Management of Chronic Stable

Coronary Artery Disease

March 14, 2013

Allen L. Dollar, MD, FACC, FACP 1
Allen L. Dollar, M.D.
Personal/Professional Financial Relationships with Industry

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Equity, stock, or options in biomedical None
industry companies or publishers

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entity

Industry funds to Emory for my None

research

Other None

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 Learning goals
• Define the term “Chronic stable CAD”
• List the three categories of therapy for chronic stable CAD
• Describe the benefits and limitations of percutaneous
coronary intervention (PCI)
• Explain the main results of the COURAGE trial
• Explain why PCI in stable CAD would not be expected to
have an impact on future MI or mortality
• List the three main categories of medication used to
reduce the symptoms of angina and their mechanism of
action
• List the lifestyle modifications which are helpful in patients
with chronic stable CAD

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 Key terms
• Chronic stable coronary artery disease
• Angina pectoris
• Percutaneous coronary intervention
• COURAGE Trial
• BARI 2D Trial
• Calcium channel blocker
• Beta blocker
• Nitrates

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 Definition of Chronic Stable Coronary
Disease?
• Usually defined as requiring at least one
‘hemodynamically-significant’ coronary lesion
• Either asymptomatic ischemia on stress test or
angina with exertion
• Stable with regards to amount of exercise needed to
provoke as well as severity and duration of symptoms
when they occur

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 Therapies for chronic stable CAD

• Lifestyle modification
• Pharmacologic therapy
• Percutaneous coronary intervention
• Coronary artery surgery

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 Goals of therapy

• Prolongation of life
• Relief of symptoms

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 Questions to think about…
• What does a ‘positive’ stress test tell you about
coronary anatomy? Risk of a future MI?
• Why is having one narrowing of 70% or more
predictive of future MI?
• Why is having all three vessels with at least a 70%
or more narrowing even more hazardous?
• Can you look at an angiogram of a patient with
stable angina and predict the site of a future MI?

Circ 1988; 78; 1157-66

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Inability of the angiogram to predict the site
of future MI
• 29 patients who presented with MI and
occluded vessel who had had a prior cath
• 97% of the infarcts happened at sites of <70%
stenosis on the first cath
• 66% of the infarcts had <50% narrowing at the
site of the future occlusion

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 History of percutaneous coronary
intervention
• 35 years: First balloon angioplasty in 1977 by
Dr. Andreas Gruentzig in Zurich
• 18 years: First stent available (Palmaz-Schatz)
1994
• 8 years: First ‘coated’ or drug eluting stents
availble March 2004

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 More questions to think about…

• What is the total length of the coronary tree?

• 50 cm
• What is the length of an average stent?
• 1-2 cm
• If you ‘fix’ a localized 80% narrowing with a stent, what
have you done to that patient’s risk of a future MI?
• Would you expect stenting in a patient with stable
coronary disease to affect mortality, symptoms, or
both?

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 The COURAGE TRIAL

Or proof that stents in stable patients

is akin to playing
Atherosclerotic Whack-A-Plaque

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 COURAGE
• 2287 patients with stable CAD randomized to
medical tx or PCI
• Followed for median of 4.6 years
• Only exclusions were left main narrowing,
markedly early positive treadmill, rest angina,
and poor LV function (EF<30)

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(11% had prior CABG)

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 The BARI 2D TRIAL

COURAGE for diabetics (and included CABG as

well as PCI)

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 When to do PCI in stable patients
• Intolerable angina despite maximal medical Rx in a
patient who does not have anatomy that requires
CABG for prolongation of life
• Markedly early positive stress test without absolute
indication for CABG (these pts were not in COURAGE)
• Older pts who are at very high risk for CABG

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 Coronary Artery Surgery
• Why might coronary surgery have an
advantage over PCI for the prevention of
future events?

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The problem

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Stent

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CABG

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 The ‘classic’ indications for CABG:

• Left main coronary narrowing (>50%)

• 3-vessel CAD (esp with poor LV function)

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SYNTAX Trial

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 SYNTAX Trial

• Multicenter international trial 85 sites in 17

countries in Europe and US
• 1800 patients with 3-vessel or LM randomized 1:1 to
PCI or CABG
• PCI group all got drug-eluting stents, average of 4
stents/patient.
• Only 2% had EF<30%
• Developed a scoring system for how complex the
CAD was
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Hybrid revascularization

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Hybrid revascularization

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 Indications for CABG in 2013:

• Left main coronary narrowing

– Good option for stenting some of these
• 3-vessel CAD (esp with poor LV function)
– Some of these pts can be stented
– Some of these pts can be managed medically

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Which patients with stable angina need to be
cathed?
• Everyone gets a non-invasive stress test
• All with markedly early positive stress get cathed
• Most with a large amount of myocardium at risk get
cathed
• If very stable symptoms and a small amount of
ischemic myocardium, cath is not necessary
• CT Coronary Angiography (CTA) may supplant many
caths

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Pharmacologic therapy for chronic stable
CAD

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 Pharmacologic therapy for chronic stable angina:

Goals

1. Reducing the incidence of MI and

death

2. Reducing symptoms

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 Pharmacologic therapy for chronic stable angina:
Reducing MI and Death
• Aspirin reduces incidence of vascular events
by 20-25% in pts with prior events or those at
risk.
• Beta blockers reduce death and MI after an
MI by 20-30%
• Statin drugs lower risk of death by 20-30% in
patients with known CAD or at high risk for
CAD

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 Pharmacologic therapy for chronic stable angina:
Reducing symptoms
• Therapy works by either ↓ O2 demand or ↑
O2 supply
• Classes of effective drugs:
– Beta blockers
– Calcium channel blockers
– Nitrates

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 Pharmacologic therapy to reduce symptoms of stable angina:
Beta Blockers
• First line therapy for chronic angina
• Benefits are mostly from blockade of Beta-1
receptors
• MVO2 proportional to
– Heart rate (BB ↓ HR at rest and with exercise)
– Contractility (BB ↓ dp/dt)
– Wall stress (BB ↓ BP)

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 Pharmacologic therapy to reduce symptoms of stable angina:
Beta Blockers
• Adverse effects of Beta Blockers
– Intolerable bradycardia
– Bronchoconstricion
– Fatigue/depression
– Worsened PVD symptoms
– Erectile dysfunction

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 Pharmacologic therapy to reduce symptoms of stable angina:
Ca++ Channel Blockers
• Prevent Ca++ entry into vascular smooth
muscle cells
– coronary and peripheral vasodilatation
– ↓ HR (with some)
– ↓ contractility (with some)
– ↓ wall stress through ↓ BP
• No survival benefits

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 Pharmacologic therapy to reduce symptoms of stable angina:
Ca++ Channel Blockers
• Verapamil: The biggest effect on ↓HR and
↓contractility but less vasodilatation
• Diltiazem: Some ↓HR and ↓contractility
• Dihydropyridines (nifideipine, nicardipine,
felodipine, amlodipine):
– Good vasodilators with little effect on HR and
contractility

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 Pharmacologic therapy to reduce symptoms of stable angina:
Nitrates
• Although nitrates do cause coronary
vasodilatation, their main effect is by
decreasing MVO2 through systemic
vasodilatation  ↓ LV wall stress
• No survival benefits

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 Pharmacologic therapy to reduce symptoms of stable angina:
Nitrates
• Chronic nitrate therapy comes in two forms:
oral and transdermal
• All chronic nitrate tx suffers from tolerance.
12-14 hrs of nitrate-free needed daily
• Rapidly acting sublingual nitrates are
sometimes useful prior to planned exercise

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 Pharmacologic therapy to reduce symptoms of stable angina:
Nitrates
• Isosorbide dinitrate:
– Shorter acting. Needs dosed 2-3 x per day
• Isosorbide mononitrate:
– Longer acting. Lasts 12 hours. Taking it twice daily
may cause tolerance.
• Transdermal nitrates: need to remove patch
for 12-14 hours daily

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 Pharmacologic therapy to reduce symptoms of stable angina:
Ranolazine
• Novel new anti-anginal agent
• Reduces Ca++ overload in ischemic muscle
and inhibits fatty acid oxidation
• Improves exercise duration
• Decreases number of anginal episodes per
week from 3.3 to 2.9

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 Pharmacologic therapy to reduce symptoms of stable angina:
Ranolazine
• Adverse effects
– Prolongs QT interval
– Can’t use in liver disease
– Can’t use with diltiazem and verapamil

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 How to choose anti-anginal drugs

• Start with beta blocker since they provide a survival

advantage and are at least as good or better at
reducing sx
• Add a calcium blocker, if needed or switch to a
calcium blocker if BB not tolerated
• Add long acting nitrates third
• Use short-acting nitrates, if tolerated, before
planned exercise.
• When all else fails, consider ranolazine.

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 Other useful interventions in the treatment
of chronic stable angina
• Keep BP well-controlled
• *****Smoking cessation*****
• Weight reduction
• Daily exercise
• Optimize lipids through dietary and
pharmacologic means

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 Some potential consequences of chronic
coronary disease
• Disabling angina
• Myocardial infarction with resultant:
– Congestive heart failure
– Arrhythmias and sudden death
– Valvular dysfunction (MR and TR)
– Intracavitary LV thrombus +/- aneurysm with
possible emboli
– Myocardial rupture and pseudoaneurysm

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 Take Home Points
• Stenting stable coronary narrowings doesn’t
prevent heart attacks or save lives
• This is also likely true of CABG, at least in the
presence of relatively preserved LV function
• In complex CAD, CABG has the advantage of
less need for further revascularization
procedures

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