CORONARY ARTERY DISEASE MANAGEMENT
When using any management guideline, always follow the Guidelines of Proper Use (page Error! Bookmark not defined.).
Definitions
● Atherosclerotic changes in the walls of coronary arteries resulting in plaque
formation and vascular remodeling
Differential diagnosis
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GERD
Esophageal spasm
Pulmonary embolism
Musculoskeletal truncal pain
Pleurodynia
Anxiety disorder
Panic disorder
Aortic stenosis
Aortic dissection
Coronary artery vasospasm
Cocaine abuse
Pericarditis
Myocarditis
Peptic ulcer disease
Gastritis
Hiatal hernia
Cholecystitis
Biliary colic
Considerations
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Can cause diminished blood flow to cardiac muscle
14 million Americans have coronary artery disease (CAD)
1.5 million myocardial infarctions per year
Greater than 500,000 deaths per year
Patient education very important
Risk factors
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Smoking
Male sex
Age
Hypertension
Hyperlipidemia
Dyslipidemia
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Diabetes mellitus
Family history
Sedentary lifestyle
Obesity
Metabolic syndrome
Rheumatoid arthritis/SLE (females > males)
Acute coronary syndrome (unstable angina or AMI)
● Unstable plaque rupture causing thrombus formation obstructing vessel
lumen leading to angina and/or AMI
● May have less than 50% blockage of artery by plaque alone
● Decreased incidence with statin and ACE inhibitor treatment
• ACE inhibitors improve endothelial function
● Decreased incidence with antiplatelet agents
Signs and symptoms
● May be asymptomatic
● Chest pain centrally or in various locations
● May occur at rest, from exertion or from emotional stress
● Arm pain
● Jaw pain
● Shortness of breath
● Dyspnea on exertion
● Diaphoresis
● Nausea
● Vomiting
● Syncope
● Sudden cardiac arrest or ventricular fibrillation (sudden death)
● Congestive heart failure
Physical Examination
● Usually normal
● S3/S4 heart sounds may be heard during anginal episode
● Levine sign — clenched fist over central chest during chest pain suggest of
angina
● Xanthelasma or xanthoma as hyperlipidemia stigmata
● Carotid or aortic bruit
● Pulmonary rales from heart failure
Evaluation options
Initial tests
● EKG
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CBC
BMP
HbA1c if diabetic or glucose intolerant
Fasting lipid profile
Thyroid function tests
Chest x-ray
BNP (B-type natriuretic peptide) if heart failure considered
C-reactive protein
Urinary albumen to creatinine ratio
Troponin for prolonged chest pain (≥ 10 minutes) in the past week that
has resolved (if angina occurring in office that appears unstable — send to
ER)
Imaging or stress testing
● Exercise with EKG monitoring
• Initial procedure of choice without ST segment baseline resting
abnormalities
• ≥ 1 mm ST segment depression 80 msec from J point most
characteristic change with positive test for ischemia
• Withhold beta-blockers for 48 hours before test if possible
• Dobutamine, adenosine and dipyridamole stress testing may be
performed in patients unable to exercise
● Stress echocardiogram — sensitivity 78% and specificity 86%
• Localizes ischemia and severity
• Assists in evaluating left ventricle wall motion, cardiac chamber size
and for valvular disease
• May be technically difficult to get good images
● Myocardial perfusion scintigraphy — sensitivity of 83% and specificity of
77%
● Do not perform exercise stress testing with symptomatic arrhythmias,
aortic stenosis or recent AMI
● Stop exercise stress testing with development of
• Chest pain
• Drop in systolic blood pressure > 10 mm Hg
• Severe shortness of breath, fatigue, dizziness or near syncope
• ST segment depression > 2 mm
• ST segment elevations > 1 mm without diagnostic Q waves
• Ventricular tachyarrhythmia
● 64 slice CT angiogram which has nearly 100% negative predictive value
● Coronary angiography
Treatment options
● Treat risk factors (see specific management sections)
● Statins
● ACE inhibitors and angiotensin receptor blockers
● Platelet inhibitors
● Aspirin (ASA) 81–325 mg PO qday
● Clopidogrel (Plavix) 12 months after ACS episode, then ASA qday
● Beta–blockers
● Stable or exertional angina
● Heart failure
● Calcium channel blockers
● Nitrates (may cause hypotension with IHSS/ASH — hypertrophic
cardiomyopathy)
● Ranolazine — reserved usually until after standard therapy has failed to
control symptoms (not a first–line drug)
● Diet
● Reduced fats
● Weight reduction as appropriate
● Increased physical activity as tolerated
● Cardiac rehabilitation
Medication treatment for stable angina
Anginal episode/week ≤ 1
• ASA
• NTG SL prn — may repeat q5minutes x 2 prn
Anginal episode/week ≥ 2
• ASA
• NTG SL prn — may repeat q5minutes x 2 prn
• Long acting NTG
May add as needed
• Beta-blocker
• ACEI or ARB to a beta-blocker
• Add calcium channel blocker when symptoms persist on beta–blocker
or beta–blocker cannot be used (do not use verapamil with beta–
blocker)
High risk patient
• ASA or clopidogrel
• ACEI or ARB added to nitrates and beta–blockers
Angina persists or not controlled on 3 medications
• Coronary angiography
Medication selections
Statins
● May causes liver and muscle disease
● Stop if CPK becomes elevated
● Read drug information for adverse reactions, cautions and
contraindications
● Avoid in heavy alcohol use
Atorvastatin (Lipitor)
• 10–20 mg PO qday initially
• 10–80 mg PO qday maintenance
• Stop if LFT’s > 3 times normal
Pravastatin (Pravachol)
• 10–40 mg PO qday — not to exceed 80 mg/day
• Hepatic and renal impairment — 10 mg PO qday
• Do not use in active liver disease
Simvastatin (Zocor)
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10–20 mg PO qday in the evening
If high risk for CAD — 40 mg PO qday in the evening
Stop if LFT’s > 3 times normal or renal failure develops
Myopathy risk greater at 80 mg PO qday dosing
Rosuvastatin (Crestor)
• 10–20 mg PO qday initially — may titrate but not to exceed 40 mg PO
qday
• Caution in liver disease
• Start at 5 mg PO qday in Asians
Lovastatin (Altoprev)
• 10–60 mg PO qhs
• Reduce if creatinine clearance < 30 mL/minute
• Stop if LFT’s > 3 times normal, renal failure or myopathy with elevated
CPK develops
• Avoid in heavy alcohol use
Fluvastatin (Lescol, Lescol XL)
• Start 20–40 mg PO qhs
• Dose range 20–80 mg PO qday
 Divide bid if 80 mg used
• Stop if LFT’s > 3 times normal, renal failure or myopathy with elevated
CPK develops
Nitrates
● Decreases preload, afterload, myocardial work and oxygen consumption
● Dilates coronary arteries
● Long-acting nitrates used continuously throughout the day will develop
tolerance in 24–48 hours and lose effectiveness, so a nitrate free period
for 8–12 hours each day with no long-acting nitrates is needed, frequently
performed during sleep periods
Short-acting nitrates
• NTG 0.3–0.6 SL prn — may repeat x 2 q5minutes prn and call 911 if 3
doses are taken and/or episode is unusually severe
• May use before anginal provoking activities
 Comes in tablets or spray
 Tablets need refrigeration and last 3–6 months, and should tingle
tongue when used
 NTG spray lasts 2–3 years
Long-acting nitrates
Timing — taken at time of day that anginal symptoms or anginal equivalent
symptoms (i.e., dyspnea) are most prevalent
• NTG 2.5 mg or 6.5 mg PO bid
• Isosorbide dinitrate (Isordil) 40–80 mg PO q8–12hr
 Starts to work in 15–30 minutes and lasts 3–6 hours
• Isosorbide mononitrate
 Standard dose — 20 mg PO bid given 7 hours apart
 Smaller patients start 5 mg PO bid given 7 hours apart and
increase to 10–20 mg PO bid given 7 hours apart over 2-3 days
 Take on empty stomach 30 minutes prior to a meal or 1 hour after
a meal
• Isosorbide mononitrate ER (extended release)
 30-120 mg PO qday
• Transdermal nitroglycerin (Nitro-Dur)
 0.2–0.4 mg/hr qday — remove for 10–12 hours each day
 Max dose 0.4-0.8 mg/hr qday
 Starts acting in 30 minutes and lasts 8–14 hours
Nitrate side–effects (some)
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Headache
Hypotension
Tachycardia
Nausea
Nitrate contraindications (some)
• Shock or hypotension
• Use of erectile dysfunction medications (sildenafil, tadalafil, or
vardenafil)
• Severe anemia
Beta-blockers
● Reduce heart rate, blood pressure and cardiac contractility which
decreases cardiac work and oxygen needs
● First choice usually in stable angina
● Prolongs survival and decreases second AMI incidence
Selective beta–1 blocker
• Metoprolol (Lopressor) initially 50 mg PO bid and may be increased to
200 mg PO bid
• Metoprolol (Toprol XL) 100 mg PO qday — NMT 400 mg PO qday
• Atenolol (Tenormin) 50 mg PO qday — NMT 200 mg PO qday
Non-selective beta–blocker
• Propranolol (Inderal) 80–120 mg PO bid — may increase at weekly
intervals as needed
• Inderal LA 80–160 mg PO qday
• NMT 320 mg PO qday
Beta–blocker side effects (some)
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Bradycardia
Hypotension
Worsening of asthma and COPD
Depression
Heart failure
Exacerbation of angina and hypertension on abrupt withdrawal (Black
Box Warning)
• Worsening of peripheral arterial disease symptoms
Contraindications (some)
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Pre-existing sinus bradycardia
2nd and 3rd degree heart block
Asthma and COPD
Sick sinus syndrome without pacemaker
Untreated pheochromocytoma
ACE inhibitors
● Reduces death, AMI, stroke, coronary stents revascularization and CABG
● May use in high risk patients even if no hypertension or heart failure
present
● Start at low dose and titrate upward as tolerated
Ramipril (Altace)
• 2.5–10 mg PO qday
Lisinopril (Zestril)
• Start at 10 mg PO qday — usual range 20–40 mg PO qday
Quinapril (Accupril)
• Initially 5–10 mg PO qday — maintain
20–80 mg PO qday
Side effects
• ACE inhibitor induced angioedema (may be treated with fresh frozen
plasma and discontinue the ACEI or ARB)
• Renal impairment
• Hyperkalemia
• Hypotension
• Do not use in pregnancy, bilateral renal artery stenosis,
hypersensitivity and history of angioedema
Calcium channel blockers
● Dilate vessels, lowers blood pressure and decreases cardiac workload
● Not as effective in decreasing angina frequency as beta–blockers, but
similar as beta–blockers in reducing need for NTG and improving exercise
tolerance
● Use calcium channel blocker when symptoms persist on beta–blocker or
beta–blocker cannot be used (do not use verapamil with beta–blocker)
Amlodipine (Norvasc)
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5–10 mg PO qday initially
10 mg PO qday maintenance
Elderly 5 mg PO qday
With hepatic impairment start with 5 mg PO qday
Diltiazem (Cardizem)
• Start 30 mg PO qid and increase every 1–2 days to control angina as
needed up to 90 mg PO qid
Diltiazem (Cardizem CD)
• Start 120–180 mg PO qday and increase as needed over 1–2 weeks —
NMT 480 mg PO qday
Calcium channel blocker side effects (some)
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Heart failure
AV block
Hypotension
Erythema multiforme
• Peripheral edema
• Headache
• Elevated LFT’s
Contraindications (some)
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Pre-existing sinus bradycardia
2nd and 3rd degree heart block
Sick sinus syndrome without pacemaker
Hypersensitivity
Ranolazine (Renexa)
● Antianginal agent (not first–line treatment)
● May be used in addition to other antianginal medications when angina is
uncontrolled
● 500 mg PO bid initially — NMT 1,000 mg PO bid
Cautions and contraindications
• Do not use in hepatic cirrhosis patients
• Contraindicated with strong CYP3A inhibitors or inducers
 Ketoconazole, itraconazole, clarithromycin, rifampin,
carbamazepine, phenytoin, St. John’s wort, nelfinavie, ritonavir,
indinavir among others
• Not for acute anginal episodes
• Avoid grapefruit products
• Lower dose to 500 mg PO bid with aprepitant, diltiazem, erythromycin,
fluconazole, grape-fruit juice or products, verapamil — read literature
for all drug interactions
Referral criteria
● Angina not controlled with 2–3 antianginal medications
● Acutely worsening angina
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