19 Cardio-2

Cardiology II
Cardiology II
Barbara S. Wiggins, Pharm.D., FCCP, FNLA,
FAHA, AACC, CLS, BCPS (AQ Cardiology)
Pharmacy Clinical Specialist-Cardiology
Medical University of South Carolina
Adjunct Associate Professor
South Carolina College of Pharmacy
Charleston, South Carolina
ACCP Updates in Therapeutics® 2012: The Pharmacotherapy Preparatory Review and Recertification Course
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Cardiology II
Learning Objectives: D. ASA 81 mg, metoprolol 5 mg x 3, and UFH

infusion 80 units/kg bolus, followed by 18
1. Distinguish between the different acute coronary units/kg/hour, nitroglycerin infusion at a rate
syndromes (ACS); ST-segment elevation myocar- of 10 mcg/minute.
dial infarction (STEMI), non–ST-segment eleva-
tion myocardial infarction (NSTEMI), and unstable 2. H.M. is a 56-year-old man who presents to the hos-
angina (UA) by diagnosis as well as treatment. pital with the chief concern of chest pain that was
2. Develop a pharmacotherapy treatment plan for a unrelieved at home with nitroglycerin. His electro-
patient presenting with the various ACS. cardiogram (ECG) shows ST-segment depression
3. Develop a pharmacotherapy treatment plan for a and T-wave inversion. Cardiac markers are drawn
patient with peripheral arterial disease (PAD). that show an elevated troponin I. The cardiolo-
4. Demonstrate an understanding of the pathophysiol- gist has requested that the patient go to the cardiac
ogy, prognosis, and economic impact of PAD. catheterization laboratory for further evaluation.
5. Identify and determine the appropriate therapeutic The patient has a history of coronary artery disease
goals for a patient with dyslipidemia based on car- (CAD) and had a myocardial infarction (MI) about
diovascular (CV) risk factors. 6 months ago. During his previous hospitalization,
6. Develop a pharmacotherapy treatment plan for a the patient was thought to have developed heparin-
patient with dyslipidemia based on various choles- induced thrombocytopenia (HIT) because his plate-
terol targets as well as CV risk factors. let count dropped to 40 x 103 cells/mm3 after his
previous catheterization. Given this patient’s diag-
nosis and history, which of the following treatment
Self-Assessment Questions: regimens would be most appropriate to use during
Answers and explainations to these questions his cardiac catheterization?
may be found at the end of this chapter. A. Abciximab.
B. Bivalirudin.
1. J.J. is a 62-year-old man who presents to the emer- C. Eptifibatide.
gency department with the chief concern of chest D. Tenecteplase.
pain. An electrocardiogram (ECG) is conducted,
which reveals a left bundle branch block (presumed
3. J.S. is a 62-year-old man (height 5′8′′, weight 120
new). The patient is treated with aspirin (ASA),
kg) with a history significant for diabetes, chronic
morphine, metoprolol, nitroglycerin, and intrave-
renal insufficiency, CAD, and hypertriglyceride-
nous heparin infusion, and preparations are being
mia, which has resulted in pancreatitis in the past.
made to take the patient directly to the cardiac cath-
His family history is also significant for his father
eterization laboratory for evaluation. From the evi-
having CAD and hypertriglyceridemia. Pertinent
dence, which one of the following medication regi-
laboratory findings include a hemoglobin A1c (A1c)
mens represents the agents that have been known
of 7.6% and a serum creatinine (SCr) of 4.0 mg/
to reduce mortality and are most appropriate in this
dL. He currently takes atorvastatin 40 mg every
setting?
evening, extended-release niacin 2000 mg/day at
A. ASA 325 mg, metoprolol 5 mg x 3, and bedtime, ASA 81 mg/day, and over-the-counter
unfractionated heparin (UFH) infusion 80 (OTC) fish oil 2 g/day. His fasting lipid profile is
units/kg bolus, followed by 18 units/kg/hour. total cholesterol (TC), 402 mg/dL; low-density li-
B. ASA 81 mg, metoprolol 5 mg x 3, and UFH poprotein cholesterol (LDL-C), unable to calculate;
infusion 60 units/kg bolus, followed by 12 high-density lipoprotein cholesterol (HDL-C), 48
units/kg/hour. mg/dL; and triglycerides (TG), 1500 mg/dL. Which
C. ASA 325 mg, metoprolol 5 mg x 3, and UFH one of the following medications and doses would
infusion 60 units/kg bolus, followed by 12 be most appropriate to initiate at this time?
units/kg/hour, nitroglycerin infusion at a rate
A. Increase atorvastatin to 80 mg and add
of 10 mcg/minute.
gemfibrozil 600 mg once daily.
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Cardiology II
B. Increase atorvastatin to 80 mg and add C. An ABI of 0.72 indicates mild to moderate

fenofibrate (TriCor) 48 mg once daily. and warrants treatment.
C. Add gemfibrozil 600 mg once daily. D. An ABI of 0.72 indicates severe disease and
D. Add fenofibrate (TriCor) 48 mg once daily. warrants treatment.
4. J.C. a 57-year-old man who smokes, presents to his

primary care physician for a physical examination,
the first one he has had in 5 years. His fasting lipid
panel on this visit reveals an LDL-C of 176 mg/dL
and an HDL-C of 43 mg/dL. He currently takes no
medications. Given this patient’s risk factors, which
one of the following would be the most appropriate
medication and LDL-C goal for J.C.?
A. Pravastatin 20 mg orally daily with an LDL-C
goal of less than 130 mg/dL.
B. Lovastatin 20 mg orally daily with an LDL-C
goal of less than 160 mg/dL.
C. Atorvastatin 20 mg/day with an LDL-C goal
of less than 130 mg/dL.
D. Simvastatin 20 mg/day with an LDL-C goal
of less than 160 mg/dL.
5. L.G., a 58-year-old man, presents to his primary

care provider with pain in his lower legs. His medi-
cal history is significant for diabetes (A1c 6 %),
hypertension (150/90 mmHg), gout, pancreatic
cancer, and hypothyroidism. Given this patient’s
medical history, which of the following therapies
has the most positive data demonstrating efficacy
and would therefore be recommended to treat this
patient’s peripheral arterial disease (PAD)?
A. β-Blocker.
B. Aspirin.
C. Pentoxifylline.
D. Warfarin therapy.
6. A.W. is a 56-year-old woman with CAD, hyper-

tension (HTN), and diabetes. She is undergoing
evaluation for PAD and has an ankle brachial index
(ABI) performed. Her results show an ABI of 0.72.
Given this information, which one of the following
would classify her results most accurately?
A. An ABI of 0.72 is considered normal and does
not warrant treatment.
B. An ABI of 0.72 indicates some presence of
disease and does not warrant treatment.
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I. ACUTE CORONARY SYNDROMES
A. Definitions and Goals

1. Definitions
Table 1. UA, NSTEMI, and STEMI Definitions

Unstable angina Chest pain that often occurs at rest, can occur suddenly, may worsen suddenly, or may be
(UA) stuttering in nature, recurring over days to weeks
Diagnosis: ST-segment depression, T-wave inversion, or no ECG changes may occur, but
no positive biomarkers for cardiac necrosis present
Non–ST-elevation MI Symptoms similar to unstable angina but differentiated on the basis of markers and ECG
(NSTEMI) Diagnosis: Positive cardiac enzyme biomarkers of necrosis (troponin I or T elevation,
CKMB fraction > 5%–10% of total CK)
ST-elevation MI Classic symptoms include worsening of chest pain lasting more than 5 minutes,
(STEMI) accompanied by shortness of breath, nausea, or weakness. Other symptoms may include
chest discomfort with or without radiation to other areas such as the arms, back, neck,
jaw, or abdomen, and diaphoresis
Diagnosis: ST elevation of > 1 mm above baseline on ECG, positive biomarkers
CK = creatine kinase; CKMB = creatine kinase myocardial band; ECG = electrocardiogram; MI = myocardial infarction.
2. Therapy goals
a. Unstable angina (UA)/non–ST-elevation myocardial infarction (NSTEMI) goals
i. Prevent total occlusion of the infarct-related artery.
(a) Glycoprotein (GP) IIb/IIIa inhibitors, other antiplatelet agents, and anticoagulants
(b) Percutaneous coronary intervention (PCI) can be either or both:
(1) Percutaneous transluminal coronary angioplasty, (i.e., “balloon”)
(2) Stent implantation
(c) Thrombolytics have no role and have an increased bleeding risk.
ii. Control chest pain and associated symptoms.
b. ST-elevation MI goals
i. Restore patency of the infarct-related artery and minimize infarct size.
(a) Thrombolytic medications or “door-to-needle” time within 30 minutes
(b) PCI intervention or “door-to-balloon” time within 90 minutes
(1) If presenting to a facility without the capability for expert, prompt intervention with
primary PCI within 90 minutes, should undergo fibrinolysis unless contraindicated
(2) Facilitated PCI consists of planned, immediate PCI after an initial pharmacologic
regimen such as full- or half-dose fibrinolysis, a GP IIb/IIIa inhibitor, or a
combination of such; might be performed as a reperfusion strategy in higher-risk
patients when PCI is not immediately available and bleeding risk is low
(3) Rescue PCI consists of PCI after failed thrombolysis and is indicated in select
patients if shock, severe heart failure (HF), and/or pulmonary edema, hemodynamic
or electrical instability, evidence of persistent ischemia
ii. Prevent complications such as arrhythmias or death.
iii. Control chest pain and associated symptoms.
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B. Invasive or Conservative Treatment Strategy

1. Calculate thrombolysis in myocardial infarction (TIMI) score (see Table 2) by adding 1 point for each
history or presentation finding.
2. Risk of mortality, new or recurrent MI, or severe recurrent ischemia through 14 days on the basis of
TIMI score: score = 0–1, mortality 7%; score = 2, mortality 8%; score = 3, mortality 13%; score = 4,
mortality 20%; score = 5, mortality 26%; and score = 6–7, mortality 41%
Table 2. TIMI Risk Score Unstable Angina/NSTEMIa

Historical Points
Age > 65 1
3 cardiac risk factors (hypertension, diabetes, 1
hyperlipidemia, smoking, family history)
Known coronary artery disease ≥ 50% stenosis 1
Presentation
Severe angina (≥ 2 episodes w/in 24 hours 1
ASA within 7 days 1
Elevated markers 1
ST-segment deviation > 0.5 mm 1
a
Risk score = total points (0–7).
ASA = aspirin; TIMI = thrombolysis in myocardial infarction.
Table 3. Selection of Initial Treatment Strategy: Invasive vs. Conservative

Initial Invasive Strategy
Recurrent angina/ischemia at rest with low-level activities despite intensive medical therapy
Elevated cardiac biomarkers (TnT or TnI)
New/presumably new ST-segment depression
Signs/symptoms of HF or new/worsening mitral regurgitation
High-risk findings from noninvasive testing
Hemodynamic instability
Sustained VT
PCI within 6 months
Prior CABG
High-risk score (e.g., TIMI, GRACE)
Reduced left ventricular function (LVEF < 40%)
Initial Conservative Strategy
Low-risk score (e.g., TIMI, GRACE) or patient/physician presence in the absence of high-risk features
CABG = coronary artery bypass grafting; GRACE = Global Registry of Acute Coronary Events; HF = heart
failure; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary intervention; TIMI = thrombolysis
in myocardial infarction; TnI = troponin I; TnT = troponin T; VT = ventricular tachycardia.
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C. Initial Management
1. “MONA” in UA/NSTEMI, “MONA” plus β-blocker in ST-segment myocardial infarction (STEMI)
Table 4. Initial Management of ACS - “MONA” plus β-Blocker

M = Morphine • Morphine 1–5 mg IV is reasonable if symptoms are not relieved despite NTG or if
symptoms recur
O = Oxygen • Oxygen if O2 saturation < 90% or high-risk features for hypoxemia
N = Nitroglycerin • Nitroglycerin spray or SL tablet 0.4 mg × three doses to relieve acute chest pain (if pain is
unrelieved after one dose, call 911)
• Nitroglycerin IV 5–10 mcg/minute, titrate to chest pain relief or 200 mcg/minute if pain
unrelieved by morphine and SL NTG
āā Hold if MAP < 80 mm Hg
āā Used in first 48 hours for treatment of persistent chest pain, HF, and HTN
āā Use should not preclude other mortality-reducing therapies (ACE inhibitor, β-blocker
āā No mortality benefits but high placebo crossover rate
• Contraindication: Sildenafil or vardenafil use within 24 hours or tadalafil use within 48
hours; SBP < 100 mm Hg or ≥ 30 mm Hg below baseline, HR < 50 beats/minute, HR > 100
beats/minute in absence of symptomatic HF or right ventricular infarction
A = Aspirin • ASA chew and swallow non–enteric-coated 162–325 mg × one dose
āā Clopidogrel – If ASA allergy or considerable gastrointestinal intolerance
β -Blocker • Oral or intravenous β-blocker (oral route preferred)
āā Mortality benefit in early phases of acute MI (metoprolol 5.7% vs. placebo 8.9%)
āā Metoprolol 5 mg IV every 5 minutes × 3 doses, followed by 25–50 mg PO 2 times/day
uptitrated as tolerated
āā IV route reasonable if a tachyarrhythmia or HTN present
• Contraindications: Hypotension, signs of HF, risk factors for cardiogenic shock, or other
relative contraindications (third-degree heart block, active asthma)
Other early hospital therapies
ACE inhibitors • Indicated orally within first 24 hours if HF, LVEF × 40%, type 2 diabetes mellitus, or
CKD
āā IV therapy contraindicated because of risk of hypotension
• Consider in all patients with CAD
• Indicated indefinitely in all patients with LVEF < 40%
• ARB indicated if contraindication to ACE inhibitor
• Contraindication: Hypotension
CCBs • Specifically, nondihydropyridine CCBs – verapamil, diltiazem
• Recommended if continuing or frequently recurring ischemia and contraindication to
β-blocker therapy or recurrent ischemia after β-blockers and nitrates fully used
āā No real benefit or detriment to mortality; primarily symptom relief effects
• Contraindication: Clinically significant LV dysfunction; immediate-release
dihydropyridine CCBs should not be administered in the absence of a β-blocker
ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; ASA = aspirin; CAD = coronary artery disease; CCBs = calcium
channel blockers; CKD = chronic kidney disease; HF = heart failure; HTN = hypertension; IV = intravenous; LVEF = left ventricular ejection
fraction; MAP = mean arterial pressure; N/A = not available; NTG = nitroglycerin; PO = oral; SBP = systolic blood pressure; SL = sublingual.
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2. Treatment algorithms for UA/NSTEMI and STEMI (see Tables 5 and 6)
Table 5. UA/NSTEMI Algorithm

Early Invasive Delayed PCI
(PCI ≤ 12 hours from (PCI > 12 hours from Early Conservative
Strategy hospitalization, high-risk patient) hospitalization) (no PCI, low-risk patient)
Anticoagulant Enoxaparin, UFH, fondaparinux Enoxaparin, UFH, fondaparinux Enoxaparin, fondaparinux or
therapya (+ UFH added at time of PCI), or (+ UFH added at time of PCI), or UFH
bivalirudin bivalirudin
Antiplatelet Clopidogrel or prasugrelb or Clopidogrel or prasugrelb or Clopidogrel +
therapy ticagrelorb + ticagrelorb + If positive stress test,
abciximab or eptifibatide initiated If high or moderate risk, initiate abciximab or eptifibatide
at time of PCIc for patients eptifibatide or tirofiban either before with UFH or enoxaparin, or
receiving UFH, enoxaparin, or angiography/PCI (if recurrent bivalirudin at time of PCI
fondaparinux ischemia) or at time of PCIc
a
If high risk of bleeding, fondaparinux or bivalirudin preferred. If CABG planned, UFH preferred.
b
If unlikely to undergo CABG, initiate prasugrel or ticagrelor at time of PCI.
c
After PCI, discontinue NTG and anticoagulation and continue abciximab for 12 hours or eptifibatide for at least 12 hours.
CABG = coronary artery bypass graft; NTG = nitroglycerin; PCI = percutaneous coronary intervention; UFH = unfractionated heparin.
Table 6. STEMI Management for Symptoms Lasting <12 Hours or Lessa

Treatment Option Primary PCI Fibrinolysis
Antiplatelet agents Clopidogrel, prasugrel, or ticagrelor Clopidogrel
Antithrombotics IV UFH with abciximab IV UFH for at least 48 hours or
(alternatively eptifibatide or IV and SC enoxaparin for hospitalization, up to 8 days
tirofiban) or bivalirudin alone (preferred, selected patients) or
IV and SC fondaparinux for hospitalization, up to 8 days
a
Algorithm for patients with symptoms for 12 hours or less. If symptoms for more than 12 hours, administer clopidogrel with PCI or coronary
artery bypass grafting or fibrinolysis for selected patients. If PCI, administer UFH or enoxaparin with abciximab or eptifibatide or bivalirudin
alone at time of PCI.
IV = intravenous; PCI = percutaneous coronary intervention; SC = subcutaneous; UFH = unfractionated heparin.
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3. Dosing of antiplatelet and anticoagulant therapy (see Tables 7–9)
Table 7. Oral Antiplatelet Agents

Aspirin CLO (Plavix)a/PRA (Efficient)b/Ticagrelor (Brilinta)c
Initial therapy Initial therapy
• ASA 162–325 mg nonenteric orally or chewed × 1 STEMI
• Pre-PCI after fibrinolytic therapy – 300 CLO 300-mg
Pre-PCI LD if within 24 hours of event; CLO 600-mg LD if > 24
• Already on ASA therapy, 81–325 mg hours after event
• Not on ASA therapy, ASA 325 mg before PCI
Pre-PCI
Post – PCI – no stent • CLO 600-mg LD or PRA 60-mg LD or TIC 180-mg LD
• continue ASA indefinitely – 81-mg dose
No stent (STEMI with or without fibrinolytic)
Post-stent • CLO 75 mg/day for at least 14 days and up to 1 year
Bare metal (BMS) or drug-eluting stent (DES)
ASA 81 mg/day Post-stent
• ASA 325 mg initially with TIC; then reduce to Bare metal (BMS) or drug eluting stent (DES)
75–100 mg/day • CLO 75 mg/day or PRA 10 mg/day (5 mg/day if < 60 kg)
or TIC (90 mg twice daily) for at least 12 months and up
to 15 months
a
Discontinue clopidogrel at least 5 days or PRA at least 7 days before elective CABG. Administer clopidogrel indefinitely if ASA allergy. Avoid
LD if patient is 75 years or older.
b
Discontinue prasugrel at least 7 days before surgery. Avoid PRA in patients with active pathologic bleeding or a history of TIA or stroke as well
as in patients older than 75 years unless patient has DM or history of myocardial infarction.
c
Discontinue ticagrelor at least 5 days before surgery. Avoid TIC in patients with active pathologic bleeding or a history of intracranial
hemorrhage.
c,b
Initiate PRA or TIC in patients with known coronary artery anatomy only to avoid use in patients needing CABG surgery.
ASA = aspirin; CABG = coronary artery bypass grafting; CLO = clopidogrel; DM = diabetes mellitus; LD = loading dose; NSTEMI = non–ST-
elevation myocardial infarction; PCI = percutaneous coronary intervention; PRA = prasugrel; STEMI = ST-elevation myocardial infarction;
TIC = ticagrelor.
Table 8. GP IIb/IIIa Inhibitor Dosing

STEMI PCI UA/NSTEMI with/without PCI Notes
Abciximab 0.25-mg/kg IV bolus; then 0.125 Not recommended Renal adjustment not
(ReoPro) mcg/kg/minute (maximum 10 necessary
mcg/kg) for 12 hours
Eptifibatide 180-mcg/kg IV bolus × 2 (10 180-mcg/kg IV bolus; then 2 mcg/ If CrCl < 50 mL/minute,
(Integrilin) minutes apart); then 2 mcg/kg/ kg/minute for 12–72 hours reduce infusion 50%; not
minute for 12–18 hours studied in patients with
SCr > 4 mg/dL
Tirofiban 25-mcg/kg IV bolus; then 0.1 0.4 mcg/kg/minute for 30 minutes If CrCl < 30 mL/minute,
(Aggrastat) mcg/kg/minute for 18 hours (LD infusion); then 0.1 mcg/kg/ reduce infusion 50%
minute for 18–72 hours
CrCl = creatinine clearance; GP = glycoprotein; IV = intravenous; LD = loading dose; NSTEMI = non–ST-elevation myocardial infarction; SCr
= Serum creatinine; STEMI = ST-elevation myocardial infarction; UA = unstable angina.
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Table 9. Anticoagulant Dosing

Unfractionated Enoxaparin Fondaparinux Bivalirudin
Heparin (Lovenox) (Arixtra) (Angiomax)
Classification — LMWH Factor Xa inhibitor DTI
UA/NSTEMI 60-unit/kg IVB 1 mg/kg SC BID for 24–48 2.5 mg SC QD 0.1-mg/kg IVB; then
(max 4000 units), hours (UA/NSTEMI) (If STEMI, give 0.25 mg/kg/hour IV
12 units/kg/hour or until end of PCI or initial 2.5 mg
IV (maximum throughout hospitalization IVB)
1000 units/hour)
for 48 hours or end
of PCI, goal aPTT
of 50–70 seconds
PCI Supplemental doses If last dose < 8 hours, Fondaparinux 0.75-mg/kg IVB, 1.75
to target ACTa nothing additional needed should not be mg/kg/hour IV
If last dose > 8 hours, 0.3 used as a sole Discontinue at end
mg/kg IVB if last dose anticoagulant for of PCI or continue
8–12 hours prior or fewer PCI for up to 4 hours
than 2 therapeutic doses postprocedure if
received before PCI needed (Hold UFH
30 minutes before
administration)
STEMI If GP IIb/IIIa, UFH If prior treatment with 2.5 mg IVB; then 0.75 mg/kg IVB, 1.75
primary PCI b 50–70 units/kg IVB enoxaparin and last dose 2.5 mg SC QD mg/kg/hour IV
If no GP IIb/IIIa, < 8 hours, nothing else
UFH 70- to 100- needed
unit/kg IVB If last dose given at least
Supplemental doses 8–12 hours earlier,
to target ACTa administer 0.3 mg/kg IVB
Dose Avoid if history If CrCl < 30 mL/minute 1 Avoid if CrCl < Adjust infusion dose in
adjustments/ of HIT mg/kg SC QD 30 mL/minute severe renal dysfunction
contraindications Avoid if history of HIT (IVB dose same).
If CrCl < 30 mL/minute,
reduce infusion to
1 mg/kg/hour. If on
hemodialysis, reduce
infusion to 0.25
mg/kg/hour
a
Target ACT 250–300 seconds for primary PCI without GP IIb/IIIa inhibitor and 200–250 seconds in patients given a concomitant GP IIb/IIIa
inhibitor.
b
If STEMI status is post-fibrinolytics, UFH dose – same as UA/NSTEMI and enoxaparin dose – if younger than 75 years, 30 mg IVB, followed
immediately by 1 mg/kg subcutaneously 2 times/day (first two doses maximum 100 mg if more than 100 kg), if older than 75 years, no IVB, 0.75
mg/kg subcutaneously 2 times/day (first two doses maximum 75 mg if more than 75 kg).
ACT = activated clotting time; aPTT = activated partial thromboplastin time; BID = twice daily; DTI = direct thrombin inhibitor; HIT =
heparin-induced thrombocytopenia; IV = intravenous; IVB = intravenous bolus; LMWH = low-molecular-weight heparin; NSTEMI = non–ST-
elevation myocardial infarction; PCI = percutaneous coronary intervention; QD = once daily; SC = subcutaneously; STEMI = ST-elevation
myocardial infarction; UA = unstable angina; UFH = unfractionated heparin.
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4. Thrombolytic dosing (see Table 10) and adjunctive therapy

a. Administer within 12 hours of symptom onset (preferably within 6 hours). Ideally, administer
within 30 minutes of hospital arrival.
b. Patients undergoing reperfusion with fibrinolytics should receive anticoagulant therapy for a
minimum of 48 hours and preferably for the duration of the index hospitalization, up to 8 days.
c. Alteplase, reteplase, and tenecteplase require concomitant UFH administration of a 60-unit/kg
bolus (maximum 4000 units) and 12 units/kg/hour (maximum 1000 units/hour), with provision for
an activated partial prothrombin time of about 50–70 seconds.
Table 10. Thrombolytic Therapy

Dosing
Alteplase (rt-PA, Activase) 15 mg IV; then 0.75 mg/kg over 30 minutes (maximum 50 mg);
then 0.5 mg/kg (maximum 35 mg) over 60 minutes
Reteplase (r-PA, Retavase) 10 units IV; repeat 10 units IV in 30 minutes
Tenecteplase < 60 kg, 30 mg IV; 60–69 kg, 35 mg IV; 70–79 kg, 40 mg IV; 80–89 kg, 45 mg IV,
(TNK-tPA, TNKase) > 90 kg, 50 mg IV (about 0.5 mg/kg)
IV = intravenously; r-PA = recombinant plasminogen activator; rt-PA = recombinant tissue plasminogen activator; tPA = tissue plasminogen
activator.
Table 11. Contraindications to Thrombolytic Therapy

Relative Contraindications Absolute Contraindications
• BP > 180/110 mm Hg on presentation • ANY prior hemorrhagic stroke
• History of TIA or CVA > 3 months prior • Ischemic stroke within 3 months (except in past 3
• History of chronic poorly controlled HTN hours)
• INR 2–3 on warfarin • Intracranial neoplasm or arteriovenous malformation
• Recent trauma, major surgery, CPR, internal • Active internal bleeding
bleeding in 2–4 weeks • Aortic dissection
• Streptokinase exposure > 5 days earlier or prior • Considerable facial trauma or closed-head trauma in
allergic reaction (if given streptokinase again) past 3 months
• Active peptic ulcer
• Age > 75 years
• Pregnancy
• Known intracranial pathology (dementia)
BP = blood pressure; CPR = cardiopulmonary resuscitation; CVA = cerebrovascular accident; HTN = hypertension; INR = international
normalized ratio; TIA = transient ischemic attack.
D. Long-term Management
1. β-Blockers
a. Indicated for all patients unless contraindicated
b. Initiate within a few days of event, if not acute, and continue indefinitely.
c. If moderate or severe left ventricular (LV) failure, initiate with gradual titration.
2. Angiotensin-converting enzyme (ACE) inhibitors
a. Indicated for all patients even if no LV dysfunction, HTN, or diabetes mellitus (DM)
b. Give oral ACE inhibitor in low doses to all patients during the first 24 hours of anterior STEMI,
HF signs (pulmonary congestion), or left ventricular ejection fraction (LVEF) less than 40%,
provided no hypotension exists (systolic BP less than 100 mm Hg) or other contraindication, to
reduce mortality and remodeling.
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c. Angiotensin receptor blocker if ACE inhibitor intolerant

d. Avoid intravenous ACE inhibitor post-MI to prevent hypotension.
3. Aldosterone receptor blockers: Indicated if post-MI with LVEF less than 40%, symptomatic HF or
DM, and receiving ACE inhibitors; however, contraindicated if creatinine clearance (CrCl) less than 30
mL/minute or serum potassium more than 5 mEq/L
4. Warfarin – Indicated either without (international normalized ratio [INR] 2.5–3.5) or with low-dose
ASA (75–81 mg/day, INR 2–2.5) if high CAD risk and low bleeding risk if patient does not require, or
is intolerant of, clopidogrel
5. Lipid management – Statins indicated with an LDL goal less than 100 mg/dL, with a goal of less than
70 mg/dL reasonable
6. Other goals – A1c less than 7%, smoking cessation, body mass index 18.5–24.9 kg/m2, exercise 3 or 4
times/week
Patient Cases
1. J.D. is a 66-year-old, 70-kg woman with a history of MI, HTN, hyperlipidemia, and DM who 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 oc-
curring with less exertion. Electrocardiography showed ST depression in leads II, III, and aVF and hyper-
dynamic T waves and positive cardiac enzymes. Home medications are ASA 81 mg/day, simvastatin 40 mg
every night, metoprolol 50 mg 2 times/day, and metformin 1 g 2 times/day. Which one of the following is
the best antiplatelet/anticoagulant strategy for this patient?
A. ASA 325 mg and clopidogrel 600 mg × 1; then 75 mg once daily, UFH titrated to 50–70 seconds
immediately plus eptifibatide 180-mcg/kg bolus × 2; then 2 mcg/kg/minute at time of PCI if
indicated.
B. ASA 325 mg and enoxaparin 80 mg subcutaneously 2 times/day plus cardiac catheterization for possible
PCI.
C. Medical management with abciximab 0.25-mg/kg bolus; then 0.125 mg/kg/minute for 12 hours plus
enoxaparin 80 mg subcutaneously 2 times/day, ASA 325 mg/day, and clopidogrel 300 mg × 1; then 75 mg
once a day.
D. Medical management with ASA 325 mg and clopidogrel 300 mg × 1; then 75 mg once a day plus
UFH 70-unit/kg bolus; then 15 units/kg/hour.
2. The patient received a percutaneous transluminal coronary angioplasty and paclitaxel-eluting stent in her
right coronary artery. Which one of the following best represents how long clopidogrel therapy should be
continued?
A. 1 month.
B. 3 months.
C. 6 months.
D. At least 12 months.
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Patient Cases (continued)

3. Which one of the following is the best lifelong ASA dose once dual therapy with ticagrelor after PCI with
stent implantation is completed?
A. 25 mg.
B. 81 mg.
C. 162 mg.
D. 325 mg.

4. R.V., a 52-year-old man (weight 100 kg) with a history of HTN and hypertriglyceridemia, presents to a
major university teaching hospital with a cardiac catheterization laboratory. He has 3 hours of crushing
10/10 substernal chest pain radiating to both arms that began while he was eating his lunch (seated), which
is accompanied by nausea, diaphoresis, and shortness of breath. He has never before experienced chest
pain of this character or intensity. He usually can walk several miles without difficulty and is a 1.5 pack/
day smoker. Home medications are lisinopril 2.5 mg/day and gemfibrozil 600 mg 2 times/day. Current vital
signs include HR 68 beats/minute and BP 178/94 mm Hg. Electrocardiography shows a 3-mm ST elevation
in leads V2–V4, I, and aVL. Serum chemistry values are within normal limits. The first set of cardiac mark-
ers shows positive myoglobin concentrations, creatine kinase (CK) 175 units/L, myocardial band (MB) 17.4
units/L, and troponin T 0.8 mcg/L (normal defined as less than 0.1 mcg/L). Which one of the following is
best to treat this patient’s STEMI?
A. Cardiac catheterization with primary PCI (stent) of occluded artery, together with abciximab 0.25
mcg/kg intravenous push; then 0.125 mg/kg/minute for 12 hours, clopidogrel, ASA, and UFH.
B. Reteplase 10-unit bolus × 2, 30 minutes apart, plus UFH 60-unit/kg bolus and a 12-unit/kg/hour
infusion, clopidogrel, and ASA.
C. Abciximab 0.25-mg/kg intravenous push and 0.125 mg/kg/minute for 12 hours plus enoxaparin 100 mg
subcutaneously 2 times/day plus tenecteplase 25-mg intravenous push × 1, ASA, clopidogrel, and UFH.
D. Tirofiban 0.04 mcg/kg/minute × 30 minutes; then 0.01 mcg/kg/minute plus UFH 60-unit/kg bolus and
a 12-unit/kg/hour infusion, clopidogrel, ASA, and UFH.
5. W.F. is a 70-year-old male smoker with a history of HTN, benign prostatic hypertrophy, and lower back
pain. Three weeks ago, he began to experience substernal chest pain with exertion (together with dyspnea),
which radiated to both arms and was associated with nausea and diaphoresis. Episodes have increased in
frequency to 4 or 5 times/day; they are relieved with rest. He has never had an ECG. Today, he awoke with
7/10 chest pain and went to the emergency department of a rural community hospital 2 hours later. He was
acutely dyspneic and had ongoing pain. Home medications are ASA 81 mg/day for 2 months, doxazosin 2
mg/day, and ibuprofen 800 mg 3 times/day. Vital signs include HR 42 beats/minute (sinus bradycardia); BP
104/48 mm Hg; and weight 61 kg. Laboratory results include blood urea nitrogen 45 mg/dL, SCr 2.5 mg/dL,
CK 277 units/L, CKMB 35.2 units/L, and troponin T 1.5 mcg/L (less than 0.1 mcg/L). His ECG shows a
3-mm ST elevation. Aspirin, clopidogrel, and sublingual nitroglycerin were given in the emergency depart-
ment. Which one of the following best describes how his treatment should be managed?
A. Alteplase plus enoxaparin intravenous bolus.
B. UFH.
C. Tenecteplase plus UFH.
D. Diagnostic cardiac catheterization for possible primary PCI.
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II. PERIPHERAL ARTERIAL DISEASE
A. Definition
1. A generic term that encompasses vascular insufficiencies in noncoronary arteries secondary to atheroscle-
rotic occlusions. The arteries that are affected supply bloodflow to the brain, visceral organs, and limbs.
a. Functional – Caused by “spasm” in the vessels. Ex. Raynaud’s disease
b. Organic – Caused by structural changes in blood vessels. Ex. Fatty buildup in the arteries
2. In North American and Europe, there are about 27 million people affected by the disease. Around 10.5
million people are symptomatic, and 16.5 million are asymptomatic. The incidence increases with age,
affecting about 20% of patients older than 70 years.
B. Symptoms – May be initially asymptomatic and then progress to intermittent claudication and possibly to
critical leg ischemia
1. Leg or hip pain during walking
2. Cold legs and feet
3. Changes in skin color
4. Pain that is reduced upon resting.
5. Numbness or tingling
C. Diagnosis
1. Ankle brachial index (ABI): Blood pressure (BP) is measured in both arms and ankles using a regular
blood pressure cuff and a Doppler. The two pressures are then compared, and a determination is made
on how adequate the bloodflow is. The specific index or reference number is determined by dividing the
ankle systolic pressure by the arm systolic pressure.
a. May be done with or without a treadmill
B Systolic pressure recorded

in the brachial artery
of the arm
A Ultrasound device
amplifies the sound
of arterial blood flow
Blood pressure cuff
D
Systolic pressure recorded
Brachial in arteries of the ankle
artery after each arterial flow
is located
C Sound of arterial
blood flow Ultrasound
located in ankle device
Figure 1. How to measure pressures to calculate ankle brachial index.

National Heart Lung and Blood Institute Diseases and Conditions Index. Available at www.
nhlbi.nih.gov/health/dci/Diseases/pad/pad_diagnosis.html.
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Cardiology II
b. Calculation of ABI
i. Right ABI = Higher right ankle pressure/higher arm pressure
ii. Left ABI = Higher left ankle pressure/higher arm pressure
Table 12. ABI Interpretation

Level Interpretation
1–1.29 Normal resting ABI
0.91–0.99 Borderline
0.41–0.9 Mild to moderate
0–0.4 Severe
ABI = ankle brachial index.
2. Pulse volume recording – Used to establish initial lower extremity diagnosis (localization and severity)
3. Duplex ultrasonography – Used to assess anatomic location and the degree of stenosis. Often used as a
follow-up procedure after a femoral-popliteal or femoral-tibial pedal bypass
4. Continuous wave Doppler ultrasound – Used to determine the location of the diseased segment as well
as the severity. Can be helpful to follow disease progression
5. Magnetic resonance imaging – Used to assess anatomic location and disease severity. Most useful in
assessing patients for endovascular intervention
6. Computed tomographic angiography – Used to determine location of the stenosis as well as degree of
stenosis
7. Contrast angiography – Provides detail on anatomy of the arteries and is used to assess patients
possibly undergoing revascularization
Table 13. Peripheral Arterial Disease Risk Factors

Age older than 50 years
Cigarette smoking
Diabetes
High cholesterol
Family history
Hypertension
Coronary disease
Stoke
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Cardiology II
PAD Population (50 years and older)
Initial clinical presentation
Asymptomatic PAD Atypical leg pain Claudication Critical limb ischemia

20%–50% 40%–50% 10%–35% 1%–2%
1-year outcomes
Progressive
functional inpairment
Alive with two limbs Amputation CV Mortatlity

50% 25% 25%
5-year outcomes
Limb morbidity CV morbidity & mortality
Stable claudication Worsening Critical limb ischemia Nonfatal cardiovascular event Mortality
70%–80% claudication 1%–2% (MI or stroke) 20% 15%–30%
10%–20%
Amputation
(see CLI data) CV causes Non-CV causes
75% 25%
Figure 2. Natural history of atherosclerotic lower extremity PAD syndromes.

Adapted from Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: Executive
Summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the
Society for Cardiovascular Angiography and Interventions. Circulation 2011;124:2129–38
D. Treatment – General
1. Diet
2. Exercise
3. Smoking cessation – Applicable to all forms of tobacco
a. Single most important intervention
b. People who smoke are given a diagnosis of PAD as much as 10 years before a nonsmoker.
4. Drug therapy
a. Statin initiation – Goal LDL-C of less than 70 mg/dL for patients deemed very high risk
b. Fibric acid agents – Used for patients with low HDL-C, normal LDL-C, and high TG
c. Antihypertensives – Goal BP of less than 140/90 mm Hg if nondiabetic and less than 130/80 mm
Hg if diabetic or chronic kidney disease
i. β-Blockers – No impact on survival
ii. ACE inhibitors
d. Diabetes control including proper foot care – Goal A1c less than 7%
e. Antiplatelet agents
i. Recommended for all patients with lower extremity disease
ii. ASA 75–325 mg orally daily is effective.
iii. Clopidogrel 75 mg orally daily is an alternative to ASA.
iv. Warfarin – Not indicated
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Cardiology II
Patient Cases
6. C.J. is a 56-year-old man who presents to his primary care provider’s office for a follow-up visit after his
evaluation for possible PAD. His medical history is significant for HTN, and he is a smoker (2 packs/day x
20 years). His ABI comes back at 0.86. From these results, which one of the following best classifies C.J.’s
PAD?
A. Normal.
B. Mild.
C. Moderate.
D. Severe.
7. C.J. currently takes lisinopril 10 mg orally daily as his only medication. He has no known drug allergies.
From his ABI results, which of the following medication regimens in addition to a statin and smoking ces-
sation would be most appropriate to initiate at this time?
A. Folic acid.
B. Warfarin.
C. ASA.
D. Clopidogrel.
E. Treatment – Claudication
1. Cilostazol (Pletal)
a. Mechanism of action – A phosphodiesterase type 3 inhibitor that causes an increase in cyclic ad-
enosine monophosphate. It has both vasodilatory and antiplatelet effects.
b. Precise mechanism in claudication is unknown.
c. Dose – 100 mg orally twice daily
d. This agent improves symptoms and increases walking distance.
e. Avoid use in patients with HF.
2. Pentoxifylline (Trental)
a. Mechanism of action – A methylxanthine derivative. Reduces blood and plasma viscosity, inhibits
neutrophil adhesion and activation, increases erythrocyte and leukocyte deformability, and lowers
plasma fibrinogen levels
b. 400 mg orally 3 times/day
c. Second-line agent
d. Questionable efficacy
3. Additional therapies evaluated: Oral vasodilator prostaglandins (beraprost or iloprost)
F. Interventional Radiology
1. Reserved for patients with lifestyle-limiting symptoms
2. May include angioplasty, or stents
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Classis Claudication Symptoms:

Muscle fatigue, cramping, or pain thst reproducibly begins
during exercise and that promply resolves with rest
Chart document the history of walking impairment (pain-free

and total walking distance) and specific lifestyle limitations
Document pulse examination
Excercise ABI
(TBI, segmental pressure, or
ABI ABI >0.90 suplex ultrasound examination)
Confirmed PAD diagnosis Abnormal Normal

results Results
Risk factor normalization:

Immediate smoking cessation No PAD or
Treat hypertention: JNC-7 guidelines consider arterial
Treat lipids: NCEP ATP III guidelines entrapment
Treat diabetes mellitus: HbAlc < 7%* syndromes
Pharmacological risk reduction:

Antiplatelet therapy
(ACE inhibition; † Class IIa)
Figure 3. Symptoms of claudication.

* A significant reduction in PAD specific endpoints by treating diabetes mellitus as not yet been proven.
† No prospective trials have specifically documented the benefit of ACE inhibition in patients without claudication and has only
been extrapolated from other “at risk” populations
Adapted from Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary
Intervention: Executive Summary. A report of the American College of Cardiology Foundation/American Heart Association Task
Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011;124:2129–38.
G. Treatment – Critical Limb Ischemia

1. Pentoxifylline (Trental) – Parenteral
2. Oral vasodilator prostaglandins (beraprost or iloprost)
3. Endovascular treatment
4. Thrombolysis
5. Surgery – Reserved for patients with significant disease: Thrombectomy, bypass grafts
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Cardiology II
Confirmed PDP
Diagnosis
No significant Lifestyle-limiting symptoms Lifestyle-limiting

functional disability symtoms with evidence
of inflow disease
Supervised exercised Pharmacological therapy:
• No claudication program Cilostazol
treatment required (Pentoxifylline)
Further anatomic
• Follow-up visits at least definition by more
Three-
annually to monitor extensive noninvasive
month trial Three-month trial
for development or angiographic
of leg, coronary, diagnostic techniques
or cerebrovascular Preprogram and
ischemic symptoms postprogram exercise
testing for efficacy Endovascular therapy or
surgical bypass per anatomy
Clinical
improvement:
Follow-up visits and
lest annually
Significant disability despite medical

therapy and/or inflow endovascular
therapy, with documentation of outflow
PAD, with favorable procedural anatomy
and procedural risk-benefits ratio
Figure 4. Evaluating for PAD diagnosis.

Adapted from Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: Executive
Summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the
Society for Cardiovascular Angiography and Interventions. Circulation 2011;124:2129–38
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III. DYSLIPIDEMIA
A. Diagnosis
1. Complete fasting lipoprotein profile preferred (i.e., TC, LDL-C, HDL-C, and TG)
2. After 9–12 hours of fasting (however, with the availability of measuring direct LDL-C, fasting not
always necessary)
B. ATP (Adult Treatment Panel) III Lipid and Lipoprotein Classification

1. LDL-C (mg/dL)
Less than 100 Optimal
100–129 Near-optimal/above optimal
130–159 Borderline high
160–189 High
190 or more Very high
2. HDL-C (mg/dL)
Less than 40 Low
60 or more High
3. TC (mg/dL)
Less than 200 Desirable
240 or more High
4. TG (mg/dL)
Less than 150 Normal
200–499 High
500 or more Very high
Classification National Institutes of Health National Heart Lung and Blood Institute. Third Report of the Expert Panel on Detection,
Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Available at www.nhlbi.nih.gov/
guidelines/cholesterol/index.htm. Accessed January 18, 2012.
C. CHD and Risk Equivalents

1. CHD: MI, coronary artery bypass graft, PCI with or without stent, acute coronary syndrome (ACS)
2. Other clinical forms of atherosclerotic disease (PAD, abdominal aortic aneurysm, and symptomatic
carotid artery disease)
3. Diabetes mellitus
4. 10-year risk of CHD is more than 20% based on Framingham.
D. Main Positive Risk Factors (exclusive of LDL-C) That Modify LDL-C Goals
1. Cigarette smoking
2. Hypertension (BP 140/90 mm Hg or higher or taking an antihypertensive drug)
3. Low HDL-C (less than 40 mg/dL)
4. Family history of premature CHD
a. CHD in male first-degree relative younger than 55 years
b. CHD in female first-degree relative younger than 65 years
5. Age (men 45 years or older; women 55 years or older)
E. Main Negative Risk Factors (exclusive of LDL-C) that Modify LDL-C Goals: High HDL-C (more than 60
mg/dL) (subtract 1 from the total number of risk factors)
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Cardiology II
F. Risk Assessment
1. For patients with several (two or more) risk factors, perform Framingham 10-year CHD
risk assessment.
2. For patients with zero or one risk factor, 10-year risk assessment is not required.
3. Ten-year CHD risk assessment is based on Framingham tables available at www.nhlbi.nih.gov/
guidelines/cholesterol/risk_tbl.htm. Accessed January 18, 2012.
a. Sex
b. Age
c. Total cholesterol
d. Smoking
e. High-density lipoprotein
f. Systolic BP
G. Three categories of risk that modify LDL-C goals
Table 14. Goal LDL-C According to Risk Category and LDL-C Concentration to Start Pharmacotherapy
Risk Categorya LD-C Goal (mg/dL) LDL-C to Start Pharmacotherapy (mg/dL)
CHD and CHD risk equivalents < 100 (optional < 70) ≥ 130; ≥ 100 optional (≥ 100 or < 100)
(10-year risk > 20%)
Multiple (2+) risk factors < 130 (optional < 100) ≥ 130 (≥ 100)
(10-year risk 10%–20%)
Multiple (2+) risk factors < 130 ≥ 160
(10-year risk < 10%)
0 or 1 risk factor < 160 ≥ 190; ≥ 160 optional
a
Risk factors: See Item D above. The LDL levels in parentheses are taken from Grundy SM, et al. Implications of recent clinical trials for the
National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227–39. Only levels that are different from
the National Cholesterol Education Panel guidelines are included in parentheses. Consider less than 70 for everyone at very high CHD risk or
with stable CHD, based on PROVE-IT (N Engl J Med 2004;350) and TNT (N Engl J Med 2005;352:1425–35) studies, which were published after
the 2004 ATP (Adult Treatment Panel) III update.
CHD = coronary heart disease; LDL = low-density lipoprotein.
Classification National Institutes of Health National Heart Lung and Blood Institute. Third Report of the Expert Panel on Detection, Evaluation,
and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Available at www.nhlbi.nih.gov/guidelines/cholesterol/index.
htm. Accessed January 18, 2012.
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Cardiology II
Patient Cases
8. M.M. is a 63-year-old woman who just finished 6 months of diet and exercise for dyslipidemia. She has a
history of gout, chronic heart failure, HTN, and asthma, as well as a 15 pack/year history of tobacco (but
she quit 3 years ago); she drinks three beers a day. Because she was adopted, no family history records are
available. Her medications are albuterol (Xopenex HFA) MDI (metered dose inhaler), lisinopril, furose-
mide, and Tums 2 tablets/day. Vital signs are BP 124/80 mm Hg; HDL 54 mg/dL; LDL 193 mg/dL; TG 148
mg/dL; and TC 236 mg/dL. According to National Cholesterol Education Panel (NCEP) guidelines, which
one of the following best describes the number of CHD risk factors that are present?
A. Zero.
B. One.
C. Two.
D. Three.
9. According to NCEP guidelines, which one of the following is the most appropriate LDL-C goal for M.M.?
A. Less than 100 mg/dL.
B. Less than 130 mg/dL.
C. Less than 160 mg/dL.
D. Less than 190 mg/dL.
H. Therapeutic Lifestyle Changes – Initiate therapeutic lifestyle changes if LDL-C is above goal.
1. Weight reduction
2. Increased physical activity
3. Therapeutic lifestyle changes in diet
4. Plant stanols/sterols (2 g/day): Soybean and tall pine tree oils
5. Viscous (soluble) fiber (10–25 g/day): Oats, barley, pectin, psyllium
6. Nutrient composition of therapeutic lifestyle changes diet
Table 15. Dietary Recommendations

Nutrient Recommended Intake
Saturated fat Less than 7% of total calories
Polyunsaturated fat Up to 10% of total calories
Monounsaturated fat Up to 20% of total calories
Total fat 25%–35% of total calories
Carbohydrate 50%–60% of total calories
Fiber 20–30 g/day
Protein About 15% of total calories
Cholesterol Less than 200 mg/day
Classification National Institutes of Health National Heart Lung and Blood Institute. Third Report of the Expert Panel on Detection, Evaluation,
and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Available at www.nhlbi.nih.gov/guidelines/cholesterol/index.
htm. Accessed January 18, 2012.
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Cardiology II
I. Management of Low HDL-C

1. If TG is 500 mg/dL or greater, TG is primary target.
2. If TG is 200–499 mg/dL, non–HDL-C is secondary target of therapy.
3. If TG is less than 200 mg/dL and HDL-C is low, consider niacin or fibrates; may add to statins after
lowering LDL-C
4. Niacin is safer in combination with statins than with fibrates (myopathy).
5. Smoking cessation, exercise
J. Management of Very High TG Concentrations (500 mg/dL or more)

1. Therapy goal: Prevent acute pancreatitis.
2. Very low-fat diets (15% or less of caloric intake), reduce or eliminate alcohol
3. TG-lowering drug usually required
4. Fibrate or niacin
5. Reduce TG before LDL-C lowering
6. After TG concentrations are reduced, lower LDL-C; achieve LDL-C goal before treating non–HDL-C.
7. Non–HDL-C cholesterol: Secondary target
a. Non–HDL-C = VLDL + LDL-C (VLDL = very low-density lipoprotein)
b. Non–HDL-C = (TC − HDL-C)
c. Non–HDL-C: Secondary target of therapy when serum TG is 200 mg/dL or greater
d. Non-HDL goal: LDL-C goal plus 30 mg/dL
e. Comparison of LDL-C and non–HDL-C goals for three risk categories
Table 16. Goal Non–HDL-C

Risk Category LDL-C Goal Non–HDL-C
CHD and CHD risk equivalents (10-year risk > 20%) < 100 < 130
Multiple (2+) risk factors (10-year risk ≤ 20%) < 130 < 160
0 or 1 risk factor < 160 < 190
CHD = coronary heart disease; HDL-C = high-density lipoprotein; LDL-C = low-density lipoprotein.
f. Therapeutic approaches to elevated non–HDL-C

i. Intensify therapeutic lifestyle changes.
ii. Intensify LDL-C–lowering drug therapy.
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Cardiology II
Table 17. Emerging Risk Factors

Emerging Risk Factor and Key Points Increased by Decreased by Measurement and Interpretation
hsCRP Inflammation Weight loss Obtain two hsCRP measurements
Is a mediator of immune response Smoking Physical activity Use lower or average
Serves as marker of inflammation Hormone Statins Patient must be clinically
May be stronger CHD risk predictor than LDL-C replacement Fibrates stable (no infection, recent
Do not know whether there are clinical benefits therapy Ezetimibe hospitalization, recent trauma).
from lowering hsCRP Aspirin If > 10 mg/L, repeat test; probably
May be useful in motivating a patient to adhere noncardiac cause of elevation.
to lifestyle modifications (i.e., a patient with Chronic inflammatory diseases
unremarkable lipid panel needing lifestyle (e.g., rheumatoid arthritis) will
modification) increase CRP levels
Use selectively (i.e., ↑ LDL-C, > 2 risk factors, &
10-year risk 10%–20%; if hsCRP ≥ 1 mg/L, use Risk level of hsCRP
more intensive treatment) Low: < 1.0 mg/L
A value > 2 mg/dL is a strong predictor of CHD risk Intermediate: 1.0–3.0 mg/L
High: > 3 mg/L
Fibrinogen Inflammation Exercise No recommendations at this time
Many factors modulate fibrinogen levels (diabetes, Smoking Stop smoking
hypertension, inflammation, obesity, sedentary Niacin
lifestyle, smoking) Fibrates
Elevated levels associated with cardiovascular events
Unknown whether it has causal role or is a marker
of vascular damage
Unknown whether there are clinical benefits to
lowering fibrinogen
Homocysteine
Patients with inborn errors in homocysteine Renal failure Replacement of No recommendations at this time
metabolism have a high risk of venous thrombosis Hypothyroidism folate, B6, B12
at early age (< 30 years). Risk may be partially Deficiency of Genetics
decreased with high-dose B vitamins folate, B6, B12
Mild-moderate elevations may predispose patients Methotrexate
to atherosclerosis Genetics
Not know whether it has causal role or is a marker
of vascular damage
Do not know if there are cardiovascular benefits to
lowering homocysteine. Lowering homocysteine
with folic acid has not been associated with
cardiovascular risk reduction
Lp(a) Inflammation Niacin No recommendations at this time
LDL-like particle controlled mostly by genetics Genetics Estrogen
May be highly thrombogenic Genetics
When elevated, may increase the risk of
cardiovascular events in patients with
diabetes, hypertension, ↑ LDL-C, ↓ HDL-C, ↑
homocysteine, ↑ fibrinogen
Unaffected by diet or exercise
Do not know if there are clinical benefits to
lowering Lp(a)
Optimal role in screening/risk determination has not
been determined
CHD = coronary heart disease; HDL-C = high-density lipoprotein cholesterol; hsCRP = high-sensitivity C-reactive protein; LDL-C = low-
density lipoprotein cholesterol; Lp(a) = lipoprotein a.
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Cardiology II
K. Elevated C-Reactive Protein in Low-Risk Individuals: JUPITER study (Ridker PM, et al. N Engl J Med
2008;359:2195–207)
1. More than 15,000 subjects with no prior CAD or DM with normal LDL (less than 130 for inclusion;
median, 108), high C-reactive protein (2 mg/L or greater) (median C-reactive protein, 4.2–4.3)
2. Rosuvastatin 20 mg versus placebo
3. Trial was terminated early because of significant reduction in cardiovascular (CV) death and CV events
(hazard ratio = 0.56; 95% confidence interval, 0.46–0.69)
IV. PHARMACOTHERAPY
A. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) Reductase Inhibitors (statins)
Acetate
HMG CoA
Competitive Inhibition Reductase
Acetyl CoA
Inhibitors
(Statins)
HMG-CoA
duc tase
-Co A Re
HMG
↓ Cholesterol
production
Mevalonate
↑ expression
of LDL-C
receptors
Farnesyl
Dolichol Ubiquinone
Pyrophosphate
↓ LDL-C,
VLDL, and
IDL particles
Squalene
LDL-C
↓ Cholesterol Lowering
Figure 5. Mechanism of action of statins.
1. Efficacy
a. Drugs of choice for high LDL-C and/or CHD or CHD risk
b. When selecting a statin, consider the percentage of LDL reduction needed.
i. (current LDL-C − goal LDL-C)/current LDL-C × 100
ii. Select an initial dose to achieve an LDL-C reduction of 30%–40% if possible.
c. Reduce LDL-C 24%–60%.
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Cardiology II
d. Reduce TG 7%–40%.
e. Raise HDL-C 5%–15%.
f. Reduce major coronary events.
g. Reduce CHD mortality.
h. Reduce coronary procedures (percutaneous transluminal coronary angioplasty/coronary artery
bypass graft).
i. Reduce stroke.
j. Reduce total mortality.
2. Mechanism of action: Inhibits enzyme responsible for converting HMG-CoA to mevalonate (rate-
limiting step in production of cholesterol)
3. Main adverse effects/monitoring
a. Myopathy (check CK at baseline and then only if muscle symptoms occur; no regular monitoring)
b. Increased liver enzymes
c. Liver function tests (LFTs) at baseline, 3 months, and yearly
4. Contraindications
a. Absolute: Severe liver disease (AST/ALT [aspartate aminotransferase/alanine aminotransferase]
more than 3 × ULN [upper limit of normal])
b. Relative: Use with certain medications (strong cytochrome P450 [CYP] 3A4 inhibitors).
5. Drug interactions
a. CYP3A4 substrates: Simvastatin, lovastatin, atorvastatin
i. Avoid, if possible, with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole,
erythromycin, clarithromycin, HIV [human immunodeficiency virus] protease inhibitors,
nefazodone, cyclosporine, telithromycin, danazol, amiodarone, verapamil). Preferable to use
pravastatin, rosuvastatin
ii. Maximal dose of simvastatin is 10 mg/day when combined with verapamil or diltiazem.
iii. Maximal dose of simvastatin is 20 mg/day when combined with amiodarone, amlodipine, or
ranolazine.
b. Fibrates: Increased risk of myopathy/rhabdomyolysis when coadministered with statins. Risk is
greater with gemfibrozil than with fenofibrate.
c. Niacin: Doses greater than 1 g/day increase the risk of myopathy/rhabdomyolysis when used
concomitantly with statins; risk is lower than with fibrates; statins and niacin are commonly used
together; monitor for muscle pain.
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Cardiology II
Table 18. Statin Doses and LDL-C-Lowering Effect

Drug and Dose LDL-C Average Reduction (%)
Lovastatin ER (Altocor)
10 mg/day 24
20 mg/day 30
40 mg/day 36
60 mg/day 41
Rosuvastatin (Crestor)
5 mg/day 45
10 mg/day 52
20 mg/day 55
40 mg/day 63
Fluvastatin (Lescol)
20 mg/day 22
40 mg/day 25
40 mg twice daily 36
Atorvastatin (Lipitor)
10 mg/day 39
20 mg/day 43
40 mg/day 50
80 mg/day 60
Lovastatin (Mevacor)
10 mg/day 21
20 mg/day 27
40 mg/day 31
40 mg twice daily 42
Simvastatin (Zocor)
5 mg/day 26
10 mg/day 30
20 mg/day 38
40 mg/day 41
80 mg/day 47
Pitavastatin (Livalo)
1 mg/day 32
2 mg/day 36
4 mg/day 43
Pravastatin (Pravachol)
10 mg/day 22
20 mg/day 32
40 mg/day 34
80 mg/day 37
**Note: For any doubling of statin dose, the LDL-C will only
decrease by an additional 6%.
LDL = low-density lipoprotein.
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Cardiology II
Table 19. Pharmacokinetic Difference Among Statin Agents

Bioavailability (%) Elimination Metabolism
Half-life (hours) Prodrug Solubility
Pravastatin 17 1.5–2 N/A No Hydrophilic
Fluvastatin 24 1 2C9 No Hydrophilic
Lovastatin <5 2–3 3A4 Yes Lipophilic
Simvastatin <5 2 3A4 Yes Lipophilic
Atorvastatin 12 14 3A4 No Lipophilic
Rosuvastatin 20 20 2C19 No Hydrophilic
Pitavastatin 51 12 2C9, 2C8 Yes Lipophilic
N/A = not applicable
Table 20. Dosing of Statin Agents in Chronic Kidney Disease

eGFR (mL/minute)
Drug 30–59 15–29 15–29
Atorvastatin 10–80 mg 10–80 mg 10–80 mg
Fluvastatin 10–80 mg 10–40 mg 10–40 mg
Lovastatin 20–80 mg 10–40 mg 10–40 mg
Pravastatin 20–80 mg 20–40 mg 20–40 mg
Rosuvastatin 5–40 mg 5–10 mg –a
Simvastatin 20–80 mg 10–40 mg 10–40 mg
Pitavastatin 1–2 mg Avoid Avoid
a
No data available; cannot recommend.
eGFR = estimated glomerular filtration rate; HD = hemodialysis.
B. Bile Acid Sequestrants

1. Principal actions
a. Reduce LDL-C 15%–26%.
b. Raise HDL-C 3%–6%.
c. May increase TG concentrations
d. Reduce major coronary events.
e. Reduce CHD mortality.
2. Mechanism of action: Bind to bile acids to disrupt enterohepatic recirculation of bile acids. Liver is
stimulated to convert hepatocellular cholesterol to bile acids.
3. Adverse effects: Gastrointestinal (GI) distress/constipation
4. Decreased absorption of other drugs: Warfarin, β-blockers, and thiazides, so administer drugs 1–2
hours before or 4 hours after bile acid
5. Contraindications: Dysbetalipoproteinemia, raised TG concentrations (especially greater than
400 mg/dL)
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Cardiology II
Table 21. Bile Acid Sequestrants

Drug Brand Dose Range (g)
Cholestyramine Questran 4–16
Colestipol Colestid 5–20
Colesevelam Welchol 2.6–3.8
Table 22. Dose-Dependent Effects of BAS on LDL-C Cholesterol Concentrations

Dose (g) % LDL-C Reduction
Colestipol 5 −12
10 −20
15 −24
Cholestyramine 4–8 −9
8–12 −13
12–16 −17
16–20 −21
20–24 −28
Colesevelam 3.8 −15
4.5 −18
BAS = bile acid sequestrant; LDL-C- low-density lipoprotein cholesterol.
C. Niacin
1. Main actions
a. Lowers LDL 15%–26%
b. Lowers TG 20%–50%
c. Raises HDL 15%–26%
d. Reduces major coronary events
e. Possibly reduces total mortality
f. Lowers lipoprotein a
2. Mechanism of action: Inhibits mobilization of free fatty acids from peripheral adipose tissue to the
liver, so reduces VLDL synthesis (LDL and TG)
3. Adverse effects: Flushing, hyperglycemia, hyperuricemia, upper GI distress, hepatotoxicity; monitor
LFTs at baseline, every 6–12 weeks, and then yearly
4. Sustained release appears to be more hepatotoxic than other preparations (e.g., over-the counter
preparations [OTCs]). Available as “Slo-Niacin” or 2 times/day generic niacin OTC, this should be
avoided
5. Extended release and sustained release are less likely to cause flushing.
6. Contraindications: Liver disease, severe gout, active peptic ulcer
7. Flushing can be minimized by taking ASA 30 minutes before niacin, taking at bedtime with food, and
avoiding hot beverages, spicy foods, and hot showers around the time of administration.
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Cardiology II
Table 23. Niacin Formulations

Drug Form Brand Name Dose Range (g)
Immediate release Niacin 1.5–3
Extended release Niaspan 1–2
Sustained release Slo-Niacin 1–2
Table 24. Dose-Dependent Effects of Extended-Release Niacin (Niaspan) on Lipid Parameters

TC (%) LDL-C (%) TG (%) HDL-C (%)
Niaspan 500 mg −2 −3 −6 +10
Niaspan 1000 mg −5 −9 −5 +15
Niaspan 1500 mg −11 −14 −28 +22
Niaspan 2000 mg −12 −17 −35 +26
HDL-C = high-density lipoprotein-cholesterol; LDL-C = low density lipoprotein-cholesterol;
TC = total cholesterol; TG = triglycerides.
D. Fibrates
1. Main actions
a. Lower LDL-C 5%–20% (with normal TG)
b. May raise LDL-C up to 45% (with very high TG)
c. Lower TG 30%–55%
d. Raise HDL-C 18%–22%
e. Reduce progression of coronary lesions
f. Reduce major coronary events
2. Mechanism of action: Reduces rate of lipogenesis in the liver
3. Adverse effects: Dyspepsia, gallstones, myopathy, increased hepatic transaminases; monitor LFTs
every 3 months during first year and then periodically
4. Contraindications: Severe renal or hepatic disease
Table 25. Fibrate Formulations and Dosing

Druga Brand Name Dose
Gemfibrozil Lopid 600 mg 2 times/day
Fenofibrate TriCor 48–145 mg/day without regard to meals
Fenofibrate Lofibra micronized 67–200 mg/day with meals
Fenofibrate Lofibra 54–160 mg/day with meals
Fenofibrate Antara 43–130 mg/day without regard to meals
Fenofibrate Fenoglide 40–120 mg/day with meals
Fenofibrate Lipofen 50–150 mg/day with meals
Fenofibrate Triglide 50–160 mg/day without regard to meals
Fenofibric acid Trilipix 45–135 mg/day without regard to meals
The fenofibrate formulations are not interchangeable.
a
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Cardiology II
E. Ezetimibe (Zetia) 10 mg/day

1. Efficacy
a. Lowers LDL-C 18%–20%
b. May raise HDL-C 1%–5%
c. Lowers TG 7%–17%
2. Mechanism of action: Inhibition of cholesterol absorption
3. Adverse effects: Headache, rash; no monitoring necessary, except LFTs when coadministered with
statins
4. Adjunctive therapy to statin
5. No outcomes data
6. In patients with familial hypercholesterolemia, combined therapy with ezetimibe and simvastatin did
not result in significant changes in intima-media thickness compared with simvastatin alone, despite
decreases in concentrations of LDL-C and C-reactive protein.
7. Possibly increased cancer risk; but evidence is conflicting
Table 26. Effect of Ezetimibe on Lipid Parameters

TC (%) LDL-C (%) TG (%) HDL-C (%)
Ezetimibea alone −12 −18 −7 +1
Ezetimibe + HMG-CoA
a,b
−17 −25 −14 +3
Ezetimibe + fenofibrate 160 mg −22 −20 −44 +19
Mean percent change from baseline.
a
Represents mean of all statins.

b
HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; TG = triglycerides.
Patient Case
10. Which one of the following medications is best to recommend for treating M.M.’s lipids (from patient case 8)?
A. Ezetimibe 10 mg/day.
B. Fenofibrate 145 mg/day.
C. Colesevelam 625 mg 6 tablets/day.
D. Atorvastatin 20 mg/day.
F. Omega-3-Acid Ethyl Esters (Lovaza)

1. Efficacy
a. Lowers TG 26%–45%
b. May raise LDL up to 45% when TG concentrations are very high
c. Raises HDL-C 11%–14%
2. Mechanism of action: Unknown. Possible inhibition of acyl CoA:1,2 diacylglycerol acyltransferase,
increased hepatic β-oxidation, or reduction in TG hepatic synthesis
3. Adverse effects: GI (e.g., burping, taste perversion, dyspepsia); at more than 3 g/day: inhibition of
platelet aggregation, bleeding
4. Dose: 4 g/day as a single daily dose or in two divided doses
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Cardiology II
REFERENCES
Acute Coronary Syndromes 6. Brilinta (ticagrelor) prescribing information. Wilm-

1. Antman EM, Hand M, Armstrong PW, et al. 2007 ington, DE: Astra Zeneca 2011.
focused update of the ACC/AHA 2004 guidelines
for the management of patients with ST-elevation Peripheral Arterial Disease
myocardial infarction: a report of the American
1. Rooke TW, Hirsch AT, Misra S, et al. 2011 ACCF/
College of Cardiology/American Heart Associa-
AHA focused update of the Guideline for the Man-
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agement of Patients with Peripheral Artery Dis-
in collaboration with the Canadian Cardiovas-
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cular Society endorsed by the American Acad-
the American College of Cardiology Foundation/
emy of Family Physicians. J Am Coll Cardiol
American Heart Association Task Force on Practice
2008;51:210–47.
Guidelines. J Am Coll Cardiol 2011;58:2020–45.
2. Wright RC, Anderson JL, Adams CD, et al. ACCF/
AHA 2011 guideline update for the management of
patients with unstable angina and non–ST-segment 2. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/
elevation myocardial infarction – (Updating the AHA 2005 Practice Guidelines for the Manage-
2007 Guideline) A report of the American College ment of Patients with Peripheral Arterial Disease
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Society for Vascular Surgery, Society for Cardio-
3. King SB III, Smith SC Jr, Hirshfeld JW Jr, et al.
vascular Angiography and Interventions, Society
2007 focused update of the ACC/AHA/SCAI
for Vascular Medicine and Biology, Society of In-
2005 guideline update for percutaneous coronary
terventional Radiology, and the ACC/AHA Task
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Force on Practice Guidelines (Writing Committee
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to Develop Guidelines for the Management of Pa-
Force on Practice Guidelines. J Am Coll Cardiol
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2008;51:172–209.
by the American Association of Cardiovascular
4. Kushner FG, Hand M, Smith SC Jr, et al. 2009 fo- and Pulmonary Rehabilitation; National Heart
cused update of the ACC/AHA guidelines for the Lung, and Blood Institute; Society for Vascular
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lines on percutaneous coronary intervention (updat-
ing the 2005 guideline and 2007 focused update):
a report of the American College of Cardiology/ Dyslipidemia
American Heart Association Task Force on Practice 1. National Institutes of Health National Heart Lung
Guidelines. J Am Coll Cardiol 2009;54:2205–41. and Blood Institute. Third Report of the Expert
5. Levine GN, Bates ER, Blankenship JC, et al. 2011 Panel on Detection, Evaluation, and Treatment of
ACCF/AHA/SCAI Guideline for Percutaneous High Blood Cholesterol in Adults (Adult Treatment
Coronary Intervention: Executive Summary. A re- Panel III). JAMA 2001;285:2486–97. Available at
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Practice Guidelines and the Society for Cardiovas- 2. Grundy SM, Cleeman JI, Bairey Merz CN, et al.
cular Angiography and Interventions. Circulation Implications of recent clinical trials for the Nation-
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3. Pasternak RC, Smith SC, Bairey-Merz CN, et al.

ACC/AHA/NHLBI advisory on the use and safety
of statins. J Am Coll Cardiol 2002;40:567–72.
4. Kastelein JJP, Akdim F, Stroes ESG, et al. Simvas-
tatin with or without ezetimibe in familial hyper-
cholesterolemia. N Engl J Med 2008;358:1431–43.
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Cardiology II
Answers and Explanations to Patient Cases
1. Answer: a lor and should not be used. Aspirin at a dose of 325 mg

In this patient, the presence of ST depression on ECG, may be administered with ticagrelor as an initial load-
positive biomarkers for myocardial necrosis, at least ing dose but should be reduced to 75 or 100 mg there-
three risk factors for CAD, and history of CAD (prior after. Therefore, a maintenance of 81 mg/day together
MI), as well as other factors, suggests a high risk of fu- with ticagrelor is the correct answer.
ture events. In such high-risk patients, cardiac catheter-
ization (invasive strategy) is used to determine whether 4. Answer: a
occluded or partially occluded epicardial arteries ex- Although this patient presented within 3 hours of chest
ist, which ones can be intervened on, and whether to pain onset and is a thrombolytic candidate (within less
make an intervention (stent or percutaneous translumi- than 6 hours of onset is preferred), up to 95% of patients
nal coronary angioplasty). Aspirin and clopidogrel or
can achieve normal, brisk TIMI-3 flow rates with pri-
prasugrel is indicated for an early invasive strategy in
mary PCI versus only 50%–60% of patients achieving
the management of an NSTEMI. The GP IIb/IIIa in-
normal TIMI-3 coronary flow with thrombolytic ther-
hibitors abciximab or eptifibatide should be initiated at
apy. Because the patient presents to a hospital that can
the time of PCI. Unfractionated heparin, enoxaparin,
or fondaparinux should be initiated on presentation and perform a primary PCI with stent implantation, this is
would be appropriate to pair with abciximab or eptifi- the therapy of choice. Although GP IIb/IIIa inhibitors
batide. Abciximab was beneficial only in clinical trials have been studied in combination with fibrinolytics and
of primary PCI or PCI during the abciximab infusion anticoagulants for STEMI, the slight increase in TIMI-
(early invasive strategy). Abciximab was not superior to 3 bloodflow rates was accompanied by a substantially
placebo when used in a conservative medical manage- increased risk of bleeding; thus, they are not recom-
ment strategy without PCI. Unfractionated heparin, to- mended. Tirofiban and UFH alone are not indicated for
gether with clopidogrel, has been studied in medically the treatment of STEMI (recommended for the medical
managed patients not pursuing catheterization (CURE management of NSTEMI ACS only).
trial) but was studied in a low-risk patient population.
Metformin should be held for 24 hours either before or 5. Answer: C
after the catheterization (especially in those with renal Unlike the patient in case 9, this patient presents with
dysfunction) to prevent lactic acidosis. a STEMI to a rural community hospital. He presents
within the window for thrombolytic therapy consid-
2. Answer: D eration (less than 6 hours after chest pain onset). He
Clopidogrel has been studied most commonly for a 30- is experiencing complete heart block and bradycar-
day poststenting procedure to prevent acute reocclusion dia, which could indicate an occlusion above the area
of coronary vessels. Because the stent is not endotheli- perfusing his sinoatrial and/or atrioventricular nodes.
alized for a longer period after drug-eluting stent place- Because he is still having ischemic chest pain and ST-
ment compared with traditional stents, a clopidogrel segment elevation, he should benefit from reperfusion
duration of at least 3 months was initially recommend- therapy. Enoxaparin is a treatment option for medical
ed for sirolimus-eluting stent and at least 6 months after
management, but the patient is at higher risk of bleed-
paclitaxel drug-eluting stent placement to prevent risk
ing from impaired enoxaparin clearance and requires
of acute stent thrombosis. However, this recommenda-
dosage adjustment. Simply treating this patient conser-
tion was recently extended to at least 1 year for both of
vatively with UFH alone in the setting of ongoing chest
these drug-eluting stents. The dose of ASA has changed
indicating that a dose of 81 mg may be initiated follow- pain, shortness of breath, and pulmonary edema is not
ing the procedure and continued indefinitely. optimal. Diagnostic catheterization and possible PCI
to determine whether an artery can be reperfused are
3. Answer: B not desirable because of the patient’s elevated SCr (2.5
Unlike other ADP (adenosine diphosphate) inhibitors, mg/dL). Because of the shorter half-life and ease of ad-
maintenance doses of ASA greater than 100 mg/day ministration of tenecteplase, it is preferable to alteplase.
have been shown to reduce the effectiveness of ticagre- Clearance of UFH is not as altered as enoxaparin and
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Cardiology II
would be a more appropriate therapy than enoxaparin • CHD in female first-degree rela-
in combination with a thrombolytic. tive younger than 65 years
• Age (men aged 45 years or older; wom-
6. Answer: B en aged 55 years or older)
From this patient’s ABI value, he has mild to moderate Major Negative Risk Factors (exclusive
disease. An ABI less than 0.9 is indicative of PAD, a value of LDL-C) That Modify LDL Goals
of 0.7–0.9 is considered mild, a value of 0.4–0.7 is mod- High HDL-C (more than 60 mg/dL)
erate, and a value less than 0.4 is considered severe. His
risk factors for PAD include hypertension and smoking. 9. Answer: B
Given her risk factors and her calculated Framingham
ABI Interpretation risk of 4%, her LDL-C goal is less than 130 according
Level Interpretation to the most recent NCEP recommendations.
1 Normal resting ABI LDL-C Concentration
0.7–0.9 Mild Risk Category (mg/dL)
0.41–0.7 Moderate CHD and CHD risk < 100 (< 70)
equivalents
0–0.4 Severe (10-year risk > 20%)
Several (2+) risk factors < 130 (< 100)
7. Answer: C (10-year risk = 10%–20%)
C.J. is taking an ACE inhibitor for his hypertension, Several (2+) risk factors < 130
which is an acceptable option, but a β-blocker would (10-year risk < 10%)
have also been an option for him. As long as C.J.’s hy- 0 or 1 risk factor < 160
pertension is controlled, lisinopril should be fine. He
is a smoker, so smoking cessation is critical to help his
disease state. Statin therapy is clearly indicated in this 10. Answer: D
patient, so that is a correct option. There is no homo-
cysteine level on which to base any recommendations LDL-C Concentrations at Which to Consider Pharma-
for folic acid therapy, and warfarin therapy is not in- cotherapy
dicated for the treatment of PAD. Clopidogrel would LDL-C Concentration
be an option if this patient were unable to take ASA Risk Category (mg/dL)
therapy. However, he has no known drug allergies, so CHD and CHD risk equivalents ≥ 130 (≥ 100 or even
statin, smoking cessation, and ASA therapy would be (10-year risk > 20%) < 100)
most appropriate. Several (2+) risk factors ≥ 130 (or ≥ 100)
(10-year risk = 10%–20%)
8. Answer: C Several (2+) risk factors ≥ 160
This patient has two risk factors: her age and HTN. (10-year risk < 10%)
Smoking is not considered a risk factor for a smoker who 0 or 1 risk factor ≥ 190
has quit. Alcohol intake is not considered a risk factor.
Chronic HF is not a CAD risk equivalent.
To calculate the percent reduction needed to reach goal,
Major Positive Risk Factors (exclusive of use the equation (actual LDL-C 193 − goal LDL-C 130)
LDL-C) That Modify LDL Goals × 100%/actual LDL-C 193. For this patient, the percent
• Cigarette smoking reduction needed to reach goal is 32%.
• Hypertension (BP 140/90 mm Hg or greater
or taking an antihypertensive drug) The HMG-CoA reductase inhibitors (statins) reduce
• Low HDL-C (less than 40 mg/dL) LDL-C 18%–55%. Atorvastatin 20 mg will provide
• Family history of premature CHD approximately a 43% reduction in LDL-C Ezetimibe
• CHD in male first-degree rela- lowers LDL-C 15%–20%. Fibric acids lower LDL-C
tive younger than 55 years 5%–20% (with normal TG) but may raise LDL (with
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Cardiology II
high TG), and they are generally not used to treat a high
LDL-C. Bile acid sequestrants lower LDL-C 15%–
30%, but they are difficult to tolerate, and the outcomes
data are not as strong as with statins. In patients with
familial hypercholesterolemia, combined therapy with
ezetimibe and simvastatin did not result in a significant
difference in intima-media thickness compared with
simvastatin alone, despite decreases in concentrations
of LDL-C and C-reactive protein, so ezetimibe is only
recommended as adjunctive therapy to statins because
no positive outcomes data are available.
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Cardiology II
Answers and Explanations to SELF-ASSESSMENT QUESTIONS
1. Answer: B person with two risk factors, and drug therapy is recom-
This patient received the standard MONA treatment mended if the level is above this goal. J.C. needs about
in addition to UFH for his ACS. However, only ASA, a 30% reduction to obtain his LDL-C goal. Pravastatin
metoprolol, and heparin have been shown to affect mor- 10 mg will provide about a 22% reduction, and atorv-
tality. The recommended doses of these agents are ASA astatin 10 mg will provide about a 39% reduction. The
325 mg, metoprolol 5 mg intravenous push × 3 doses, other two options are incorrect because the LDL-C goal
and UFH with a bolus dose of 60 units/kg, followed by for J.C. is less than 130 mg/dL, not 160 mg/dL.
an infusion of 12 units/kg/hour.The dose of 80 units/
kg and 18 units/kg/hr is utilized in the setting of non- 5. Answer: B
cardiac indications such as DVT treatment. Although This patient has several risk factors for developing PAD.
nitroglycerin is highly used in the initial management Several therapies are recommended for these patients,
of ACS, its primary role is to vasodilate the coronary Aspirin therapy should be initiated in all patients with
vessels to improve bloodflow and increase oxygen sup- CAD is therefore the correct answer. Anticoagulation
ply to the affected vessel, but the drug has no impact therapy with warfarin has no role in the management of
on mortality. PAD, and it is not indicated. Pentoxifylline has limited
data and is not recommended as first-line therapy. Al-
2. Answer: B though this patient has hypertension, a β-blocker has no
Given that J.J. experienced a significantly low platelet proven efficacy in this patient population.
count with his last cardiac catheterization with suspect-
ed HIT, the use of any GP IIb/IIIa inhibitor or throm- 6. Answer: C
bolytic therapy would be unwise because these agents A normal ABI is a level of 1 or greater. An ABI value
need to be combined with UFH. Therefore, bivalirudin, of less than 0.9 is indicative of PAD. A value of 0.7–0.9
a direct thrombin inhibitor, would be the treatment of correlates with mild disease, 0.4–0.7 indicates moder-
choice in patients undergoing PCI with HIT. ate disease, and less than 0.4 indicates severe disease.
Therefore, M.P., given that she has an ABI of 0.72, has
3. Answer: D mild disease, and Answer C is correct.
The management of very high TG concentrations (500
mg/dL or greater) includes TG-lowering medications
such as a fibrate or niacin. Given that this patient is
already taking niacin, the next likely option would be
to add a fibrate because fibrates lower LDL 5%–20%
(with normal TG) and lower TG up to 55%. Increas-
ing the statin dose is unlikely to provide any additional
benefit. However, because J.W. has renal insufficiency,
the choice and dose of fibrate are important. The use of
gemfibrozil is not recommended when the CrCl drops
below 50 mL/minute, and the dose of fenofibrate (Tri-
Cor) is recommended to be reduced to 48 mg once daily
when the CrCl is between 30 mL/minute and 80 mL/
minute; therefore, Answer D would be the best option
for J.W.
4. Answer: C
This patient has two risk factors for CAD: that of his
age and that he is a smoker. The NCEP guidelines rec-
ommend an LDL-C goal of less than 130 mg/dL for a
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Cardiology II

Learning Objectives: D. ASA 81 mg, metoprolol 5 mg x 3, and UFH

B. Increase atorvastatin to 80 mg and add C. An ABI of 0.72 indicates mild to moderate

4. J.C. a 57-year-old man who smokes, presents to his

5. L.G., a 58-year-old man, presents to his primary

6. A.W. is a 56-year-old woman with CAD, hyper-

I. ACUTE CORONARY SYNDROMES

A. Definitions and Goals

Table 1. UA, NSTEMI, and STEMI Definitions

B. Invasive or Conservative Treatment Strategy

Table 2. TIMI Risk Score Unstable Angina/NSTEMIa

Table 3. Selection of Initial Treatment Strategy: Invasive vs. Conservative

Table 4. Initial Management of ACS - “MONA” plus β-Blocker

2. Treatment algorithms for UA/NSTEMI and STEMI (see Tables 5 and 6)

Table 5. UA/NSTEMI Algorithm

Table 6. STEMI Management for Symptoms Lasting <12 Hours or Lessa

3. Dosing of antiplatelet and anticoagulant therapy (see Tables 7–9)

Table 7. Oral Antiplatelet Agents

Table 8. GP IIb/IIIa Inhibitor Dosing

Table 9. Anticoagulant Dosing

4. Thrombolytic dosing (see Table 10) and adjunctive therapy

Table 10. Thrombolytic Therapy

Table 11. Contraindications to Thrombolytic Therapy

c. Angiotensin receptor blocker if ACE inhibitor intolerant

Patient Cases (continued)

II. PERIPHERAL ARTERIAL DISEASE

B Systolic pressure recorded

Figure 1. How to measure pressures to calculate ankle brachial index.

Table 12. ABI Interpretation

Table 13. Peripheral Arterial Disease Risk Factors

PAD Population (50 years and older)

Initial clinical presentation

Asymptomatic PAD Atypical leg pain Claudication Critical limb ischemia

Alive with two limbs Amputation CV Mortatlity

Limb morbidity CV morbidity & mortality

Figure 2. Natural history of atherosclerotic lower extremity PAD syndromes.

Classis Claudication Symptoms:

Chart document the history of walking impairment (pain-free

Document pulse examination

Confirmed PAD diagnosis Abnormal Normal

Risk factor normalization:

Pharmacological risk reduction:

Figure 3. Symptoms of claudication.

G. Treatment – Critical Limb Ischemia

No significant Lifestyle-limiting symptoms Lifestyle-limiting

Significant disability despite medical

Figure 4. Evaluating for PAD diagnosis.

B. ATP (Adult Treatment Panel) III Lipid and Lipoprotein Classification

C. CHD and Risk Equivalents

G. Three categories of risk that modify LDL-C goals

Table 15. Dietary Recommendations

I. Management of Low HDL-C

J. Management of Very High TG Concentrations (500 mg/dL or more)

Table 16. Goal Non–HDL-C

f. Therapeutic approaches to elevated non–HDL-C

Table 17. Emerging Risk Factors

A. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) Reductase Inhibitors (statins)

Figure 5. Mechanism of action of statins.

Table 18. Statin Doses and LDL-C-Lowering Effect

Table 19. Pharmacokinetic Difference Among Statin Agents

Table 20. Dosing of Statin Agents in Chronic Kidney Disease

B. Bile Acid Sequestrants

Table 21. Bile Acid Sequestrants