Clopidogrel vs Ticagrelor
Clinical Comparison
Clinical Context
In ACS, NICE recommends ticagrelor + aspirin as first-line DAPT due to the PLATO trial showing reduced cardiovascular death. Clopidogrel is used when ticagrelor is contraindicated or not tolerated, and remains the antiplatelet of choice for stroke and peripheral arterial disease. The choice depends on the clinical context and patient tolerance.
Drug Profiles
Clopidogrel
Thienopyridine antiplatelet agent
Mechanism
Irreversibly inhibits the P2Y12 ADP receptor on platelets, preventing ADP-mediated platelet aggregation. Requires hepatic CYP2C19 conversion to active metabolite (prodrug)
Indications
- Secondary prevention of atherosclerotic events (post-MI, stroke, PAD)
- Dual antiplatelet therapy (DAPT) with aspirin post-ACS
- Post-PCI stent thrombosis prevention
Common Doses
75 mg OD maintenance; 300 mg loading dose (600 mg for PCI)
Route
Oral
Onset & Duration
Onset 2 hours (after loading dose); irreversible platelet inhibition lasting 7-10 days
Ticagrelor
Cyclopentyl-triazolo-pyrimidine (direct P2Y12 inhibitor)
Mechanism
Directly and reversibly inhibits the P2Y12 ADP receptor on platelets — not a prodrug, no hepatic activation required
Indications
- Acute coronary syndrome (NSTEMI and STEMI) with aspirin
- Post-MI secondary prevention (60 mg BD beyond 12 months)
Common Doses
180 mg loading dose; 90 mg BD for 12 months; 60 mg BD for extended prevention
Route
Oral
Onset & Duration
Onset 30 minutes; reversible — platelet function recovers within 3-5 days
Key Differences
| Category | Clopidogrel | Ticagrelor |
|---|---|---|
| Prodrug vs direct | Prodrug — requires CYP2C19 activation | Direct-acting — no hepatic activation needed |
| Efficacy in ACS | Effective but inferior to ticagrelor (PLATO trial) | Superior — 16% relative reduction in CV death, MI, stroke |
| Dosing | Once daily (75 mg) | Twice daily (90 mg BD) |
| Offset time (pre-surgery) | Stop 7 days before surgery | Stop 3-5 days before surgery (reversible) |
| Dyspnoea | Not associated with dyspnoea | Dyspnoea in ~14% (self-limiting but can affect compliance) |
| Stroke/PAD indication | Licensed for stroke and PAD | Not licensed for stroke or PAD |
| Cost | Cheap generic | More expensive |
Prodrug vs direct
Prodrug — requires CYP2C19 activation
Direct-acting — no hepatic activation needed
Efficacy in ACS
Effective but inferior to ticagrelor (PLATO trial)
Superior — 16% relative reduction in CV death, MI, stroke
Dosing
Once daily (75 mg)
Twice daily (90 mg BD)
Offset time (pre-surgery)
Stop 7 days before surgery
Stop 3-5 days before surgery (reversible)
Dyspnoea
Not associated with dyspnoea
Dyspnoea in ~14% (self-limiting but can affect compliance)
Stroke/PAD indication
Licensed for stroke and PAD
Not licensed for stroke or PAD
Cost
Cheap generic
More expensive
Key Advantages
Clopidogrel
- Once-daily dosing
- Cheaper than ticagrelor
- No dyspnoea side effect
- Used for stroke and PAD (ticagrelor is not)
- Irreversible — consistent effect once platelets are inhibited
Ticagrelor
- No CYP2C19 dependency — consistent efficacy regardless of metaboliser status
- Faster onset of action than clopidogrel
- Superior mortality reduction in ACS (PLATO trial: NNT 91 for all-cause mortality)
- Reversible binding — shorter offset for surgery
Key Cautions
Clopidogrel
- Prodrug — CYP2C19 poor metabolisers have reduced efficacy (~2-14% of population)
- Avoid omeprazole (CYP2C19 inhibition reduces clopidogrel activation)
- Stop 7 days before elective surgery
- GI bleeding risk (less than aspirin)
Ticagrelor
- Twice-daily dosing — adherence can be an issue
- Dyspnoea (14% — usually self-limiting, rarely requires stopping)
- Higher cost than clopidogrel
- Not licensed for stroke or PAD
- Contraindicated with strong CYP3A4 inhibitors and with aspirin >100 mg/day
Clinical Verdict
Ticagrelor is first-line with aspirin for ACS (NSTEMI/STEMI) due to proven mortality benefit. Clopidogrel is used for stroke, PAD, or when ticagrelor is not tolerated (dyspnoea, poor BD adherence).
Medical Disclaimer: This comparison is for educational purposes only and is not a substitute for professional medical advice. Always consult a qualified healthcare professional before making prescribing decisions. Verify all drug information with current clinical guidelines (BNF, NICE, SmPCs).
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