Prasugrel versus Ticagrelor Comparison
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Direct answer
Both prasugrel and ticagrelor outperform clopidogrel after percutaneous coronary intervention for acute coronary syndrome, and both owe their edge to escaping CYP2C19 dependence. Prasugrel (60 mg load, 10 mg daily) cut the TRITON-TIMI 38 composite of cardiovascular death, myocardial infarction and stroke by 19 per cent and halved stent thrombosis, at the price of more major and fatal bleeding — it is contraindicated after prior stroke or TIA and dose-reduced to 5 mg in patients over 75 or under 60 kg. Ticagrelor (180 mg load, 90 mg twice daily) reduced the same composite by 16 per cent in PLATO with a survival advantage and no excess overall major bleeding, provided aspirin stays at or below 100 mg daily; its signatures are dyspnoea, ventricular pauses early in therapy and the twice-daily burden.
What you must remember
- TRITON-TIMI 38 (prasugrel): 19 per cent relative reduction in CV death/MI/stroke versus clopidogrel in ACS going to PCI; stent thrombosis roughly halved; but TIMI major bleeding including fatal events increased.
- PLATO (ticagrelor): 16 per cent composite reduction across the full ACS spectrum, all-cause mortality 4.5 versus 5.9 per cent, with dyspnoea in roughly 14 per cent and early ventricular bradyarrhythmias.
- Contraindication drill: prasugrel never after prior stroke or TIA; caution (5 mg or avoidance) above age 75 or below 60 kg; ticagrelor needs aspirin 75-100 mg only — higher aspirin erases its benefit.
- Pharmacokinetic freedom: prasugrel is a prodrug needing one CYP step (not CYP2C19-dependent) with the least interpatient variability; ticagrelor is a direct-acting reversible P2Y12 antagonist metabolised mainly by CYP3A4 — neither is defeated by clopidogrel's CYP2C19 loss-of-function alleles.
- Bleeding logistics: stop ticagrelor 5 days and prasugrel 7 days before elective surgery; both have no reversal agent — platelet transfusion after offset.
- Fibrinolysis rule: neither drug belongs with lytic therapy; clopidogrel 300 mg load is the lytic-era P2Y12.
- Indian context: clopidogrel remains National List of Essential Medicines stock and the default cost-effective choice; generic ticagrelor is now widely used in NSTEMI/STEMI pathways in private and teaching hospitals, while prasugrel use is selective — the exam expects you to know which patient justifies which.
Choosing between them at the cath table
A 54-year-old, 72 kg man with diabetic anterior STEMI arriving for primary PCI: prasugrel 60 mg is defensible — highest and fastest inhibition, biggest stent-thrombosis reduction, low bleeding anatomy. An 80-year-old with a prior TIA and NSTEMI: prasugrel is contraindicated outright; ticagrelor 180 mg (or clopidogrel with care) proceeds, keeping aspirin at 75 mg. A 45-year-old medically managed unstable angina: ticagrelor has PLATO's non-PCI cohort behind it; prasugrel was only studied in patients going to PCI — a subtle indication boundary examiners probe. A patient with severe asthma or on verapamil-like CYP3A4 substrate loads: watch ticagrelor's dyspnoea and interaction profile. The question behind every choice is the same trade TRITON and PLATO quantified: ischaemic risk (young, diabetic, stent thrombosis history, complex anatomy) versus bleeding risk (elderly, low weight, prior stroke, anaemia, fall risk).
Practical prescribing follows: load, then maintenance with aspirin 75 mg lifelong, proton pump inhibitor cover if warranted, and clear documentation of the planned stop date pre-surgery.
Where students lose marks
The aspirin-dose trap tops the list: ticagrelor plus aspirin above 100 mg daily loses its mortality benefit — a PLATO pharmacodynamic interaction, so the answer to "maximum aspirin dose with ticagrelor" is 100 mg. Second, dyspnoea: it is not heart failure and rarely needs drug withdrawal; explain adenosine-mediated and sensory mechanisms, reassure, and observe — a viva answer that shows clinical maturity. Third, reversibility misleads: ticagrelor's offset is faster than clopidogrel's label suggests but still days, so "reversible binding equals quick reversibility" is wrong. Fourth, the population boundary — TRITON enrolled only PCI-bound ACS; prasugrel has no mandate in conservatively managed patients. Indian pattern: remember tenecteplase-dominated thrombolysis in far-flung centres, where clopidogrel remains the safe partner, and the price gradient that keeps generic clopidogrel (and aspirin-clopidogrel fixed-dose combinations) dominant across government supply chains.
Frequently asked questions
What did TRITON-TIMI 38 show for prasugrel?
A 19 per cent reduction in cardiovascular death, myocardial infarction and stroke with halved stent thrombosis, offset by significantly more major and fatal bleeding.
In which patients is prasugrel contraindicated?
Any prior stroke or transient ischaemic attack, with dose reduction to 5 mg or avoidance above age 75 or under 60 kg.
Why must aspirin be capped at 100 mg with ticagrelor?
Higher aspirin doses attenuated ticagrelor's benefit in PLATO, so maintenance aspirin is 75-100 mg daily.
Which P2Y12 inhibitor suits a medically managed acute coronary syndrome?
Ticagrelor, which has PLATO's non-invasive cohort evidence; prasugrel was studied only in patients undergoing PCI.
How should dyspnoea on ticagrelor be managed?
Reassure and observe in most cases — it is usually non-specific, dose-related and not cardiac; continue therapy unless severe or intolerable.