Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention: A prospective multicentre registry study

Hyung Joon Joo; Sung Gyun Ahn; Jae Hyoung Park; Ji Young Park; Soon Jun Hong; Seok Yeon Kim; Woong Gil Choi; Hyeon Cheol Gwon; Young Hyo Lim; Weon Kim; Woong Chol Kang; Yun Hyeong Cho; Yong Hoon Kim; Jung Han Yoon; Won Yong Shin; Myeong Ki Hong; Scot Garg; Yangsoo Jang; Do Sun Lim

doi:10.1038/s41598-017-18134-y

Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention: A prospective multicentre registry study

Hyung Joon Joo, Sung Gyun Ahn, Jae Hyoung Park, Ji Young Park, Soon Jun Hong, Seok Yeon Kim, Woong Gil Choi, Hyeon Cheol Gwon, Young Hyo Lim, Weon Kim, Woong Chol Kang, Yun Hyeong Cho, Yong Hoon Kim, Jung Han Yoon, Won Yong Shin, Myeong Ki Hong, Scot Garg, Yangsoo Jang, Do Sun Lim

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Abstract

Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19∗R (∗2 or∗3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19∗2/∗2, CYP2C19∗2/∗3, and CYP2C19∗3/∗3 (Group 3) than in patients with CYP2C19∗1/∗1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154-6.263, p = 0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.

Original language	English
Article number	1229
Journal	Scientific reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-18134-y
Publication status	Published - 2018 Dec 1

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Publisher Copyright:
© 2018 The Author(s).

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Joo, H. J., Ahn, S. G., Park, J. H., Park, J. Y., Hong, S. J., Kim, S. Y., Choi, W. G., Gwon, H. C., Lim, Y. H., Kim, W., Kang, W. C., Cho, Y. H., Kim, Y. H., Yoon, J. H., Shin, W. Y., Hong, M. K., Garg, S., Jang, Y., & Lim, D. S. (2018). Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention: A prospective multicentre registry study. Scientific reports, 8(1), Article 1229. https://doi.org/10.1038/s41598-017-18134-y

Joo, HJ, Ahn, SG, Park, JH, Park, JY, Hong, SJ, Kim, SY, Choi, WG, Gwon, HC, Lim, YH, Kim, W, Kang, WC, Cho, YH, Kim, YH, Yoon, JH, Shin, WY, Hong, MK, Garg, S, Jang, Y & Lim, DS 2018, 'Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention: A prospective multicentre registry study', Scientific reports, vol. 8, no. 1, 1229. https://doi.org/10.1038/s41598-017-18134-y

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title = "Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention: A prospective multicentre registry study",

abstract = "Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19∗R (∗2 or∗3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19∗2/∗2, CYP2C19∗2/∗3, and CYP2C19∗3/∗3 (Group 3) than in patients with CYP2C19∗1/∗1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154-6.263, p = 0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.",

author = "Joo, {Hyung Joon} and Ahn, {Sung Gyun} and Park, {Jae Hyoung} and Park, {Ji Young} and Hong, {Soon Jun} and Kim, {Seok Yeon} and Choi, {Woong Gil} and Gwon, {Hyeon Cheol} and Lim, {Young Hyo} and Weon Kim and Kang, {Woong Chol} and Cho, {Yun Hyeong} and Kim, {Yong Hoon} and Yoon, {Jung Han} and Shin, {Won Yong} and Hong, {Myeong Ki} and Scot Garg and Yangsoo Jang and Lim, {Do Sun}",

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doi = "10.1038/s41598-017-18134-y",

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T1 - Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention

T2 - A prospective multicentre registry study

AU - Joo, Hyung Joon

AU - Ahn, Sung Gyun

AU - Park, Jae Hyoung

AU - Park, Ji Young

AU - Hong, Soon Jun

AU - Kim, Seok Yeon

AU - Choi, Woong Gil

AU - Gwon, Hyeon Cheol

AU - Lim, Young Hyo

AU - Kim, Weon

AU - Kang, Woong Chol

AU - Cho, Yun Hyeong

AU - Kim, Yong Hoon

AU - Yoon, Jung Han

AU - Shin, Won Yong

AU - Hong, Myeong Ki

AU - Garg, Scot

AU - Jang, Yangsoo

AU - Lim, Do Sun

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19∗R (∗2 or∗3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19∗2/∗2, CYP2C19∗2/∗3, and CYP2C19∗3/∗3 (Group 3) than in patients with CYP2C19∗1/∗1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154-6.263, p = 0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.

AB - Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19∗R (∗2 or∗3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19∗2/∗2, CYP2C19∗2/∗3, and CYP2C19∗3/∗3 (Group 3) than in patients with CYP2C19∗1/∗1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154-6.263, p = 0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.

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SN - 2045-2322

VL - 8

JO - Scientific reports

JF - Scientific reports

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ER -

Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention: A prospective multicentre registry study

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