Antiplatelet Drugs

Antiplatelet drugs inhibit platelet activation and aggregation, preventing arterial thrombosis in coronary, cerebral and peripheral artery disease. They are used for acute coronary syndrome, after stenting, after ischaemic stroke or transient ischaemic attack, and in symptomatic peripheral artery disease. Bleeding is their main risk. They are not a substitute for anticoagulation in atrial fibrillation or venous thromboembolism.

Classification. Cyclooxygenase inhibitors (aspirin); P2Y12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor, cangrelor, ticlopidine); glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban); phosphodiesterase inhibitors (dipyridamole, cilostazol); protease-activated receptor 1 antagonist (vorapaxar).

Mechanism. Aspirin blocks thromboxane A2 formation. P2Y12 inhibitors block ADP-mediated activation. Glycoprotein IIb/IIIa inhibitors block the final common pathway of fibrinogen binding. Dipyridamole and cilostazol raise cyclic nucleotides in platelets.

Pharmacokinetics. Clopidogrel is a prodrug activated by CYP2C19, so loss-of-function alleles (frequent in many populations) reduce effect. Prasugrel is a prodrug with reliable activation. Ticagrelor is active, reversible and twice daily. Cangrelor is intravenous and short acting.

• Aspirin: foundation of therapy, irreversible.
• Clopidogrel: irreversible P2Y12 inhibitor; variable response.
• Prasugrel: potent, irreversible; avoided after stroke.
• Ticagrelor: potent, reversible; dyspnoea, bradycardia.
• Cangrelor: intravenous bridging.
• Glycoprotein IIb/IIIa inhibitors: high-risk percutaneous coronary intervention and bailout.
• Dipyridamole, cilostazol: secondary stroke prevention and intermittent claudication.

• Acute coronary syndrome: aspirin 300 mg loading, then 75 to 100 mg daily, plus ticagrelor 180 mg loading then 90 mg twice daily, or prasugrel 60 mg loading then 10 mg daily (5 mg if under 60 kg or over 75 years) after angiography, or clopidogrel 300 to 600 mg loading then 75 mg daily when other agents are unavailable or unsuitable.
• Dual therapy duration: 12 months after acute coronary syndrome, 6 months after elective stenting, and 1 to 3 months in high bleeding risk, followed by single antiplatelet therapy long term.
• Minor ischaemic stroke or high-risk transient ischaemic attack: aspirin plus clopidogrel for 21 days, then single therapy. Clopidogrel 75 mg or aspirin 75 mg alone for long-term secondary prevention.
• Peripheral artery disease: clopidogrel 75 mg or aspirin 75 mg daily; cilostazol 100 mg twice daily for claudication.
• Gastroprotection: a proton pump inhibitor with dual therapy in patients at bleeding risk. Prefer pantoprazole over omeprazole with clopidogrel.
• Perioperative: continue aspirin unless bleeding risk is high. Stop clopidogrel 5 days, ticagrelor 3 to 5 days and prasugrel 7 days before planned surgery, after discussion with cardiology if a recent stent is present.
• Selection: match to indication, bleeding risk, stent type, cost and availability. Where cost limits access, aspirin plus clopidogrel is effective.

Contraindications. Active bleeding, previous intracranial haemorrhage (prasugrel contraindicated after stroke or transient ischaemic attack), severe thrombocytopenia, severe hepatic impairment, and hypersensitivity.

Adverse effects. Bleeding (gastrointestinal, intracranial, procedural), bruising, dyspnoea and bradycardia (ticagrelor), rash and neutropenia (ticlopidine), thrombotic thrombocytopenic purpura (ticlopidine, rarely clopidogrel), headache (dipyridamole), and tachycardia and heart failure risk (cilostazol).

Management of bleeding. Stop the drug, apply local measures, give tranexamic acid 1 g intravenously, and consider platelet transfusion for life-threatening bleeding (less effective with ticagrelor while active drug circulates). Desmopressin 0.3 micrograms/kg may help.

Interactions. Anticoagulants, NSAIDs, SSRIs and corticosteroids raise bleeding risk. Omeprazole and esomeprazole reduce clopidogrel activation. CYP3A4 inhibitors and inducers alter ticagrelor exposure. Ticagrelor maintenance aspirin dose should stay at 100 mg or under.

Monitoring. Haemoglobin, platelets, signs of bleeding, kidney function, and adherence, especially in the first months after stenting.

Referral and escalation. Major bleeding or recurrent ischaemic events needs urgent review. Do not stop dual therapy early after a stent without cardiology advice.

Special groups. Older adults and low body weight: higher bleeding risk, use reduced prasugrel dose or ticagrelor. Pregnancy: low-dose aspirin is used, other agents avoided. Kidney disease: higher bleeding risk. CYP2C19 loss-of-function carriers: prefer ticagrelor or prasugrel where available.