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Effect of clopidogrel discontinuation at 1 year after drug eluting stent placement on soluble CD40L, P-selectin and C-reactive protein levels: DECADES (Discontinuation Effect of Clopidogrel After Drug Eluting Stent): a multicenter, open-label study

Effect of clopidogrel discontinuation at 1 year after drug eluting stent placement on soluble CD40L, P-selectin and C-reactive protein levels: DECADES (Discontinuation Effect of Clopidogrel After Drug Eluting Stent): a multicenter, open-label study
Effect of clopidogrel discontinuation at 1 year after drug eluting stent placement on soluble CD40L, P-selectin and C-reactive protein levels: DECADES (Discontinuation Effect of Clopidogrel After Drug Eluting Stent): a multicenter, open-label study
Antiplatelet therapy with clopidogrel has been shown to reduce major adverse cardiac events in acute coronary syndromes and after percutaneous interventions. This effect is not only due to its anti-platelet effect but also possibly due to an anti-inflammatory effect. The effect of clopidogrel cessation after one year of therapy on markers of inflammation has been investigated in diabetics and showed an increase in platelet aggregation as well as hsCRP and surface P-selectin levels. This was an exploratory multicenter prospective open-label single arm study of 98 non-diabetic patients who had received one or more drug eluting stents and were coming to the end of their 12 months course of clopidogrel therapy. The effect of clopidogrel cessation on expression of biomarkers: sCD40L, soluble P-selectin and hsCRP was measured right before clopidogrel cessation (day 0), and subsequently at 1, 2, 3 and 4 weeks after drug withdrawal. A median increase in sCD40L expression from 224 to 324.5 pg/ml was observed between baseline and 4 weeks after clopidogrel cessation, which corresponded to a 39% mean percent change based on an ANCOVA model (P < 0.001). Over the 4 weeks observation period the change in sCD40L expression correlated weakly with soluble P-selectin levels (at 4 weeks Spearman's correlation coefficient = 0.32; P = 0.0024). Increase in P-selectin expression from baseline was statistically significant at week 1 and 2. Conversely, hsCRP level decreased by 21% at 1 week (P = 0.008) and was still reduced by 18% by 4 weeks (P = 0.062). The change in sCD40L expression appeared to vary with the type of drug eluting stent. Patients treated with drug eluting stents at 1 year after implantation display significant increase in sCD40L and decrease in hsCRP after clopidogrel cessation. Further studies should elucidate if this increase in sCD40L levels reflects solely the removal of the inhibitory effects of clopidogrel on platelet activity or rather an increase in pro-inflammatory state. The latter hypothesis may be less likely given decrease in hsCRP levels. Randomized studies are urgently needed to establish potential link of clopidogrel discontinuation and vascular outcomes.
410-417
Wykrzykowska, J.J.
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Warnholtz, A.
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De Jaeger, P.
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Curzen, N.
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Oldroyd, K.G.
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Collet, J.P.
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Ten Berg, J.M.
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Rademaker, T.
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Goedhart, D.
b78f1acc-3158-4cc3-ac05-6f0106913093
Lissens, J.
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Kint, P.P.
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Serruys, P.W.
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Wykrzykowska, J.J.
2cc9d8d9-3a42-421a-baab-35dc83e34cf2
Warnholtz, A.
c15d6351-788b-4c65-bcec-c4c3013dc1ce
De Jaeger, P.
05e40563-6e21-4c8e-83c4-bf1272eebbe9
Curzen, N.
70f3ea49-51b1-418f-8e56-8210aef1abf4
Oldroyd, K.G.
cbfbab64-e32f-46c8-b0ab-28f911644b6d
Collet, J.P.
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Ten Berg, J.M.
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Rademaker, T.
57af4243-8e3c-4ed7-be76-472a13f74731
Goedhart, D.
b78f1acc-3158-4cc3-ac05-6f0106913093
Lissens, J.
797ef2ce-2f48-4e6c-b38c-6740ad9431b4
Kint, P.P.
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Serruys, P.W.
b31c7391-6f62-493b-ae67-d2e67af8bea9

Wykrzykowska, J.J., Warnholtz, A., De Jaeger, P., Curzen, N., Oldroyd, K.G., Collet, J.P., Ten Berg, J.M., Rademaker, T., Goedhart, D., Lissens, J., Kint, P.P. and Serruys, P.W. (2009) Effect of clopidogrel discontinuation at 1 year after drug eluting stent placement on soluble CD40L, P-selectin and C-reactive protein levels: DECADES (Discontinuation Effect of Clopidogrel After Drug Eluting Stent): a multicenter, open-label study. Journal of Thrombosis and Thrombolysis, 28 (4), 410-417. (doi:10.1007/s11239-009-0354-y). (PMID:19504052)

Record type: Article

Abstract

Antiplatelet therapy with clopidogrel has been shown to reduce major adverse cardiac events in acute coronary syndromes and after percutaneous interventions. This effect is not only due to its anti-platelet effect but also possibly due to an anti-inflammatory effect. The effect of clopidogrel cessation after one year of therapy on markers of inflammation has been investigated in diabetics and showed an increase in platelet aggregation as well as hsCRP and surface P-selectin levels. This was an exploratory multicenter prospective open-label single arm study of 98 non-diabetic patients who had received one or more drug eluting stents and were coming to the end of their 12 months course of clopidogrel therapy. The effect of clopidogrel cessation on expression of biomarkers: sCD40L, soluble P-selectin and hsCRP was measured right before clopidogrel cessation (day 0), and subsequently at 1, 2, 3 and 4 weeks after drug withdrawal. A median increase in sCD40L expression from 224 to 324.5 pg/ml was observed between baseline and 4 weeks after clopidogrel cessation, which corresponded to a 39% mean percent change based on an ANCOVA model (P < 0.001). Over the 4 weeks observation period the change in sCD40L expression correlated weakly with soluble P-selectin levels (at 4 weeks Spearman's correlation coefficient = 0.32; P = 0.0024). Increase in P-selectin expression from baseline was statistically significant at week 1 and 2. Conversely, hsCRP level decreased by 21% at 1 week (P = 0.008) and was still reduced by 18% by 4 weeks (P = 0.062). The change in sCD40L expression appeared to vary with the type of drug eluting stent. Patients treated with drug eluting stents at 1 year after implantation display significant increase in sCD40L and decrease in hsCRP after clopidogrel cessation. Further studies should elucidate if this increase in sCD40L levels reflects solely the removal of the inhibitory effects of clopidogrel on platelet activity or rather an increase in pro-inflammatory state. The latter hypothesis may be less likely given decrease in hsCRP levels. Randomized studies are urgently needed to establish potential link of clopidogrel discontinuation and vascular outcomes.

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Published date: 2009
Organisations: Human Development & Health

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Local EPrints ID: 355195
URI: http://eprints.soton.ac.uk/id/eprint/355195
PURE UUID: 44c9b439-f109-48fb-93a8-d9d637c8e7ac
ORCID for N. Curzen: ORCID iD orcid.org/0000-0001-9651-7829

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Date deposited: 13 Aug 2013 15:59
Last modified: 15 Mar 2024 03:23

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Contributors

Author: J.J. Wykrzykowska
Author: A. Warnholtz
Author: P. De Jaeger
Author: N. Curzen ORCID iD
Author: K.G. Oldroyd
Author: J.P. Collet
Author: J.M. Ten Berg
Author: T. Rademaker
Author: D. Goedhart
Author: J. Lissens
Author: P.P. Kint
Author: P.W. Serruys

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