CAD
Denis Katatwire
MMED1-Internal Medicine

Outline
i. Introduction
ii. Epidemiology
iii. Aetiology
iv. Pathophysiology
v. Clinical presentation
vi. Diagnosis.
vii. Treatment

Introduction
• Coronary artery disease (CAD) is a pathological process
characterized by atherosclerotic plaque accumulation in the
epicardial arteries, whether obstructive or non-obstructive.
• This process can be modified by lifestyle adjustments,
pharmacological therapies, and invasive interventions
designed to achieve disease stabilization or regression.
• The disease can have long, stable periods but can also become
unstable at any time, typically due to an acute
atherothrombotic event caused by plaque rupture or erosion.

Cont…
• However, the disease is chronic, most often progressive, and
hence serious, even in clinically apparently silent periods.
• The dynamic nature of the CAD process results in various
clinical presentations, which can be conveniently categorized
as either
i. Acute coronary syndromes (ACS)
ii. Chronic coronary syndromes (CCS).

Acute coronary syndromes (ACS)
i. Unstable angina
ii. ST- Elevation Myocardial infarction (STEMI)
iii. Non ST-elevation Myocardial infarction (NSTEMI)

Chronic coronary syndromes (CCS)
i. Suspected CAD and ‘stable’ anginal symptoms, and/or
dyspnoea
ii. New onset of heart failure (HF) or LV dysfunction and
suspected CAD
iii. Asymptomatic and symptomatic with stabilized symptoms
<1 year after an ACS, or patients with recent
revascularization
iv. Asymptomatic and symptomatic >1 year after initial
diagnosis or revascularization
v. Angina and suspected vasospastic or microvascular disease
vi. Asymptomatic with CAD detected at screening

Epidemiology
• CAD is the commonest cause of deaths worldwide
• Mortality rates have declined over the past four decades in
western countries however this condition remains responsible
for ~one-third of all deaths in individuals over age 35.
• Mortality is on the rise in Low and middle income countries
Tanzania being among
• The 2016 Heart Disease and Stroke Statistics update of the
AHA reported that 15.5 million people in the USA. have CHD.
• The reported prevalence increases with age for both women
and men.
• For those US people, the lifetime risk of developing CHD with
≥2 major risk factors is 37.5% for men and 18.3% for women.

Risk factors
MODIFIABLE risk factors:
• Hyperlipidemia (the most important risk factor)
• Obesity
• Diabetes mellitus
• Hypertension
• CKD
• Sedentary lifestyle/Physical inactivity
• Obesity
• Diet: high caloric intake & increase in intake of saturated
animal fats and hydrogenated vegetable fats, which contain
atherogenic trans-fatty acids
• Excess alcohol use
• Smoking

Cont…
• NON-MODIFIABLE risk factors
• Age
• Sex: Male>Female before menopause, after menopause the
risk may be the same or be higher in females
• Family history of premature cardiac death/coronary artery
disease

Pathophysiology
• Central to an understanding of the pathophysiology of
myocardial ischemia is the concept of myocardial supply and
demand.
• In normal conditions, for any given level of a demand for
oxygen, the myocardium will control the supply of oxygen-rich
blood to prevent underperfusion of myocytes and the
subsequent development of ischemia and infarction.
• The major determinants of myocardial oxygen demand
(MVO2) are heart rate, myocardial contractility, and
myocardial wall tension (stress).

Cont…
• An adequate supply of oxygen to the myocardium requires a
satisfactory level of oxygen-carrying capacity of the blood
(determined by the inspired level of oxygen, pulmonary
function, and hemoglobin concentration and function) and an
adequate level of coronary blood flow.
• Blood flows through the coronary arteries in a phasic fashion,
with the majority occurring during diastole.
• By reducing the lumen of the coronary arteries,
atherosclerosis limits appropriate increases in perfusion when
the demand for flow is augmented, as occurs during exertion
or excitement.

Cont…
• >90% of patients with IHD have atherosclerosis of one or
more of the coronary arteries.
• When the luminal reduction is severe, myocardial perfusion in
the basal state is reduced.
• Coronary blood flow also can be limited by spasm, arterial
thrombi, and, rarely, coronary emboli as well as by ostial
narrowing due to aortitis.
• Congenital abnormalities such as the origin of the left anterior
descending coronary artery from the pulmonary artery may
cause myocardial ischemia and infarction in infancy, but this
cause is very rare in adults.

Cont
• Myocardial ischemia also can occur if myocardial oxygen
demands are markedly increased and particularly when
coronary blood flow may be limited, as occurs in severe left
ventricular hypertrophy due to aortic stenosis.
• The latter can present with angina that is indistinguishable
from that caused by coronary atherosclerosis largely owing to
subendocardial ischemia.
• A reduction in the oxygen-carrying capacity of the blood, as in
extremely severe anemia or in the presence of
carboxyhemoglobin, rarely causes myocardial ischemia by
itself but may lower the threshold for ischemia in patients
with moderate coronary obstruction.

Cont…
• Not infrequently, two or more causes of ischemia coexist in a
patient, such as an increase in oxygen demand due to left
ventricular hypertrophy secondary to hypertension and a
reduction in oxygen supply secondary to coronary
atherosclerosis and anemia.
• Abnormal constriction or failure of normal dilation of the
coronary resistance vessels also can cause ischemia. When it
causes angina, this condition is referred to as microvascular
angina.

The process of coronary atherosclerosis
Initiation of atherosclerosis
• The major risk factors for atherosclerosis: high levels Of LDL,
low HDL, cigarette smoking, hypertension, and diabetes
mellitus impair the normal functions of the endothelium by
activating the pro inflammatory pathways resulting in
endothelial cell activation and dysfunction = impaired
functions include local control of vascular tone, maintenance
of an antithrombotic surface, and control of inflammatory cell
adhesion and diapedesis.

Cont…
• This causes the formation of initial lesions of atherosclerosis
where the “fatty streak” are deposited on the intima.
• In the long run, the loss of normal endothelial functions leads
to inappropriate constriction, luminal thrombus formation,
and abnormal interactions between blood cells especially
monocytes and platelets, and the activated vascular
endothelium.
• Functional changes in the vascular milieu ultimately result in
the subintimal collections of fat, smooth muscle cells,
fibroblasts, and intercellular matrix that define the
atherosclerotic plaque.

Cont…
• This process develops at irregular rates in different segments
of the epicardial coronary tree and leads eventually to
segmental reductions in cross-sectional area.
• This process commonly occurs at the sites of increased
turbulence in coronary flow, such as at branch points in the
epicardial arteries.
• Slowly developing occlusions may stimulate collateral vessels
over time = ANGIOGENESIS, which protect against distal
myocardial ischemia and infarction even with an eventual
high-grade stenosis.

Cont…
• With progressive worsening of a stenosis in a proximal
epicardial artery, the distal resistance vessels (when they
function normally) dilate to reduce vascular resistance and
maintain coronary blood flow.
• A pressure gradient develops across the proximal stenosis,
and poststenotic pressure falls. When the resistance vessels
are maximally dilated, myocardial blood flow becomes
dependent on the pressure in the coronary artery distal to the
obstruction.

Cont…
• In these circumstances, ischemia, manifest clinically by angina
or electrocardiographically by ST-segment deviation, can be
precipitated by increases in myocardial oxygen demand
caused by physical activity, emotional stress, and/or
tachycardia.
• Changes in the caliber of the stenosed coronary artery due to
physiologic vasomotion, loss of endothelial control of dilation
(as occurs in atherosclerosis), pathologic spasm (Prinzmetal’s
angina), or small platelet-rich plugs also can upset the critical
balance between oxygen supply and demand and thereby
precipitate myocardial ischemia.

Cont...
• A fixed obstructive lesion of 75% or greater (i.e., only 25% or
less lumen remaining) generally causes symptomatic ischemia
induced by exercise; with this degree of obstruction, the
augmented coronary flow provided by compensatory
vasodilation is no longer sufficient to meet even moderate
increases in myocardial demand.
• A 90% stenosis can lead to inadequate coronary blood flow
even at rest.

Cont…
• Although only a single major coronary epicardial trunk may
be affected, two or all three—lateral anterior descending
(LAD), left circumflex (LCX), and right coronary artery (RCA)—
are often
involved.
• Clinically significant stenosing plaques may be located
anywhere within these vessels but tend to predominate within
the first several centimetres of the LAD and LCX and along the
entire length of the RCA.

Role of Acute Plaque Change;
• In most patients the myocardial ischemia underlying unstable
angina, acute MI, and (in many cases) sudden cardiac death is
precipitated by abrupt plaque change followed by thrombosis
• Thus, these important manifestations are termed the acute
coronary syndromes.
• Most often, the initiating event is disruption of previously only
partially stenosing plaques with any of the following:
i. Rupture/fissuring, exposing the highly thrombogenic plaque
constituents
ii. Erosion/ulceration, exposing the thrombogenic
subendothelial basement membrane to blood.
iii. Hemorrhage into the atheroma, expanding its volume.

Atherosclerotic Plaque:
• = Focal accumulation of smooth muscle cells, foam cells,
cholesterol crystals and lipid under the endothelium of the
artery (within the Tunica Intima).
• Given time, this plaque can protrude into the lumen of the vessel
reducing blood flow
• Often develops at branch points or curves within the
vasculature….. Therefore blood is slowed and/or turbulent.
• As the atheroma within the coronary arteries enlarges, the blood
flow to the heart decreases and therefore so does the O2 supply
• The heart is not in danger of hypoxia until 50% of the vessel is
occluded.

Cont...
• As the heart senses a decrease in O2, there is attempted
compensation:
i. Increase Heart Rate
ii. Increase Blood Pressure
iii. THE two above = Aggravation/Worsening of the atheroma
• When 70-75% of the artery is occluded, Angina Pectoris will
occur with exertion.

Cont…
• The events that trigger abrupt changes in plaque configuration
and superimposed thrombosis are complex and poorly
understood.
• Influences, both intrinsic (e.g., plaque structure and composition)
and extrinsic (e.g., blood pressure, platelet reactivity) are
important.
• Acute alterations in plaque imply the inability of a plaque to
withstand mechanical stresses.
• The structure and composition of a plaque are dynamic and
contribute to a propensity to disruption.

Cont……
• Plaques that contain large areas of foam cells and extracellular
lipid, and those in which the fibrous caps are thin or contain few
smooth muscle cells or have clusters of inflammatory cells, are
more likely to rupture, and are therefore called "vulnerable
plaques."
• Fissures frequently occur at the junction of the fibrous cap and
the adjacent normal plaque-free arterial segment, a location at
which the blood flow-inducing mechanical stresses within the
plaque are highest and the fibrous cap is thinnest.

Cont…
• It is now recognized that the fibrous cap can undergo
continuous remodelling.
• The balance of synthetic and degradative activity of collagen,
the major structural component of the fibrous cap, accounts
for its mechanical strength and determines plaque stability
and prognosis.
• Collagen is produced by smooth muscle cells and degraded
by the action of metalloproteinases, enzymes elaborated by
macrophages in atheroma.

Cont…
• Thus, there is considerable evidence that inflammation
destabilizes the mechanical integrity of plaques since
macrophages increase the levels of metalloproteinases
thinning the fibrous cap of the atheromatous plaque.
• Moreover, drugs such as statins (inhibitors of HMG Co-A
reductase, a key enzyme in the synthesis of cholesterol) that
reduce clinical events associated with IHD, are thought to
stabilize plaques by their lipid-lowering effect, as well as by
reducing plaque inflammation.

Cont…
• Influences extrinsic to plaque are also important. Adrenergic
stimulation can elevate physical stresses on the plaque
through systemic hypertension or local vasospasm.
• Indeed, the adrenergic stimulation associated with awakening
and arising induces a pronounced circadian periodicity for
the time of onset of acute MI, with a peak incidence between
6 a.m. and 12 noon, concurrent with a surge in blood pressure
and immediately following heightened platelet reactivity.

Cont….
• Intense emotional stress can also contribute to plaque
disruption; this is most dramatically illustrated by the marked
increase in the incidence of sudden death that is associated
with natural or other disasters such as earthquakes
• It is now recognized that the pre-existing culprit lesion in
patients who develop myocardial infarction and other acute
coronary syndromes is not necessarily a severely stenotic and
hemodynamically significant lesion prior to its acute change.

Cont…
• Pathologic and clinical studies show that plaques that
undergo abrupt disruption leading to coronary occlusion often
are those that previously produced only mild to moderate
luminal stenosis.
• ~2/3 of plaques that rupture with subsequent occlusive
thrombosis caused occlusion of only 50% or less before plaque
rupture, and 85% had initial stenosis less than 70%.
• Thus, the worrisome conclusion is that a rather large number of
now asymptomatic adults in the industrial world have a real but
unpredictable risk of a catastrophic coronary event.

Cont……
• Regrettably, it is presently impossible to reliably predict plaque
disruption or subsequent thrombosis in an individual patient.
• Accumulating evidence indicates that plaque disruption and the
ensuing platelet aggregation and intraluminal thrombosis are
common, repetitive, and often clinically silent complications of
atheroma.
• Moreover, healing of subclinical plaque disruption and overlying
thrombosis is an important mechanism of growth of
atherosclerotic lesions.

Role of Inflammation
• Inflammatory processes play important roles at all stages of
atherosclerosis, from its inception to the development of
complications.
• The establishment of the initial lesion requires the interaction
between endothelial cells and circulating leukocytes, leading to
the accumulation of T cells and macrophages in the arterial wall.
• Entry of leukocytes into the wall is a consequence of the
release of chemokines by endothelial cells, and the increased
expression of adhesion proteins (ICAM-1, VCAM-1, E-selectin and
P-selectin) in these cells.

Cont……
• T cells located in the arterial wall produce cytokines such as TNF,
IL-6 and IFN-γ that stimulate endothelial cells and activate
macrophages, which become loaded with oxidized LDL. At later
stages of atherosclerosis, destabilization and rupture of the
plaque may involve the secretion of metalloproteinases by
macrophages…… These enzymes weaken the plaque by digesting
collagen at the fibrous cap or the shoulder of the lesion.
• Because of the important role of inflammation in the
pathogenesis of atherosclerosis, several proteins involved in
inflammation may serve as potential markers of atherosclerosis =
CRP), an acute phase reactant made in the liver, has been
suggested as a predictor of risk of coronary heart disease.

Role of Coronary Thrombus
• Partial or total thrombosis associated with a disrupted plaque
is critical to the pathogenesis of the acute coronary
syndromes.
• In the most serious form, acute transmural MI, thrombus
superimposed on a disrupted but previously only partially
stenotic plaque converts it to a total occlusion.
• In contrast, with unstable angina, acute subendocardial
infarction, or sudden cardiac death, the extent of luminal
obstruction by thrombosis is usually incomplete (mural
thrombus), and it may wax and wane with time.

Cont….
• Mural thrombus in a coronary artery can also embolize. Indeed,
small fragments of thrombotic material in the distal
intramyocardial circulation or microinfarcts may be found at
autopsy of patients who have had unstable angina or sudden
death.
• Finally, thrombus is a potent activator of multiple growth-
related signals in smooth muscle cells, which can contribute to
the growth of atherosclerotic lesions

• Vasoconstriction compromises lumen size, and, by increasing
the local mechanical forces, can potentiate plaque disruption.
• Vasoconstriction at sites of atheroma is stimulated by:
i. Circulating adrenergic agonists
ii. Locally released platelet contents
iii. Impaired secretion of endothelial cell relaxing factors
relative to contracting factors (e.g., endothelin) due to
atheroma-associated endothelial dysfunction , and possibly
iv. Mediators released from perivascular inflammatory cells.

Cont...
• The acute coronary syndromes—angina, acute MI, and sudden
death—share a common pathophysiologic basis in coronary
atherosclerotic plaque disruption and associated intraluminal
platelet-fibrin thrombus formation.
• The critical consequence is downstream myocardial ischemia.
• Stable angina results from increases in myocardial oxygen
demand that outstrip the ability of markedly stenosed
coronary arteries to increase oxygen delivery but is not usually
associated with plaque disruption.

Cont…..
• Unstable angina derives from a sudden change in plaque
morphology, which induces partially occlusive platelet
aggregation or mural thrombus, and vasoconstriction leading to
severe but transient reductions in coronary blood flow.
• In some cases, distal microinfarcts occur secondary to
thromboemboli. In MI, acute plaque change induces total
thrombotic occlusion.
• Finally, sudden cardiac death frequently involves a coronary
lesion in which disrupted plaque and often partial thrombus and
possibly embolus have led to regional myocardial ischemia that
induces a fatal ventricular arrhythmia.

Subendocardial infarction
• Involves a small area in the subendocardial wall of the left
ventricle, ventricular septum or papillary muscles.
• Subendocardial area is particularly susceptible to ischaemia
• Being the innermost layer/subendocardium, is preferentially
injured first
• ECG: ST segment depression

Transmural infarction
• Associated with atherosclerosis involving a major coronary
artery.
• It extend through the whole thickness of the heart muscle and
usually a result of complete occlusion of the area’s blood
supply
• ECG: ST segment elevation and Q waves

Clinical presentation
• In ~50%, a precipitating factor appears to be vigorous physical
exercise, emotional stress, or a medical or surgical illness.
• Circadian variations have been reported such that clusters are
seen in the morning within a few hours of awakening (highly
likely to autonomic activation observed with cardiac rhthym).
• Chest pain of the angina nature:
i. Most common presenting complaint
ii. Heavy, squeezing, and crushing, sometimes as stabbing or
burning
iii. Severe
iv. Lasts longer… around 30 minutes

Cont…
v. Central portion of the chest and/or the epigastrium, and, on
occasion, it radiates to the back, neck, lower jaw and arms.
Less common sites of radiation include the abdomen, back,
lower jaw, and neck.
vi. Often accompanied by weakness, sweating, nausea,
vomiting, anxiety, and a sense of impending doom.
vii. Occurs at rest

Atypical/asymptomatic presentation
• Diabetes mellitus
• Old age
• Female sex
• Inferior MI

Physical exam
• Anxious and restless
• Levine sign
• Diaphoresis
• Tachycardia and/or hypertension
• 4th and 3rd heart sounds may be heard
• Pericardial friction rub - ??transmural STEMI
• Reduced volume of carotid pulse
• Temperature elevations up to 38°C 1st week after STEMI.
• Hypotension/shock

Diagnosis
• Thorough hx taking
• Thorough P. Exam
• Laboratory findings
i. Cardiac biomarkers
ii. ECG
iii. ECHO

Cont…
• MI progresses through the following temporal stages/MI
Evolution:
i. Acute (first few hours–7 days)
ii. Healing (7–28 days)
iii. Healed (≥29 days).

Serum cardiac biomarkers
• Cardiac-specific troponin T (cTnT) and cardiac-specific
troponin I (cTnI):
i. Is a contractile protein that is normally not found in serum
ii. Released only when myocardial necrosis occurs
iii. +ve troponin levels are considered virtually diagnostic of MI
iv. Preferred biochemical markers for MI because
Cardiomyocytes has more troponin than CK-MB per gram
therefore high specificity and sensitivity
v. Serum levels increase within 3 – 12 hrs. from the onset of
chest pain, peak 24 – 48 hrs
vi. Remain elevated for 7–10 days after STEMI

Cont…
• CK levels: 3 CK isoenzymes are as follows:
i. CK with muscle subunits (CK – MM) = skeletal muscles
ii. CK with brain subunit (CK – BB) = brain
iii. CK – MB, which is found predominantly in the heart
iv. CK – MB levels increase within 4-8 hrs of the onset of chest
pain, reach peak values within 24 hrs, and return baseline
after 48 – 72 hrs.
v. Therefore it rises early and return to baseline early
compared to Troponins can enable early detection of MI
and show resolution of MI early compared to Troponins

Cont…
• Other markers may be sensitive but not specific:
i. Myoglobin
ii. ESR
iii. PMNs Leukocytosis on FBP

ECG Findings

ECG findings of Unstable Angina
• Normal ST or ST segment depression 0f >_0.05mV or 1/2
small box in 2 contiguous leads of the same territory
• T-wave inversion of >_0.1mV

ECG findings of NSTEMI
• Normal ST or ST segment depression 0f >_0.05mV or 1/2
small box in 2 contiguous leads of the same territory
• T-wave inversion of >_0.1mV

ECG findings of STEMI
• ST segment elevation 0f >_2mm in 2 contiguous precordial
leads and >_1 mm in 2 adjacent limb leads
• Nature of ST-Elevation: Convex (remember acute pericarditis
cause diffuse concave ST segment elevation)
• Secondary/Reciprocal changes in the other leads: ST
depression and T wave changes
• LBBB:
• Dead man sign

ECHO
i. RMWA
ii. LV function: E. function
iii. RV infarction
iv. Ventricular aneurysm
v. Pericardial effusion
vi. LV thrombus
vii. Ventricular septal defect

Cont…
i. Radionuclide imaging techniques: less sensitivity and
specificity for STEMI
ii. MRI Imaging

Exercise Stress Test;
• Used to confirm diagnosis of angina
Criteria for +ve stress test:
• > 2mm ST segment depression
• Hypotension defined by decrease of more than 10mmHg in
SBP
• Contraindications:
• If the patient has chest pain now
• Patient cant do exercise
• Baseline abnormalities (LBBB, LVH, pace maker)
• +++Cardiac imaging; coronary angiogram can be used to
definitively diagnose or rule out coronary artery disease.

Mechanical complications of ACS
1. Rupture of the left ventricular free wall: Fibrinolytic therapy,
No history of previous angina or MI, ST-segment elevation or
Q wave development on the initial electrocardiogram (ECG),
Peak MB-creatine kinase above 150 international units/L are
known risk factors
• Usually leads to hemopericardium and death from cardiac
tamponade… first suggested by the development of sudden
profound right heart failure and shock. Emergent
pericardiocentesis will confirm the diagnosis and transiently
relieve the tamponade. Transthoracic echocardiography can
further confirm the diagnosis
Rx: ECHO-guided pericardiocentesis & Surgery

Cont…
2. Rupture of the interventricular septum: risk factors are
single-vessel disease (especially LAD), extensive myocardial
damage, and poor septal collateral circulation.
• Present with the precipitous onset of hemodynamic
compromise characterized by hypotension, biventricular
failure (often predominantly right-sided failure), and a new
murmur (harsh, loud, and holosystolic)
• Rx: Surgical repair

Cont…
3. Mitral regurgitation
• Caused by ischemic papillary muscle displacement, left
ventricular dilatation or true aneurysm, and papillary muscle
or chordal rupture.
• Some patients with moderate to severe MR (but without
papillary muscle rupture) are hemodynamically stable. Many
such patients improve with medical therapy and
revascularization (by fibrinolysis or primary angioplasty); a
minority will eventually require mitral valve repair or
replacement with coronary artery bypass grafting

Cont…
4. Ventricular dilatation
5. Ventricular aneurysm

Non mechanical complications of ACS
• Congestive heart failure/LV failure
• RV failure with: jugular venous distention, Kussmaul’s sign,
hepatomegaly with or without hypotension.
• Cardiogenic shock
• Arrhythmias:
i. PVC
ii. VT
iii. VF (commonest cause of death within the 1st 24 hours of
onset of symptoms with ½ of them occurring within the
1st hour)
iv. SVT
v. AV/intraventricular conduction disturbances
• Pericarditis
• Thromboembolism

Differential dx
i. Acute pericarditis
ii. Pulmonary embolism
iii. Acute aortic dissection
iv. Costochondritis
v. PUD/Gastritis
vi. Oesophagitis

Management

Cont…
• Emergency ECG: and interpretation
• Resuscitation, ACLS, Defibrillation for VF
• Aspirin: Rapid inhibition of cyclooxygenase-1
in platelets followed by a reduction of thromboxane A2 levels
is achieved by buccal absorption through chewing
300mg START
Then 75mg daily…. For lifetime unless contraindicated
• The same for CLOPIDEGROL..DUAT..Up to a year…then ASA
For Life time unless patient contraindicated
• Oxygen therapy if SPO2 is less than 90%

Role of glucocorticoids and NSAIDs
• With the exception of aspirin, they should be avoided in
patients with STEMI.
• They can impair infarct healing and increase the risk of
myocardial rupture, and their use may result in a larger infarct
scar.
• In addition, they can increase coronary vascular resistance,
thereby potentially reducing flow to ischemic myocardium.

Cont…
• Sublingual nitroglycerin: Up to three doses of 0.4 mg should
be administered at about 5-min intervals: decrease chest
discomfort: decrease myocardial oxygen demand & increasing
myocardial oxygen supply: contraindicated with bradycardia
and shock/hypotension
• ……… contraindicated who used phosphodiesterase-5 inhibitor
sildenafil/tadalafil for erectile dysfunction within the
preceding 24 h, because it may potentiate the hypotensive
effects of nitrates. An idiosyncratic reaction to nitrates,
consisting of sudden marked hypotension, sometimes occurs
but can usually be reversed promptly by the rapid
administration of ??intravenous atropine.

Cont…
• Morphine: ANALGESIA, reduce sympathetically mediated
arteriolar and venous constriction, and the resulting venous
pooling may reduce cardiac output and arterial pressure.
Morphine also has a vagotonic effect and may cause
bradycardia or advanced degrees of heart block, particularly in
patients with inferior infarction. These side effects usually
respond to atropine (0.5 mg intravenously).
Every 5 min intravenous injection of small doses (2–4 mg).
• Beta blockers = useful in the control of the pain of STEMI by
diminishing myocardial O2 demand and hence ischemia,
reduce the risks of reinfarction and ventricular fibrillation.
Contraindicated if the patients signs of AHF, Bradycardia,
Hypotension/Cardiogenic shock, Heart block.
Carvedilol, metoprolol

Cont…
• CCBs: Amlodipine/nifedipine are of little use however they
very important in case of Prinzmetal's angina

Reperfusion therapy
• When ST-segment elevation of at least 2 mm in 2 contiguous
precordial leads and 1 mm in 2 adjacent limb leads is present,
a patient should be considered a candidate for reperfusion
therapy that is selecting patients for fibrinolysis versus
primary PCI (angioplasty, or stenting).
• CABG can be done if the anatomy of coronary disease is
complex, there is recurrent angina despite primary PCI is or as
an elective procedure after resolution of the ACS
• In the absence of ST-segment elevation, fibrinolysis is not
helpful, and evidence exists suggesting that it may be harmful

Cont…
• Reperfusion in patients with STEMI can be accomplished by
the pharmacologic (fibrinolysis) or catheter-based (primary
PCI) approaches.
• Implementation of these strategies varies based on the mode
of transportation of the patient and capabilities at the
receiving hospital.
• Transport time to the hospital is variable from case to case,
but the goal is to keep total ischemic time within 120 min.
There are three possible scenarios:
i. If EMS has fibrinolytic capability and the patient qualifies
for therapy, prehospital fibrinolysis should be started within
30 min of EMS arrival on scene.

Cont…
ii. If EMS is not capable of administering prehospital
fibrinolysis and the patient is transported to a non-PCI-
capable hospital, the hospital door-to-needle time should
be within 30 min for patients in whom fibrinolysis is
indicated.
iii. If EMS is not capable of administering prehospital
fibrinolysis and the patient is transported to a PCI-capable
hospital, the hospital door-to-balloon time should be within
90 min. Interhospital transfer : It is also appropriate to
consider emergency interhospital transfer of the patient to
a PCI-capable hospital for mechanical revascularization if:

Cont…
(1) there is a contraindication to fibrinolysis
(2) PCI can be initiated promptly (within 90 minutes after the
patient presented to the initial receiving hospital or within
60 min compared to when fibrinolysis with a fibrin-specific
agent could be initiated at the initial receiving hospital)
(3) Fibrinolysis is administered and is unsuccessful (i.e., “rescue
PCI”). Secondary nonemergency interhospital transfer can
be considered for recurrent ischemia.
(4) If the patient arrives at a non-PCI-capable hospital, the
door-to-needle time should be within 30 min. If the patient
arrives at a PCI-capable hospital, the door-to-balloon time
should be within 90 min.

Fibrinolysis
• Indicated for STEMI when the door to balloon time is more
>_90 minutes or when PCI can not be done
• 4 types of thrombolytics:
i. tissue plasminogen activator (rtPA)
ii. Streptokinase
iii. Urokinase
iv. Anistreplase

Cont…
• Streptokinase 250,000IU infusion over 30minutes, then
100,000IU per hour for 24hours
OR
Alteplase (rtPA) 100mg IV infusion over 2hours

Absolute Contraindicationsto thrombolytictherapy:
• Haemorrhagic cerebrovascular accidents (CVA)
• Intracranial neoplasia, recent cranial surgery or trauma within
1 month
Uncontrolled severe hypertension because of an increased risk
of intracranial bleeding.
• Major thoracic or abdominal surgery within 10days
• Prolonged cardiopulmonary resuscitation
• Current severe bleeding from gastrointestinal tract (GIT) or
other organs
• Known bleeding disorders

Cont…
Complications of thrombolytic therapy:
1. Allergy (Anaphylaxis)
2. Embolism
3. Major bleeding:
i. Thrombolytic agent should be stopped
ii. Fresh frozen Plasma administered
iii. Tranexamic acid administered
iv. Fibrinogen should be assayed for possible replacement.

Cont...
Anticoagulation:
• Unfractionated Heparin (UFH) 10,000units IV bolus, then
maintenance infusion starts with 6,000U over 6hours to keep
PTT or clotting time 2-3 times above baseline.
• PTT should be performed 12hourly according to lab
instruction.
• In patients with grossly impaired renal function (CrCl<20
ml/min),, UFH is an option for anticoagulation.

Cont…
Monitoring
• UFH is monitored using the aPTT (2-3 x normal) or antiXa.
• Monitoring should be done 6 hourly until 2 consecutive
therapeutic results are obtained and 24 hourly thereafter.
• Heparin should be started concurrently with warfarin and
continued for at least 5 days after start of warfarin.
• Heparin should not be discontinued until 2 consecutive
therapeutic INR of 2-3 is achieved at least 24 hours apart (but
not before day 5 of overlap).

Cont…
Complications:
• Bleeding
-ANTIDOTE: protamine sulfate slow infusion = 1mg for every
100 units of heparin (those infused in few past hours)
- Protamine sulphate can cause more bleeding by causing
platelet aggregation leading to thrombocytopenia.
• HIT: ~0.5% (medical patients) - 3 % (after major surgery)
MECHANISM: Heparin-induced production of antibodies against
heparin-platelet factor 4 complexes. The formed antibodies
cause platelets activation resulting in a prothrombotic state.
The antibodies also cause endothelial activation.
Thrombocytopenia is largely due to clearance of activated
platelets by reticulo-endothelial system

Cont…
• Suspected cases should be screened with the 4T
(Thrombocytopenia, Timing of Platelet count fall, Thrombosis
or other sequelae and other causes of thrombocytopenia)
pretest.
• If positive, further use of UFH should be stopped.
• Since paradoxical thrombosis continues in spite of the
thrombocytopenia, anticoagulation should be continued with
either a Bivalirudin, fondaparinux or DOAC.
• The risk of HIT is 10 times with UFH>LMWH

Cont..
Low Molecular weight Heparin (LMWH)
• Enoxaparin 1mg/kg twice daily
• LMWH forms a complex with antithrombin III therefore
inactivating factor Xa and to a lesser extent activated factor II
(FIIa)
• Can accumulate in patients with impaired renal function
(enoxaparin > dalteparin > tinzaparin).
• Requires serum creatinine, FBC, PT and APTT
• Enoxaparin should be avoided in patients with CrCl of
<20ml/min.

Cont…
LMWH-Adverse effects:
• Bleeding =Protamine sulphate reverses ~60% of anticoagulant
activity of LMWH. If the last dose of LMWH is within 8 hours,
protamine sulfate should be given at a dose of 1mg per 100
antiFXa units up to a maximum of 50mg (1mg of enoxaparin
corresponds approximately to 100 antiFXa units) If over 8
hours has elapsed before the last administration of LMWH, a
lower dose of protamine sulfate may be given (0.5mg per 100
antiFXa units).
• HIT: - Use alternative anticoagulant Bivalirudin, fondaparinux
or DOAC

Cont…
Fondaparinux
• Synthetic heparin-like anticoagulant with reversible selective
antithrombin (AT) dependent antiFXa activity.
• Indications…. previous history of HIT anticoagulants
• 5mg daily for <50kg, at 7.5mg daily for patients weighing 50-
100kg, while >100kg at 10mg daily, all by subcutaneous route.
• To be avoided in patients with CrCl of <30ml/min. Warfarin
should be commenced concurrently with fondaparinux and
continued for at least 5 days, not discontinued until 2
consecutive therapeutic INR of 2-3 is achieved at least 24
hours apart.

Cont…
VIKA
• Warfarin
=Inhibition of vitamin K epoxide reductase and vitamin K
reductase resulting into inhibition of gamma carboxylation
required for carboxylation of the coagulation proteins factors
II, VII, IX and X, as well as the anticoagulatory proteins C and S.
• Must be initiated with a rapidly acting anticoagulant (UFH or
LMWH) and after 5 or more days when the necessary
anticoagulant effect of warfarin is achieved for most
conditions.
• Dosage: 5-10mg

Cont…
Monitoring treatment:
• Use PT (and/or INR)
• INR is checked daily as from day 3 of warfarin initiation and
dosage adjusted until a stable therapeutic effect is achieved.
• Targeted INR range is 2-3
• After stabilizing can be assessed at 4-6-8 weeks interval
• A higher INR is recommended for patients with mechanical
heart valve replacement and those with failed anticoagulant
therapy despite well-documented INR values in range of
2-3.

Cont…
Complications:
• Bleeding:
=Serious bleeding and major overdose may require
factor replacement and intravenous administration of vitamin
K.
• skin necrosis
• Purple toe syndrome
• Rash
• Hepatitis.

Cont…
Direct Orally-active Anticoagulants (DOACs):
• DOACs exhibit a comparable efficacy and a significantly lower
bleeding risk when compared with warfarin
• They can be administered once or twice daily without need for
monitoring.
• They have fewer clinically related drug interactions
• They have fast onset of action like the LMWH and can replace
these parenteral agents.
• Initial heparin anticoagulation not required for rivaroxaban but
initial higher doses of anticoagulant must be given in the 1st
few weeks of therapy.

Cont…
• Two groups of DOACS
i. Direct Factor Xa inhibitors: Rivaroxaban, apixaban (these
two have an antidote: Andexanet alfa; a modified factor
Xa), edoxaban,
-Monitoring: Possible aFXa Test
i. Direct Thrombin inhibitors: Dabigatran (Idarucizumab is the
antidote of choice), Argatroban
-possible monitoring Thrombin Time (TT)

Long term therapy
• Lifestyle interventions and risk factors control
i. Smoking cessation
ii. Optimal BP control
iii. Diet advice = DASH Diet
iv. Weight control with target of BMI of 22.5-25kg/m2
v. Encouraging physical activity: 30 minutes per day/150 per
week of vigorous exercise/300 minutes of moderate
intensity exercise
vi. Moderation of alcohol use (limit their consumption to 14
units per week and women to 8 units per week (1 unit is
equal to 125 mL of wine or 250 mL of beer))
vii. Adherence to prescribed treatment

Pharmacotherapy
• Antiplatelet therapy with low-dose aspirin (75–100 mg) is
indicated (IA).
• DAPT in the form of aspirin plus ticagrelor or prasugrel (or
clopidogrel if ticagrelor or prasugrel are not available or are
contraindicated), is recommended for 12 months after PCI,
unless there are contraindications such as excessive risk of
bleeding (IA).
• A PPI in combination with DAPT is recommended in patients at
high risk of gastrointestinal bleeding (IB).
• In patients with an indication for oral anticoagulation, oral
anticoagulants are indicated in addition to antiplatelet therapy
(IC).

Cont…
• In patients who are at high risk of severe bleeding
complications, discontinuation of P2Y12 inhibitor therapy
after 6 months should be
considered (IIaB)
• In STEMI patients with stent implantation and an indication for
oral anticoagulation, triple therapy should be considered for
1–6 months (according to a balance between the estimated
risk of recurrent coronary events and bleeding) (Iia C)
• DAPT for 12 months in patients who did not undergo PCI
should be considered unless there are contraindications such
as excessive risk of bleeding (IIa C)

Cont…
• In patients with LV thrombus, anticoagulation should be given
for up to 6 months guided by repeated imaging IIa C
• In high ischaemic-risk patients who have tolerated DAPT
without a bleeding complication, treatment with DAPT in the
form of ticagrelor 60 mg twice a day on top of aspirin for
longer than 12 months may be considered for up to 3 years
(IIb B)
• In low bleeding-risk patients who receive aspirin and
clopidogrel, low-dose rivaroxaban (2.5 mg BID) may be
considered ( IIb B)
• The use of ticagrelor or prasugrel is not recommended as part
of triple antithrombotic therapy with aspirin and oral
anticoagulation (III C)

B-Blockers
• Oral treatment with beta-blockers is indicated in patients with
heart failure and/or LVEF <_40% unless contraindicated
• Intravenous beta-blockers should be considered at the time of
presentation in patients undergoing primary PCI without
contraindications, with no signs of acute heart failure, and
with an SBP >120 mmHg
• Routine oral treatment with beta-blockers should be
considered during hospital stay and continued thereafter in all
patients without contraindications
• Intravenous beta-blockers must be avoided in patients with
hypotension, acute heart failure or AV block, or severe
bradycardia.

Lipid lowering therapies
• It is recommended to start high-intensity Statin therapy as
early as possible, unless contraindicated, and maintain it long
term.
• LDL-C goal of < 1.8 mmol/L (70 mg/dl) or a reduction of at
least 50% if the baseline LDL-C is between 1.8–3.5 mmol/L
(70–135 mg/dl) is recommended.
• It is recommended to obtain a lipid profile in all STEMI
patients as soon as possible after presentation.
• In patients with LDL-C >_1.8 mmol/L (70 mg/dl) despite a
maximally tolerated statin dose who remain at high risk,
further therapy to reduce LDL-C should be considered.

ACE inhibitors/ARBs
• ACE inhibitors are recommended, starting within the first 24 h
of STEMI in patients with evidence of heart failure, LV systolic
dysfunction, diabetes, or an anterior infarct.
• An ARB, preferably valsartan, is an alternative to ACE inhibitors
in patients with heart failure and/or LV systolic dysfunction,
particularly those who are intolerant of ACE inhibitors.
• ACE inhibitors should be considered in all patients in the
absence of contraindications

MRAs
• MRAs are recommended in patients with an LVEF <_40% and
heart failure or diabetes, who are already receiving an ACE
inhibitor and a beta-blocker, provided there is no renal failure
or hyperkalaemia.

??
• Killip score and its importance
• TIMI score and its applications

References
• Harrison's Principles of Internal Medicine; 18Th Edition
• ESC Guidelines for CAD
• AHA/ACC guidelines on CAD