Al-Esraa University College

Pharmacy Department

Therapeutics I
Lec1
Acute Coronary Syndrome
Dr.Mohammed Ali Alobaidy
F.I.C.M.S – Clinical Pharmacy

Background
Acute coronary syndrome (ACS) is a spectrum of conditions compatible with acute myocardial ischemia or infarction
because of an abrupt reduction in coronary blood flow.
• ACS can be divided into:
1- ST-segment elevation myocardial infarction (STEMI).
2- Non–ST-segment elevation acute coronary syndrome (NSTE-ACS)

• a. STEMI
i. Defined by characteristic symptoms of myocardial ischemia in association with persistent ST elevation on ECG with
positive troponins
ii. STEMI is an indication for immediate coronary angiography to determine whether reperfusion can be performed.

• b. NSTE-ACS
i. Suggested by the absence of persistent ST elevation
ii. NSTE-ACS can be divided into unstable angina (UA) and non-STEMI (NSTEMI) according to whether cardiac
biomarkers of necrosis are present.
 ACS in Clinical practice
• Patients presenting with ischemic chest pain but without ST segment elevation and without
laboratory evidence of infarction are classified as having unstable angina

• Patients with ischemic chest pain, without ST segment elevation, but who develop a
positive cardiac injury profile (i.e., elevated troponin) within hours of presentation are
(referred to as NSTEMI).

• Patients with NSTEMI and unstable angina continue to have some blood flow, although
limited, through the affected coronary artery.

• Patients with NSTEMI usually thrombi comprised largely of platelets and fibrinogen.
Thrombolytic therapy is not beneficial in these patients and is a major point of
differentiation.

• The presence of ST segment elevation (STEMI) is used to identify patients who will benefit
from thrombolytic therapy.
Complications
• The primary complications of AMI can be divided
into three major groups:
Heart failure, arrhythmias, and recurrent
ischemia and reinfarction.

• Compensatory mechanisms can eventually worsen

the imbalance between myocardial oxygen supply
and consumption by increasing the myocardial
oxygen demand.

• If 40% or more of the left ventricle is damaged,

cardiogenic shock and death can occur.
Clinical Assessment & Diagnosis
• Prolonged substernal chest pain or pressure, shortness of breath, diaphoresis,
nausea, and vomiting

• Sometimes it’s confused with indigestion or other

gastrointestinal (GI) complaints.

• Elderly patients present with hypotension or cerebrovascular symptoms

rather than chest pain.

• Tachycardia (heart rate >120 beats/minute) suggests a large area of damage

Diagnosis
1. A 12-lead ECG should be performed and interpreted within 10 minutes of
presentation.
Note: Serial ECGs may be performed if initial is nondiagnostic.

2. Serial cardiac troponins (I or T) should be obtained at presentation and

3–6 hours after symptom onset.

3. Creatine kinase (CK)- within 3 to 6 hours after myocardial damage, and

peak in 12 to 24 hours

4. Lactate dehydrogenase (LDH ) generally appears 24 to 48 hours after the

onset of chest pain and peaks in 3 to 6 days.

5. Aspartate aminotransferase, White blood cell count, and C-reactive

protein may also be obtained
 Management
Therapeutic Objectives
• The immediate therapeutic objectives are to minimize the amount of myocardial necrosis that develops,
to alleviate his symptoms, and to prevent his death. ((always remember time is muscle)).
• The long-term therapeutic objectives are to prevent or minimize recurrent ischemic symptoms,
reinfarction, heart failure, and sudden cardiac death.

1- STEMI
a. Requires urgent revascularization either interventionally (PCI) or with drug therapy (Fibrinolytics)
b. Primary percutaneous coronary intervention (PCI) is preferred over fibrinolytic (drug) therapy.
c. Fibrinolytic therapy is indicated for patients with STEMI in whom PCI cannot be performed or
unavailable

2- NSTE-ACS
Requires urgent invasive therapy (diagnostic Angiography +/- revascularization) for high risk patients
or Medical therapy (anti-ischemia agents or called ischemia guided therapy) for low risk patients.

Q: How to assess the risk of patients with NSTE-ACS?

Early Hospital Management

• All patients should receive Anti-ischemic drugs and analgesia, the Emergency
protocol is : (MONA + B) explained bellow:
Morphine 1–5 mg IV every 5–30 min is reasonable if symptoms are not relieved despite
Morphine
maximally tolerated anti-ischemic medications

Oxygen Oxygen if Sao2 < 90%, respiratory distress, or high-risk features of hypoxemia

- NTG spray or sublingual tablet (0.3–0.4 mg) every 5 min for up to three doses to relieve acute
chest pain
Nitroglycerin
- NTG IV 5–10 mcg/min; titrate to chest pain relief or 200 mcg/min for persistent ischemia, HF,
or HTN (No Mortality Benefit)
Aspirin: chew and swallow non–enteric coated 160–325 mg x 1 dose and continued indefinitely.
Aspirin • Clopidogrel: If aspirin allergy or GI intolerance
(Mortality Benefit)
Oral β-blocker (class Ia) should be initiated within 24 hr in patients who do not have: 1- signs of
Beta blocker HF, 2- evidence of low-output state, 3- increased risk of cardiogenic shock, or 4- other
contraindications to β-blockade. (Mortality Benefit)
β-Blockers
• β-blockers decrease myocardial oxygen consumption, limit the amount of myocardial damage, and reduce
some of the complications of MI, specifically sudden death attributed to ventricular fibrillation.

• Unless there are contraindications to their use, β-blocking agents should be prescribed for all patients having
an AMI, and they should be continued indefinitely.

• Metoprolol succinate, Atenolol, and Bisoprolol are used in the acute setting due to their β-1 selectivity, ease
of dosing and administration, and weight of evidence.
• Oral carvedilol, a nonselective β- and α-blocker, has been used specifically in patients with left ventricular
dysfunction.

Calcium channel blocker

• As a group, they dilate coronary and peripheral vessels.
• calcium channel blockers would protect cardiac cells during the peri-infarction period.
• the use of verapamil and diltiazem should be limited to patients who do not tolerate β-blocker therapy and
who do not have systolic dysfunction.
• No real benefit or detriment to mortality; primarily for symptom relief.
• Immediate-release nifedipine should be avoided.

Pharmacotherapy
• Thrombolytics Therapy:

1- Streptokinase is a polypeptide derived from β-hemolytic streptococcal cultures.

It acts by converting plasminogen to plasmin thus encouraging the breakdown of
formed fibrin to fibrinogen degradation products.

Disadvantages of Streptokinase are:

1- Hypotension during infusion
2- Risk of anaphylaxis
3- Risk of resistance if used twice in 12 months
4- High risk of hemorrhage because it is not clot specific

• Streptokinase have used an IV infusion of 1.5 MU administered over 60 minutes.

2- Alteplase: or t-PA, is a naturally occurring enzyme produced commercially by recombinant DNA
technology. t-PA has a binding site for fibrin, which allows it to bind to a thrombus and preferentially
lyses it over the circulating plasminogen (specific to the thrombus).
• accelerated dosage regimens of t-PA, The recommended regimen is a 15 mg bolus followed by a 50
mg infusion over 30 minutes and then the remaining 35 mg over 60 minutes.

3- Reteplase and Tenectiplase: is a genetically modified plasminogen activator that is similar to t-PA.
Reteplase has a longer half-life.
• reteplase was administered in two bolus doses of 10 MU, given 30 minutes apart.
• TNK was administered as a bolus of 30 to 50 mg over 5 to 10 seconds, based on body weight
* They, therefore, have the advantage of convenience of administration compared with alteplase,
and they are the preferred option in pre hospital settings, particularly when administered by
paramedics.

• Urokinase has not gained widespread use as a thrombolytic agent for patients with STEMI.

** The guidelines recommend a “door-to-needle time” of 30 minutes, meaning the

diagnosis of STEMI and initiation of thrombolytic therapy should ideally take place
within 30 minutes from the time the patient arrives at the hospital door.

• Guidelines recommend a 60 U/kg bolus of UFH at the initiation of t-PA, to avoid

rebound thrombosis after cessation of Thrombolytic therapy.

• The replacement of UFH with a LMWH, factor Xa inhibitor, or the addition of

an antiplatelet agent such as a GP IIb/IIIa inhibitor to thrombolytic therapy
have been evaluated for patients with STEMI.
2- Magnesium sulphate
• The potential mechanisms by which magnesium may benefit a patient include an
antiarrhythmic effect, an antiplatelet effect, reversal of vasoconstriction, reduction of
catecholamine secretion, and enhancement of adenosine triphosphate production.
• Q: What is Torsade de pointes?

3- Antiarrhythmics
• Ventricular arrhythmias, including ventricular fibrillation, are common complications
associated with myocardial ischemia and AMI.
• Lidocaine, procainamide, and amiodarone and dofitilide are the drugs of choice for the
treatment of ventricular arrhythmias in the peri-infarction period.
• Flecainide is contraindicated in patients with structural heart diseases

4- Stool Softeners
• It is common to administer agents such as docusate to prevent constipation in AMI
patients because straining causes undesirable stress on the cardiovascular system.

5- Nondrug Therapy
• PCI is superior to thrombolytic therapy.
• PCI consists of the insertion of a guidewire though a catheter into the
occluded coronary vessel.
• Door to needle time is 120 minutes (2 hrs).
Anti platelets therapy before PCI
• Antiplatelet therapy is essential to prevent clot formation and improve survival. Key components
include:

• 1. Aspirin: A loading dose of 300 mg.

• 2. P2Y12 Inhibitors: A loading dose is administered before PCI to inhibit platelet activation and
aggregation:
• - Clopidogrel: 300-600 mg loading dose, followed by 75 mg daily.
• - Ticagrelor: 180 mg loading dose, followed by 90 mg twice daily.
• - Prasugrel: 60 mg loading dose, followed by 10 mg daily (adjusted to 5 mg for certain patients).

• 3. Glycoprotein IIb/IIIa Inhibitors: Sometimes used in high-risk patients or those with large
thrombus burden, in addition to aspirin and P2Y12 inhibitors.

• After PCI Dual antiplatelet therapy (DAPT) is crucial to minimize the risk of thrombotic events
and improve PCI outcomes.

Long term therapy

1- Angiotensin-Converting Enzyme Inhibitors
• After an AMI, the heart undergoes processes that initially compensate for the loss of contractile
function but may increase the long-term risk for development of heart failure. This is referred to as
“Remodeling” of the ventricle.
• Based on the studies, oral ACE inhibitor therapy should be started within the first 24 hours of
an AMI, preferably after completion of thrombolytic therapy and BP stabilization (systolic
BP >100 mmHg), and should be continued indefinitely.
• ACE inhibitor therapy is particularly beneficial in patients with EF < 40% (even if asymptomatic)
or clinical evidence of heart failure, DM, HT.

2- Aldosterone Antagonists
• Patients who received spironolactone exhibited a 30% reduction in mortality.

• Eplerenone, is a selective inhibitor of the mineralocorticoid receptor with fewer side effects (no
risk for gynecomastia).
• guidelines recommend an aldosterone antagonist in STEMI patients without significant renal
dysfunction or hyperkalemia (potassium <5 mEq/L) who are already receiving therapeutic doses of
an ACE inhibitor and Betablockers, have an EF <40%, and have either symptomatic heart failure
or diabetes.
3- β-Blockers
• The benefits of β-blockers in reducing reinfarction and mortality are believed to outweigh their risks,
• Metoprolol or carvedilol are considered first-line choices in patients with heart failure, whereas atenolol or
metoprolol should be considered in patients with stable asthma or bronchospastic pulmonary disorder.

4- Lipid-Lowering Agents
• In addition their lipid-lowering properties, statins are believed to exhibit pleiotropic effects, which include
plaque stabilization, anti-inflammation, antithrombogenicity, enhancement of arterial compliance, and
modulation of endothelial function. (aim for LDL lower than 70 mg/dl)
• When triglycerides are >200 mg/dL, drug therapy with niacin or a fibrate is beneficial
• High-intensity statin therapy (atorvastatin 40–80 mg/day, rosuvastatin 20–40 mg/day) should be initiated or
continued in all patients without CIs
• CIs: Pregnancy; note dosing restrictions on CYP3A4-interacting medications, caution with fibrates
➢ Q: Statin intensity?

5- Antithrombotic Agents (whether individual antiplatelet or DAPT)

Antiplatelet therapy should be lifelong because of its effects on secondary prevention of reinfarction.
• Most clinicians use dosages of 81 to 325 mg daily or every other day.
• Clopidogril is alternative if aspirin is contraindicated

Dual Antiplatelet therapy (DAPT)

• It means the use of aspirin with one of the P2Y12 antagonists group (Clopidogril, Prasugril, Ticagrilor).

• Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 receptor inhibitor is indicated for all patients with
ACS.

• DAPT should be continued after ACS (with or without stent) for at least 12 months.

• Durations of DAPT may be reasonable beyond 12 months if patient not at high risk and no significant history
of bleeding on DAPT.

• In general, shorter durations of DAPT are appropriate for those with a lower ischemic risk and a high bleeding
risk, whereas longer-duration DAPT may be reasonable for patients at higher ischemic risk with a lower
bleeding risk.

• What is Cangrilor?
- Anti ischemia protocol for NSTEMI patients?

Thank You For Listening