Download Ischemic Heart Disease

Ischemic Heart Disease
Dr. Emtenan AlHarbi
Clinical pharmacy department
Learning objectives
• Identify risk factors for development of ischemic
heart disease
• Differentiate between pathophysiology of chronic
stable angina and acute coronary syndrome (ACS)
• Recognize symptoms and diagnostic criteria of IHD
• Identify the appropriate therapeutic regimen and
monitoring plan for management of IHD
Introduction
• IHD = Ischemic Heart Disease.
• CHD = Coronary Heart Disease.
• CAD = Coronary Artery Disease.
IHD
• Ischemic heart disease (IHD) is primarily caused by
coronary atherosclerotic plaque formation that leads
to an imbalance between oxygen supply and demand
resulting in myocardial ischemia.
• Chest pain is the symptom of myocardial ischemia
due to coronary artery disease (CAD).
Epidemiology and etiology
• In Saudi Arabia:
– Overall prevalence of CAD in KSA is 5.5%
– Prevalence in males and females were 6.6% and
4.4% (p< 0.0001).
– Urban Saudis have a higher prevalence of 6.2%
compared to rural Saudis of 4% (p< 0.001).
Epidemiology
• Men > women
• In women: it increase after menopause by 2-3 fold.
The major epicardial coronary arteries
Causes of Ischemia ?
•
•
Narrowing of major coronary arteries by atherosclerotic plaques.
 Atherosclerosis of 1 or more of the major coronary articles or
their branches is major cause .
When there is an imbalance between:
– The coronaries’ ability to supply adequate oxygen and blood
flow
– The myocardium’s demand for oxygen
 Neither factor should be thought of as more important than the
other. Both must be in balance.
Introduction
Normal
= coronary perfusion
pressure /coronary
vascular resistance
CPP (aortic diastolic
pressure – LV end
diastolic pressure)
= Oxygen
supply
= Oxygen
demand
Arterial Po2
Ventricular
wall tension
Coronary
blood flow
Myocardial
contractility
Hg/ Hct
content
HR
Introduction
IHD
Risk factors of IHD
Modifiable
Cigarette smoking *
Hyperlipidemia*( Fasting
cholesterol and triglycerides)
Diabetes*(Fasting blood
glucose)
Obesity*
Non-modifiable
Male Gender*
Age * 45 years or greater for
males,
55 years or greater for females
Family history of premature CV
disease
Hypertension*
Physical inactivity
* statistically significant risk factors in KSA
Risk factors for atherosclerotic plaques
Why ?
• Cigarette smoking accelerates coronary atherosclerosis and increases
the risk of thrombosis, plaque instability, myocardial infarction, and
death . By increasing myocardial oxygen needs and reducing oxygen
supply, it aggravates angina.
• Hypertension is associated with an increased risk of adverse clinical
events from coronary atherosclerosis as well as stroke. In addition, the
left ventricular hypertrophy that results from sustained hypertension
aggravates ischemia.
• Diabetes mellitus accelerates coronary and peripheral atherosclerosis
• Dyslipidemias and increases in the risk of angina, myocardial infarction,
and sudden coronary death.
Treatment-general approach
Angina symptoms
Diagnostic workup
Anti-anginal therapy
Primary and secondary
prevention
History and physical
Stress test and
angiography
Control risk factors
(HTN, metabolic
syndrome cigarette
smoking obesity)
General treatment strategies for angina follow in clockwise fashion from the top
Clinical classification of chest pain
Non- Anginal CP
Other way to classify the chest pain
Characteristics
Cardiac
Gastrointestinal
Musculoskeletal
History
RF for CAD
Gastritis or
indigestion
Trauma
Type of pain
Heavy pressure,
crushing or
squeezing sensation
Burning sensation Sore, achy feeling,
sharp pain
Precipitating
factor
Exertion or stress
Food
consumption
Physical
movement
Relived by
Rest or NG
Antacid
Rest, heat, or
analgesia
Medications that may cause chest pain
1.
2.
3.
4.
5.
6.
7.
Bisphosphonate
NSAIDs
Potassium chloride
Some antineoplastic e.g. flurouracil,
Corticosteroids.
Ferrous sulphate.
Antiarrythmics e.g. flecainide, propafenone,
quinidine
Treatment-general approach
Angina symptoms
Diagnostic workup
Anti-anginal therapy
Primary and secondary
prevention
History and physical
Stress test and
angiography
Control risk factors
(HTN, metabolic
syndrome cigarette
smoking obesity)
General treatment strategies for angina follow in clockwise fashion from the top center .
Common clinical manifestations of IHD
Stable Angina:
chronic pattern of transient angina
pectoris precipitated by physical activity
or emotional upset, relieved by rest
with in few minutes. Temporary
depression of ST segment with no
permanent myocardial damage
ACS s: Occur at rest Disruption of atherosclerotic
plaque with subsequent thrombus formation
1. Myocardial Infarction: Region of myocardial
necrosis due to prolonged cessation of blood
supply . Results from acute thrombus at side of
coronary atherosclerotic stenosis. In both
NSTEMI or STEMI the Cardiac enzymes are +ve
2. Unstable Angina: Increased frequency and
duration of Angina episodes, may progress to
MI if not treated
Silent Ischemia:
Asymptomatic episodes of myocardial
ischemia. Detected by
electrocardiogram and laboratory
studies.
Variant or prinzemetal angina:
Typical anginal discomfort usually at rest. Develops
due to coronary artery spasm rather than increase
myocardial oxygen demand . Occur at rest
Affect young people/ no RF for CAD..
Cigarette smoking, cocaine and cold temperature
are the provoking factors.
UA: Unstable angina, NSTEMI: Non ST Elevation Myocardial Infarction, STEMI: ST Elevation Myocardial Infarction
Canadian Cardiovascular Society (CCS) grading of angina
Stable vs Unstable angina
Angina is considered stable:
– When it only occurs with prolonged exertion
– Or imposes a slight limitation of ordinary activity (ie,
CCS class I and II)
– Or when it has stabilized with CCS class III symptoms.
Angina is unstable:
– When it is occurs at rest lasting more than 20 minutes
– Angina of at least CCS class III severity of new-onset
– Or previously diagnosed angina that increases in
frequency, duration, or severity by at least one CCS
class to at least level III.
The clinical performance measures for chronic
stable CAD recommended by the ACC and AHA
•
•
•
•
•
•
•
•
•
Blood pressure measurement
Lipid profile
Symptom and activity assessment
Smoking cessation
Antiplatelet therapy
Drug therapy for lowering LDL cholesterol
Β-blocker therapy for prior MI
ACE inhibitor therapy
Screening for diabetes.
Risk factors modifications
Risk factors
Goals
Treatment strategies
Benefits
Smoking
Complete cessation
Encourage quitting.
Suggest medications to facilitate
quitting. Use of the nicotine patch in
conjunction with bupropion..
Suggest smoking cessation program.
Decreased BP (decreased O2
demand).
Decreased risk of vasospasm
(increased O2 delivery).
Hypertension
Systolic BP less than 140
mm Hg.
Diastolic BP less
than 90 mm Hg.
Antihypertensive agents.
Reduce caloric intake.
Emphasize vegetable, fruit, low-fat
dairy intake.
Moderate/eliminate alcohol intake.
Smoking cessation program.
Weight management.
Decreased myocardial O2 demand
Hypercholesterole
mia
LDL less than 100 mg/dL.
HDL greater than 40
mg/dL (women >
50).
Triglycerides less
than 150 mg/dL.
Lipid-lowering agents.
Diet.
Weight management.
Increased physical activity.
Plaque stabilization.
Halts CAD progression.
Modest plaque regression.
Diabetes
Systolic BP less than 130
mmHg.
Diastolic BP less
than 80 mmHg.
HbA1c less than 76.5%.
Dietary modification.
Tighter control of blood sugar levels.
Exercise.
Slows disease progression.
Obesity
Body mass index less than
25 kg/m2.
Dietary modification. Exercise.
Decreased BP.
Improved glucose tolerance
and lipid profile.
Others: influenza vaccine (AHA/ACC recommendation)
Prognosis
• Prognostic indicators in patients with stable angina are:
• LV function: Ejection fraction (<40%) is poor
prognostic sign.
• Severity and location of lesion: Critical lesions of
left main and proximal left anterior descending
coronary arteries are associated with a greater risk.
• Unstable angina, recent MI, or both is(are) (a)
strong predictor of increased risk.
• Response of symptoms to medical treatment.
Treatment desired outcomes
Prevent ACSs and death
Alleviate acute symptoms
Prevent recurrent symptoms
Avoid or minimize adverse effects
Pharmacological therapy
1. Pharmacotherapy to prevent ACSs and death
• Antiplatelets
• Statin.
• ACE inhibitors/ ARBs.
2. Pharmacotherapy to relieve symptoms
• Short-acting nitrates
• 3. Pharmacotherapy to prevent recurrent ischemic symptoms
• B-blockers
• Calcium channel blockers
• Long acting nitrates.
• Ranolazine.
Pharmacotherapy to prevent ACSs and death
(Antiplatelet Drugs(
• Aspirin is an irreversible inhibitor of platelet cyclooxygenase and thereby
interferes with platelet activation.
• Chronic administration of 75–325 mg orally per day has been shown to
reduce coronary events in :
– Patients with chronic stable angina
– Patients who have or have survived unstable angina and myocardial
infarction.
Pharmacotherapy to prevent ACSs and death
(Antiplatelet Drugs(
• There is a dose-dependent increase in bleeding when aspirin is used
chronically.
– It is preferable to use an enteric-coated formulation in the range of 81162 mg/d.
– Administration of this drug should be considered in all patients with
IHD in the absence of gastrointestinal bleeding, allergy, or dyspepsia.
Pharmacotherapy to prevent ACSs and death
(Antiplatelet Drugs(
• Clopidogrel (300–600 mg loading and 75 mg/d) is an oral agent that
blocks P2Y12 ADP receptor–mediated platelet aggregation.
• It provides benefits similar to those of aspirin in patients with stable
chronic IHD and may be substituted for aspirin if aspirin causes the side
effects listed above.
• Clopidogrel combined with aspirin reduces death and coronary ischemic
events in patients with an ACS and also reduces the risk of thrombus
formation in patients undergoing implantation of a stent in a coronary
artery. (at least a year with implantation of a drug-eluting stent)
Pharmacotherapy to prevent ACSs and death
(ACE inhibitor (
• The angiotensin-converting enzyme (ACE) inhibitors are widely used in the
treatment of survivors of myocardial infarction, patients with hypertension
or chronic IHD including angina pectoris, and those at high risk of vascular
diseases such as diabetes.
• the routine administration of ACE inhibitors to IHD patients who have
normal LV function and have achieved blood pressure and LDL goals on
other therapies does not reduce the incidence of events and therefore is
not cost-effective.
Pharmacotherapy to relieve symptoms
(Short-acting nitrates)
• Their major mechanisms of action include systemic venodilation with
concomitant reduction in left ventricular end-diastolic volume and
pressure, thereby reducing myocardial wall tension and oxygen demand ;
dilation of epicardial coronary vessels; and increased blood flow in vessels.
• Also exert antithrombotic activity.
• Nitrates improve exercise tolerance in patients with chronic angina and
relieve ischemia in patients with unstable angina as well as patients with
Prinzmetal's variant angina.
Pharmacotherapy to relieve symptoms
(Short-acting nitrates)
• Dilate coronary arteries with augmentation of coronary blood flow
• Side effects: generalized warmth, transient throbbing headache, or
lightheadedness, hypotension
• ER if no relief after X2 nitro's: unstable angina or MI
Problems with Nitrates
• Drug tolerance.
• Continued administration of drug will decrease effectiveness.
• Prevented by:allowing 8 – 10 hours nitrate free interval each day.
• Elderly/inactive patients: long acting nitrates for chronic antianginal
therapy is recommended
Nitroglycerin and Nitrates for Patients with Ischemic
Heart Disease
Compound
Nitroglycerin
(relieve angina and 5min
before stress)
Route
Dose
Duration of Effect
Sublingual tablets
0.3–0.6 mg up to 1.5 mg
Approximately 10 min
Spray
0.4 mg as needed
Similar to sublingual tablets
2% 6 × 6 in. 15 ×15 cm
Ointment
Effect up to 7 h
7.5–40 mg
Transdermal
0.2–0.8 mg/h every 12 h
Oral sustained release
2.5–13 mg
8–12 h during intermittent
therapy
4–8 h
Intravenous
5–200 mcg/min
Tolerance may be seen in 7–8 h
Isosorbide dinitrate
Sublingual
Oral
Spray
Chewable
Oral slow release
Intravenous
Ointment
2.5–10 mg
5–80 mg, 2–3 times daily
1.25 mg daily
5 mg
40 mg 1–2 daily
1.25–5.0 mg/h
100 mg/24 h
20 mg twice daily
Up to 60 min
Up to 8 h
2–3 min
2–2 ½ h
Up to 8 h
Tolerance in 7–8 h
Not effective
Isosorbide mononitrate
Oral
12–24 h
60–240 mg once daily
Source: Modified from RJ Gibbons et
Pharmacotherapy to prevent recurrent ischemic
symptom (Long-Acting Nitrates)
• They can provide effective plasma levels for up to 24 hours.
• Individual dose titration is important to prevent side effects (headache
and dizziness).
• To minimize the effects of tolerance, the minimum effective dose should
be used and a minimum of 8 h each day kept free of the drug to restore
any useful response(s).
Pharmacotherapy to prevent recurrent ischemic
symptom ( Beta Blockers)
Drugs
Selectivity
Partial Agonist Activity
Usual Dose for Angina
Acebutolol
β1
Yes
200–600 mg twice daily
Atenolol b
β1
No
50–200 mg/d
Betaxolol
β1
No
10–20 mg/d
Bisoprolol
β1
No
10 mg/d
Esmolol (continuous intravenous)a
β1
No
50–300 mcg/kg/min
Labetalol
None
Yes
200–600 mg twice daily
Metoprolol b
β1
No
50–200 mg twice daily
Nadolol
None
No
40–80 mg/day
Nebivolol
β1 (at low doses)
No
5–40 mg/day
Pindolol
None
Yes
2.5–7.5 mg 3 times daily
Propranolol
None
No
80–120 mg twice daily
a. An attractive agent to use in patients with relative contraindications to beta blockade.
b. Preferable in patients with mild bronchial obstruction and insulin-requiring diabetes mellitus.
Source: Modified from RJ Gibbons et al.
Pharmacotherapy to prevent recurrent ischemic
symptom ( Beta Blockers)
• They reduce myocardial oxygen demand by inhibiting the increases in
heart rate, arterial pressure, and myocardial contractility caused by
adrenergic activation.
• The therapeutic aims include relief of angina and ischemia but causes only
small reductions at rest.
Pharmacotherapy to prevent recurrent ischemic
symptom ( Beta Blockers)
• These drugs also can reduce mortality and reinfarction rates in patients
after myocardial infarction and are moderately effective antihypertensive
agents.
• Reducing the dose or even discontinuation may be necessary if these side
effects develop and persist. Since sudden discontinuation can intensify
ischemia, the doses should be tapered over 2 weeks.
Pharmacotherapy to prevent recurrent ischemic
symptom ( Beta Blockers)
• Relative contraindications include:
• Asthma and reversible airway obstruction in patients with chronic lung
disease, atrioventricular conduction disturbances, severe bradycardia.
• Side effects include:
• reduced exercise tolerance, nightmares, bradycardia, impaired
atrioventricular conduction, left ventricular failure, bronchial asthma, and
intensification of the hypoglycemia produced by oral hypoglycemic agents
and insulin.
Pharmacotherapy to prevent recurrent ischemic
symptom (Calcium Channel Blockers)
• Anti-anginal agents prevent angina
• Helpful: episodes of coronary vasospasm
• Decreases myocardial oxygen demand and increase myocardial oxygen
supply
• Potent arterial vasodilators: decrease systemic vascular resistance, blood
pressure, left ventricular wall stress with decrease myocardial oxygen
consumption
Pharmacotherapy to prevent recurrent ischemic
symptom (Calcium Channel Blockers)
• Nifidpin and other Dihydropyridines CCB
• Reduce systemic vascular resistance and arterial pressure lead to
decrease in blood pressure, trigger increase heart rate
• Undesirable effect associated with increased frequency of
myocardial infarction and mortality.
• Potential to adversely decrease left ventricular contractility.
• Amlodipine and the other second-generation dihydropyridine CCB
– They are newer CCB with low (-) inotropic effects and have
complementary actions on coronary blood supply and myocardial
oxygen demands.
Calcium Channel Blockers in Clinical Use for Ischemic
Heart Disease
Table 243–6. Drugs
Usual Dose
Duration of Action
Side Effects
Dihydropyridines
Amlodipine
5–10 mg qd
Long
Headache, edema
Felodipine
5–10 mg qd
Long
Headache, edema
Isradipine
2.5–10 mg bid
Medium
Headache, fatigue
Nicardipine
20–40 mg tid
Short
Headache, dizziness, flushing,
edema
Nifedipine
Immediate release:* 30–90 mg
daily orally
Short
Hypotension, dizziness, flushing,
nausea, constipation, edema
Short
Similar to nifedipine
Short
Hypotension, dizziness, flushing,
bradycardia, edema
Slow release: 30–180 mg orally
Nisoldipine
20–40 mg qd
Nondihydropyridines
Diltiazem
Immediate release: 30–80 mg 4
times daily
Slow release: 120–320 mg qd
Verapamil
Immediate release: 80–160 mg
tid
Slow release: 120–480 mg qd
Long
Short
Long
Source: Modified from RJ Gibbons et
Hypotension, myocardial
depression, heart failure, edema,
bradycardia
Drug selection
• Verapamil is very negatively inotropic , preferred
because of effect on slowing heart rate and
vasodilator of coronary arteries .
• Patients with resting bradycardia or AV block, a
dihydropyridine calcium blocker is better choice
• Patients with CHF: amlodipine can be added if
additional therapy is needed.
Drug selection
• Primary coronary vasospasm: no treatment with beta
blockers, it could increase coronary constriction
• Nitrates and CCB are preferred
• Concomitant hypertension: BB or CCB are useful in
treatment
• Ischemic Heart Disease & Atrial Fibrillation:
treatment with BB, verapamil can slow ventricular
rate
Combination Therapy
• If patients do not respond to initial antianginal
therapy – a drug dosage increase is recommended
unless side effects occur.
• Combination therapy: successful use of lower
dosages of each agent while minimizing individual
drug side effects
Pharmacological therapy
• Effects of antianginal medications on oxygen demand
and supply
Agent
HR
BB
↓
CCB- Verapamil,
diltiazem
↓
Dihydropyridines
↔or ↑
Nitrates
↑
Wall tension
Contractility
Oxygen
supply
↑or ↔
↓
↔
↓
↓
↓
↓
↓
↔
↑
↑
↑
Additional medical therapy
• Ranolazine or piprazine derivative, may be useful for patients with chronic
angina despite standard medical therapy.
• Its antianginal action is believed to occur via inhibition of the late inward
sodium current (INa).
• The benefits of INa inhibition include limitation of the Na overload of
ischemic myocytes and prevention of Ca2+ overload via the Na+–Ca2+
exchanger.
• A dose of 500–1000 mg orally twice daily is usually well tolerated.
• Ranolazine is contraindicated in patients with hepatic impairment or with
conditions or drugs associated with QTc prolongation and when drugs that
inhibit the CYP3A metabolic system are being used.
Interventional approach
• Pharmacologic management is as effective as revascularization , if one or
two vessels are involved and there are no differences in survival, recurrent
MI, or other measures of effectiveness.
• Multi-vessel involvement, especially if the patient has left main CAD, or
two- to three-vessel involvement with significant left ventricular
dysfunction is best managed with revascularization.
Interventional approach
• Percutaneous coronary intervention (PCI)
– Indicated for patients with one or more critical coronary stenosis
(greater than 70% occlusion)
Interventional approach
Types:
1. Percutaneous transluminal coronary angioplasty (PCTA)
2. Intracoronary bare-metal stent placement.
3. Intracoronary drug eluting stent placement.
4.
Rotational atheroectomy.
Interventional approach
• Coronary artery bypass surgery (CABG)
– Indicated for patients with three or more critical coronary stenosis
(greater than 70% occlusion) or is refractory to medical treatment).
Interventional approach
• Coronary artery bypass surgery (CABG)
– Indicated for patients with three or more critical coronary stenosis
(greater than 70% occlusion) or is refractory to medical treatment).
Interventional approach
• Coronary artery bypass surgery (CABG)
Outcome evaluation
•
•
•
•
•
Assessing for drug effectiveness and safety.
Subjective measures.
Objective measures.
Monitoring major adverse effects.
Comprehensive monitoring plan including lipid
profile, FBG, TSH/T4 and U/E
Outcome evaluation
• Duration of therapy
• Treatment with aspirin +BCN is life long
• Patients who undergo PCI or CABG may be able to
reduce antianginal therapy
Follow-up
• Follow-up for patients who have chronic stable
angina should scheduled every 3 to 6 months,
particularly in the first year, and continued yearly.
• Patients should be instructed to contact their doctors
of any change in the character or severity of their
symptoms, or in their exercise tolerance.
• Clinic visits should include an assessment of the
nature, frequency, and severity of recurrent
symptoms.
• Physical examination should assess for the presence
of CHF and cardiac murmurs such as mitral
regurgitation or AS.
Follow-up
• An ECG should be obtained in any patient with a change in symptoms.
• Follow-up echocardiography is suggested when a patient develops signs or
symptoms of CHF.
• Stress testing is recommended when symptoms have changed or
progressed.
• In asymptomatic individuals, the routine use of stress testing is less
certain, and not recommended in most cases.
• Regular exercise, starting with low-level activity, should be encouraged.
Unstable angina
• When episodes of angina occur at rest and when there is an increase in
the severity, frequency, and duration of chest pain in patients with
previously stable angina.
• Unstable angina is mainly due to decrease in oxygen supply caused when
small platelet clots occurring in the vicinity of an atherosclerotic plaque.
•
In most cases, formation of labile partially occlusive thrombi at the site of
a fissured or ulcerated plaque is the mechanism for reduction in flow.