Edward Lee Carter: Prasugrel Dosing Matters in P2Y12 Inhibitor Comparisons After PCI
Edward Lee Carter, Clinical Pharmacist Practitioner at U.S. Department of Veterans Affairs, shared on LinkedIn:
“Prasugrel just got named the ‘best’ P2Y12 inhibitor after PCI. But three different doses were hiding inside that one word.
That’s the conclusion from a widely discussed JAMA Cardiology network meta analysis (Maqsood et al.) comparing prasugrel, ticagrelor, and clopidogrel after PCI 15 trials, nearly 49,000 patients, prasugrel coming out on top for MACE with no apparent bleeding penalty.
A September 16 letter to the editor asks a sharper question: on top of what dose?
The prasugrel ‘node’ in that network pooled trials spanning 3.75 mg, 5 mg, and 10 mg maintenance dosing not interchangeable regimens. PRASFIT ACS tested 3.75 mg in a Japanese population, a dose never approved for general U.S. use.
Guideline preference for prasugrel over ticagrelor also draws heavily on ISAR REACT 5, which used the standard 10 mg maintenance dose and even that single trial built in its own dose variation, reducing to 5 mg per protocol for patients high 75 or low 60 kg.
Averaging outcomes across that dose range into one ‘prasugrel’ estimate can quietly launder the bleeding signal of the regimen most U.S. clinicians would actually write.
The authors’ reply included a sensitivity analysis limited to standard dose trials that’s the number worth reading, not the headline pooled estimate.
This isn’t a knock on the analysis; NMAs are a legitimate, often underused tool, and this one drew on solid, well conducted trials.
It’s a case study in a specific failure mode: a network meta analysis is only as informative as the homogeneity of what feeds each node.
‘Prasugrel’ isn’t one drug exposure across dose ranges pharmacokinetically or clinically and neither is ‘ticagrelor’ across full and half dose strategies, or ‘clopidogrel’ across loading protocols.
Before a ranking reshapes practice, it’s worth opening the supplement and checking what was actually pooled.”
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