CORONARY ARTERY DISEASE

Eylem Körceğez,PhD
Eastern Mediterranean University
Clinical Pharmacy

Clinical
Pharmacy
CORONARY ARTERY DISEASE (CAD)
is also known as:

• CORONARY HEARTH DISEASE

• ATHEROSCLEROTIC HEART DISEASE
• CORONARY ATHEROSCLEROSIS
• CORONARY ARTERIOSCLEROSIS
• HEARTH DISEASE
CAD

• Coronary hearth disease (CAD) is a major public health problem.

• It is is the most common type of heart disease.

• CAD is the leading cause of death all over the world in both men and
women.
CAD: a definition

• CAD occurs because of narrowing and/or blockage of the coronary

arteries that supply blood and oxygen to the heart.

• CAD usually results from the build up of cholesterol and other

material called plaque on the inner walls (atherosclerosis).
CAD and Atherosclerosis
• Normal cut-section of artery
• Tear in artery wall
• Fatty material is deposited in vessel wall
• Narrowed artery becomes blocked by a blood clot
CAD and Atherosclerosis

• Over time, plaque can harden or rupture (break open).

• If the plaque ruptures, blood cell fragments called platelets stick to

the site of the injury.

• They may clump together to form blood clots.

CAD and Atherosclerosis

• Blood clots can further narrow the coronary arteries and reduces the
flow of oxygen-rich blood to the heart. This worsens angina.

• If a clot becomes large enough, it can mostly or completely block a

coronary artery and cause a chest pain (angina) or myocardial
infarction (MI, heart attack)
CAD- Complications

• Acute coronary syndromes (ACS)

• Unstable angina

• Myocardial infarction

• Heart failure

• Abnormal heart rhythm (arrhythmia).

 CAD and MI

• Most MI happen when a blood clot suddenly cuts off the hearts' blood
supply, causing permanent heart damage.

• If blood flow isn’t restored quickly, the section of heart muscle begins to
die.

• Without quick treatment, MI can lead to serious health problems or

death.
 Myocardial infarction (MI)
• commonly known as a heart attack,

• occurs when blood flow decreases or

stops to a part of the heart,

• causing damage to the heart muscle.

Myocardial infarction (MI)-Cause
• Most MIs occur due to coronary artery
disease.

• The complete blockage of a coronary

artery caused by a rupture of
an atherosclerotic plaque is usually the
underlying mechanism of an MI.
 Myocardial infarction (MI)- Symptoms

• The most common symptom is angina (chest pain) or discomfort which

may travel into the shoulder, arm, back, neck, or jaw.

• Often it occurs in the center or left side of the chest and lasts for more
than a few minutes.

• The discomfort may occasionally feel like heartburn.

Myocardial infarction (MI)- Other symptoms
• Shortness of breath,
• nausea,
• feeling faint,
• cold sweat,
• feeling tired.

• About 30% of people have atypical symptoms.

Myocardial infarction (MI)- Other symptoms

• Women more often present without chest pain and instead have
neck pain, arm pain, or feel tired.

• Among those over 75 years old, about 5% have had an MI with little
or no history of symptoms.
Myocardial infarction (MI)-Complications

• An MI may cause:
• heart failure,
• arrhythmia (irregular heartbeat)
• cardiogenic shock, or
• cardiac arrest.
Myocardial infarction (MI)-Diagnosis

• A number of tests are useful to help with diagnosis, including

• electrocardiograms (ECGs),
• blood tests, and
• coronary angiography.
 Myocardial infarction (MI)-Diagnosis

• An ECG, which is a recording of the heart's electrical activity, may confirm

an ST elevation MI (STEMI) if ST elevation is present.

• Commonly used blood tests include troponin and less often creatine
kinase MB.
Myocardial infarction (MI)- Treatment

• Treatment of an MI is time-critical.

• Aspirin is an appropriate immediate treatment for a suspected MI.

• Nitroglycerin or opioids may be used to help with chest pain;

however, they do not improve overall outcomes.

• Supplemental oxygen is recommended in those with

low oxygen levels or shortness of breath.
 Myocardial infarction (MI)-Treatment

• In a STEMI, treatments attempt to restore blood flow to the heart, and

include:
• percutaneous coronary intervention (PCI),
• where the arteries are pushed open and may be stented, or
• thrombolysis (fibrinolytic therapy)
• The blockage is removed using medications.
• The most commonly used drug for thrombolytic therapy is tissue
plasminogen activator (tPA),
 Myocardial infarction (MI) -Treatment
• People who have a non-ST elevation myocardial infarction
(NSTEMI):
• are often managed with heparin anticoagulant (blood
thinner),
• with the additional use of percutaneous coronary
intervention (PCI) in those at high risk.
Myocardial infarction (MI)-Treatment

• In people with blockages of multiple coronary arteries and diabetes:

• coronary artery bypass surgery (CABG) may be recommended
rather than angioplasty.

• After an MI;
• lifestyle modifications,
• aspirin, beta blockers, and statins, are typically recommended.
 CAD and Hearth Failure /Arrhytmia

• Over time, CAD can weaken the heart muscle and lead to heart
failure and arrhythmias.

• Heart failure is a condition in which the heart can't pump enough blood
to meet the body’s needs.

• Arrhythmias are problems with the rate or rhythm of the heartbeat.

CAD

• CAD may remain asymptomatic until it manifests as MI, sudden death

or cardiac dysfunction (such as arrhythmias or cardiac failure).

• Some patients may therefore suffer consequences of myocardial

ischaemia without any history of warning symptoms.
CAD- Symptoms

• Angina (chest pain)

• Dyspnea (Shortness of breath)

• Dizziness

• Nausea

• Extreme weakness

• Some people don’t have any symtoms.

Angina
• About half of all patients known to have CAD complain of
angina pectoris.
• Angina is chest pain or discomfort.
• It may feel like pressure or squeezing in the chest.
• Angina pain may even feel like indigestion or "crushing"
or "heavy" feeling,
• The pain also can occur in the shoulders, arms, neck, jaw,
or back.
Angina

• Typically, angina is precipitated by exercise, stress or emotion and is

relieved by sublingual glyceryl trinitrate (GTN) or rest.

• In unstable angina, pain may occur at rest, particularly at night, with

increasing frequency.

• Unstable angina is associated with increasing risk of myocardial

infarction and it requires immediate medical referral.
CAD- Risk factors
CAD-Diagnosis
• History • Investigations
• Symptoms • Cardiac enzymes
• Physical examination • Creatine kinase (CK)
• Lactate Dehydrogenase (LDH)
• Aspartate Aminotransferase
• Troponin
• ECG (often normal)
• Exercise testing (Stress test)
• Angiography (guides management)
EKG or ECG (Electrocardiogram)
• An EKG is a simple, painless test
that detects and records the
heart's electrical activity.

• The test shows how fast the

heart is beating and its rhythm
(steady or irregular).
EKG or ECG (Electrocardiogram)
• EKG records strength and timing of
electrical signals as they pass
through the heart.

• An EKG can show signs of heart

damage due to CAD and signs of a
previous or current heart attack.
 Exercise stress testing

• Heart rate,
• Respiratory rate,
• Blood pressure,
• Electrocardiogram (ECG or EKG), and
• How tired the patient feel are
monitored during the test.
Coronary Angiography

• This test uses dye and special x rays to

show the insides of the coronary arteries.

• Special x rays are taken while the dye is

flowing through the coronary arteries.

• The dye lets the physician study the flow of

blood through the heart and blood vessels.
 Management
• Risk factor reduction (primary prevention)
• Heart-healthy eating
• Maintaining a healthy weight
• Managing stress
• Physical activity
• Quitting smoking
• Blood pressure control
• Lipid control
• Diabetes control
• Drug therapy
• Secondary prevention
• Symptom control
• Coronary intervention and surgery
• Angioplasty ± stent (PTCA)
• Coronary Artery Bypass Grafts (CABG)
 Management
• Heart-Healthy Eating
• Fat-free or low-fat dairy products, such as fat-free milk
• Fish high in omega-3 fatty acids, such as salmon, about twice a week
• Fruits, such as apples, bananas, oranges, pears etc
• Legumes, such as kidney beans, lentils, chickpeas, black-eyed peas, and
lima beans
• Vegetables, such as broccoli, cabbage, and carrots
• Whole grains, such as oatmeal, brown rice, and corn tortillas
Management

• When following a heart-healthy diet, a patient should avoid eating:

• A lot of red meat
• Palm and coconut oils
• Sugary foods and beverages
Management
• Two nutrients in the diet make blood cholesterol levels rise:
• Saturated fat—found mostly in foods that come from animals
• Trans fat (trans fatty acids)—found in foods made with hydrogenated oils
and fats, such as stick margarine; baked goods, such as cookies, cakes, and
pies; crackers and coffee creamers.

• Saturated fat raises the blood cholesterol more than anything else in the
diet.

• Trans fats raise LDL cholesterol levels and lower HDL cholesterol levels.
 Management
• Not all fats are bad.
• Monounsaturated and polyunsaturated fats actually help lower blood
cholesterol levels.
• AvoCADos
• Corn, sunflower, and soybean oils
• Nuts and seeds, such as walnuts
• Olive, canola, peanut, safflower, and sesame oils
• Peanut butter
• Salmon and trout
• Tofu
 Aims of Drug Therapy

• Prevent disease progression (secondary prevention)

• Lowering the risk of blood clots forming (blood clots can cause a MI)
• Preventing complications of coronary heart disease
• Reducing risk factors in an effort to slow, stop, or reverse the buildup of
plaque
• Control symptoms
• Relieving symptoms
Drug Therapy
• Secondary prevention: Prevent disease progression
• Antiplatelets
• Statins
• Beta-blockers
• ACE inhibitors /ARBs

• Symptom control
• Beta-blockers
• CCB
• Nitrates (short and long acting)
Antiplatelets

Generic Name Brand Name

aspirin Coraspin, Ecopirin
clopidogrel Plavix
prasugrel Effient
ticagrelor Brilinta
 Antiplatelets
• Antiplatelet medicines prevent blood clots from forming in the arteries.

• This can prevent a MI or stroke.

• Antiplatelets may be used by people who:
• Have coronary artery disease.
• Had a MI.
• Had angioplasty or bypass surgery.
• Had a stroke or transient ischemic attack (TIA).
• Have peripheral arterial disease.
Antiplatelets- Aspirin

• Aspirin (acetylsalicylic acid) is an antiplatelet drug used to treat and

prevent CAD.

• Aspirin is used more frequently than any other drug in the world.

• All patients unless contra-indicated

• Allergy or GI bleeding

• Aspirin 75–162 mg daily is recommended in all patients with CAD

 Antiplatelets- Aspirin
• Covalently and irreversibly inhibits cyclooxygenase (COX) and

• Inhibits platelet thromboxane (TX) A(2) biosynthesis.

• Non-selective COX inhibition, however, predisposes to bleeding,

predominantly secondary to dose dependent gastro-intestinal toxicity.

Antiplatelets- Aspirin
• Monitor for side effects.
• Stomach pain or discomfort
• Nausea
• Bleeding
• Nose bleeding
• Vaginal bleeding that is different (heavier, more frequent, at a different
time of the month) than what you are used to.
• Bloody or black stools, or rectal bleeding.
• Bloody or pink urine.
• A sudden, severe headache that is different from past headaches. (It may
be a sign of bleeding in the brain.
Antiplatelets- Clopidogrel

• Clopidogrel, an antiplatelet agent and is used to inhibit blood clots.

• The drug is an irreversible inhibitor of the P2Y12 adenosine

diphosphate receptor .

• P2Y12 protein is found mainly but not exclusively on the surface

of blood platelets, and is an important regulator in blood clotting.
 Antiplatelets- Clopidogrel
• Clopidogrel use is associated with several serious adverse drug
reactions such as:
• severe neutropenia,
• various forms of hemorrhage, and
• cardiovascular edema.
 Antiplatelets- Clopidogrel
• Clopidogrel 75 mg daily if:
• Aspirin intolerant (try PPI first)

• Allergic to Aspirin

• Combination : After ACS or PCI with stent placement

(Aspirin+Clopidogrel/Prasugrel/Ticagrelor)

• Aspirin: Probably life-long treatment

• Clopidogrel duration depends on reason
 Antiplatelets-Ticagrelor
• is a platelet aggregation inhibitor .

• Ticagrelor is an antagonist of the P2Y12 receptor.

• Ticagrelor is used for the prevention of thrombotic events in people

with CAD.

• The drug is combined with acetylsalicylic acid unless the latter is

contraindicated.
Lipid management
Goal:
• Treatment with statin therapy
• Use statin therapy to achieve an LDL-C of <100 mg/dL; for very high
risk patients an LDL-C <70 mg/dL is reasonable
• Patients who have triglycerides 500 mg/dL should be started on
fibrate therapy in addition to statin therapy to prevent acute
pancreatitis.
• For all patients, it may be reasonable to recommend omega-3 fatty
acids from fish or fish oil capsules (1 g/d) for cardiovascular disease
risk reduction.
Statins
• All patients unless contra-indicated
• Active or chronic liver disease
• Unexplained persistent elevation of serum transaminases
• Pregnant or lactacing women
• Conditions predisposing to renal failure (sepsis, trauma severe
endocrine/metabolic disorders)
• Different dosing strategies
• Target LDL-C of <100 mg/dL
• Aggressive LDL reduction
• e.g. Simvastatain 40 mg daily
• Very aggressive LDL reduction (?ACS only)
• e.g. Atorvastatin 80 mg daily
Statins
• Monitoring
• Effectiveness
• Lipid profile
• Toxicity
• Symptoms of myopathy
• Markers for myopathy (creatine kinase) if symptoms
• Liver function tests (AST/ALT)
• Baseline and during treatment
• Especially high dose statins
• Probable lifelong treatment
Beta-blockers

• Beta blockers are a group of drugs that inhibit the sympathetic activation
of β-adrenergic receptors.

• Protective effect and symptom control

• Beta-blocker therapy should be used in all patients with heart failure or

prior myocardial infarction, unless contraindicated.
Beta-blockers

• Carvedilol, metoprolol, or bisoprolol have been shown to reduce

mortality.

• Beta-blocker therapy should be started and continued for beyond 3

years as chronic therapy in all patients who have had myocardial
infarction or ACS.
Beta-blockers

• Cardioselective blockers (e.g., metoprolol, bisoprolol) primarily

block β1 receptors in the heart, causing :
• decreased heart rate and cardiac contractility,
• slower AVN conduction, and
• decreased cardiac workload.
Beta-blockers

• Beta blockers are contraindicated in patients with:

• symptomatic bradycardia,
• AV block (Heart block)
• decompensated heart failure, and
• Asthma (Selective blockers of β1 receptors can be used)
Beta-blockers

• Initiation and cessation of β blocker therapy should always be gradual

to avoid side effects or symptoms of withdrawal:

• angina exacerbation
• rebound tachycardia,
• hypertension,
• acute cardiac death
Beta-blockers

• Cessation of β blocker therapy

• Taper off is needed when discontinue
• Reduce 50% dose for 3 days
• Then reduce another 50% for 3 days.
Beta-blockers
• Monitoring
• Effectiveness
• Heart rate (50-60 bpm if tolerated)
• Blood pressure
• Toxicity
• Side effects
• Nightmares
• Fatigue (especially on initiation)
• Impotence
ACE Inhibitors
• ACE inhibitors improve outcomes in patients with CAD, heart failure,
and hypertension.
• ACE inhibitors should be started and continued indefinitely in all
patients with:
• Heart failure.
• post-MI
• CAD
• Diabetic nephropathy
• CKD
• Stroke prevention
ACE Inhibitors
• Up-titrate treatment to target dose.
• Monitor treatment before and at the start and end of up-titration
• Monitoring
• Effectiveness
• Blood pressure
• Toxicity
• Side effects
• Cough
• Hyperkalemia
• Angioedema
• Renal dysfunction
ARB
The use of ARBs is recommended in patients who have:
• Heart failure
• Myocardial infarction
• ACE-inhibitor intolerant

• The use of ARBs in combination with an ACE inhibitor is not

recommended.
Calcium Channel Blockers (CCB)

• Protective effects from post-MI studies for rate limiting drugs

(verapamil / diltiazem)
• Alternative rate control if Beta-blocker contra-indicated or not
tolerated

• Demonstrated benefit for symptom control for all CCB.

Calcium Channel Blockers (CCB)
Calcium Channel Blockers (CCB)

• Monitor for effect (symptoms and blood pressure) and side effects:
• Dizziness,flushing, headache, and a feeling of fatigue caused by a
decrease in blood
• Peripheral edema (swelling in the feet and lower legs)
• Reflex tachycardia.
• Constipation and AV block (verapamil/ diltiazem)
Nitrates

• Nitrate therapy is the oldest treatment modality for angina pectoris.

• In addition to sublingual nitroglycerin, longer-acting preparations are

available to provide angina prophylaxis.
Nitrates

• Nitrates work as venodilators and arterial dilators, and by these

actions in patients with angina.

• can reduce myocardial oxygen demands while maintaining or

increasing coronary artery flow.
Nitrates

• Long-acting nitrates are available in sublingual, chewable, oral, buccal,

intravenous and topical forms.
• isosorbide mononitrate
• glyceryl trinitrate
Nitrates

• Long-acting nitrates have a duration of action of 2 to 24 hours,

depending on the preparation used.

• They can be combined with calcium-channel blockers, beta-blockers

or both when trying to improve on the antianginal efficacy of single-
drug therapy.
Nitrates
• Monitor for effect (symptoms) and side effects
• Headache
• flushing
• Dizziness
• Nausea
• Hypotension
• Drug interactions:
• Sildenafil (Viagra),
• Tadalafil (Cialis)
• Vardenafil (Levitra)
Increase the blood pressure lowering effects of nitrates and may cause
excessive blood pressure reduction.
Options
• Secondary prevention: Prevent disease progression
• Antiplatelets
• Statins
• Beta-blockers
• ACE inhibitors /ARBs
• Symptom control
• Beta-blockers
• CCB
• Nitrates (short and long acting)
Possible treatment regimen

Secondary prevention

• Aspirin 75 daily (or clopidogrel 75mg daily)

• Simvastatin 40mg daily

• Beta-blocker (or rate limiting calcium antagonist) dosed to heart rate

• ACE inhibitor to target dose if high risk

Possible treatment regimen

Symptom control

• GTN Spray as required.

• Beta-blocker (or rate limiting calcium antagonist) dosed to heart rate.

• Avoid combining Beta-blocker and rate limiting CCB.

Percutaneous Coronary intervention (PCI)

• Patients should be considered for PCI, especially if uncontrolled or

high risk)

• Angiography to determine best option:

• Medical management
• Angioplasty / coronary stent
• Combination antiplatelets post-PCI
• Duration depends on presentation and intervention
• Coronary artery bypass grafts
Angiography
Most accurate way to examine the
coronary arteries.

It requires a surgical procedure called

cardiac catheterization.

During the procedure, catheters are placed

in the artery of the leg or arm, and directed
using an x-ray machine to the opening of
each of the coronary arteries
 Angiography

• is a procedure that uses a special dye

(contrast material) and x-rays to see how
blood flows through the arteries in the
heart.
 Angiography

• is used to detect and obstruction in the

coronary arteries.
Stent deployment
Drug interactions (general)

• All angina medication (except statins/aspirin) lower blood pressure

• Caution using angina medication with other drugs that lower blood
pressure

• Avoid other drugs that cause GI irritation

• Avoid using two drugs that reduce heart rate if possible

Pharmaceutical care

• Education and support on lifestyle modification

• Smoking, Diet, Alcohol, Exercise

• Selection of evidence based therapy

• Secondary prevention
• Aspirin, Beta-blockers, statins, ACE inhibitors/ARBs
Pharmaceutical care-2
• Assessment for appropriate treatment
• Symptom control
• Beta-blocker, CCB, nitrate

• Co-morbidities, contra-indications etc

• Monitoring of treatment
• Symptoms, side effects, biochemistry etc

• Education on medication
• Regimen, rationale, side effects, benefits, lack of obvious benefit, adherence