according to acti-
vated partial thromboplastin time (aPTT) or activated clotting time (ACT) to maintain
therapeutic anticoagulation according to speci�c hospital protocol, usually continued for
48 hours or until PCI
(1) Intravenous UFH: Initial bolus of 60 units/kg (maximum 4000 units)
(2) Initial infusion of 12 units/kg/hour (maximum 1000 units/hour)
(c) Risks include bleeding, thrombocytopenia, and HIT with or without thrombosis.
(d) Monitoring includes aPTT or ACT, Hgb/Hct, and Plt.
(e) Unlike other anticoagulants, UFH is not renally cleared and can be used safely in those
with renal impairment.
ii. Enoxaparin: Molecular weight is one-third of UFH with balanced anti-factor Xa (anti-Xa) and
anti-IIa activity.
(a) Given as subcutaneous injection at least 2 inches on either side of the navel at a 90-degree
angle into 1 inch of pinched skin (avoid injection into muscle); alternate dosing sites
(1) Dosing varies depending on the reperfusion strategy and the time from the last dose
to the procedure (Table 9).
(2) 30-mg intravenous bolus given in STEMI (if age younger than 75) and in select
patients with NSTE-ACS
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(3) Speci�c periprocedural dosing for PCI in relation to time of last subcutaneous dose
(see section (b) that follows for patients undergoing an invasive strategy)
(4) Decrease dosing interval to once daily when CrCl is less than 30 mL/minute.
(b) Does not require routine anti-Xa monitoring; requires SCr to calculate CrCl for dosing;
monitor Hgb, Hct, Plt
(c) Risks include bleeding, injection site hematomas, spinal or epidural hematomas, retroper-
itoneal hematoma/bleeding, thrombocytopenia including HIT with or without thrombo-
sis, mechanical prosthetic valve thrombosis (in pregnancy)
iii. Fondaparinux
(a) Selective inhibitor of activated factor X
(b) Longest half-life of anticoagulants (17 hours)
(c) Given as a subcutaneous injection into fatty tissue at a 90-degree angle into a pinched
skinfold; alternate dosing sites between the left and right anterolateral and posterolateral
abdominal wall
(1) Dosing NSTE-ACS: 2.5 mg subcutaneously daily, continued for the duration of hos-
pitalization or until PCI
(2) Not to be used as the sole anticoagulant during PCI (class III)
(3) Contraindicated if CrCl is less than 30 mL/minute
(d) Does not require routine anti-Xa monitoring; requires SCr to calculate CrCl to assess for
contraindication; monitor Hgb, Hct, Plt
(e) Risks include bleeding, thrombocytopenia, and spinal or epidural hematomas.
(f) No increased risk of HIT
iv. Bivalirudin
(a) A direct thrombin inhibitor; directly inhibits thrombin in both circulating and bound clots
and inhibits thrombin-mediated platelet aggregation
(b) Given as an intravenous bolus with �xed-rate infusion and usually continued until the end
of PCI (with or without delay after infusion in some high-risk patients)
(1) Early invasive strategy dosing: 0.1-mg/kg LD followed by 0.25 mg/kg per hour (only
in patients with planned PCI), continued until diagnostic angiography or PCI
(2) PCI dosing: 0.75-mg/kg intravenous bolus, 1.75 mg/kg/hour intravenously continued
throughout the procedure
(3) Adjust the infusion rate to 1 mg/kg/hour when the CrCl is less than 30 mL/minute or
to 0.25 mg/kg/hour in patients receiving hemodialysis.
(4) Can extend duration of infusion for up to 4 hours after procedure for prolonged anti-
platelet protection
(c) Does not require monitoring for adjustment during PCI; monitor SCr (adjustment required
for infusion only in those with impaired CrCl), Hgb, Hct, Plt
(d) Can be given in patients with history of or suspected HIT undergoing PCI
h. Guideline recommendations for speci�c anticoagulants
i. In an ischemia-guided strategy, UFH, enoxaparin, and fondaparinux are class I recommended
options.
ii. In an invasive strategy, UFH, enoxaparin, and bivalirudin are class I recommended options.
(a) Fondaparinux should not be used as the sole anticoagulant to support PCI (class III). An
additional 85 units/kg of intravenous UFH is required immediately before PCI revascu-
larization to reduce the risk of catheter thrombosis if fondaparinux was initially chosen as
the anticoagulant strategy if no GP IIb/IIIa inhibitor is used and 60 units/kg intravenously
if a GP IIb/IIIa inhibitor is used; re-bolus as needed according to target ACT.
(b) Use of enoxaparin during PCI may be reasonable in patients treated with upstream subcu-
taneous enoxaparin with an ischemia-guided strategy.
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GP IIb/IIIa inhibitors.
ACT = activated clotting time; HIT = heparin-induced thrombocytopenia; IVB = intravenous bolus; LMWH = low-molecular-weight heparin.
5. Fibrinolytic therapy is indicated for patients with a STEMI in whom PCI cannot be done (Table 10).
a. In the absence of contraindications (Table 11), �brinolytic therapy should be given to patients
with a STEMI (class I when onset of ischemic symptoms is within the previous 12 hours) when it
is expected that primary PCI cannot be done within 120 minutes of �rst medical contact, with an
ideal door-to-needle time of less than 30 minutes.
b. When a �brinolytic agent is given as a reperfusion strategy, UFH, enoxaparin, and fondaparinux
are recommended.
c. Patients undergoing reperfusion with �brinolytics should receive anticoagulant therapy after
�brinolysis for at least 48 hours with intravenous UFH or intravenous/subcutaneous enoxaparin
during hospitalization, up to 8 days (preferred, selected patients), or intravenous/subcutaneous
fondaparinux during hospitalization, up to 8 days.
i. UFH administration of a 60-unit/kg bolus (maximum 4000 units) and 12 units/kg/hour
(maximum 1000 units/hour), to obtain an aPTT of 1.5–2.0 times control (about 50–70 seconds)
for at least 48 hours
ii. Enoxaparin 30 mg intravenously (if 75 or older, omit bolus), followed in 15 minutes by a
1-mg/kg subcutaneous injection (if 75 or older, 0.75 mg/kg) every 12 hours for the duration
of index hospitalization, for up to 8 days, or until revascularization. Maximum 100 mg for
the �rst two doses. If 75 or older, maximum 75 mg for the �rst two doses. If CrCl is less than
30 mL/minute, extend dosing interval to daily administration.
iii. Fondaparinux administered with an initial 2.5-mg intravenous dose, followed in 24 hours
by 2.5-mg/day subcutaneous injections (contraindicated if CrCl is less than 30 mL/min-
ute) for the duration of the index hospitalization, for up to 8 days, or until revascularization
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ii. In general, shorter durations of DAPT are appropriate for those with a lower ischemic risk and
a high bleeding risk, whereas longer-duration DAPT may be reasonable for patients with a
higher ischemic risk and a lower bleeding risk.
iii. Trials comparing shorter DAPT durations have evaluated newer-generation stents in all
patients undergoing PCI (including elective cases).
iv. Compared with �rst-generation stents, newer-generation stents have an improved safety pro-
�le and a lower risk of stent thrombosis.
v. Proton pump inhibitors can reduce the risk of gastrointestinal (GI) bleeding from DAPT.
d. Long-term DAPT
i. In general, longer-duration DAPT may be reasonable for patients at a higher ischemic risk with
a lower bleeding risk.
ii. Trials evaluating the need for an extended DAPT duration (greater than 12 months) in patients
with and without ACS undergoing PCI show a reduction in stent thrombosis and ischemia end
points with increased bleeding for patients continued on DAPT beyond 12 months.
iii. The risk of stent thrombosis is greater on DAPT cessation; however, continued DAPT beyond
1 year is not associated with reduced CV or total mortality.
iv. A longer duration of P2Y12 inhibitor therapy is an individualized approach according to the
patient’s risk of ischemia and bleeding.
(a) DAPT may be reasonable beyond 12 months if the patient is at high risk and has no signif-
icant history of bleeding while receiving DAPT (class IIb).
(b) A DAPT score derived from the DAPT study may help in deciding whether to prolong or
extend DAPT in patients treated with coronary stent implantation (Table 12).
(1) Derived from the DAPT study, which included 11,648 patients with mainly clopido-
grel as the P2Y12 inhibitor
(2) For those with a high DAPT score (2 or greater), prolonged DAPT reduces net
(ischemic plus bleeding) events.
(3) For those with a low DAPT score (less than 2), the bene�t-risk ratio for prolonged
DAPT is not favorable (increased bleeding without a reduction in ischemic events).
(4) Duration of DAPT for more or less than 12 months should jointly be made by the
clinician and the patient, balancing the risks of stent thrombosis and ischemic com-
plications with the risks of bleeding.
v. Ticagrelor has been shown to reduce CV end points of death, MI, and revascularization to a
greater extent than placebo at a reduced dose of 60 mg twice daily (after at least 12 months of
90 mg twice daily) with less bleeding than extended use of 90 mg twice daily (N Engl J Med
2015;372:1791-800).
2. β-Blockers
a. Indicated for all patients unless contraindicated
b. If not initiated orally within the �rst 24 hours, reevaluate for possible initiation before discharge.
c. Continue for at least 3 years (when EF is greater than 40%).
d. If moderate or severe LV failure, initiate carvedilol, bisoprolol, or metoprolol succinate with grad-
ual titration. Continue inde�nitely in patients with an EF less than 40%.
3. Angiotensin-converting enzyme (ACE) inhibitors
a. ACE inhibitors should be initiated and continued inde�nitely for all patients with an LVEF of 40%
or less and in those with hypertension, diabetes mellitus, or stable chronic kidney disease, unless
contraindicated.
b. ACE inhibitors may be acceptable in all other patients with cardiac or other vascular disease.
c. Angiotensin receptor blockers (ARBs) are indicated if the patient has contraindications to or is
intolerant of ACE inhibitors.
d. Contraindications include hypotension, pregnancy, and bilateral renal artery stenosis.
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7. Vaccination
a. Pneumococcal vaccination is recommended for patients 65 and older and in high-risk patients
(including smokers with asthma) with CV disease.
b. An annual in uenza vaccination is recommended for patients with CV disease.
8. Patient education
a. All patients should be counseled on the duration of DAPT and the avoidance of premature
discontinuation.
b. Patients should be educated about appropriate cholesterol management, blood pressure control,
smoking cessation, and lifestyle management.
c. Risk factor modi�cation should be addressed in all patients after ACS.
9. Cardiac rehabilitation: All eligible patients should be referred to a comprehensive CV rehabilitation
program.
E. Special Populations
1. Antiplatelet recommendations in patients going on to CABG
a. Aspirin should be continued preoperatively to patients undergoing CABG (81–325 mg).
b. In patients referred for elective CABG, clopidogrel and ticagrelor should be discontinued for at
least 5 days before surgery and prasugrel for at least 7 days before surgery.
c. In patients referred for urgent CABG, clopidogrel and ticagrelor should be discontinued for at least
24 hours to reduce major bleeding.
d. In patients referred for CABG, short-acting GP IIb/IIIa inhibitors (epti�batide or tiro�ban) should
be discontinued for at least 2 hours before surgery to limit blood loss and transfusion.
2. Combined oral anticoagulant therapy and antiplatelet therapy in patients with atrial �brillation (AF)
undergoing PCI
a. Triple therapy with an oral anticoagulant, low-dose aspirin, and a P2Y12 inhibitor should be mini-
mized because it substantially increases the risk of bleeding.
b. New AF guidelines and consensus recommendations based on clinical trial data represent a para-
digm shift from older management with triple therapy:
i. Many trials have shown that double antithrombotic therapy (anticoagulant plus P2Y12 inhib-
itor without aspirin) reduces bleeding events compared with triple therapy without signal for
increasing ischemic events.
(a) Double therapy with a P2Y12 inhibitor plus dose-adjusted vitamin K antagonist (WOEST
trial)
(b) Double therapy with a P2Y12 inhibitor plus rivaroxaban 15 mg daily (PIONEER AF)
(c) Double therapy with a P2Y12 inhibitor plus dabigatran 150 mg twice daily (RE-DUAL)
(d) Double therapy with a P2Y12 inhibitor plus apixaban 5 mg twice daily (AUGUSTUS)
ii. De-escalation time from triple to dual therapy varies depending on ischemic and bleeding risks.
(a) Aspirin therapy can be discontinued at time of discharge or can be continued for 1–3
months, depending on risks.
(b) Triple therapy may be extended beyond hospital discharge for a limited time (i.e., 1–3
months) in select patients at the highest risk of ischemic events and lowest risk of bleeding.
iii. In AF, direct-acting oral anticoagulants are preferred to vitamin K antagonists because of their
reduced bleeding risk.
(a) Warfarin remains the drug of choice in patients with mechanical heart valves and in those
with moderate to severe mitral stenosis.
(b) If warfarin is used for triple therapy, it is reasonable to maintain the international normal-
ized ratio (INR) at the lower end of the therapeutic range (i.e., 2–2.5).
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iv. Clopidogrel is the preferred P2Y12 inhibitor, though ticagrelor may be reasonable in patients at
high ischemic/thrombotic and low bleeding risks (i.e., avoid prasugrel).
(a) Discontinue antiplatelet therapy at 1 year in most patients.
(b) However, the same considerations apply for shortening the duration (i.e., 6 months in
those with high bleeding risk) and extending the duration (i.e., more than 12 months in
those at high thrombotic risk with low bleeding risk) as for those without AF.
c. Proton pump inhibitors should be considered for those with a history of GI bleeding (and is reason-
able in those without a known history of GI bleeding) who need triple antithrombotic therapy.
3. Older patients (i.e., 75 or older)
a. Doses should be individualized by weight or CrCl to reduce adverse events caused by age-related
changes in pharmacokinetics and dynamics, volume of distribution, comorbidities, drug interac-
tions, and increased drug sensitivity.
b. Bivalirudin, rather than GP IIb/IIIa inhibitors plus UFH, is reasonable in older patients, given its
similar ef�cacy but less risk of bleeding (class IIa).
c. If enoxaparin is used as an anticoagulant in older patients (older than 75), the bolus should be
omitted, and the dosing strategy should be 0.75 mg/kg subcutaneously every 12 hours; should not
exceed 75 mg for the �rst two doses
d. CABG may be preferred to PCI in older patients, particularly those with diabetes mellitus or
complex three-vessel disease (e.g., SYNTAX score greater than 22), with or without involvement
of the proximal left anterior descending artery.
4. Chronic kidney disease
a. CrCl should be estimated in patients with ACS, and doses of renally cleared medications should
be adjusted accordingly.
b. Patients with chronic kidney disease undergoing coronary and LV angiography should receive
adequate hydration and reduced contrast volume.
5. Women
a. Women of all ages have higher rates of in-hospital and long-term complications from ACS than
men.
b. Women derive the same bene�t from aspirin, P2Y12 inhibitors, anticoagulants, β-blockers, ACE
inhibitors, and statins as men, but women may be at higher risk of adverse events.
i. Women have a higher rate of bleeding complications, renal failure, and vascular complications.
ii. A risk score has been developed to reduce bleeding risk.
c. Women with NSTE-ACS and high-risk features (e.g., troponin positive) should undergo an early
invasive strategy.
d. Women with NSTE-ACS and low-risk features should not undergo early invasive treatment because
of the lack of bene�t and the potential for harm (class III).
e. Hormone therapy with estrogen plus progestin, or estrogen alone, should not be initiated for sec-
ondary prevention and should not be continued in previous users unless the bene�ts outweigh the
estimated risks.
i. Hormone therapy increases the risk of thrombotic events, especially in the �rst year of therapy,
and does not provide CV protection.
ii. Women who are more than 1 year past the initiation of hormone therapy who want to continue
such therapy for another compelling indication should weigh the risk-bene�t, recognizing the
greater risk of CV events and breast cancer (combination therapy) or stroke (estrogen).
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Patient Cases
1. A 66-year-old woman (weight 70 kg) with a history of MI, hypertension, hyperlipidemia, and diabetes mel-
litus presents with sudden-onset diaphoresis, nausea, vomiting, and dyspnea, followed by a bandlike upper
chest pain (8/10) radiating to her left arm. She had felt well until 1 month ago, when she noticed her typical
angina was occurring with less exertion. Her ECG reveals ST-segment depression in leads II, III, and aVF and
hyperdynamic T waves and positive cardiac enzymes. Blood pressure is 150/90 mm Hg, and all laboratory
results are normal; SCr is 1.2 mg/dL. Home medications are aspirin 81 mg/day, simvastatin 40 mg every night,
metoprolol 50 mg twice daily, and metformin 1 g twice daily. Which regimen is best for this patient?
A. Aspirin 325 mg, ticagrelor 180 mg one dose, and UFH 60-unit/kg bolus; then 12 units/kg/hour titrated
to 50–70 seconds with an early invasive approach.
B. Aspirin 325 mg and enoxaparin 70 mg subcutaneously twice daily with an early invasive approach.
C. An ischemia-guided strategy with tiro�ban 25 mcg/kg; then 0.15 mg/kg/minute plus enoxaparin 80 mg
subcutaneously twice daily, aspirin 325 mg/day, and clopidogrel 300 mg one dose; then 75 mg once daily.
D. An ischemia-guided strategy with aspirin 325 mg and ticagrelor 180 mg one dose; plus UFH 70-unit/kg
bolus; then 15 units/kg/hour.
2. A 45-year-old patient underwent an elective percutaneous transluminal coronary angioplasty and drug-eluting
stent placement in her right coronary artery. Which best represents the minimum time DAPT should be
continued?
A. 1 month.
B. 3 months.
C. 6 months.
D. 12 months.
3. A 52-year-old man (weight 100 kg) with a history of hypertension and hypertriglyceridemia presents at a major
university teaching hospital with a cardiac catheterization laboratory. He has had 3 hours of crushing 10/10
substernal chest pain radiating to both arms that began while he was eating his lunch (seated), which is accom-
panied by nausea, diaphoresis, and shortness of breath. He has never before had chest pain of this character or
intensity. He usually can walk several miles without dif�culty and smokes 1.5 packs/day of cigarettes. Home
medications are lisinopril 2.5 mg/day and aspirin 81 mg daily. Current vital signs include heart rate 68 beats/
minute and blood pressure 178/94 mm Hg. His ECG reveals a 3-mm ST-segment elevation in leads V2 –V4, I,
and aVL. Serum chemistry values are within normal limits. The �rst set of cardiac markers shows positive
troponins, 0.8 mcg/L (normal de�ned as less than 0.1 mcg/L). Which regimen is best for this patient’s STEMI?
A. Reperfusion with primary PCI and stenting of occluded artery, together with tirofaban 25 mcg/kg; then
0.15 mg/kg/minute, clopidogrel 300 mg one dose, and aspirin 325 mg one dose.
B. Reperfusion with a reteplase 10-unit bolus twice, 30 minutes apart, plus a UFH 60-unit/kg bolus and a
12-unit/kg/hour infusion, clopidogrel, and aspirin.
C. Reperfusion with tenecteplase 25-mg intravenous push one dose, enoxaparin 30-mg intravenous bolus
plus 100 mg subcutaneously twice daily, aspirin 325 mg one dose, ticagrelor 180 mg one dose, and bivali-
rudin 0.75 mg/kg followed by 1.75 mg/kg/hour.
D. Reperfusion with primary PCI with stenting, prasugrel 60 mg one dose, aspirin 325 mg one dose, and
bivalirudin 0.75 mg/kg followed by 1.75 mg/kg/hour.
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A. Precipitating Factors
1. Medication related (nonadherence to medications, recent addition of negative inotropic drugs, initiation
of medications that enhance salt retention, excessive alcohol or illicit drug use)
2. Disease related (nonadherence to sodium or uid restriction, acute myocardial ischemia, uncorrected
high blood pressure, pulmonary embolus, AF or other arrhythmias, concurrent infections, other acute
CV disorders)
B. Diagnosis
1. Must include a detailed history and physical examination
2. B-type natriuretic peptide (BNP) or NT-proBNP is useful to support the diagnosis and establish the
prognosis for acute decompensated heart failure (ADHF).
a. Useful for excluding ADHF in patients with dyspnea of unknown etiology (ADHF can be
excluded when results are less than 100 pg/mL and less than 300 pg/mL, for BNP and NT-proBNP,
respectively)
b. NT-proBNP cutpoints of 450, 900, and 1800 pg/mL (for ages younger than 50, 50–75, and older
than 75, respectively)
c. May be elevated with older age, female sex, renal dysfunction, and other cardiopulmonary disor-
ders like pulmonary embolism
d. NT-proBNP is preferred in patients receiving angiotensin receptor neprilysin inhibitor (ARNI)
therapy because BNP concentrations may be affected by ARNI therapy
3. Hemodynamic monitoring (Table 13)
a. Routine use of hemodynamic monitoring with invasive intravenous lines (e.g., Swan-Ganz pul-
monary artery catheters) is not recommended; however, signs and symptoms of congestion and
perfusion (Table 14) or noninvasive means to determine hemodynamic values are commonly used
to determine status of decompensation.
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b. Hemodynamic monitoring with pulmonary artery catheters helps in evaluating patients refractory
to initial therapy, patients with unknown or unclear volume status, and patients with clinically
signi�cant hypotension or worsening renal function.
c. Use of hemodynamic monitoring for mechanical circulatory support is beyond the scope of this
chapter.
C. Clinical Presentation
1. Patients with ADHF can be categorized into four subsets on the basis of uid status and cardiac func-
tion (Figure 2).
2. “Wet or dry” is commonly used to describe volume status.
3. “Warm or cold” is used to describe cardiac function or ability to perfuse tissues.
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Compensated Pulmonary
congestion
3 Warm and Dry
Warm and Wet
2 Category IV:
Category III:
Hypoperfusion Pulmonary congestion
and hypoperfusion
1 Cold and Dry
Cold and Wet
10 15 20 25
PCWP (mm Hg)
Figure 2. Forrester hemodynamic subsets based on signs and symptoms or hemodynamic parameters in acute
decompensated heart failure.
PCWP = pulmonary capillary wedge pressure.
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3. β-Blockers
a. Do not discontinue in patients whose condition is stable on dose before admission (i.e., recent
initiation or titration was not responsible for decompensation).
b. Consider discontinuation if ADHF caused by recent drug initiation or increase, evidence of new or
worsening low output or cardiogenic shock, symptomatic hypotension or bradycardia
c. Initiation is recommended after optimization of volume status and successful discontinuation of
intravenous diuretics, vasodilators, and inotropic agents.
d. Should be initiated at a low dose only in stable, euvolemic patients
e. Caution should be used when initiating in patients who have received inotropes during their hospi-
tal course.
4. Digoxin
a. Continue at dose to achieve serum digoxin concentration of 0.5–0.8 ng/mL.
b. Consider discontinuation in symptomatic bradycardia, life-threatening arrhythmias, elevated con-
centrations, or signs/symptoms of digoxin toxicity.
c. Avoid discontinuation unless there is a compelling reason to do so, because digoxin withdrawal
has been associated with worsening HF symptoms.
d. Caution if renal function begins to deteriorate or often uctuates
F. Diuretics (Box 2; Table 16): Used primarily to treat patients with pulmonary and peripheral congestion or
wet (subset II or IV) HF
1. Considered �rst-line therapy for management of ADHF associated with uid overload
2. No difference between bolus and continuous administration of intravenous diuretics
3. Administering high-dose intravenous diuretic (2.5 times the previous oral dose) is associated with
greater uid removal.
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I. Vasopressin Antagonists
1. Use is limited because of their signi�cant cost and their limited effects on meaningful long-term ADHF
outcomes.
a. Should be viewed as “add on” therapy to aggressive diuresis and not as initial or adjunctive therapy
for uid removal
b. Strict free water restriction is guideline recommended (expert opinion).
2. Tolvaptan is FDA approved for clinically signi�cant hyponatremia associated with HF.
a. In those at risk of or having active cognitive symptoms despite water restriction (i.e., serum sodium
less than 125 mEq/L)
b. In those with less marked hyponatremia (i.e., less than 135 mEq/L) having neurologic symptoms
and who have no correction with uid restriction, including patients with HF and syndrome of
inappropriate secretion of antidiuretic hormone)
3. Clinical use:
a. Oral dosing: 15 mg daily; then titrated to 30–60 mg as needed
b. Pharmacology: Binds to and inhibits the V2 receptor, located in the renal tubule where water reab-
sorption is regulated
i. Exerts its clinical effect within 2–4 hours and lasts about 24 hours
ii. Increases serum sodium by about 2–4 mEq/L within 12–24 hours
iii. Increases net urinary output and reduces total body weight (1–2 kg)
c. Initiate only in the hospital setting to allow monitoring of volume status and serum sodium
concentrations.
d. An overly rapid rise in serum sodium (maximum correction in any 24-hour period of chronic hypo-
natremia should be less than 9 mEq/L) can result in hypotension, hypovolemia, and neurologic
sequelae.
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e. Contraindicated with CYP3A4 inhibitors (tolvaptan is a substrate of 3A4) and in those with an
eCrCl less than 10 mL/minute
f. The FDA warns against use beyond 30 days (i.e., hepatotoxicity).
g. Trials show effectiveness in correcting sodium with maintained therapy but no improvement in
global clinical status or mortality and no reductions in rehospitalization.
i. Role in long-term management of HF remains unclear.
ii. Hyponatremia redevelops after therapy cessation.
Patient Case
Questions 5–7 pertain to the following case.
A 72-year-old man is admitted to the hospital for HF decompensation. The patient has progressively increased
dyspnea when walking (now 10 ft [3 m], previously 30 ft [6 m]) and orthopnea (now four pillows, previously two
pillows), increased bilateral lower-extremity swelling (3+), 13 kg of weight gain in the past 3 weeks, and dietary
nonadherence. He has a history of idiopathic dilated cardiomyopathy (LVEF 25%, NYHA class III), paroxys-
mal AF, and hyperlipidemia. Pertinent laboratory values are as follows: BNP 2300 pg/mL (0–50 pg/mL), K+ 4.9
mEq/L, BUN 32 mg/dL, SCr 2.0 mg/dL (baseline 1.9 mg/dL), aspartate aminotransferase (AST) 40 IU/L, alanine
aminotransferase 42 IU/L, INR 1.3, aPTT 42 seconds, blood pressure 108/62 mm Hg, heart rate 82 beats/minute,
and SaO2 95%. Home medications include carvedilol 12.5 mg twice daily, lisinopril 40 mg/day, furosemide 80 mg
twice daily, spironolactone 25 mg/day, and digoxin 0.125 mg/day.
6. After being initiated on intravenous loop diuretics with only minimal urinary output, the patient is transferred
to the coronary care unit for further management of diuretic-refractory decompensated HF. His SaO2 is now
87% on a 4-L nasal cannula, and an arterial blood gas is being obtained. His blood pressure is 110/75 mm
Hg and heart rate is 75 beats/minute. The patient’s SCr and K+ concentrations have begun to rise and are now
2.7 mg/dL and 5.4 mmol/L, respectively. In addition to a one-time dose of intravenous chlorothiazide, which
regimen is most appropriate for this patient?
A. Nitroglycerin 20 mcg/minute.
B. Sodium nitroprusside 0.3 mg/kg/minute.
C. Dobutamine 5 mcg/kg/minute.
D. Milrinone 0.5 mcg/kg/minute.
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C. Symptomatic Bradycardia
1. If unstable, atropine 0.5 mg every 3–5 minutes (maximum dose 3 mg). (Note: Unstable = hypotension,
acutely altered mental status, signs of shock, ischemic chest discomfort, acute HF)
2. If atropine fails, transcutaneous pacing, dopamine 2–10 mcg/kg/minute, or epinephrine 2–10 mcg/minute
D. Symptomatic Tachycardia
1. If unstable, synchronized cardioversion
2. If stable, determine whether the QRS complex is narrow or wide.
a. Narrow-complex tachycardia (QRS less than 120 milliseconds); usually atrial arrhythmias
i. Regular ventricular rhythm: Supraventricular tachycardia (SVT) or sinus tachycardia likely
(a) Vagal maneuvers or adenosine 6-mg intravenous push, followed by a 20-mL saline ush,
then a 12-mg intravenous push (may repeat once)
(1) Rapid push followed by elevation of arm to increase circulation
(2) Larger doses may be needed in patients taking theophylline or caffeine.
(3) Initial dose should be reduced to 3 mg in patients taking dipyridamole or carbamaz-
epine and in patients after heart transplantation, and when the drug is being given by
central access.
(4) Use adenosine cautiously in severe CAD.
(5) Adenosine should not be given to patients with asthma.
(6) Do not give adenosine for unstable or for irregular or polymorphic wide-complex
tachycardias because it can cause degeneration to ventricular �brillation (VF).
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(b) If vagal maneuvers or adenosine fails to convert paroxysmal SVT, calcium channel block-
ers (CCBs) or β-blockers can be used. If Wolff-Parkinson-White syndrome, avoid ver-
apamil, diltiazem, and digoxin
ii. Irregular (narrow complex) ventricular rhythm: AF (or possibly atrial utter)
(a) General management should focus on control of the rapid ventricular rate.
(1) Usually non-dihydropyridine CCBs (diltiazem, verapamil) or β-blockers; digoxin
sometimes useful
(2) Rate is acceptable if it is less than 110 beats/minute at rest in asymptomatic persistent
AF.
(b) If the patient is hemodynamically unstable, synchronized cardioversion is recommended.
(c) Patients with AF for more than 48 hours are at high risk of cardioembolic events and
should not be immediately cardioverted, if stable.
(d) Transesophageal echocardiography before cardioversion is an alternative strategy to
ensure the absence of left atrial clot.
(e) Risk of thromboembolic event surrounding cardioversion (both pharmacologic and elec-
trical) is greatest within the �rst 10 days.
(f) Cardioversion
(1) If AF for up to 7 days, either elective direct current conversion or chemical cardioversion
(A) Flecainide, dofetilide, propafenone, ibutilide, or amiodarone (proven ef�cacy)
(B) Digoxin and sotalol are not recommended and may be harmful.
(C) Disopyramide, quinidine, and procainamide are less effective or incompletely
studied.
(2) If AF lasts greater than 7 days, administer either elective direct current conversion or
chemical cardioversion with dofetilide, amiodarone, or ibutilide (proven ef�cacy).
b. Wide-complex tachycardia (QRS greater than 120 milliseconds): Usually ventricular arrhythmias
i. VT or unknown mechanism
(a) Consider adenosine only if regular and monomorphic.
(b) Intravenous procainamide, amiodarone (or sotalol); lidocaine second line
(c) Avoid procainamide and sotalol if prolonged QTc.
ii. De�nite SVT with aberrancy: Probably transiently slowed or converted by adenosine
iii. Polymorphic (irregular) VT
(a) Induced primarily when the QTc interval is greater than 500 milliseconds (torsades de
pointes)
(b) If unstable, polymorphic (irregular) VT requires immediate de�brillation with the same
strategy as VF.
(c) If stable, intravenous magnesium 1- to 2-g intravenous bolus (maximum 16 g every 24
hours) may be given; however, this is supported only by observational studies in the set-
ting of wide QRS.
(d) Withdrawal of QT-prolonging medications, correction of low magnesium or K+
concentrations
(1) Class I and III antiarrhythmic drugs (AADs)
(2) Assess for drug interactions by CYP3A4 (e.g., azole antifungals, erythromycin).
(3) Assess for other QTc-prolonging drugs (e.g., haloperidol, ziprasidone, droperidol,
promethazine, macrolide and quinolone antibiotics, tricyclic antidepressants, or drugs
contraindicated with dofetilide such as sulfamethoxazole/trimethoprim or thiazides).
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AAD = antiarrhythmic drug; Ca2+ = calcium; HR = heart rate; Na+ = sodium. ↑ = increases; ↓ = decreases; Ø = no effect.
Table 20. AAD Properties and Dosing (class I and III agents only)
AEs, Contraindications,
Drug PK, and Drug Interactions Dosing by Indication
Class Ia: Na channel blockers
+
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Table 20. AAD Properties and Dosing (class I and III agents only) (Cont’d)
AEs, Contraindications,
Drug PK, and Drug Interactions Dosing by Indication
Class Ia: Na+ channel blockers
Disopyramide AEs: Anticholinergic effects, TdP, ADHF AF conversion: IR 200 mg (if < 50 kg) or 300 mg
(Norpace, (potent negative inotropic effect) (if > 50 kg) PO every 6 hr
Norpace CR) CIs: Cardiogenic shock, congenital long QT AF maintenance: 400–800 mg/day in divided doses
syndrome, second- or third-degree AVB, (recommended adult dose 600 mg/day given as IR
glaucoma 150 mg PO every 6 hr or as CR 300 mg PO every 12 hr)
PK: Half-life 4–8 hr If < 50 kg, moderate renal dysfunction (CrCl > 40 mL/
Substrate of CYP2D6 min) or hepatic dysfunction, max 400 mg/day
DI: May enhance the effect of β-blockers If severe renal dysfunction (IR only; avoid CR)
CrCl 30–40 mL/min, 100 mg every 8 hr
CrCl 15–30 mL/min, 100 mg every 12 hr
CrCl < 15 mL/min, 100 mg every 24 hr
VTs: Use has fallen out of favor because of the
availability of newer agents with less toxicity
Class Ib: Na+ channel blockers
Lidocaine AEs: CNS (perioral numbness, seizures, Pulseless VT/VF conversion or VT with a pulse:
(Xylocaine) confusion, blurry vision, tinnitus) 1–1.5 mg/kg IVP; repeat 0.5–0.75 mg/kg every 3–5 min
CI: Third-degree AVB (max 3 mg/kg)
PK: Reduce dose in those with HF, liver disease, (If LVEF < 40%, 0.5–0.75 mg/kg IVP)
low body weight, and renal dysfunction and in (Amiodarone DOC in pulseless VT/VF; lidocaine
older adults acceptable if amiodarone not available)
DI: Amiodarone (increased lidocaine VT maintenance: 1–4 mg/min
concentrations) Reduce maintenance infusion in liver disease
Mexiletine AEs: CNS (tremor, dizziness, ataxia, nystagmus) VT maintenance: 200–300 mg PO every 8 hr;
(Mexitil) CI: Third-degree AVB max 1200 mg/day
PK: Half-life 12–20 hr Reduce dose by 25%–30% in hepatic impairment
Substrate CYP2D6, CYP1A2
Inhibitor CYP1A2
Class Ic: Na+ channel blockers (Note: Avoid in patients with HF or after MI; increased risk of sudden death)
Propafenonea AEs: Metallic taste, dizziness, ADHF, AF conversion:
(Rythmol, bronchospasm, bradycardia, heart block 600 mg PO × 1 (ef�cacy 45% at 3 hr)
Rythmol SR) (negative inotropy and β-blocking properties) 450 mg PO × 1 (weight < 70 kg)
CIs: HF (NYHA III–IV), liver disease, valvular AF maintenance:
disease (TdP), CAD, MI
HCl: 150–300 mg PO every 8–12 hr
PK: Half-life 10–25 hr
HCl (SR): 225–425 mg PO every 12 hr
Substrate CYP2D6, CYP1A2, CYP3A4
Reduce dose 70%–80% in hepatic impairment
Inhibitor CYP1A2, CYP2D6
DIs: Digoxin ↑ by 70%; warfarin ↑ by 50% as
well as drugs that inhibit CYP 2D6, 1A2, 3A4
(increased propafenone)
Flecainidea AEs: Dizziness, tremor, ADHF (negative AF conversion: 300 mg PO × 1 (ef�cacy 50% at 3 hr)
(Tambocor) inotropy), vagolytic, anticholinergic, AF maintenance: 50–150 mg PO BID
hypotension Reduce dose by 50% when CrCl < 35 mL/min
CIs: HF, CAD, valvular disease, LVH (TdP)
PK: Half-life 10–20 hr
Substrate CYP2D6, CYP1A2
Inhibitor CYP2D6
DI: Digoxin ↑ by 25%
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Table 20. AAD Properties and Dosing (class I and III agents only) (Cont’d)
AEs, Contraindications,
Drug PK, and Drug Interactions Dosing by Indication
Class III: K channel blockers
+
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Table 20. AAD Properties and Dosing (class I and III agents only) (Cont’d)
AEs, Contraindications,
Drug PK, and Drug Interactions Dosing by Indication
Class III: K channel blockers
+
Ibutilide AEs: TdP 8%, AV heart block (β-blocking AF conversion: 1 mg IV (≥ 60 kg) or 0.01 mg/kg IV
(Corvert) properties) (< 60 kg); repeat in 10 min if ineffective (ef�cacy 47% at
CIs: Baseline QTc > 440 ms, LVEF < 30%, 90 min)
concomitant AADs BW: Potentially fatal arrhythmias (e.g., polymorphic VT)
PK: Half-life 2–12 hr (avg 6) can occur with ibutilide, usually in association with TdP;
DIs: CYP3A4 inhibitors or QT-prolonging drugs patients with chronic AF may not be the best candidates
ECG monitoring during and 4 hr after DCC for ibutilide conversion
Dronedarone AEs: Worsening HF, QT prolongation, AF maintenance: 400 mg orally BID
(Multaq) hypokalemia or hypomagnesemia with d/c if QTc ≥ 500 ms
K+-sparing diuretics, hepatic failure BW: Risk of death is doubled when used in patients
CIs: QTc ≥ 500 ms or PR ≥ 280 ms, NYHA class with symptomatic HF with recent decompensation
IV HF or NYHA class II–III HF with recent necessitating hospitalization or NYHA class IV
ADHF, severe hepatic impairment, second- or symptoms; use is contraindicated in these patients
third-degree AVB, or HR < 50 beats/min Use in patients with permanent AF doubles the risk
PK: Half-life 13–19 hr of death, stroke, and hospitalization for HF; use is
Substrate 3A4 contraindicated in patients with AF who will not or
Inhibitor intestinal P-gp cannot be converted to normal sinus rhythm
DIs: CYP3A4 inhibitors, QT-prolonging drugs,
simvastatin, tacrolimus/sirolimus, warfarin,
and other CYP3A4 substrates with narrow
therapeutic range, digoxin and other P-gp
substrates (dabigatran, rivaroxaban)
a
Indicates that pill-in-pocket approach can be used for selected patients.
AV = atrioventricular; AVB = atrioventricular block; CAD = coronary artery disease; CI = contraindication; CNS = central nervous system;
CR = controlled release; d/c = discontinue; DCC = direct current cardioversion; D5W = dextrose 5%; DI = drug interaction; DOC = drug of choice;
HCl = hydrochloride; HCTZ = hydrochlorothiazide; HR = heart rate; IR = immediate release; LVH = left ventricular hypertrophy; ms = millisecond(s);
NAPA = N-acetylprocainamide; NS = normal saline; NTE = not to exceed; NYHA = New York Heart Association; PK = pharmacokinetics;
QTc = corrected QT interval; SR = sustained release; TdP = torsades de pointes; VF = ventricular �brillation; VT = ventricular tachycardia.
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iii. AAD therapy (amiodarone, ecainide, mexiletine, propafenone, sotalol) may be considered to
improve symptoms associated with arrhythmias in patients receiving adequate doses of a β-blocker
or CCB (class IIb; LOE C).
(a) Flecainide and propafenone are not recommended to suppress premature ventricular con-
tractions in patients with reduced LV function (class III).
(b) Sotalol should be used with caution in patients with chronic kidney disease and should be
avoided in patients with a prolonged QT interval at baseline or excessive prolongation of
QT interval (500 milliseconds) on therapy initiation (class I; LOE B).
(c) Amiodarone appears to have less overall proarrhythmic risk than other AADs in patients
with HF and may be preferred to other membrane-active AADs unless a functioning
de�brillator has been implanted (class IIb; LOE C).
iv. Amiodarone, sotalol, and other β-blockers are useful after de�brillator implantation to reduce
shocks and suppress nonsustained VT in patients who are unsuitable for ICD therapy, in addi-
tion to optimal medical therapy for patients with HF.
2. Sustained VT
a. Immediate de�brillation (ACLS management)
b. Evaluate cardiac structure and function.
c. ICDs indicated for most patients with SHD
G. Implantable Cardioverter-De�brillators
1. For primary prevention of SCD
a. Previous MI, at least 40 days earlier, and EF of 35% or less
b. Nonischemic dilated cardiomyopathy, LVEF of 35% or less receiving optimal chronic medications
for at least 3 months
c. Syncope with SHD and inducible VT/VF during electrophysiologic study
d. High risk of life-threatening VT/VF; congenital long QT syndrome with recurrent symptoms or
torsades de pointes while receiving a β-blocker
e. Must have reasonable survival expectation for more than 1 year
2. For secondary prevention of SCD
a. Previous episode of resuscitated VT/VF, hemodynamically unstable VT with no completely revers-
ible cause, or sustained VT in presence of heart disease
b. Must be receiving optimal chronic medications (β-blockers, ACE inhibitors)
c. Must have reasonable survival expectation for more than 1 year
3. General medication considerations with ICD (Table 21)
a. β-Blockers
i. Considered mainstay therapy
ii. Effective in suppressing ventricular ectopic beats and in reducing SCD in a spectrum of car-
diac disorders in patients with and without HF (nonsustained VT)
b. Amiodarone
i. No better than ICD in reducing SCD as a lone agent; no mortality bene�t
ii. Can be used to treat symptomatic nonsustained VT if β-blockers not effective when ICD not
indicated
iii. Can be used in combination with β-blockers to decrease �ring of ICD (de�brillator storm)
c. Sotalol
i. No mortality advantage
ii. Can suppress VT and be used to decrease frequency of ICD �ring
iii. Greater proarrhythmic potential; avoid in patients with severely depressed LVEF or signi�cant
HF; renal dosing necessary
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I. Drug-Induced Arrhythmias: Review all potential drug etiologies and treat appropriately.
1. Drug-induced QT prolongation
a. Discontinue offending agent if QT prolongation is signi�cant (i.e., greater than 450 milliseconds).
b. Ensure proper renal and hepatic dosing adjustments.
c. Review electrolyte abnormalities and thyroid function tests.
d. Ensure that all electrolytes are maintained at critical concentrations: K+ greater than 4 mmol/L and
less than 5 mmol/L and magnesium greater than 2 mg/dL.
e. Ensure that all ECG parameters are within normal limits (e.g., QT interval less than 500
milliseconds).
2. Drug-induced bradycardia or atrioventricular block
a. β-Blocker, CCB, digoxin
b. Administer antidote, if appropriate (e.g., calcium for CCB toxicity).
3. Review for drug interactions. AADs have drug interactions that may cause signi�cant outcomes.
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Patient Cases
Questions 8 and 9 pertain to the following case.
A 68-year-old man is admitted after an episode of syncope, with a presyncopal syndrome of seeing black spots
and dizziness before passing out. Telemetry monitor showed sustained VT for 45 seconds. His medical history
includes HF NYHA class III, LVEF 30%, two MIs, hypertension for 20 years, LV hypertrophy, DM, and diabetic
nephropathy. His medications include lisinopril 5 mg/day, furosemide 20 mg twice daily, metoprolol 25 mg twice
daily, digoxin 0.125 mg/day, glyburide 5 mg/day, atorvastatin 40 mg, and aspirin 81 mg/day. His blood pressure is
120/75 mm Hg, with heart rate 80 beats/minute, BUN 30 mg/dL, and SCr 2.2 mg/dL.
8. Which is the best therapy to initiate for conversion of his sustained VT?
A. Amiodarone 150 mg intravenously for 10 minutes, then 1 mg/minute for 6 hours, then 0.5 mg/minute.
B. Sotalol 80 mg twice daily titrated to QTc of about 450 milliseconds.
C. Dofetilide 500 mcg twice daily titrated to QTc of about 450 milliseconds.
D. Procainamide 20 mg/minute, with a maximum of 17 mg/kg.
9. The patient presents to the ED 3 months after amiodarone maintenance initiation (he refused ICD placement)
after a syncopal episode, during which he lost consciousness for 30 seconds, according to witnesses. He also
has rapid heart rate episodes during which he feels dizzy and lightheaded. He feels very warm all the time (he
wears shorts, even though it is winter), cannot sleep, and has lost 3 kg in weight. He received a diagnosis of
hyperthyroidism caused by amiodarone therapy. On telemetry, he has runs of nonsustained VT. Which best
predicts the duration of amiodarone-associated hyperthyroidism in this patient?
A. Never.
B. 1 month.
C. 6 months.
D. 18 months.
10. A 64-year-old woman presents to the ED with the chief concern of palpitations. Her medical history includes
hypertension controlled with a diuretic and an inferior-wall MI 6 months ago. She is pale and diaphoretic but
can respond to commands. The patient’s laboratory values are within normal limits. Her vital signs include
blood pressure 95/70 mm Hg and heart rate 145 beats/minute; telemetry shows sustained VT. Although ini-
tially unresponsive to β-blockers, the patient is successfully treated with lidocaine. Subsequent electrophys-
iologic testing reveals inducible VT, and sotalol 80 mg orally twice daily is prescribed. Two hours after the
second dose, the patient’s QTc is 520 milliseconds. Which regimen change would be most appropriate for this
patient?
A. Continue sotalol at 80 mg orally twice daily.
B. Increase sotalol to 120 mg orally twice daily.
C. Discontinue sotalol and initiate dofetilide 125 mcg orally twice daily.
D. Discontinue sotalol and initiate amiodarone 400 mg orally three times daily.
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A. De�nitions
1. Hypertensive emergency
a. Severe elevations in blood pressure (usually greater than 180/120 mm Hg) with evidence of new or
worsening target-organ damage
b. Acute target-organ damage can include hypertensive encephalopathy, intracranial hemorrhage,
acute ischemic stroke, or other acute neurologic de�cit; UA or acute MI; acute LV failure with pul-
monary edema; dissecting aortic aneurysm; retinopathy or papilledema; decreased urinary output
or acute renal failure; eclampsia
c. Actual blood pressure may not be as important as the rate of blood pressure rise.
d. Requires immediate blood pressure lowering (not necessarily to normal ranges) to prevent or limit
further target-organ damage
e. In general, oral therapy is discouraged for hypertensive emergencies.
2. Hypertensive urgency
a. Situations associated with severe blood pressure elevation in otherwise stable patients without
acute or impending change in target-organ damage or dysfunction
b. Short-term risk is not as high; therefore, blood pressure reduction occurs over several days, not
immediately.
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2. Hypertensive urgency
a. Treated by reinstitution or intensi�cation of antihypertensive drug therapy
b. No indication for referral to the ED, immediate reduction in blood pressure in the ED, or
hospitalization
c. No proven bene�t exists from rapid reductions in blood pressure.
d. Choice of agent used in this setting varies, and in many cases, adjusting chronic oral therapy
(increasing doses), reinitiating therapy in the nonadherent, or adding a new agent (i.e., diuretic) to
long-term therapy is appropriate.
e. All patients with hypertensive urgency should be reevaluated within 7 days (preferably after 1–3
days).
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Patient Cases
11. A 68-year-old man with a history of stage 5 chronic kidney disease receiving hemodialysis, hypertension,
CAD post-MI, moderately depressed LVEF, and gastroesophageal re ux disease presents with acute-onset
shortness of breath and chest pain. After his recent dialysis, he was nonadherent to medical therapy for 2
days and noticed he had gained 2 kg in 24 hours. His baseline orthopnea worsened to sleeping sitting up in a
chair for the 2 nights before admission. He admits smoking cocaine within the past 24 hours and developed
acute-onset chest tightness with diaphoresis and nausea, and his pain was 7/10. He went to the ED, where
his blood pressure was 250/120 mm Hg. He had crackles halfway up his lungs on examination, and chest
radiography detected bilateral uffy in�ltrates with prominent vessel cephalization. His ECG revealed sinus
tachycardia, heart rate 122 beats/minute, and ST-segment depressions in leads 2, 3, and aVF. He was admitted
for a hypertensive emergency. Laboratory results are as follows: BUN 48 mg/dL, SCr 11.4 mg/dL, BNP 2350
pg/mL, troponin T 1.5 ng/L (less than 0.1 mcg/L), creatine kinase 227 units/L, and creatine kinase-MB 22
units/L. Which medication is best for this patient’s hypertensive emergency?
A. Intravenous nitroglycerin 5 mcg/minute titrated to a 25% reduction in MAP.
B. Labetalol 2 mcg/minute titrated to a 50% reduction in MAP.
C. Sodium nitroprusside 0.25 mcg/kg/minute titrated to a 25% reduction in MAP.
D. Clonidine 0.1 mg orally every 2 hours as needed for a 50% reduction in MAP.
12. A 56-year-old white woman with a long history of hypertension because of nonadherence and recently diag-
nosed HF (EF 35%) presents to the local ED with blood pressure 210/120 mm Hg and heart rate 105 beats/
minute. She states that she felt a little lightheaded but that she now feels okay. She ran out of her blood pressure
medications (including hydrochlorothiazide, carvedilol, and lisinopril) 3 days ago. Her current laboratory val-
ues are within normal limits. Which medication is best for this patient?
A. Sodium nitroprusside 0.25 mcg/kg/minute titrated to a 25% reduction in MAP.
B. Labetalol 80 mg intravenously; repeat until blood pressure is less than 120/80 mm Hg.
C. Resumption of home medications; refer for follow-up within 2 days.
D. Resumption of home medications; initiate amlodipine 10 mg daily; refer for follow-up in 1 week.
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REFERENCES
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Hypertensive Emergency
1. Marik PE, Varon J. Hypertensive crises: challenges
and management. Chest 2007;131:1949-62.
2. Rhoney D, Peacock WF. Intravenous therapy for
hypertensive emergencies, part 1. Am J Health
Syst Pharm 2009;66:1343-52.
3. Rhoney D, Peacock WF. Intravenous therapy for
hypertensive emergencies, part 2. Am J Health
Syst Pharm 2009;66:1448-57.
4. Watson K, Broscious R, Devabhakthuni S, et al.
Focused update on pharmacologic management of
hypertensive emergencies. Curr Hypertens Rep
2018;20:56.
5. Whelton PK, Carey RM, Aronow WS, et al. 2017
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/
ASPC/NMA/PCNA guideline for the prevention,
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hospital, where he cannot be assessed quickly enough patient receiving β-blockers, the dosing strategy is
(within 90–120 minutes) (Answer D is incorrect). inappropriate as an initial dose (Answer D is incorrect).
Because of the shorter half-life and ease of adminis- Finally, inotropes are generally reserved for patients
tration of tenecteplase, tenecteplase may be preferable when other therapies have failed.
to alteplase. Clearance of UFH with tenecteplase is not
as altered as with enoxaparin, and it would be a more 7. Answer: A
appropriate therapy than enoxaparin in combination Signs of a decreased CO state in HF (e.g., increased
with a thrombolytic (Answer C is correct). SCr, decreased mental status, cool extremities) sug-
gest a cold and wet state, and adjunctive therapy is
5. Answer: C indicated. Positive inotropic agents such as milrinone
This patient, who has ADHF, is receiving a β-blocker. will increase CO to maintain perfusion to vital organs.
Although long-term β-blockers can improve HF symp- Milrinone will also vasodilate the peripheral vessels
toms and reduce mortality, they can also worsen symp- to unload the heart (lower SVR). Although dobuta-
toms in the short term. It is recommended to keep mine would be a potential choice in this patient, it is
the maintenance β-blocker therapy at the same or at a not recommended in patients receiving β-blockers, and
slightly lower dose compared with the outpatient ther- the initial starting dose is too aggressive (Answer B is
apy in patients with ADHF; increasing the β-blocker incorrect). Although this patient has low blood pres-
dose before reaching euvolemia might acutely worsen sure, his elevated SVR suggests that he will tolerate
his clinical picture (Answer A is incorrect). In patients the vasodilatory effects of milrinone as long as it is
admitted with volume overload without substantial signs appropriately renally adjusted for worsening renal dys-
of reduced CO, it is reasonable to try intravenous loop function (Answer A is correct). Nitroprusside would be
diuretics initially (Answer C is correct). As gut edema relatively contraindicated in patients with an SBP less
increases, oral loop diuretics (notably furosemide) than 100 mm Hg and is absolutely contraindicated in
become less effective because of decreased absorp- patients with an SBP less than 90 mm Hg (Answer C is
tion. Sodium nitroprusside could be useful if signs and incorrect). Phenylephrine has no positive beta effects;
symptoms of hypoperfusion were present. Because this therefore, it will not augment contractility. In addition,
patient presents mainly with warm and wet symptoms, it will cause vasoconstriction through alpha stimula-
diuretics would be �rst-line (Answer B is incorrect). tion, which will further increase SVR and probably
Milrinone is an inotropic drug. Because of their adverse worsen CO (Answer D is incorrect). Vasoconstrictors
effects, inotropes are recommended in cold and wet are reserved for patients in cardiogenic shock.
exacerbations only after vasodilatory medications have
failed (Answer D is incorrect). 8. Answer: A
Treatment options for sustained VT depend on concom-
6. Answer: A itant disease states, particularly LVEF (40% cutoff). In
Intravenous vasodilators such as nitroglycerin (Answer a patient with LV dysfunction, class I agents such as
A) and sodium nitroprusside (Answer B) are reasonable procainamide are contraindicated (Answer D is incor-
if intravenous diuretics fail and the patient progresses rect). In a patient whose CrCl is less than 60 mL/minute,
to acute pulmonary edema. Both agents rapidly cause sotalol requires a considerable dose reduction to avoid
venous vasodilation and reduce pulmonary �lling an excess risk of torsades de pointes. Sotalol is not an
pressures, which can relieve acute shortness of breath. effective cardioversion drug but is more useful for pre-
Answer A, nitroglycerin, is optimal for this patient, venting future episodes of arrhythmias (maintaining
given his declining renal function and the concern sinus rhythm) once sinus rhythm is achieved (Answer
for increased risk of thiocyanate toxicity with sodium B is incorrect). Dofetilide is indicated only for AF, not
nitroprusside in this setting (Answer B is incorrect). for ventricular arrhythmias; similarly, cardioversion
Dobutamine is typically used in states of low CO rates with dofetilide are low (Answer C is incorrect).
decompensation and is counteracted by concomitant Amiodarone is �rst-line therapy for sustained VT in
β-blocker therapy, making it a poor choice in patients patients with severe renal insuf�ciency, HF, and SHD
receiving β-blockers (Answer C is incorrect). Although (Answer A is correct).
milrinone is a more acceptable inotropic agent in a
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11. Answer: A
Hypertensive emergency should be treated immedi-
ately by no more than a 25% reduction in MAP over
the �rst hour, followed by a further reduction to a blood
pressure of 160/100 mm Hg over the next 2–6 hours.
The patient’s comorbidities guide the optimal therapy.
His dialysis and SCr of 11.4 mg/dL are contraindica-
tions to sodium nitroprusside (Answer C is incorrect)
because of possible thiocyanate toxicity. Labetalol
(and β-blockers in general) is controversial in patients
who have taken cocaine, but its nonselective nature
makes it an option; however, a reduction of 50% ini-
tially is too rapid a decrease in blood pressure for safety
(Answer B is incorrect). Clonidine is not appropriate
for a hypertensive emergency because its oral form is
dif�cult to titrate and can lead to precipitous drops in
blood pressure beyond the goal 25% reduction and pos-
sibly stroke or worsening MI (Answer D is incorrect).
Nitroglycerin is optimal, considering the patient’s lack
of contraindications to this therapy and his evolving
MI and symptoms of HF (Answer A is correct).
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arm was discontinued early because of its signi�cantly reports) associated with medications. Excerpta Medica
(61%) higher mortality rate compared with the ICD arm (Answer D) is a comprehensive database of more than
(Answer A is incorrect). Although this trial had a small 7000 journals from 74 countries dating from 1974 to
sample size that prevented a statistically signi�cant dif- the present. Recently published articles appear in the
ference in total mortality in ICD-treated patients versus system within 10 days of article publication, and it often
patients treated with either amiodarone or metoprolol, contains data not found in a typical Medline search.
the incidence of sudden death was signi�cantly lower in
patients with an ICD (Answer C is correct; 33% vs. 13%; 12. Answer: B
p=0.005). The Antiarrhythmics Versus Implantable MedWatch is a post-FDA approval program established
De�brillators trial also evaluated ICD implantation ver- by the FDA for health care professionals to report the
sus AAD therapy (primarily amiodarone) in survivors adverse events that occur after a drug is approved.
of SCD. Patients with ICDs had a signi�cantly higher Although MedWatch is commonly used only for report-
rate of survival than did those treated with drug therapy ing serious reactions to the FDA and would not be man-
(89% vs. 82%; p<0.02), making Answer C preferable to datory in this case (Answer A is incorrect), it can be used
all the other options (Answers B and D are incorrect). to report any adverse event. Information recorded on
these forms is reported to the manufacturer and used to
10. Answer: C determine whether black box warnings are necessary or
The number needed to treat can be calculated as 1/abso- whether new adverse effects occur with a drug. The Joint
lute risk reduction. Because the absolute risk reduction Commission requires that all institutions have a de�ni-
in mortality at 60 months was 7.2% with ICD versus pla- tion of an ADR that can be understood and remembered
cebo, 1/0.072 would be used to calculate the number of by all health care professionals at the institution (Answer
patients needed to treat to prevent one death during this B is correct). In addition, The Joint Commission requires
time. About 14 patients (Answer C) would need to be that each drug dose administered be monitored for
treated with ICD to prevent one death in 60 months ver- adverse effects, that each institution have a system in
sus placebo. Other calculations in this fashion, including place for reporting ADRs, and that the institution ensure
relative risk reduction and 100% minus the absolute or that the reporting mechanism identi�es all key ADRs.
relative risk reduction, provide no useful information The Naranjo algorithm is used to determine the likeli-
for interpreting the trial results and yield an incorrect hood of cause and effect from a presumed drug-induced
number of patients (Answers A, B, and D are incorrect). event but is not required (Answer C is incorrect). Answer
D is incorrect because serious adverse effects are report-
11. Answer: D able to the FDA, as are severe and life-threatening events.
International Pharmaceutical Abstracts (Answer A) is a
database of primarily pharmaceutical abstracts in more 13. Answer: B
than 750 journals, including foreign and state pharmacy Because the pharmacy and therapeutics committee
journals, in addition to key U.S. medical and pharmacy wants to discover whether the new drug is worth the
journals. Many of the citations are not included on extra cost for the added mortality bene�ts it can pro-
Medline, so a broader search can be done; however, sub- vide for patients with decompensated HF compared
ject descriptors are not consistently de�ned in a uniform with available therapies, a cost-effectiveness analysis
way, and multiword terms are often cited backward. (Answer B is correct) is the best pharmacoeconomic
The Iowa Drug Information Service database (Answer analysis. Cost-minimization analysis (Answer A is
B) offers full-text articles from 1966 to the present in incorrect) determines whether a therapeutically equiv-
about 200 medical and pharmacy journals (based pri- alent drug within a class that provides the same thera-
marily in the United States). This database is updated peutic outcome as other available drugs can be used for
monthly, and newly available articles may take longer less cost. Cost-utility analysis (Answer D is incorrect)
to access from this service. The Clin-Alert database determines whether a drug can improve the quality of a
(Answer C) contains more than 100 medical and phar- patient’s life more than other available therapies. Cost-
macy journals focused on adverse events, drug interac- bene�t analysis (Answer C is incorrect) evaluates new
tions, and medical-legal issues. This database is used programs or services to determine whether they pro-
primarily to look up adverse events (especially recent vide enough bene�t to justify their cost.
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