Ticagrelor: Mechanism, Uses, Contraindications & Key Clinical Pearls
Ticagrelor is a potent, reversible P2Y12 receptor inhibitor widely used in acute coronary syndrome (ACS) to prevent thrombotic complications. Compared with clopidogrel, it offers faster onset, stronger platelet inhibition, and improved cardiovascular outcomes, making it a preferred agent in many ACS protocols.
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How Ticagrelor Works
Ticagrelor blocks the P2Y12 receptor on platelets, preventing ADP-mediated platelet activation.
This results in:
Rapid onset of antiplatelet action
More consistent platelet inhibition
Reduced risk of stent thrombosis
Improved mortality in ACS (as shown in the PLATO trial)
Unlike clopidogrel, ticagrelor is not a prodrug, so its action is not dependent on liver enzyme activation.
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Indications
Ticagrelor is commonly used in:
✔ Acute Coronary Syndrome
STEMI (with or without PCI)
NSTEMI
Unstable angina
Usually combined with low-dose aspirin (dual antiplatelet therapy).
✔ Post-PCI Antiplatelet Strategy
To reduce risk of:
Stent thrombosis
Recurrent MI
Stroke
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Dosage
Loading dose: 180 mg once
Maintenance: 90 mg twice daily for 12 months in ACS
May reduce to 60 mg twice daily for long-term secondary prevention
Always used with aspirin 75–100 mg/day.
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Contraindications
Ticagrelor should NOT be used in the following situations:
1. Active bleeding
2. History of hemorrhagic stroke
3. Severe hepatic impairment
4. Allergy or hypersensitivity
5. Concomitant use of strong anticoagulants or fibrinolytics
6. High-dose aspirin (>100–150 mg daily)
7. GFR < 15 ml/min (increased bleeding risk)
8. ACS in patients with cancer with platelet count < 50,000
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Important Precautions
🔹 Dyspnea
A common side effect due to increased adenosine levels.
Usually mild and transient; does not require stopping unless severe.
🔹 Bradyarrhythmias
Ticagrelor can cause ventricular pauses, especially early in therapy.
🔹 Drug interactions
Avoid:
Strong CYP3A4 inhibitors (ketoconazole, clarithromycin)
Strong CYP3A4 inducers (rifampicin, phenytoin)
High-dose aspirin
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Advantages Over Clopidogrel
Faster onset
Reversible binding
Consistent platelet inhibition
Better clinical outcomes in ACS
Not affected by genetic polymorphisms (CYP2C19)
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When to Prefer Clopidogrel Instead
High bleeding risk
Severe dyspnea with ticagrelor
Cost concerns
Chronic anticoagulation needed
Very low platelets
Post-CABG needing long-term antiplatelet therapy
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Clinical Pearls
Always pair ticagrelor with low-dose aspirin only.
Avoid in patients with active bleeding or prior hemorrhagic stroke.
Check platelet count, renal function, and hepatic function before starting.
Educate patients on dyspnea—it is common but usually harmless.
Twice-daily dosing requires good compliance.
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