ASPIRIN-MOA, Therapeutic uses and Adverse effects ****(rationale of usage in MI)

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aspirin AND myocardial infarction

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2025 ACC AHA acute coronary syndrome guideline aspirin dose acute myocardial infarction

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Aspirin

Mechanism of action (MOA)

Aspirin is an NSAID and antiplatelet drug. It irreversibly acetylates cyclooxygenase (COX) enzymes.

Dose range / main action	Mechanism	Result
Low dose: mainly antiplatelet	Irreversible inhibition of platelet COX-1	Decreased thromboxane A2 (TXA2) synthesis
Higher doses	Inhibits COX-1 and COX-2	Decreased prostaglandins, giving analgesic, antipyretic, and anti-inflammatory effects

Antiplatelet mechanism

Arachidonic acid → via platelet COX-1 → prostaglandin H2 → TXA2

TXA2 normally causes:

Platelet activation and aggregation
Vasoconstriction
Recruitment of more platelets to the thrombus

Therefore:

Aspirin → irreversible COX-1 inhibition → ↓ TXA2 → ↓ platelet aggregation and vasoconstriction → reduced arterial thrombus formation.

Platelets cannot synthesize new COX because they have no nucleus. Hence, a single dose impairs platelet function for the platelet's lifespan, about 7-10 days. Endothelial cells can synthesize new COX and restore prostacyclin (PGI2), which inhibits platelet aggregation and causes vasodilation. Low-dose aspirin therefore preferentially shifts the balance toward PGI2.
Braunwald’s Heart Disease, p. 1123; Katzung’s Basic and Clinical Pharmacology, p. 1008.

Therapeutic uses of aspirin

1. Antiplatelet uses

Acute coronary syndrome (ACS): unstable angina, NSTEMI, STEMI
Acute and long-term treatment after myocardial infarction
Secondary prevention of recurrent MI, ischemic stroke, and cardiovascular death
After PCI and coronary stenting, usually as part of dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor
After coronary artery bypass grafting
Transient ischemic attack and ischemic stroke prevention
Peripheral arterial disease

In established coronary, cerebrovascular, or peripheral arterial disease, aspirin lowers the risk of cardiovascular death, MI, and stroke by about 20%.
Braunwald’s Heart Disease, p. 1123.

2. Analgesic

For mild-to-moderate pain, such as headache, dental pain, musculoskeletal pain, and dysmenorrhea.

3. Antipyretic

Reduces fever by lowering hypothalamic prostaglandin synthesis.

4. Anti-inflammatory

At higher doses, it can be used in inflammatory disorders, though it is now less commonly used for this purpose because safer NSAID alternatives are available.

5. Other selected uses

Acute rheumatic fever
Kawasaki disease, under specialist-directed protocols
Low-dose aspirin for prevention of pre-eclampsia in selected high-risk pregnancies

Rationale for aspirin use in myocardial infarction

Most acute MIs result from rupture or erosion of an atherosclerotic coronary plaque, followed by platelet activation and formation of a platelet-rich thrombus that partially or completely occludes the coronary artery.

Sequence in MI

Atherosclerotic plaque ruptures.
Subendothelial collagen and tissue factor are exposed.
Platelets adhere, activate, and release ADP and TXA2.
TXA2 promotes further platelet aggregation and vasoconstriction.
The thrombus enlarges and blocks coronary blood flow.
Myocardial ischemia progresses to necrosis.

How aspirin helps

Aspirin blocks platelet TXA2 formation. This:

Reduces ongoing platelet activation and aggregation
Limits growth of the coronary thrombus
Reduces recurrent ischemia, reinfarction, stroke, and cardiovascular death
Complements reperfusion treatment such as PCI or fibrinolysis
Works synergistically with P2Y12 inhibitors, which block ADP-mediated platelet activation

Important: aspirin is an antiplatelet, not a thrombolytic. It does not directly dissolve an established clot. Rather, it prevents further platelet-rich thrombus formation and reduces recurrent occlusion.

Current ACS guidance recommends administering aspirin as early as possible, unless there is an absolute contraindication. The 2025 ACC/AHA ACS guideline recommends an initial 162-325 mg oral loading dose, followed by 75-100 mg daily maintenance aspirin.

Adverse effects

Common and important

System	Adverse effect	Basis / comments
Gastrointestinal	Dyspepsia, nausea, gastritis, peptic ulcer, GI bleeding	Decreased protective gastric prostaglandins plus impaired platelet aggregation
Bleeding	Easy bruising, epistaxis, prolonged bleeding, intracranial hemorrhage	Irreversible inhibition of platelet function
Hypersensitivity	Urticaria, angioedema, bronchospasm, anaphylactoid reactions	More likely in aspirin-sensitive asthma
Respiratory	Aspirin-exacerbated respiratory disease: bronchospasm, rhinitis, nasal polyps	Shunting of arachidonic acid toward leukotriene production
Renal	Sodium and water retention, reduced GFR, acute kidney injury in susceptible patients	Reduced renal prostaglandin synthesis
CNS, salicylism	Tinnitus, dizziness, headache, impaired hearing	Classically suggests salicylate toxicity
Metabolic in overdose	Respiratory alkalosis followed by high-anion-gap metabolic acidosis	Salicylate poisoning
Children with viral illness	Reye syndrome	Avoid in children/adolescents with influenza or varicella
Skin	Rash, rarely Stevens-Johnson syndrome	Hypersensitivity reaction
Uric acid	Low doses may decrease urate excretion and precipitate gout	Relevant in hyperuricemia/gout

The principal antiplatelet-dose toxicity is bleeding, especially upper GI bleeding. Risk increases with higher doses, prior peptic ulcer or GI bleed, anticoagulants, other antiplatelets, corticosteroids, SSRIs, older age, liver disease, renal disease, thrombocytopenia, and uncontrolled hypertension.
Goldman-Cecil Medicine, p. 47; Katzung’s Basic and Clinical Pharmacology, p. 1008.

Important contraindications and precautions

Avoid or use only with specialist advice in:

Active bleeding or active peptic ulcer disease
Hemophilia, severe thrombocytopenia, or major bleeding disorder
Aspirin allergy or aspirin-induced asthma
Children/adolescents with viral fever because of Reye syndrome risk
Severe renal or hepatic impairment
Concurrent anticoagulant treatment, unless the expected cardiovascular benefit outweighs bleeding risk
Before surgery or invasive procedures, depending on the procedure and thrombotic risk

One-line exam summary

Aspirin irreversibly inhibits platelet COX-1, reducing TXA2-mediated platelet aggregation and vasoconstriction. In MI, it prevents propagation and recurrence of the platelet-rich coronary thrombus, thereby reducing reinfarction and mortality, but may cause GI irritation, ulceration, bleeding, bronchospasm, renal impairment, salicylism, and Reye syndrome.

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