CardiologyTier 2Topic

Pharmacology of major drug classes used - antiplatelet drugs

Classes and mechanisms

Class	Agents	Mechanism
COX-1 inhibitor	Aspirin	Irreversible COX-1 acetylation -> dec TXA2
P2Y12, irreversible	Clopidogrel, prasugrel	Prodrugs; irreversible P2Y12 blockade
P2Y12, reversible	Ticagrelor	Direct-acting, not a prodrug, BD dosing
GPIIb/IIIa	Tirofiban, abciximab	Blocks the final common pathway; IV, bail-out at PCI
PDE inhibitor	Dipyridamole, cilostazol	inc cAMP

Aspirin's effect lasts the platelet lifespan (~7-10 days) - it outlives the drug

Use and pharmacogenomics

DAPT after ACS or PCI is among the commonest reasons for perioperative antithrombotic decisions
CYP2C19 loss-of-function alleles are common and reduce clopidogrel activation
- Higher prevalence in East Asian populations

Platelet activation cascade

Adhesion - vWF to GPIb at the injured endothelium
- -> activation by thrombin, ADP and TXA2
- -> GPIIb/IIIa cross-links fibrinogen between platelets
- -> aggregation

Where each drug acts

Aspirin - irreversible COX-1 acetylation -> dec TXA2 generation
P2Y12 inhibitors - block the ADP amplification loop
Clopidogrel requires CYP2C19 activation -> variable and sometimes inadequate response
Prasugrel and ticagrelor - more potent, more consistent, more bleeding

Monitoring

No routine platelet function testing in standard practice
Assess bleeding risk and adherence at each review
Check haemoglobin and iron studies if bleeding suspected
Genotype-guided P2Y12 selection is available but not routine in Australia

ACS

Aspirin + ticagrelor or prasugrel, both superior to clopidogrel (PLATO, TRITON-TIMI 38)
- Prasugrel contraindicated after stroke or TIA; caution if >75 yrs or <60 kg
- Ticagrelor: dyspnoea, bradycardia, BD dosing; avoid with strong CYP3A4 inhibitors and in moderate-severe hepatic impairment
DAPT 12 months standard
3-6 months then P2Y12 monotherapy if high bleeding risk (STOPDAPT-2, SMART-CHOICE)

Stable CAD after PCI

DAPT ~6 months, then aspirin alone; shorter if high bleeding risk

AF plus PCI

DOAC + clopidogrel; drop aspirin early - triple therapy only briefly

Stroke or TIA

Aspirin + clopidogrel for 21 days after minor stroke or high-risk TIA, then single agent

Peripheral arterial disease

Single antiplatelet, clopidogrel preferred
Consider low-dose rivaroxaban + aspirin in high-risk atherosclerosis (COMPASS)

Primary prevention

Not routine - bleeding offsets benefit

Interactions

PPIs - omeprazole and esomeprazole inhibit CYP2C19 -> dec clopidogrel activation
- Use pantoprazole or rabeprazole with clopidogrel
NSAIDs - ibuprofen blocks aspirin access to COX-1; all increase GI bleeding
Strong CYP3A4 inhibitors raise ticagrelor levels
Anticoagulants - additive bleeding

Adverse effects

GI bleeding - add a PPI if risk factors present
Intracranial haemorrhage
Aspirin - dyspepsia, aspirin-exacerbated respiratory disease, urate retention
Ticagrelor - dyspnoea in a substantial minority, ventricular pauses
Prasugrel - the most bleeding of the three
Clopidogrel - variable response; rarely TTP

Monitor

Haemoglobin, bleeding symptoms
Adherence - premature DAPT cessation after stenting risks stent thrombosis
Reassess duration at each review rather than defaulting to 12 months

13 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.

Get premium access