Adenosine diphosphate-inducible platelet reactivity shows a pronounced age dependency in the initial phase of antiplatelet therapy with clopidogrel

被引:59
作者
Gremmel, T. [1 ]
Steiner, S. [1 ]
Seidinger, D. [1 ]
Koppensteiner, R. [1 ]
Panzer, S. [2 ]
Kopp, C. W. [1 ]
机构
[1] Med Univ Vienna, Div Angiol, Dept Internal Med 2, A-1090 Vienna, Austria
[2] Med Univ Vienna, Div Blood Grp Serol, Dept Blood Grp Serol & Transfus Med, A-1090 Vienna, Austria
关键词
advanced age; clopidogrel; platelet function testing; STENT IMPLANTATION; INHIBITION; AGGREGATION; ASPIRIN; IMPACT; INTERVENTION; PRASUGREL; EVENTS; HUMANS; COUNT;
D O I
10.1111/j.1538-7836.2009.03644.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Until recently, there were hardly any data on the antiplatelet effect of clopidogrel in advanced age. Like other metabolic processes, the conversion of clopidogrel to its active metabolite may be impaired in older patients, leading to high on-treatment residual ADP-inducible platelet reactivity. Objective: To investigate the age dependency of clopidogrel-mediated platelet inhibition. Patients and methods: This was a prospective observational study. We determined adenosine 5'-diphosphate (ADP)-inducible platelet reactivity using light transmission aggregometry (LTA) and the VerifyNow P2Y12 assay in 191 patients on dual antiplatelet therapy after angioplasty and stenting for cardiovascular disease. Results: ADP-inducible platelet reactivity increased linearly with age after adjustment for cardiovascular risk factors, type of intervention, medication, C-reactive protein (CRP) and renal function [using LTA 0.36% of maximal aggregation per year, 95% CI 0.08-0.64%, P = 0.013; using the VerifyNow P2Y12 assay 3.2 P2Y12 reaction units (PRU) per year, 95% CI 1.98-4.41 PRU, P < 0.001]. ADP-inducible platelet reactivity was significantly higher in patients aged 75 years or older compared with younger patients (P = 0.003 for LTA and P < 0.001 for the VerifyNow P2Y12 assay). Further, high on-treatment residual ADP-inducible platelet reactivity was significantly more common among patients aged 75 years or older (P = 0.02 for LTA and P < 0.001 for the VerifyNow P2Y12 assay). Conclusion: ADP-inducible platelet reactivity shows a pronounced age dependency in the initial phase of antiplatelet therapy with clopidogrel. The clinical implications of these findings need to be addressed in future trials.
引用
收藏
页码:37 / 42
页数:6
相关论文
共 30 条
[1]   IMPAIRMENT OF LIDOCAINE CLEARANCE IN ELDERLY MALE-SUBJECTS [J].
ABERNETHY, DR ;
GREENBLATT, DJ .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1983, 5 (06) :1093-1096
[2]   The association of cigarette smoking with enhanced platelet inhibition by clopidogrel [J].
Bliden, Kevin P. ;
DiChiara, Joseph ;
Lawal, Lookman ;
Singla, Anand ;
Antonino, Mark J. ;
Baker, Brian A. ;
Bailey, William L. ;
Tantry, Udaya S. ;
Gurbel, Paul A. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2008, 52 (07) :531-533
[3]   Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis [J].
Buonamici, Piergiovanni ;
Marcucci, Rossella ;
Migliorini, Angela ;
Gensini, Gian Franco ;
Santini, Alberto ;
Paruccia, Rita ;
Moschi, Guia ;
Gori, Anna Maria ;
Abbate, Rosanna ;
Antoniucci, David .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 49 (24) :2312-2317
[4]   Early potent antithrombotic effect with combined aspirin and a loading dose of clopidogrel on experimental arterial thrombogenesis in humans [J].
Cadroy, Y ;
Bossavy, JP ;
Thalamas, C ;
Sagnard, L ;
Sakariassen, K ;
Boneu, B .
CIRCULATION, 2000, 101 (24) :2823-2828
[5]   P2Y12 receptor antagonists:: a rapidly expanding group of antiplatelet agents [J].
Cattaneo, M .
EUROPEAN HEART JOURNAL, 2006, 27 (09) :1010-1012
[6]   Platelet aggregation studies: autologous platelet-poor plasma inhibits platelet aggregation when added to platelet-rich plasma to normalize platelet count [J].
Cattaneo, Marco ;
Lecchi, Anna ;
Zighetti, Maddalena Loredana ;
Lussana, Federico .
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2007, 92 (05) :694-697
[7]   Relationship between aspirin and clopidogrel responses in acute coronary syndrome and clinical predictors of non response [J].
Cuisset, Thomas ;
Frere, Corinne ;
Quilici, Jacques ;
Morange, Pierre-Emmanuel ;
Camoin, Laurence ;
Bali, Laurent ;
Lambert, Marc ;
Juhan-Vague, Irene ;
Alessi, Marie-Christine ;
Bonnet, Jean-Louis .
THROMBOSIS RESEARCH, 2009, 123 (04) :597-603
[8]   PHARMACOKINETICS OF TERFENADINE IN HEALTHY ELDERLY SUBJECTS [J].
ELLER, MG ;
WALKER, BJ ;
WESTMARK, PA ;
RUBERG, SJ ;
ANTONY, KK ;
MCNUTT, BE ;
OKERHOLM, RA .
JOURNAL OF CLINICAL PHARMACOLOGY, 1992, 32 (03) :267-271
[9]  
Geisler T, 2008, J THROMB HAEMOST, V6, P54
[10]   Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation [J].
Geisler, Tobias ;
Langer, Harald ;
Wydymus, Magdalena ;
Goehring, Katrin ;
Zuern, Christine ;
Bigalke, Boris ;
Stellos, Konstantinos ;
May, Andreas E. ;
Gawaz, Meinrad .
EUROPEAN HEART JOURNAL, 2006, 27 (20) :2420-2425