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Reduced prasugrel dose shows promise in older stable CAD patients
A 5-mg dose of prasugrel compared with a 10-mg dose was associated with improvements in platelet response compared with clopidogrel in a cohort of older patients with stable CAD.
Researchers evaluated the reduced maintenance dose of 5 mg prasugrel for pharmacodynamic and pharmacokinetic properties. The blinded crossover study compared the prasugrel (Effient, Daiichi Sankyo/Eli Lilly) regimen with clopidogrel 75 mg in three periods of 12 days each.
The analysis included 73 very elderly patients and 82 non-elderly patients (aged ≥ 45 years to ≤ 65 years) with stable CAD who were receiving aspirin.
The primary outcome measure was a comparison of the noninferiority of maximum platelet aggregation for the studied prasugrel dose in the older patient cohort with the 75th percentile for the 10 mg dose in the younger patient cohort.
Results indicated noninferiority of the 5 mg dose with regard to pharmacodynamics.
This dose was associated with a maximum platelet aggregation of 57% ± 14%, which the researchers reported was significantly lower than the 63% ± 14% associated with clopidogrel in the very elderly population (P<.001). However, the 5 mg dose yielded a higher maximum platelet aggregation than was observed in the 10 mg dose in the non-elderly population (46% ± 12%; P<.001).
No differences between the age groups were observed with regard to pharmacodynamic response by light transmission aggregometry, VerifyNow P2Y12 and vasodilator-associated stimulated phosphoprotein.
There were more very elderly poor responders in the clopidogrel arm than in the prasugrel arm.
Prasugrel 5 mg and clopidogrel 75 mg had similar rates of mild bleeding. The 10 mg prasugrel dose yielded slightly more mild bleeding.
“In aspirin-treated stable CAD patients, prasugrel 5 mg in [very elderly] attenuated platelet inhibition while meeting pre-specified noninferiority criterion vs. prasugrel 10 mg in [non-elderly], with significantly better [pharmacodynamic] response and fewer poor responders compared to clopidogrel 75 mg in [very elderly],” the researchers concluded.
Disclosure: Erlinge has received speaker fees from Accumetrics, AstraZeneca, Daiichi Sankyo/Eli Lilly and Sanofi-Aventis; and for membership on advisory boards of AstraZeneca, Eli Lilly and Merck. The study was funded by Daiichi Sankyo/Eli Lilly.