Download Chronic Stable Angina

Chronic Stable Angina
By:
Dara Al-Fakhouri
Lana Jaber
Lujain Shawagfeh
Amal Al-Qato
Tala Al-Foqaha
How significant is it? -Epidemiology

In the US  13M diagnosed with CAD,
9M with angina.

60-79 years of age  23% men & 15%
women with IHD
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80 years  33% men & 22% women with
IHD
Epidemiology-Cont’d

Number 1 cause of death in men, 27% of
deaths in women.

IHD accounts for the vast majority of
morbidity and mortality of cardiac
disease.

In ~50% of patients, angina pectoris is the
initial manifestation of IHD.
Chronic Stable Angina is one type of IHD
Types of IHD
1- Chronic stable angina
2- Acute coronary syndrome:
- Unstable angina
- STEMI
- NSTEMI
3- Silent Ischemia
Types of angina
1- Chronic stable angina:
Exertional angina, typical or classic angina,
angina of effort, atherosclerotic angina.
2- Unstable Angina:
Pre-infarction angina, Crescendo angina,
angina at rest.
3- Prinzmetal’s Angina:
Vasospastic Angina, variant angina
4- Silent Ischemia
Stable Angina and ACS
Reasons for imbalance?
- Atherosclerotic plaques,Vasospasm,
Thrombus formation.
- Hypoxia, anemia, CO poisoning.
- Tachycardia
In Chronic stable angina  Atherosclerotic
plaques
Conditions Provoking or
Exacerbating Ischemia
Increased demand:
• Non-Cardiac:
1- Hyperthermia
2- Hyperthyroidism
3- Sympathomimetic toxicity
4- HTN
5- Anxiety
-
Conditions Provoking or
Exacerbating Ischemia
Increased demand:
• Cardiac:
1- Hypertrophic cardiomyopathy
2- Dilated cardiomyopathy
3- Aortic stenosis
4- Tachycardia
-
Conditions Provoking or
Exacerbating Ischemia
Decreased Supply:
1- Anemia
2- SC disease
-
Clinical presentation
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Reproducible symptoms
No acute distress
Characterization of chest pain:
Quality
Location
Duration
Factors provoking pain
Factors relieving pain
Characterization of chest pain
Clinical Presentation
Some patients, most commonly women and
patients with diabetes may present with
atypical symptoms, including indigestion,
gastric fullness, and shortness of breath.
Diabetic patients may experience associated
symptoms such as dyspnea and diaphoresis,
without having any of the classic chest pain
symptom!
Diagnosis
medical history , physical exam and
laboratory analysis are necessary.
 Lab analysis should include blood
glucoese , fasting lipids , Hb and organ
functions.
 three measurements within 24 hours are
used to exclude the diagnosis of MI. (CK,CKMB,TroponinI and II usually normal in CSA
and UA and elevated in MI)

Diagnosis tests
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12-lead ECG record is normal with chronic stable angina
(done within 10 minutes of presentation to emergency
department)
Coronary angiography detects the location and degree of
atherosclerosis
Considered the gold standard for diagnosis of IHD when:
-stress testing are abnormal
-symptoms of angina are poorly controlled
Treadmill or bicycle exercise ECG, commonly referred to as a
“stress test,” is considered positive for IHD if the ECG shows at
least a 1 mm deviation of the ST-segment (depression or elevation).
Pharmacologic stress test: Dobutamine (beta1 agonist) is a
pharmacologic stressor used in patients who are unable to exercise
and is commonly used with echocardiography to identify stressinduced wall motion abnormalities indicative of coronary disease.
Classification
Canadian Cardiovascular Society
Classification System
Class I
Class II
Class II - Cont’d
Class II – Cont’d
Class III
Class IV
Our Case
Chief Complaint
“Doc, I have a strong chest pain and
my drugs are not working.”
He reports that most often the chest discomfort
is located in the center and he rated it 3-4/10 on
average, and this discomfort fades when reducing
the activity.

He has had two coronary artery bypass
operations in the past.

He had acute anterior wall MI with
CABG surgeries in 1998 and 1999.

posterior lateral MI in 1990and PTCA to
the circumflex.
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Dyslipidemia.

Chronic low back pain.

Depression.

Jack palmer is a 72-year old man with
coronary artery disease.

He is an avid golfer and prefers to walk.

This is becoming progressively more
difficult to him due to angina.
A coronary angiogram performed 1 month
ago revealed significant disease in the right
coronary artery proximal to his graft, but
this was high risk for angioplasty.

His dose of isosorbide mononitrate was
increased from 60 to 120mg once daily,
But had no effect on his angina.

He is still using about 30 nitroglycerin
tablet a week, and this relieve his chest
pain.
Lisinopril for HTN
 Aspirin as antiplatelet
 Celecoxib for back pain
 Simvastatin for hyperlipidemia
 Diltiazem for IHD and HTN
 Carvedilol for MI
 St. John’s wort for depression

He complains of occasional lightheadedness with a pulse around 50bpm and
his SBP around 100mm Hg.
Treatment of stable angina
Note
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If the patient has DM add ACE or ARBs
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If the patient had MI then add ACE or
ARBs and BB
Lifestyle Modification
Stop Smoking!
Avoid Stress
Exercise
Change Dietary Habits
Pharmacotherapy to prevent
ischemic symptoms
1- Nitrate
1. Nitrate

Nitrate therapy should be first step in
managing acute attack for patient with
chronic stable angina or for prophylaxis of
symptoms.its leading to reductions in
preload and afterload reduction of
myocardial oxygen demand ,Nitrate –free
interval (10-12 hours/day) is recommended
to avoid tolerance development .
Nitroglycerin (NTG)
Isosorbide dinitrate (ISDN)
Isosorbide mononitrate (ISMN)
2.Ranolazine
Case Questions
Problem identification
1.a what drug-related problems appear to
be present in this patient ??
 Angina pectoris , poorly controlled on
current drug therapy
 Dyslipidemia , poorly controlled
 Metabolic syndrome
 Important risk-to-benefit consideration
COX-2 inhibitor therapy
1.b could any of these problems
potentially be caused or
exacerbated by his current therapy
?
Medical management of angina must take into consideration
the patient hemodynamic status. Although both diltiazem and
carvedilol are reasonable antianginal drugs, they are likely the
cause of his relatively low heart rate and blood pressure and
associated light headedness. According to the
ACCF/AHA/ACP/AATS/PCN/SCAT/STS guidelines βblockers and calcium channel blockers (CCBs), each alone or
in combination, constitute medical therapy for relief of
symptoms for chronic stable angina.
 However, combining nondihydropyridines (diltiazem and
verapamil) with β-blockers should be avoided due to notable
risk for slowing AV nodal conduction, heart rate, and /or
contractility.
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Both classes reduce angina episodes,
increase exercise duration, and reduce acute
sublingual nitroglycerin (NTG) use. The
patient’s isosorbide mononitrate (ISMN), an
alternative agent for symptoms relief that
dose not reduce heart rate, is commonly
associated with hypotension especially at his
higher dosage. According to a statement by
AHA selective COX-2 inhibitors such as
celecoxib increase the risk of MI, stroke,
heart failure, and hypertension . This
warrants careful consideration of the risk
associated with treatment against the benefit
of symptom relief.
2.What are the goals of pharmacotherapy for
IHD in this case ??
 Reduce
symptoms of chest pain.
 Improve exercise tolerance.
 Slow progression of coronary
atherosclerosis.
 Prevent recurrent cardiac events.
Desired outcome
3.a Dose this patient posses any
modifiable risk factors for IHD ??

He has poorly controlled dyslipidemia. His LDL C
and TGs are too high and his HDL-C is too low.
According to the 2001 NCEP guidelines for
secondary prevention, his LDL-C goal is less than
100mg/dl and this is the primary target for therapy.
In 2004 these guidelines were updated to include a
therapeutic option to set the goal at an LDL less
than 70mg/dl for very high risk patients – those
who have had a recent MI, or those who have
cardiovascular disease combined with diabetes,
sever or poorly controlled risk factors, or
metabolic syndrome( a cluster of risk factors
associated with obesity that include high TGs and
low HDL).
Therapeutic Alternatives
Additional goals include HDL-C greater than 40
mg/dl . And TGs less than 150mg/dl. Because his TGs
are in the range of 200-499 mg/dl, a secondary
target is non-HDL cholesterol <130 mg/dl.
 He meets the definition of metabolic syndrome,
which imparts a high long term risk for both
atherosclerotic cardiovascular disease and
diabetes. According to ATP III, the metabolic
syndrome should be managed as a secondary
target of therapy, after achieving LDL goal, to
minimize risk of future CHD events.
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The standard diagnosis of metabolic syndrome
according to ATP III to include any three of the
following five characteristics:

Abdominal obesity: waist circumference >40 for
men and >35 for women.
TGs >150 mg/dl.
HDL-C <40mg/dl for men and <50 mg/dl for
women.
Blood pressure >130/85 mm Hg.
Fasting serum glucose >110 mg/dl.
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2005 AHA/NHLBI modifications to the ATP III
definition of metabolic syndrome:
Waist circumference ≥40 for men and ≥35 for
women.
TGs ≥150 mg/dl or on drug treatment for
elevated TGs.
HDL-C <40mg/dl in men and <50mg/dl for
women or on drug treatment for reduced HDLC.
Blood pressure ≥130/85 mmHg or on drug
treatment for hypertension.
Fasting serum glucose ≥100mg/dl or on drug
treatment for elevated glucose.
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This patient meets the criteria for the definition of
metabolic syndrome on the basis of abdominal
obesity, elevated TGs and low HDL-C.
This patient is currently taking celecoxib for lower
back pain, which may put him at risk for
cardiovascular events. According to the AHA,
celecoxib increase risk of MI, stroke, heart failure
and hypertension. And a black box warning has
recently been added to the Celebrex package to
highlight this risk.
3.B What pharmacotherapeutic options are available
for treating this patient’IHD?? Discuss the agents in
each class with respect to their utility in his care??
 Nitrates are useful as antianginals because of their
ability to dilate coronary and systemic vessels,
leading to reductions in preload and afterload.
Products with rapid onset and short duration are
most useful in terminating acute attacks or
preventing anticipated acute attacks caused by
exertion. Agents with longer durations of action
must be used for long term prophylaxis and are
often used in combination with β-blockers or
CCBs to prevent or reduce angina and increase
exercise tolerance in symptomatic CAD.
All nitrates can produce tolerance within as little
as 12-24 hrs. Generally a 10-12 hrs. nitrate free
interval each day is recommended
 NTG oral products are generally not used for
prophylaxis. NTG transdermal patches allow for
once daily application, whereas NTG topical paste
is typically applied three to four times daily.
 Isosorbide dinitrate (ISDN) oral products are
typically given two to three times daily when used
for prophylaxis.
 ISMN is available in two types of oral
formulations:(a) a tablet that must be taken orally
in two divided doses 7 hrs apart ( e.g.: monoket,
Ismo)(b) an extended release tablet that may be
taken once daily ( e.g.: Imdur).

 CCBs
are useful in treating angina. They are grouped
according to their chemistry into three major classes :
 Benzodiazepines (diltiazem)
 Phenylalkylamines (verapamil)
 Dihydropyridines (amlodipine, isradipine, felodipine,
nicradipine, nefidipine)
 Verapamil and Diltiazem also have the potential to
reduce myocardial oxygen demand by reducing
myocardial contractility and heart rate.
 In contrast, the Dihydropyridines are noted for
clinically exerting very little negative inotropic effect
because of induction of a reflex sympathetic response
brought by their marked systemic vasodilatory capacity
.
β-blockers are useful antianginal drugs because of their
ability to inhibit the effects of catecholamines on the heart
and blood vessels. They reduce myocardial oxygen demands
by reducing heart rate, contractility and blood pressure.
 There are numerous β-blockers available for the treatment
of heart disease. They are available as both cardioselective
and nonselective agents.
 Atenolol,metoprolol and bisoprolol are examples of
cardioselective β-blockers that are relatively specific for β1receptors in the heart , although this specificity is lost at
high doses.
 Propranolol, nadolol and timolol are nonselective agents
that antagonize both β1 and β2 receptors.
 Carvedilol is nonselective β-adrenergic blocking agent with
α1 blocking activity. The maximum dose is 25 mg BID if wt
is <85kg and 50mg if wt is >85kg.
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 Ranolazine
(Ranexa) is an antianginal agent approved
for the use for treatment of chronic stable angina for
use in combination with amlodipine, β-blockers or
nitrates in patients who have achieved adequate
response with these agents.
 Antiplatelet therapy
 Aspirin exerts its antiplatelet
effect by inhibiting
thromboxane A2 production. Aspirin monotherapy in a
dose of 81-162 mg daily is recommended as the initial
antiplatelet agent of choice for MI prevention in
patients with IHD.
 Clopidogril(plavix) serve as antithrombotic alternative
for aspirin .
 ACEIs
are indicated in patients with CAD
who also have diabetes, LV dysfunction or
CKD.
 ARBs
is also indicated in patients with CSA or
multiple risk factors for a cardiovascular event.
Or patients who can’t tolerate ACEIs side
effects.
 Other
considerations include risk factors
management such as : achievement of ideal
body wt. and LDL and HDL goals.
Optimal plan
4. Given the patient information provided, construct a
complete pharmacotherapeutic plan for optimizing
management of his IHD.
 Currently, the main issues for this patient are
refractory angina and occasional light-headedness
associated with relatively low heart rate and blood
pressure. Due to this bradycardia and low-normal
blood pressure it is advisable to discontinue diltiazem
and cautiously replace it with amlodipine 2.5 mg once
daily, which will provide anianginal effectiveness without
lowering heart rate or depressing contractility.
Carvedolo could be titrated to a maximum dose of 50
mg BID (since wt. <85 kg) but his current blood
pressure and heart rate limit us in this regard.
Verapamil should be avoided since it slows cardiac
conduction and thus heart rate.
 Decrease aspirin to enteric-coated 81 mg once daily to
minimize risk of GI bleeding.
 Serious consideration should be given to discontinuing
celecoxib in this patient due to increased risk of cardiac
events associated with the use of selective COX-2
inhibitors. Add other pain killer .
 Risk factors modification is also necessary . The patient’s
LDL level is above goal and should be deceased. He is
currently taking a moderate dose of simvastatin(40 mg
daily) and upward titration or switching to a more potent
statin (Atorvastatin) would be appropriate. After reaching
LDL-C goal, if his non-HDL-C remains above 130 mg/dl,
may consider treatment with niacin(NIASPAN) or fibrate
(FENOFIBRATE) to increase HDL-C and decrease TGs.
Physical activity and dietary modifications.
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 Follow-up
question
1. What drug therapy changes would you
recommend to avoid or minimize drug
interactions with Ranolazine?
 St. John’s wort is a strong CYP3A inducer and
should be avoided in combination with ranolazine
( it may increase plasma concentrations of
ranolazine. Add other antidepressant .
 Although plasma levels of simvastatin , aCYTP3A4
substrate, may increase 2-folds with ranolazine
1000 mg BID dose adjustments are not
recommended.
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Outcome evaluation

5.when the patient returns to the clinic in 2 weeks for a
follow up visit, how will you evaluate the response to his
new antianginal regimen for efficacy and adverse effects??

Efficacy: ask him about the number and the severity of anginal
attacks and the provocative factors for attacks. If the attacks
remain, is the character and duration of attacks similar to
before? What distance can he walk before experiencing
symptoms? Dose sublingual NTG relieve the pain? How many SL
NTGs have been used per day or per week ? Have any attacks
occurred at rest , which is a sign of unstable angina and would
require hospital admission?.
Adverse
effects:
Check vital signs. His current heart rate and blood pressure are
relatively low and associated with lightheadedness. The
conversion from diltiazem to amlodipine should have allowed his
heart rate to increase somewhat but hopefully did not lower his
blood pressure any further. Ask the patient about symptoms of
dizziness, lightheadedness, headache, and facial flushing. Check
for the presence of edema, which is the most common adverse
effect of amlodipine.
6. What information will you communicate to the patient
about his antianginal regimen to help him experience the
greatest benefit and fewest adverse effects?
General information: Keep all medicines in original containers
to avoid confusing them, and keep them out of reach of
children. Do not stop any of your medicines abruptly
without talking to your physician. If you miss a dose of
medicine, take it as soon as you remember but not if it is
approaching your next schedule dose. Do not double doses.
Consider using a pill box to help ensure good compliance
with medications. Keep track of the number of chest pain
episodes you experience while using the new medicine.
Keep track of how many NTG tablets you use.
Patient Education
Amlodipine
This medicine was prescribed to treat your angina in place of
diltiazem.. Take a 10-mg tablet by mouth once daily in the
morning. This medicine may cause flushing, dizziness, headache,
or swelling in your ankles and feet.
 ISMN
This medicine is for prevention of chest pain attacks. Take a 120-mg
tablet once daily in the morning. Do not break, crush, or chew it
before swallowing. It is designed to last for only 12 hours (while
you are awake) so that you may have a nitrate-free interval each
day to prevent tolerance to the medication. This medicine can
cause dizziness or lightheadedness, especially when getting up
from a lying or sitting position. It may also cause headache, rapid
pulse, and flushing of the face and neck.

 Nitroglcerin
SL
Used at start of angina if the pain not released you
can take another one after 5 mint and if the pain
also not released you can take another one after 5
mint and if the pain is not relieved after 5 mint you
must to go to emergency because of MI ( acute
condition ).Store them away of heat and moisture
and light.
 Aspirine
Aspirin is give you some protection against
recurrence MI or occurring of stroke if you feel any
pain in your stomach or you see blood in the stool
you must to tell your doctor
 Carvedilol:
 This medicine
is prescribed for multiple reasons—to
prevent episodes of chest pain, to lower your risk of a
recurrent heart attack and death from coronary artery
disease, and to slow progression of heart failure. Take 6.25
mg twice daily with food about 12 hours apart. This
medicine may cause dizziness, drowsiness, and fatigue.
 Celecoxib
This medicine, and other NSAIDs, may increase your risk of
cardiac events such as heart attack and stroke. We
recommend that you stop taking Celebrex® and try
physical therapy, exercise, weight loss, and/or heat/cold
therapy for your back pain. If this is ineffective, consider
Tylenol® 500-1,000 mg every 6 hours as needed, not to
exceed 4,000 mg in 24 hours.
Ranolazine
We give you this drug to improve your ischemic condition and
this drug has also less effect on BP and HR so this good in your
case because your pulse is low and your BP also low .
Ranolazine interacts with a number of other medicines, and it is
critical that you avoid new medicines until you have discussed
these with your physician or pharmacist. Avoid grapefruits and
grapefruit juice as well. This drug is generally well tolerated. The
most common adverse effects are constipation, nausea, dizziness,
and headache.
 Lisinopril
Reduce your likelihood of having a heart attack or stroke, or dying
from a heart problem. Take this blood pressure medication once
daily. Call 911 if you notice swelling of your lips ,tongue or throat ,
or if you feel that you are having trouble in breathing.

Thank you!