Key Facts

Antiplatelet agents are the cornerstone of secondary prevention in cardiovascular disease. Understanding when to use single vs dual antiplatelet therapy, duration of treatment, and management of bleeding complications is essential.

Pharmacology

• Aspirin: irreversibly acetylates COX-1 → prevents thromboxane A2 synthesis → inhibits platelet aggregation for platelet lifespan (~7–10 days)
• Clopidogrel: thienopyridine pro-drug → active metabolite via CYP2C19 → irreversibly inhibits P2Y12 ADP receptor
• Prasugrel: thienopyridine pro-drug → faster and more complete P2Y12 inhibition than clopidogrel
• Ticagrelor: cyclopentyl-triazolo-pyrimidine → reversible, direct P2Y12 inhibition → faster offset than clopidogrel
• Cangrelor: IV P2Y12 inhibitor → ultra-short acting; used in cath lab

Pathophysiology

• Platelet activation: vascular injury → collagen exposure → platelet adhesion (vWF/GP Ib) → activation (ADP, TXA2) → aggregation (GPIIb/IIIa cross-linking via fibrinogen)
• Aspirin: blocks TXA2-mediated amplification
• P2Y12 inhibitors: block ADP-mediated amplification
• Both reduce platelet plug formation → reduce arterial thrombosis risk

Indications

• Secondary prevention of CVD: aspirin 75 mg OD lifelong (post-MI, post-stroke, PAD)
• ACS (NSTEMI/STEMI): DAPT — aspirin + ticagrelor (or clopidogrel/prasugrel) for 12 months
• PCI with stent: DAPT for 6–12 months (DES) or 1 month (BMS); extended if high thrombotic risk
• Ischaemic stroke/TIA: aspirin 300 mg immediately (after CT excludes haemorrhage) → clopidogrel 75 mg OD long-term (NICE NG128)
• PAD: clopidogrel 75 mg OD preferred over aspirin (CAPRIE trial)
• Primary prevention: generally NOT recommended (ASCEND, ARRIVE trials — risk outweighs benefit in most)

Side Effects

• GI bleeding: most common serious ADR; increased with dual therapy
• Aspirin: dyspepsia, GI ulceration, bronchospasm (aspirin-sensitive asthma)
• Clopidogrel: rash, diarrhoea, TTP (very rare)
• Ticagrelor: dyspnoea (~14% — often asymptomatic), bradycardia, raised uric acid
• Prasugrel: higher bleeding risk than clopidogrel — avoid in prior stroke/TIA

Red Flags

• Major bleeding on antiplatelet: GI haemorrhage, intracranial haemorrhage
• Stent thrombosis after premature DAPT cessation — potentially fatal
• Dyspnoea on ticagrelor — usually benign but assess; may need to switch
• TTP on clopidogrel: microangiopathic haemolytic anaemia, thrombocytopenia, neurological symptoms — rare but life-threatening

Before Starting

• FBC: baseline platelet count
• U&Es: renal function (relevant for dose adjustments)
• Coagulation: baseline PT/INR (if on concurrent anticoagulant)
• GI risk assessment: history of ulceration, concurrent NSAID/anticoagulant, H. pylori

Monitoring

• Platelet function testing: not routine in UK; available for assessing clopidogrel resistance (VerifyNow P2Y12 assay)
• FBC: if suspected bleeding or TTP
• CYP2C19 genotyping: emerging — identifies clopidogrel poor metabolisers (may switch to ticagrelor/prasugrel)

Special Tests

• OGD: if GI bleeding on antiplatelet therapy
• H. pylori testing: eradicate if positive, especially before long-term antiplatelet use

Prescribing

ACS (STEMI/NSTEMI):

• Aspirin 300 mg loading → 75 mg OD
• Ticagrelor 180 mg loading → 90 mg BD (preferred in ACS — PLATO trial)
• Or clopidogrel 300–600 mg loading → 75 mg OD (if ticagrelor contraindicated)
• Continue DAPT for 12 months; then aspirin alone lifelong

PCI with DES:

• DAPT for 6–12 months (may shorten to 3 months if high bleeding risk; extend to >12 months if high thrombotic risk)

Ischaemic Stroke/TIA:

• Aspirin 300 mg immediately (after CT) → clopidogrel 75 mg OD long-term (NICE NG128)
• Or aspirin + clopidogrel for 21 days (minor stroke/TIA), then clopidogrel alone (CHANCE/POINT trials)

GI Protection

• Co-prescribe PPI: if GI risk factors (age >65, prior GI bleed, concurrent NSAID/anticoagulant)
• Avoid omeprazole with clopidogrel: CYP2C19 inhibition reduces clopidogrel activation → use lansoprazole or pantoprazole instead

Bleeding Management

• Minor: apply pressure, observe; consider withholding dose
• Major: stop antiplatelet, resuscitate, tranexamic acid 1 g IV, platelet transfusion (if life-threatening and taking irreversible agent)
• Note: platelet transfusion is less effective for ticagrelor (reversible) — drug clearance takes ~3–5 days

Surgical Considerations

• Elective surgery: stop clopidogrel 7 days before; ticagrelor 5 days; prasugrel 7 days
• Emergency surgery: proceed with increased bleeding risk; platelet transfusion if necessary
• Never stop DAPT prematurely after PCI without cardiology advice — stent thrombosis risk

Referral Criteria

• Cardiology: DAPT duration decisions, stent thrombosis
• Haematology: suspected TTP, complex bleeding
• Gastroenterology: GI bleeding management

• Secondary prevention with aspirin: reduces recurrent vascular events by ~25%
• DAPT post-ACS: reduces stent thrombosis and recurrent MI
• PLATO trial: ticagrelor vs clopidogrel in ACS → 16% relative reduction in cardiovascular death/MI/stroke
• Premature DAPT cessation: stent thrombosis risk (~2–3% in first month; potentially fatal)
• Bleeding: major GI bleeding ~1–2%/year; intracranial <0.5%/year
• Aspirin in primary prevention: generally not recommended (bleeding risk ≈ benefit)

Antiplatelet Agent Comparison

Key Landmark Trials