Acute coronary syndrome (ACS) results from an imbalance between myocardial oxygen supply and demand due to diminished blood flow from an occlusive coronary artery thrombus. ACS is classified as ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation ACS (NSTE-ACS), which includes non-STEMI and unstable angina. Treatment involves antiplatelet and anticoagulant medications, revascularization procedures like percutaneous coronary intervention (PCI), and lifestyle modifications to prevent recurrent events.

1. Acute coronary syndrome

2. ACS:
• results primarily from diminished myocardial blood flow secondary to an
occlusive or partially occlusive coronary artery thrombus (imbalance between
myocardial oxygen demand and supply).
• ACS is classified according to electrocardiogram (ECG) changes into STEMI or
NSTE-ACS (NSTEMI and UA).
• patients presenting with suspected ACS, approximately 31% have STEMI, 32%
NSTEMI, 26% UA, 8% another cardiac diagnosis, and 4% a noncardiac final
diagnosis.

3. Etiology:
• MI type 1 is atheromatous plaque rupture, fissuring, or erosion of an
unstable atherosclerotic plaque.it generally occurs in coronary arteries
where the stenosis occludes less than 50% of the lumen prior to the event.
the predominant cause of ACS in more than 90% of patients.
• MI type 2 is related to a reduction in myocardial oxygen supply or an
increase in myocardial demand in the absence of a coronary artery process.
• MI type 3 is defined as MI resulting in death without the possibility of
measuring biomarkers.
• while MI types 4 and 5 occur during revascularization procedures..

4. STEMI :
• A STEMI occurs when symptoms of myocardial ischemia occur in
conjunction with new ST-segment elevation with subsequent release
of biomarkers of myocardial necrosis, mainly troponins T or I.
• Transmural manifestation with possible pathogenic Q wave changes.

5. NSTEMI
• NSTEMI is limited to the subendocardial myocardium and is not as
extensive as STEMI.
• NSTEMI differs from UA in that ischemia is severe enough to produce
myocardial necrosis resulting in the release of a detectable amount of
troponins T or I, from the necrotic myocytes in the bloodstream

7. • For NSTEMI AND STEMI mortality rate is lower in patient undergoing
PCI compered to patient receiving no revascularization in hospital.
• In hospital mortality rate for NSETMI is lower than STEMI.
• post-discharge mortality rates may be higher for NSTEMI than STEMI.

8. Plaque Rupture and Clot Formation
• ruptured plaque platelet adhesion thromboxane A2
vasoconstriction and potentiate platelet activation
changes in glycoprotein (GP) IIb/IIIa surface receptors of platelets occurs that
cross-links platelets to each other through fibrinogen bridges
• Also there is an incrase in the production of thrombin (factor IIa), which
converts fibrinogen to fibrin through enzymatic activity. Fibrin stabilizes the
clot and traps red blood cells.

9. Ventricular Remodeling Following an Acute MI
• it is characterized by left ventricular (LV) dilation and reduced
pumping function of the LV, leading to HF.
• ACE inhibitors, ARBs, β-blockers, and aldosterone antagonists are all
agents that slow down or reverse ventricular remodeling through
inhibition of the renin–angiotensin–aldosterone system and/or
through improvement in hemodynamics (decreasing preload,
afterload ),also improve survival.

10. Symptoms
• often described as crushing, burning, or a heavy pressure. It most often occurs
when an individual is at rest, as a severe new onset, or as increasing angina that is
at least 20 minutes in duration. The classic symptom of ACS is midline anterior
chest discomfort. Accompanying symptoms may include arm, back, or jaw pain,
nausea, vomiting, or shortness of breath.
• Patients less likely to present with classic symptoms include elderly patients,
diabetic patients, and women.
Signs
• No signs are classic for ACS.
• Patients with ACS may present with signs of acute decompensated HF including
jugular venous distention and an S3 sound on auscultation.
• Patients may also present with arrhythmias, and therefore may have tachycardia,
bradycardia, or heart block.

11. Labs
• Troponin I or T are measured at the time of first assessment and
repeated at least once after 3 to 6 hours. And beyond 6 hours in
whom normal troponin level where obtained at fisrt with a
suspension of ACS.
• CBC, K, Mg, Scr, APTT, INR.
• mean length of hospital stay is 3 days

12. Other Diagnostic Tests
• The 12-lead ECG is the first step in management. Patients are risk-
stratified into two groups: STEMI and suspected NSTE-ACS.
• echocardiogram, is performed to identify patients with low LV
ejection fractions (EF) (≤40%) who are at high risk of death following
hospital discharge.
• Selected low-risk patients may undergo early stress testing

13. TIMI Risk Score for NSTE-ACS
One point is assigned for each of the seven medical history and clinical presentation findings. The point total is calculated, and the patient is assigned a risk for experiencing the composite endpoint of death, MI, or urgent need for revascularization as
follows:
•Age 65 years or older
•Three or more CHD risk factors: smoking, hypercholesterolemia, hypertension, diabetes mellitus, family history of premature CHD death/events
•Known CAD (50% or greater stenosis of at least one major coronary artery on coronary angiogram)
•Aspirin use within the past 7 days
•Two or more episodes of chest discomfort within the past 24 hours
•ST-segment depression 0.5 mm or greater
•Positive biochemical marker for infarction
High-Risk Medium-Risk Low-Risk
TIMI Risk Score 5-7 points TIMI Risk Score 3-4 points TIMI Risk Score 0-2 points
TIMI Risk Score Mortality, MI, or Severe Recurrent Ischemia Requiring Urgent Revascularization Through 14 Days
0/1 4.7%
2 8.3%
3 13.2%
4 19.9%
5 26.2%
6/7 40.9%
GRACE Risk Factors for Increased Mortality and the Composite of Death or MI in ACS
Signs and symptoms of heart failure
Low systolic blood pressure
Elevated heart rate
Older age
Elevated serum creatinine
Baseline risk factors on clinical evaluation: cardiac arrest at admission, ST-segment deviation, elevated troponin
A high-risk patient is defined as a GRACE Risk Score more than 140 points

14. General Approach to Treatment
• oxygen administration (if oxygen saturation is low, less than 90%).
• continuous multi-lead ST-segment monitoring for arrhythmias and
ischemia.
• frequent measurement of vital signs.
• bed rest for 12 hours in hemodynamically stable patients.
• and pain relief

16. in case of non PCI:
• clopidogril is the preferred P2Y12 inhibitor when fibrinolytic therapy is
utilized. No loading dose recommended if age older than 75 years.
• IV UFH: given for up to 48 hours or until revascularization.
• Enoxaparin or fondaparinux: given for the duration of hospitalization,
up to 8 days or until revascularization.
• In patients with STEMI receiving a fibrinolytic or who do not receive
reperfusion therapy, administer clopidogrel for at least 14 days and
ideally up to 1 year

17. PCI (SETMI):
•PCI lower risk of hemorrhage compered to fibrinolysis.
• PCI open 90% of the occluded vessel while fibrinolysis open 60%.
•PCI: those with contraindications to fibrinolytics, and those with
continuing symptoms 12 to 24 hours after symptom onset.
•For STEMI, one important measure is the time from first medical contact
to the time the occluded artery is opened with PCI. This first medical
contact-to-primary PCI time should be equal to or less than 90 minutes
•primary PCI can be performed within the first 120 minutes of medical
contact

18. STEMI treatment :
• All patient with STEMI should receive intranasal oxygen (if oxygen
saturation is low), sublingual (SL) nitroglycerin (NTG), aspirin, a P2Y12
inhibitor (clopidogrel, prasugrel, or ticagrelor depending on reperfusion
strategy), and anticoagulation with bivalirudin, unfractionated heparin
(UFH), enoxaparin, or fondaparinux (within the first day of hospitalization,
and preferably in the ED).
• An ACE inhibitor is recommended to be administered within the first 24
hours in patients with STEMI who have either an anterior wall MI or an
LVEF less than or equal to 40% (0.40) and no contraindications.
• The use of IV β-blockers is reasonable at the time of presentation for
patients with hypertension (HTN) and ongoing ischemia. (within the first
day of presentation)

19. Treatment of STEMI (fibrinolytic) :
• Administration of a fibrinolytic agent is indicated in patients with STEMI who
present within 12 hours of the onset of chest discomfort to a hospital not
capable of primary PCI.
• not able to be transferred and undergo primary PCI within 120 minutes of
medical contact.
• The mortality benefit of fibrinolysis is highest with early administration and
diminishes after 12 hours. The use of fibrinolytics between 12 and 24 hours
after symptom onset should be limited to patients with ongoing ischemia.
• In patients who have a contraindication to fibrinolytics and PCI, or who do not
have access to a facility that can perform PCI, treatment with an anticoagulant
(other than UFH) for up to 8 days can be administered.
• alteplase, reteplase, and tenecteplase are acceptable as first-line agents.
• Streptokinase is second line.

20. Indications
1.Ischemic chest discomfort at least 20 minutes in duration but 12 hours or less since
symptom onset and ST-segment elevation of at least two contiguous leads of ≥2 mm in
men and ≥1.5 mm in women in leads V2-V3 and/or of ≥1 mm in other leads, or new or
presumed new left bundle-branch block
2.Ongoing ischemic chest discomfort at least 20 minutes in duration 12-24 hours since
symptom onset and ST-segment elevation of at least 1 mm in height in two or more
contiguous leads
Absolute Contraindications
•Active internal bleeding (not including menses)
•Previous intracranial hemorrhage at any time; ischemic stroke within 3 months (except acute ischemic
stroke within 4.5 hours)
•Known intracranial neoplasm
•Known structural cerebral vascular lesion (eg, arteriovenous malformation)
•Suspected aortic dissection
•Significant closed head or facial trauma within 3 month
Indications and Contraindications to Fibrinolytic Therapy for Management of ST-Segment Elevation Myocardial
Infarction2

21. Aspirin:
• MOA: inhibiting the synthesis of TXA2 through an irreversible inhibition of
platelet cyclooxygenase-1.
• Current data suggest that an initial dose of 162 to 325 mg is required
• long-term therapy with doses 81-162 mg once daily orally starting hospital day
2.
• Because of increased bleeding risk in patients receiving aspirin plus a P2Y12
inhibitor compared with aspirin alone, low-dose aspirin (81 mg daily) is
preferred following PCI. Low-dose aspirin should be continued indefinitely.
• SE:GI bleeding , dyspepsia and nausea.

22. Platelet P2Y12 Inhibitors
• Clopidogrel, prasugrel, and ticagrelor are oral agents that block a subtype of
the ADP receptor, the P2Y12 receptor, on platelets, preventing the binding of
ADP to the receptor and subsequent expression of platelet GP IIb/IIIa
receptors, reducing platelet activation and aggregation.
• Clopidogrel(CYP2C19) and prasugrel(CYP 3A4 and 2B )are prodrugs, Ticagrelor
is metabolized primarily by CYP3A.
NSTE-ACS indication May be used regardless of
treatment strategy;
additional non-ACS
indications
Reasonable over clopidogrel
in patients treated with PCI
who are not at high risk for
bleeding
Preferable to clopidogrel for
NSTE ACS patients treated
with early or invasive or
ischemia-guided approach
No US guideline
recommendation; May be
considered in P2Y12
inhibitor—naïve patients
undergoing PCI
STEMI indication Preferred when fibrinolytics
used
Superior to clopidogrel in
STEMI or in other high-risk
patients like DM; Not studied
in patients receiving
fibrinolytic therapy
Superior to clopidogrel; Not
studied in patients receiving
fibrinolytic therapy
No US guideline
recommendation; May be
considered in P2Y12
inhibitor—naïve patients
undergoing PCI
Clopidogril prasugrel ticagrelor Cangrelor

23. • Prasugrel has the fewest significant drug–drug interactions of the oral P2Y12
inhibitors.
• Both prasugrel and ticagrelor are more potent ADP inhibitors than
clopidogrel.
• Clopidogril is associated withCYP2C19 genotype, while Prasugrel and
ticagrelor efficacy are not associated with it.
• clopidogrel loading dose of 600 mg is recommended over administration of
300 mg for patients undergoing PCI, then 75 mg daily.
• consider alternative P2Y12 receptor inhibitor if documented clopidogrel
ineffectiveness (eg, poor metabolism, stent thrombosis during clopidogrel
therapy) or drug–drug interactions (eg, avoid moderate and strong CYP2C19
inhibitors);
• The recommended duration of P2Y12 inhibitors for a patient undergoing PCI
for ACS, either STEMI or NSTE-ACS, is at least 12 months for patients
receiving either a BMS or DES

24. • If CABG surgery is planned, clopidogrel and ticagrelor should be withheld
preferably for 5 days, and prasugrel at least 7 days, to reduce the risk of
postoperative bleeding, and restarted postoperatively, unless the need
for immediate revascularization outweighs the bleeding risk. Low-dose
aspirin should be continued
• Do not use prasugrel in patients with active pathologic bleeding or a
history of transient ischemic attack ,stroke or >75 year.
• Do not use ticagrelor in patients with active pathologic bleeding or a
history of intracranial hemorrhage, or in patients planned to undergo
urgent CABG surgery;

26. Glycoprotein IIb/IIIa Receptor Inhibitors: abciximab, eptifibatide, or
tirofiban
• block the final common pathway of platelet aggregation, namely, cross-linking of platelets
by fibrinogen bridges between the GP IIb and IIIa receptors on the platelet surface.
• STEMI undergoing primary PCI who are treated with UFH, abciximab (IV or intracoronary
administration), eptifibatide, or tirofiban may be administered.
• Don’t use if fibrinolytic therapy or not doing PCI.
• Don’t use in hemogenic o ischemic stroke.
• The dose of tirofiban should be halved in patients with CrCl less than 30 mL/min (0.50
mL/s). No dosage adjustment for renal function is necessary for abciximab.
• immune-mediated thrombocytopenia when stop treatment specially abciximab

27. Anticoagulants: UFH, enoxaparin or fondaparinux , bivalirudin
• If PCI, anticoagulation is discontinued immediately following the PCI
procedures.
• In patients receiving an anticoagulant plus a fibrinolytic, UFH is continued for a
minimum of 48 hours and if either enoxaparin or fondaparinux is selected,
those agents are continued for the duration of hospitalization, up to 8 days.
• In patients who do not undergo reperfusion therapy, it is reasonable to
administer anticoagulant therapy for up to 48 hours for UFH or for the duration
of hospitalization for enoxaparin or fondaparinux
• Most common side effect of UFH and enoxaparin is heparin-induced
thrombocytopenia,in this case use bivalirudin.

28. • If pretreated with UFH, stop UFH infusion for 30 minutes prior to
administration of bivalirudin (bolus plus infusion).

29. beta blockers
• β-blockers should be initiated within 24 hours of hospital admission to all
patients in the absence of contraindications.
• Oral beta blockers are preferred over IV in the contemporary management of
ACS.
• The most serious side effects of β-blocker are hypotension, acute HF,
bradycardia, and heart block.
• initial acute administration of β-blockers is not appropriate for patients who
present with acute HF, in this case it is initiated before discharge after acute HF
treatment.
• β-Blockers should be continued for at least 3 years in patients with normal LV
function and indefinitely in patients with LV systolic dysfunction and an LVEF
less than or equal to 40% (0.40)
• Patients already taking β-blockers can continue taking them.2

30. Statins
• A high-intensity statin (either atorvastatin 80 mg or rosuvastatin 40 mg)
should be administered to all patients without contraindications prior to
PCI and continued after that.
• Calcium Channel Blockers
• Calcium channel blockers in the setting of STEMI are used for relief of
ischemic symptoms in patients who have certain contraindications to β-
blockers.
• Administration of an agent that lowers HR, either diltiazem or verapamil,
is preferred unless the patient has LV systolic dysfunction, bradycardia, or
heart block, and then either amlodipine or felodipine is preferred.

31. nitrates
• One SL NTG tablet should be administered every 5 minutes for up to
three doses in order to relieve myocardial ischemia.
• IV NTG should then be initiated in all patients with an ACS who have
persistent ischemia, HF, or uncontrolled high BP in the absence of
contraindications. IV NTG should be continued for approximately 24
hours after ischemia is relieved
• nitrates are tachycardia, flushing, headache, and hypotension.
• Nitrate administration is contraindicated in patients who have received
oral phosphodiesterase-5 inhibitors, such as sildenafil and vardenafil,
within the last 24 hours, and tadalafil within the last 48 hour

33. • A- IV NTG, ticagrelol: For selected patients
• B- Clopidogrel for in case of PCI :Preferred in patients at high risk for
bleeding.
• C- If pretreated with UFH, stop UFH infusion for 30 minutes prior to
administration of bivalirudin bolus plus infusion.
• D-SC enoxaparin:May require IV supplemental dose of enoxaparin;
• E-Parogrel :Do not use if prior history of stroke/transient ischemic attack
(TIA), age older than 75 years, or body weight less than or equal to 60
kg.
• F- Subcut enoxaparin or UFH can be continued at a lower dose for
venous thromboembolism prophylaxis following PCI.
• G-fondaparinux: Requires an IV supplemental dose of UFH.

34. • All patient with NSTE-ACS should receive intranasal oxygen (if oxygen
saturation is low), sublingual (SL) nitroglycerin (NTG), asoirin, a P2Y12
inhibitor (clopidogrel, prasugrel, or ticagrelor depending on reperfusion
strategy), and anticoagulation with bivalirudin, unfractionated heparin
(UFH), enoxaparin, or fondaparinux (within the first day of
hospitalization, and preferably in the ED).
• Oral β-blockers should be initiated within the first 24 hours in patients
without cardiogenic shock.
• Morphine is also administered to patients with refractory angina as
described previously.
• Fibrinolytic Therapy
• Fibrinolytic therapy is not indicated in any patient with NSTE-ACS because
increased mortality

35. Nitrates,B-blokersCalcium Channel Blockers and aspirin:
Same as STEMI.
Anticoagulant:
• If fondaparinux is chosen for a patient initially receiving a conservative
strategy who subsequently undergoes angiography and PCI, should be
administered in combination with UFH .
• Therapy should be continued for up to at least 48 hours for UFH until the
patient is discharged from the hospital, or 8 days, whichever is shorter for
either enoxaparin or fondaparinux, or until the end of PCI or angiography
procedure (or up to 72 hours following PCI for bivalirudin).
• For patients undergoing CABG during the same hospitalization, UFH can
be continued until a few hours before CABG and LMWH should be
stopped 12 hours prior to the surgery.

36. • patients with NSTE-ACS with an initial ischemia-guided approach, either
clopidogrel (a 300 or 600-mg loading dose followed by 75 mg daily) or
ticagrelor can be used in addition to low-dose aspirin.(ticagrelol is
preferred for up to 12 month)
• In PCI ticagrelor and prasugrel are preferred in patients not at high-risk of
bleeding. Initiate within 1 hour following PCI

37. Glycoprotein IIb/IIIa Receptor Inhibitors
• The role of GPIs in NSTE-ACS is diminishing as P2Y12 inhibitors are
used earlier in therapy, and bivalirudin is selected more commonly as
the anticoagulant in patients receiving an early intervention approach

38. • The most recent practice guidelines recommend an early invasive (within 24
hours) strategy with coronary angiography and revascularization with either
PCI or coronary artery bypass graft (CABG) surgery for patients with NSTE-
ACS at an elevated risk for death or MI, including those with a high risk score
or patients with refractory angina, acute HF, other symptoms of cardiogenic
shock, or arrhythmias

39. Antiplatelet Therapy Pharmacotherapy in PCI and STEMI and NSTE-
ACS
• All patients undergoing PCI with ACS should receive an initial dose of 162- or
325-mg of aspirin followed by a daily aspirin dose of 81 mg/day indefinitely.
• A P2Y12 inhibitor antiplatelet should be administered as early as possible
concomitantly with asoirin and then an oral P2Y12 agent should ideally be
continued for at least 12 months following PCI
• Earlier discontinuation of the P2Y12 inhibitor can be reasonable in patients at a
high bleeding risk or with overt bleeding

40. drug-eluting stent (DES) and a bare metal
stent (BMS)
• Compared to BMS, DES reduce the rate of smooth muscle cell growth
and thus stent restenosis.
• DES has a high risk of developing stent thrombosis.
• dual antiplatelet therapy (DAPT—aspirin plus a P2Y12 inhibitor) is
indicated for at least 1 year regardless of whether or not a patient
with STEMI or NSTE-ACS receives a stent.
• The use of a BMS over a DES should be considered in patients who
are anticipated to be nonadherent to 12 months of DAPT.

41. Secondary Prevention Following MI
• goals
(a) control modifiable CHD risk factors.
(b) prevent the development of systolic HF;
(c) prevent recurrent MI and stroke;
(d) prevent death, including sudden cardiac death; and (e) prevent
stent thrombosis following PCI

42. • β-blocker should be continued for at least 3 years in patients with normal LV
function and indefinitely in patients with LVEF of less than or equal to 40%
(0.40) or HF symptoms.46 It may be reasonable to continue a β-blocker
indefinitely in patients without contraindications and with normal LVEF.
• P2Y12 inhibitor should be continued for at least 12 months for patients
undergoing PCI and for patients with NSTE-ACS receiving an ischemia-guided
strategy of treatment. For patients with STEMI managed with fibrinolytics,
clopidogrel should be continued for at least 14 days and ideally 1 year.
• All patients should receive aspirin indefinitely (75-100 mg daily).
• For patient not at high-risk of bleeding and who have not had overt bleeding,
new guidelines indicate it is reasonable to continue dual antiplatelet therapy
after 12 months.

43. • Beta blockers and calcium channel blockers as described before.
• all patients should be prescribed short-acting, SL NTG or lingual NTG spray
to relieve any anginal symptoms when necessary and instructed on its
use.
• Administration of ACE inhibitors should be continued indefinitely.
Hypotension should be avoided because coronary artery filling may be
compromised.

44. • Administration of ACE inhibitors, candesartan, valsartan, and losartan
should be continued indefinitely. Hypotension should be avoided
because coronary artery filling may be compromised.
Aldosterone Antagonists
• To reduce mortality, administration of an aldosterone antagonist, either
eplerenone or spironolactone, should be considered within the first 7
days following MI in all patients who are already receiving an ACE
inhibitor (or ARB) and a β-blocker and have an LVEF of less than or equal
to 40% (0.40) and either HF symptoms or DM
• patients with serum potassium concentrations greater than 5 mmol/L (5
mEq/L) or SCr greater than 2.5 mg/dL (221 μmol/L) for men, 2 mg/dL
(177 μmol/L) for women should not receive an aldosterone antagonist.

45. Statins:
• all patients, regardless of low-density lipoprotein cholesterol level,
should ideally be prescribed a high-intensity statin. Patients aged greater
than 75 years may be prescribed a moderate-intensity statin

46. But what antithrombotic therapy is best for patients with a chronic or new indication for longer-
term anticoagulant therapy following hospital discharge such as atrial fibrillation, the presence of
a mechanical heart valve, venous thromboembolism, or LV thrombus?
• TT, when needed, should consist of warfarin (INR target 2-2.5), low-dose
aspirin 81 mg orally daily, and clopidogrel 75 mg orally daily. The anticoagulant
should be discontinued if possible (such as in 3-6 months post-MI in patients
at risk of LV thrombus but without actual thrombi present), and then either
clopidogrel or preferably aspirin, discontinued after at least 1 month in a
patient with a BMS and after at least 6 months in a patient with a DES.
• Concomitant use of a proton pump inhibitor is recommended in patients
receiving TT undergoing PCI.