BACKGROUND: Stent thrombosis occurs frequently within the first weeks after cessation of longterm clopidogrel therapy. We investigated if rebound platelet hyperreactivity occurs to provide a mechanism for this clinical observation. METHODS: ADP- and TRAP-induced platelet aggregation was measured by impedance aggregometry in 28 patients with coronary stent implantation (observational group, OG) before and 1, 2, 6 and 17 weeks after clopidogrel cessation. Data were compared intraindividually as well as to 67 controls (control group, CG). RESULTS: On-clopidogrel platelet activity was significantly reduced (ADP-stimulation, OG vs. CG, 30 ± 3 U vs. 67 ± 3 U, p < 0.001) and reached control levels 1 week after clopidogrel cessation (ADP-stimulation, OG vs. CG, 70 ± 4 U vs. 67 ± 3 U, p = n.s.). Most patients (57%) showed a significant platelet hyperaggregation after 2 weeks (ADP, OG vs. CG, 83 ± 6 U vs. 67 ± 3 U, p = 0.02) to 6 weeks (ADP, OG vs. CG, 85 ± 5 U vs. 67 ± 3 U, p = 0.01) post-cessation. This temporary hyperaggregability was also observed in intra-individual time courses (ADP, 2 vs. 17 weeks, 83 ± 6 U vs. 73 ± 4 U, p = 0.007; 6 vs. 17 weeks, 85 ± 5 U vs. 73 ± 4 U, p = 0.0002). After 17 weeks post-cessation, ADP-induced platelet aggregation returned towards physiological levels. The total capacity of platelet aggregability as reflected by stimulation with thrombin receptor activating peptide (TRAP) was not different between time points confirming a clopidogrel-specific rebound effect. CONCLUSION: Abrupt clopidogrel cessation after 1 year of clopidogrel treatment results in ADP specific platelet hyperreactivity between 2 and 6 weeks post withdrawal. This mechanism may contribute to explain increased rates of stent thrombosis at this time as it was observed in clinical studies.
BACKGROUND: Stent thrombosis occurs frequently within the first weeks after cessation of longterm clopidogrel therapy. We investigated if rebound platelet hyperreactivity occurs to provide a mechanism for this clinical observation. METHODS:ADP- and TRAP-induced platelet aggregation was measured by impedance aggregometry in 28 patients with coronary stent implantation (observational group, OG) before and 1, 2, 6 and 17 weeks after clopidogrel cessation. Data were compared intraindividually as well as to 67 controls (control group, CG). RESULTS: On-clopidogrel platelet activity was significantly reduced (ADP-stimulation, OG vs. CG, 30 ± 3 U vs. 67 ± 3 U, p < 0.001) and reached control levels 1 week after clopidogrel cessation (ADP-stimulation, OG vs. CG, 70 ± 4 U vs. 67 ± 3 U, p = n.s.). Most patients (57%) showed a significant platelet hyperaggregation after 2 weeks (ADP, OG vs. CG, 83 ± 6 U vs. 67 ± 3 U, p = 0.02) to 6 weeks (ADP, OG vs. CG, 85 ± 5 U vs. 67 ± 3 U, p = 0.01) post-cessation. This temporary hyperaggregability was also observed in intra-individual time courses (ADP, 2 vs. 17 weeks, 83 ± 6 U vs. 73 ± 4 U, p = 0.007; 6 vs. 17 weeks, 85 ± 5 U vs. 73 ± 4 U, p = 0.0002). After 17 weeks post-cessation, ADP-induced platelet aggregation returned towards physiological levels. The total capacity of platelet aggregability as reflected by stimulation with thrombin receptor activating peptide (TRAP) was not different between time points confirming a clopidogrel-specific rebound effect. CONCLUSION: Abrupt clopidogrel cessation after 1 year of clopidogrel treatment results in ADP specific platelet hyperreactivity between 2 and 6 weeks post withdrawal. This mechanism may contribute to explain increased rates of stent thrombosis at this time as it was observed in clinical studies.
Authors: D E Cutlip; D S Baim; K K Ho; J J Popma; A J Lansky; D J Cohen; J P Carrozza; M S Chauhan; O Rodriguez; R E Kuntz Journal: Circulation Date: 2001-04-17 Impact factor: 29.690
Authors: Gouri Shanker; Jimmy L Kontos; Delrae M Eckman; Deborah Wesley-Farrington; David C Sane Journal: J Thromb Thrombolysis Date: 2006-12 Impact factor: 2.300
Authors: Andrew T L Ong; Eugène P McFadden; Evelyn Regar; Peter P T de Jaegere; Ron T van Domburg; Patrick W Serruys Journal: J Am Coll Cardiol Date: 2005-06-21 Impact factor: 24.094
Authors: Dietmar Trenk; Willibald Hochholzer; Martin F Fromm; Ligia-Emilia Chialda; Andreas Pahl; Christian M Valina; Christian Stratz; Peter Schmiebusch; Hans-Peter Bestehorn; Heinz Joachim Büttner; Franz-Josef Neumann Journal: J Am Coll Cardiol Date: 2008-05-20 Impact factor: 24.094
Authors: P Michael Ho; Eric D Peterson; Li Wang; David J Magid; Stephan D Fihn; Greg C Larsen; Robert A Jesse; John S Rumsfeld Journal: JAMA Date: 2008-02-06 Impact factor: 56.272
Authors: Joanna J Wykrzykowska; Ascan Warnholtz; Peter de Jaeger; Nick Curzen; Keith G Oldroyd; Jean Philippe Collet; Jurrien M Ten Berg; Tessa Rademaker; Dick Goedhart; Jurgen Lissens; Peter-Paul Kint; Patrick W Serruys Journal: J Thromb Thrombolysis Date: 2009-11 Impact factor: 2.300
Authors: Thomas Gremmel; Karin Frühwirth; Christoph W Kopp; Alexandra Kaider; Sabine Steiner; Tamam Bakchoul; Ulrich J H Sachs; Renate Koppensteiner; Simon Panzer Journal: Clin Res Cardiol Date: 2012-01-11 Impact factor: 5.460
Authors: Christoph B Olivier; Katharina Schnabel; Christoph Brandt; Patrick Weik; Manfred Olschewski; Qian Zhou; Christoph Bode; Philipp Diehl; Martin Moser Journal: Clin Res Cardiol Date: 2014-07-16 Impact factor: 5.460
Authors: Samuel Pearce; Julian T Maingard; Hong Kuan Kok; Christen D Barras; Jeremy H Russell; Joshua A Hirsch; Ronil V Chandra; Ash Jhamb; Vincent Thijs; Mark Brooks; Hamed Asadi Journal: Clin Neuroradiol Date: 2021-03-01 Impact factor: 3.649
Authors: Wardati Mazlan-Kepli; Rachael L Macisaac; Matthew Walters; Philip Michael William Bath; Jesse Dawson Journal: Br J Clin Pharmacol Date: 2017-04-20 Impact factor: 4.335