CARDIOVASCULAR DISEASES

LECTURE 5
CAD
Academic year 2020-2021

ASS.S Pro. Dr. KHALID O.MOHSIN

D.M.C.A.B.M
CONSULTANT IN MEDICINE
HEAD OF INTERNAL MEDICINE DEPARTMENT
MISANUNIVERSITY /COLLEGE OF MEDICNE
ACADEMIC YEAR 2020-2021
 Management
• The management of angina pectoris involves:
• a careful assessment of the likely extent and
severity of arterial disease
• the identification and control of significant
risk factors (e.g. smoking, hypertension,
hyperlipidaemia , DM)
• the use of measures to control symptoms
• the identification of high-risk patients and
application of treatments to improve life
expectancy.
 Management
Symptoms alone are a poor guide to the
extent of coronary artery disease; exercise
or pharmacological stress testing is
therefore advisable in all patients who are
potential candidates for revascularization.
An algorithm for the investigation and
treatment of patients with stable angina is
shown in Figure 10.
Figure 10 A scheme for the investigation and treatment of stable angina on effort. (PCI =
percutaneous coronary intervention; CABG = coronary artery bypass grafting)
 Management
Treatment should start with a careful
explanation of the problem and a
discussion of the potential lifestyle
and medical interventions that may
relieve symptoms and improve
prognosis (Table 8).
 Management
Anxiety and misconceptions often
contribute to disability; for example, some
patients avoid all forms of exertion
because they believe that each attack of
angina is a 'mini heart attack' that results
in permanent damage.
Effective management of these
psychological factors can make a huge
difference to the patient's quality of life.
ADVICE TO PATIENTS WITH STABLE
ANGINA
*Do not smoke
• Aim at ideal body weight
• Take regular exercise (exercise up to, but not
beyond, the point of chest discomfort is
beneficial and may promote collateral vessels)
• Avoid severe unaccustomed exertion, and
vigorous exercise after a heavy meal or in
very cold weather
• Take sublingual nitrate before undertaking
exertion that may induce angina
 AAnti-anginal drug treatment
• Four groups of drugs are used to help
relieve or prevent the symptoms of angina:
• Nitrates
• β-blockers
• Calcium antagonists
• Potassium channel activators.
 Antiplatelet therapy
• Low-dose (75-150 mg) aspirin
• reduces the risk of adverse events
• such as myocardial infarction
• and should be prescribed for all
patients with coronary artery
disease indefinitely .
 Antiplatelet therapy
• Clopidogrel (75 mg daily) is an equally
effective antiplatelet agent that can be
prescribed if aspirin causes troublesome
dyspepsia or other side-effects.
 Nitrates

• Nitrates
• These drugs act directly on vascular
smooth muscle to produce venous and
arteriolar dilatation; their beneficial effects
in angina are due to a reduction in
myocardial oxygen demand (lower preload
and afterload) and an increase in
myocardial oxygen supply (coronary
vasodilatation).
 Nitrates

• Sublingual glyceryl trinitrate (GTN)

administered from a metered-dose aerosol
(400 μg per spray) or as a tablet (300 or 500 μg)
allowed to dissolve under the tongue or
crunched and retained in the mouth will usually
relieve an attack of angina in 2-3 minutes.
• Unwanted side-effects include headache
(which may be more distressing than the
angina), symptomatic hypotension and, rarely,
syncope. To avoid these symptoms the tablet
may be spat out as soon as the angina is
relieved.
 Nitrates

Patients often need to be reassured that GTN is not

habit-forming and will not lose its effect if used
repeatedly.
They should also be encouraged to use the drug
prophylactically before engaging in exercise that is
liable to provoke symptoms.
Sublingual GTN has a short duration of action (Table
11)
however, a variety of alternative nitrate preparations
can provide a more prolonged therapeutic effect.
GTN can be given transcutaneously as a patch (5-10
mg daily), or as a slow-release buccal tablet (1-5 mg
6-hourly).
 Nitrates

GTN is subject to extensive first-pass

metabolism in the liver and is therefore
virtually ineffective when swallowed;
however, other nitrates such as isosorbide
dinitrate (10-20 mg 8-hourly) and isosorbide
mononitrate (20-60 mg once or twice a day)
can be given by mouth.
Headache is common but tends to diminish if
the patient perseveres with the treatment.
 Nitrates

Continuous nitrate therapy causes pharmacological

tolerance and this should be avoided by using a
regimen that includes a nitrate-free period of 6-8
hours every day.
A variety of once-daily preparations with a built-in
nitrate-free period are available.
It is usually advisable to schedule the medication
so that drug levels are low during the night when
the patient is inactive; however, if nocturnal
angina is a prominent symptom, long-acting
nitrates can be given at the end of the day instead.
 TABLE 11 DURATION OF ACTION OF SOME NITRATE PREPARATIONS

Preparation Peak action Duration of

action
Sublingual GTN 4-8 mins 10-30 mins
Buccal GTN 4-10 mins 30-300 mins
Transdermal 1-3 hrs Up to 24 hrs
GTN
Oral isosorbide 45-120 mins 2-6 hrs
dinitrate ISDN
Oral isosorbide 45-120 mins 6-10 hrs
mononitrate
 Beta-blockers
• Beta-blockers
• These drugs lower myocardial oxygen
demand by reducing heart rate, blood
pressure and myocardial contractility.
• Unfortunately, they can exacerbate the
symptoms of peripheral vascular disease
and may provoke bronchospasm in
patients with obstructive airways disease.
 Beta-blockers
In theory, non-selective β-blockers may
aggravate coronary vasospasm by
blocking the coronary artery β2-
adrenoceptors and it is usually advisable
to use a once-daily cardioselective
preparation (e.g. atenolol 50-100 mg daily,
slow-release metoprolol 50-200 mg daily,
bisoprolol 5-10 mg daily).
 Beta-blockers

A β-blocking drug should not be

withdrawn abruptly because this may
have a rebound effect and precipitate
dangerous arrhythmias, worsening
angina or myocardial infarction (the
β-blocker withdrawal syndrome).
CALCIUM ANTAGONISTS (CCB)
• Calcium antagonists
• These drugs inhibit the slow inward current
caused by the entry of extracellular calcium
through the cell membrane of excitable
cells, particularly cardiac and arteriolar
smooth muscle, and lower myocardial
oxygen demand by reducing blood
pressure and myocardial
contractility.
 CALCIUM ANTAGONISTS
• Dihydropyridine calcium antagonists,
such as nifedipine and nicardipine, often
cause a reflex tachycardia; this may be
counterproductive and it is often best to use
these drugs in combination with a β-blocker.
• In contrast, (Non- Dihydropyridine ) . e.g.
verapamil and diltiazem are particularly
suitable for patients who are not receiving a
β-blocker because they inhibit conduction
through the AV node and tend to cause a
bradycardia or even atrioventricular block in
susceptible individuals.
 CALCIUM ANTAGONISTS
CCB
• The calcium antagonists may
reduce myocardial contractility
and can aggravate or precipitate
heart failure.
• Other unwanted effects include
peripheral oedema, flushing,
headache and dizziness.
 CCB
• The dosage and some of the
distinguishing features of these
drugs are listed Table 12.
 TABLE 12 CALCIUM ANTAGONISTS USED FOR
THE TREATMENT OF ANGINA

Drug Dose Feature

Nifedipine 5-20 mg 8-hourly* May cause marked

tachycardia
Nicardipine 20-40 mg 8-hourly May cause less
myocardial depression
than the other drugs in
this group
Amlodipine 2.5-10 mg daily Ultra-long-acting skin
allergy

* Once- or twice-daily slow-release preparations are

available.
 TABLE 12 CALCIUM ANTAGONISTS USED FOR
THE TREATMENT OF ANGINA

Drug Dose Feature

Verapamil 40-80 mg 8-hourly* Commonly causes
constipation;
useful anti-
arrhythmic
properties
Diltiazem 60-120 mg 8- Similar anti-
hourly* arrhythmic
properties to
verapamil

* Once- or twice-daily slow-release preparations are

available.
 Potassium channel activators
Potassium channel activators
This class of drug has arterial and
venous dilating properties but does not
exhibit the tolerance seen with nitrates.
Nicorandil (10-30 mg 12-hourly orally) is
the only drug in this class currently
available for clinical use.
 Drugs in stable angina pectoris
• Although each of these groups of drug
has been shown to be superior to placebo
in relieving the symptoms of angina, there
is little convincing evidence that one
group is more effective than another.
• Moreover, many commonly used
combinations of anti-anginal drugs have
not been evaluated in well-controlled
clinical trials.
 Drugs in stable angina pectoris
• Nevertheless, it is conventional to start
therapy with
• Low-dose aspirin
• Sublingual GTN
• A β-blocker
• Then add a calcium channel antagonist
or a long-acting nitrate later, if
necessary.
Drugs in stable angina pectoris
• The goal is the control of angina with
minimum side-effects and the simplest
possible drug regimen.
• There is little or no evidence that
prescribing multiple anti-anginal drugs is
of benefit, and revascularisation should be
considered if an appropriate combination
of two drugs fails to achieve a
symptomatic response.
 Invasive treatment
• The most widely used invasive options for
the treatment of ischaemic heart disease
include
1-Percutaneous coronary intervention
(PCI) including percutaneous
transluminal coronary angioplasty,
PTCA)
2-Coronary artery bypass graft (CABG)
surgery.
 Invasive treatment
• Percutaneous coronary intervention
(PCI)
• This is performed by passing a fine
guide wire across a coronary
stenosis under radiographic control
and using it to position a balloon
which is then inflated to dilate the
stenosis ( Fig. 11).
Figure 11 Percutaneous coronary intervention. A sequence of images from
a 58-year-old woman with stable angina. Severe stenosis of the circumflex
artery (arrow). A balloon has been advanced into the stenosis, over a
guidewire, and has been inflated. (Note the waisting caused by the lesion.)
Residual stenosis and dissection (tramline shadow-arrow) after balloon
dilatation. A stent is deployed on a balloon. The stent is visible on plain
fluoroscopy (arrow). Angiogram after stenting. A short balloon is used to
dilate the stent at high pressure. Final result.
 Invasive treatment
• A coronary stent is a piece of coated
metallic that can be deployed on a balloon
and used to maximize and maintain
dilatation of a stenosed vessel.
• The routine use of stents in appropriate
vessels reduces both acute complications
and the incidence of clinically important
restenosis (Table 13).
 Stents and Stent thrombosis
1-Bare-metal stents (BMS)
2- Drug-eluting stent (DES)
first-generation drug-eluting stents
(G1-DES),
and second-generation drug-eluting
stents (G2-DES)
 Invasive treatment
• PCI provides an effective
symptomatic treatment but
there is no evidence that it
improves survival in patients
with chronic stable angina.
 Invasive treatment
1-PCI in nativ coronary artery is mainly
used in single or two-vessel disease
2- Graft stenoses in bypass grafts can
be dilated,
and the technique is often used to
provide palliative therapy for patients
with recurrent angina after CABG.
 Invasive treatment
Coronary surgery is usually the preferred
option in patients with
Three-vessel
Left main disease
although recent trials have
demonstrated that PCI is also
feasible in such patients.
 TABLE 13 ANGIOPLASTY AND
INTRACORONARY STENTS IN ANGINA

'In comparison with simple balloon

angioplasty, intracoronary stents
afford superior acute and long-term
clinical and angiographic results
with lower rates of
Restenosis (e.g. 17% vs 40%)
Recurrent angina (13% vs 30%).'
TABLE 14 PERCUTANEOUS CORONARY INTERVENTION
VS MEDICAL THERAPY IN STABLE ANGINA

'PCI is more effective than medical therapy

for
Alleviating angina pectoris
Improving exercise tolerance
Does not reduce mortality.
It carries risks of
Procedure-related myocardial infarction,
Emergency coronary artery bypass grafting
Repeat procedures for restenosis
 PCI
• The main acute complications of PCI are
• occlusion of the target vessel or a side branch
by thrombus or a loose flap of intima (coronary
artery dissection), and consequent myocardial
damage.
• This occurs in about 2-5% of procedures and can
often be corrected by deploying a stent; however,
emergency CABG is sometimes required.
 PCI

• Minor myocardial damage,

as indicated by elevation of
sensitive intracellular
markers (troponins), occurs
in up to 10% of cases.
 PCI
The main long-term complication of
PCI is restenosis (Table 14), which
occurs in up to one-third of cases;
this is due to a combination of
elastic recoil and smooth muscle
proliferation (neo-intimal hyperplasia)
and tends to occur within 3 months.
Especailly
 PCI
• Drug-eluting stents (DES) can
reduce this risk even further by
allowing an antiproliferative drug,
such as sirolimus or paclitaxel, to
elute slowly from the coating and
prevent neo-intimal hyperplasia
and in-stent restenosis.
 PCI

• Recurrent angina (affecting

up to 15-20% of patients
receiving an intracoronary
stent at 6 months) may
require further PCI or
bypass grafting.
 PCI
The risk of complications and the likely
success of the procedure are closely
related to the
1- morphology of the stenoses,
2- the experience of the operator
3- the presence of important
comorbidity (e.g. diabetes, peripheral
arterial disease).
 PCI
A good outcome is less likely if the target lesion is
Complex diseases
Long
Eccentric or calcified
Lies on a bend or within a tortuous vessel
Involves a branch
Contains acute thrombus.
 PCI
In combination with Aspirin and
Heparin
adjunctive therapy with Potent platelet
inhibitors, such as clopidogrel or
glycoprotein IIb/IIIa receptor antagonists
has been shown to improve the outcome of
PCI, with lower short- and long-term rates
of
death and myocardial infarction.
 CABG
Coronary artery bypass grafting (CABG)
1-The left internal mammary arteries
(LIMA),
2-Radial arteries
3-Reversed segments of the patient's own
saphenous vein (SVG)
4-Total Arterial Revascularization in Coronary
Artery Bypass Grafting Surgery (TAR) (LIMA.
RIMA)
can be used to bypass coronary artery stenoses
(Figs 12 and 13).
 Figure 12 Coronary artery bypass graft surgery. Narrowed or
stenosed arteries are bypassed using saphenous vein grafts
connected to the aorta, or by utilising the internal mammary artery.
Figure 13 Three-dimensional reconstruction of multislice computed tomography of
the heart. The image shows the patent saphenous vein grafts (SVG) to the right
coronary artery (RCA), obtuse marginal branch (OM) and diagonal branch (LADD),
and left internal mammary artery graft (LIMA) to the left anterior descending (LAD)
coronary artery.
 CABG
This usually involves major surgery under
cardiopulmonary bypass, but in some
cases, grafts can be applied to the beating
heart: 'off-pump' surgery.
The operative mortality is approximately
1.5%,
but risks are higher in :
1- elderly patients
2- those with poor left ventricular function
3- those with significant comorbidity, such
as renal failure.
TABLE 15 CORONARY ARTERY BYPASS GRAFTING
(CABG) FOR STABLE ANGINA

'CABG is superior to medical

treatment for at least 10 years after
surgery in terms of survival.
Greatest benefit occurred in those
with
1-Asignificant stenosis in the left
main coronary artery
2-Those with three-vessel disease
3-Impaired ventricular function.
 CABG
• Approximately 90% of patients are free of
angina 1 year after surgery, but fewer than
60% of patients are asymptomatic 5 or
more years after CABG.
• Early post-operative angina is usually due
to graft failure arising from technical
problems during the operation or poor 'run
off' due to disease in the distal native
coronary vessels.
 CABG

Late recurrence of angina

may be due to
Progressive disease in the
native coronary arteries
Graft degeneration.
 CABG
• Less than 50% of vein grafts are patent
10 years after surgery.
• However, arterial grafts have a much
better long-term patency rate with more
than 80% of internal mammary artery
grafts patent at 10 years.
• This has lead many surgeons to
consider total arterial revascularisation
(TAR) during CABG surgery.
 CABG
• Aspirin (75-150 mg daily) and clopidogrel
(75 g daily) have both been shown to improve
graft patency, and one or other should be
prescribed indefinitely if well tolerated.
• Intensive lipid-lowering therapy has also
been shown to slow the progression of disease in
the native coronary arteries and bypass grafts,
and to reduce clinical cardiovascular events;
• Serum LDL cholesterol concentrations
should therefore be reduced below 3.2 mmol/l
(∼120 mg/dl).
 CABG
• There is substantial excess
cardiovascular morbidity and
mortality in patients who continue to
smoke after bypass grafting.
• Persistent smokers are twice as
likely to die in the 10 years following
surgery compared with those who
give up at surgery.
 CABG
CABG has been shown to improve survival in patients
with
1- Left main coronary stenosis
2- Symptomatic patients with three-vessel
coronary disease (i.e. involving left
anterior descending, circumflex and right
coronary arteries, Table 15)
3- Two-vessel disease involving the
proximal left anterior descending coronary
artery.
 CABG
Improvement in survival is most marked in
those with
1- Impaired left ventricular function
2- Positive stress testing prior to
surgery
3- Those who have undergone left
internal mammary artery grafting.
 CABG
Neurological complications are common,
with a 1-5% risk of perioperative stroke.
Between 30% and 80% of patients develop
short-term cognitive impairment that is
often mild and typically resolves within 6
months.
There are also reports of long-term
cognitive decline that may be evident in
more than 30% of patients at 5 years.
 Table 16 COMPARISON OF PERCUTANEOUS CORONARY
INTERVENTION (PCI) AND CORONARY ARTERY BYPASS
GRAFTING (CABG)

PCI CABG

Death < 0.5% < 1.5%

Myocardial infarction* 2% 10%
Hospital stay 12-36 hrs 5-8 days
Return to work 2-5 days 6-12 weeks
Recurrent angina 15-20% at 6 months 10% at 1 year
Repeat 10-20% at 2 years 2% at 2 years
revascularisation
Neurological Rare Common (see text)
complications
Other complications Emergency CABG Diffuse myocardial damage
Vascular damage related to Infection (chest, wound)
access site Wound pain

* Defined as CK-MB > 2 ×normal

 TABLE17 COMPARISON OF PERCUTANEOUS CORONARY
INTERVENTION (PCI) VS CORONARY ARTERY BYPASS GRAFT (CABG)
SURGERY IN STABLE ANGINA

'Systematic reviews and meta-analyses have

found similar rates of death, Myocardial infarction
and Quality of life.
PCI is associated with a greater need for
repeat procedures, although this has been
halved by the introduction of intracoronary
stent implantation.
For patients with multi-vessel disease or
diabetes, CABG appears to confer better
survival rates at 4-5 years.
 Prognosis
1-Symptoms are a poor guide to prognosis
2-Nevertheless, the 5-year mortality of
patients with severe angina (NYHA class III
or IV ) is nearly double that of patients with
mild symptoms.
3-Exercise testing and other forms of stress
testing are much more powerful predictors
of mortality; for example, in one study, the
4-year mortality of patients with stable
angina and a negative exercise test was 1%,
compared to more than 20% in those with a
strongly positive test.
 Prognosis
In general, the prognosis of
coronary artery disease is related
to the
1-Number of diseased vessels
(one-, two- or three-vessel
coronary artery disease)
2-The degree of left ventricular
dysfunction.
 Prognosis
• A patient with single-vessel disease and
good LV function has an excellent outlook
(5-year survival > 90%)
• whereas a patient with severe LV
dysfunction and extensive three-vessel
disease has a poor prognosis (5-year
survival < 30%) without revascularization.
• Spontaneous symptomatic improvement
due to the development of collateral vessels
is common.