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.

Erlinge, David; Gurbel, Paul A; James, Stefan; Lindahl, Tomas L; Svensson, Peter; Ten Berg, Jurrien M; Foley, David P; Wagner, Henrik; Brown, Patricia B; Luo, Junxiang; Zhou, Chunmei; Moser, Brian A; Jakubowski, Joseph A; Small, David S; Winters, Kenneth J; Angiolillo, Dominick J

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.

Mark

; Gurbel, Paul A ; James, Stefan ; Lindahl, Tomas L ; Svensson, Peter ^LU ; Ten Berg, Jurrien M ; Foley, David P ; Wagner, Henrik ^LU ; Brown, Patricia B and Luo, Junxiang , et al. (2013) In Journal of the American College of Cardiology 62(7). p.577-583

Abstract: 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... (More); 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 for prasugrel 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 patients, prasugrel 5-mg in VE attenuated platelet inhibition while meeting prespecified non-inferiority criterion versus prasugrel 10-mg in NE, with significantly better PD response and fewer poor responders compared to clopidogrel 75-mg in VE. (Less)

Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/3913591

author

Erlinge, David ^LU

; Gurbel, Paul A ; James, Stefan ; Lindahl, Tomas L ; Svensson, Peter ^LU ; Ten Berg, Jurrien M ; Foley, David P ; Wagner, Henrik ^LU ; Brown, Patricia B and Luo, Junxiang , et al. (More)

Erlinge, David ^LU

; Gurbel, Paul A ; James, Stefan ; Lindahl, Tomas L ; Svensson, Peter ^LU ; Ten Berg, Jurrien M ; Foley, David P ; Wagner, Henrik ^LU ; Brown, Patricia B ; Luo, Junxiang ; Zhou, Chunmei ; Moser, Brian A ; Jakubowski, Joseph A ; Small, David S ; Winters, Kenneth J and Angiolillo, Dominick J (Less)

organization

publishing date

2013

type

Contribution to journal

publication status

published

subject

Cardiac and Cardiovascular Systems

in

Journal of the American College of Cardiology

volume

62

issue

7

pages

577 - 583

publisher

Elsevier

external identifiers

wos:000323605200003
pmid:23747759
scopus:84881362012
pmid:23747759

ISSN

0735-1097

DOI

10.1016/j.jacc.2013.05.023

language

English

LU publication?

yes

id

33cfcb1a-ee2e-41a7-9d71-b21fddb83a38 (old id 3913591)

alternative location

http://www.ncbi.nlm.nih.gov/pubmed/23747759?dopt=Abstract

date added to LUP

2016-04-01 10:47:26

date last changed

2022-05-13 20:16:22

@article{33cfcb1a-ee2e-41a7-9d71-b21fddb83a38,
  abstract     = {{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-&lt;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 for prasugrel 10-mg in NE, using a prespecified one-sided 97.5% confidence interval for the difference &lt;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&lt;0.001) in VE, but higher than prasugrel 10-mg in NE (46±12%) (p&lt;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 patients, prasugrel 5-mg in VE attenuated platelet inhibition while meeting prespecified non-inferiority criterion versus prasugrel 10-mg in NE, with significantly better PD response and fewer poor responders compared to clopidogrel 75-mg in VE.}},
  author       = {{Erlinge, David and Gurbel, Paul A and James, Stefan and Lindahl, Tomas L and Svensson, Peter and Ten Berg, Jurrien M and Foley, David P and Wagner, Henrik and Brown, Patricia B and Luo, Junxiang and Zhou, Chunmei and Moser, Brian A and Jakubowski, Joseph A and Small, David S and Winters, Kenneth J and Angiolillo, Dominick J}},
  issn         = {{0735-1097}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{577--583}},
  publisher    = {{Elsevier}},
  series       = {{Journal of the American College of Cardiology}},
  title        = {{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.}},
  url          = {{http://dx.doi.org/10.1016/j.jacc.2013.05.023}},
  doi          = {{10.1016/j.jacc.2013.05.023}},
  volume       = {{62}},
  year         = {{2013}},
}

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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.