普拉格雷5 mg用于极高龄患者的血小板抑制效果稍弱但且疗效不劣于10 mg应用于非高龄患者:一项针对冠心病患者的药效学和药动学研究(GENERATIONS试验)

Prasugrel 5-mg in the very elderly attenuates platelet inhibition but maintains non-inferiority to prasugrel 10-mg in non-elderly patients: The GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients
2013-08-09 15:52发表评论
作者:Erlinge D, Gurbel PA, James S, Lindahl TL, Svensso
期刊: J AM COLL CARDIOL2013年6月期卷

OBJECTIVES:

We assessed pharmacodynamic (PD) response for the reduced prasugrel 5-mg maintenance dose in very elderly (≥75y; VE) patients.

BACKGROUND:

In TRITON-TIMI 38, prasugrel 10-mg reduced ischemic events versus clopidogrel 75-mg, but increased bleeding in VE patients.

METHODS:

We examined PD and active-metabolite pharmacokinetics with prasugrel 5-mg and 10-mg and clopidogrel 75-mg in a three-period (12 days each), blinded, cross-over study in VE (n=73, mean 79±3y) or non-elderly (≥45-<65y, NE) (n=82, 56±5y) stable coronary artery disease (CAD)patients on background aspirin. Assays included light transmission aggregometry (LTA), VerifyNow® P2Y12 (VN-P2Y12), and VASP. The primary comparison was non-inferiority of maximum platelet aggregation (MPA) comparing the median for prasugrel 5-mg in VE versus the 75th percentile forprasugrel 10-mg in NE, using a prespecified one-sided 97.5% confidence interval for the difference <15%.

RESULTS:

Prasugrel 5-mg in VE met the primary pharmacodynamic non-inferiority criterion versus prasugrel 10-mg in NE. For prasugrel 5-mg, MPA was significantly lower (mean±SD, 57±14%) than clopidogrel (63±14%) (p<0.001) in VE, but higher than prasugrel 10-mg in NE (46±12%) (p<0.001). PD response by LTA, VN-P2Y12, and VASP during all treatments appeared similar between age cohorts. Prasugrel 5-mg resulted in fewer VE poor responders versus clopidogrel. Rates of mild bleeding were higher with prasugrel 10-mg, but similar for prasugrel 5-mg versus clopidogrel 75-mg.

CONCLUSIONS:

In aspirin-treated stable CAD patientsprasugrel 5-mg in VE attenuated platelet inhibition while meeting prespecified non-inferioritycriterion versus prasugrel 10-mg in NE, with significantly better PD response and fewer poor responders compared to clopidogrel 75-mg in VE.

学科代码:内科学 心血管病学 神经病学   关键词:coronary artery disease ,全球精选文摘 爱思唯尔医学网, Elseviermed
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