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Multicenter Study
. 2020 Jan 1;27(1):13-24.
doi: 10.5551/jat.48934. Epub 2019 May 14.

Association between High Platelet Reactivity Following Dual Antiplatelet Therapy and Ischemic Events in Japanese Patients with Coronary Artery Disease Undergoing Stent Implantation

Masakatsu Nishikawa  1 , Yoshihiro Takeda  2 , Naoei Isomura  3 , Takashi Tanigawa  4 , Mamoru Nanasato  5 , Kengo Tsukahara  6 , Kazuo Kimura  6 , Tadateru Takayama  7 , Atsushi Hirayama  7 , Masafumi Kato  8 , Hideo Nishikawa  8 , Yuki Nishimura  1 , Takaaki Isshiki  9 , Hiroyoshi Yokoi  10   11 ; j-CHIPS group
Affiliations
Multicenter Study

Association between High Platelet Reactivity Following Dual Antiplatelet Therapy and Ischemic Events in Japanese Patients with Coronary Artery Disease Undergoing Stent Implantation

Masakatsu Nishikawa et al. J Atheroscler Thromb. .

Abstract

Aim: Although high on-treatment platelet reactivity (HTPR) with dual antiplatelet therapy (DAPT) correlates with long-term adverse outcomes in patients undergoing percutaneous coronary intervention, the correlation in Japanese patients remains unclear. Therefore, we examined the relationship between platelet reactivity during DAPT with aspirin and clopidogrel and 1-year clinical outcomes following successful coronary stent implantation.

Methods: A prospective, multicenter registry study (j-CHIPS) was conducted in patients undergoing coronary stenting and receiving aspirin and clopidogrel at 16 hospitals in Japan. A VerifyNow point-of-care assay was used to assess platelet reactivity, and a cutoff value to define HTPR was established.

Results: Between February 2011 and May 2013, 1047 patients were prospectively enrolled, of which 854 patients with platelet function evaluation at 12-24 h after PCI were included in the final analysis. After 1 year of follow-up, the incidence of the primary endpoint (a composite of all-cause mortality, myocardial infarction, stent thrombosis, and ischemic stroke) was significantly higher in patients with HTPR than in those without (5.9% vs. 1.5%, p=0.008), and HTPR showed a modest ability to discriminate between patients who did and did not experience major adverse cardiac and cerebrovascular events (area under the curve, 0.60; 95% confidence interval, 0.511-0.688, p=0.039). HTPR status did not identify patients at risk for major or minor bleeding events.

Conclusion: HTPR was significantly associated with adverse ischemic outcomes at 1 year after PCI in Japanese patients receiving maintenance DAPT, indicating its potential as a prognostic indicator of clinical outcomes in this high-risk patient population.

Keywords: Coronary stent implantation; Dual antiplatelet therapy; High on-treatment platelet reactivity.

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Conflict of interest statement

M Nishikawa has received honoraria from Daiichi Sankyo and clinical research funding from Daiichi Sankyo and Otsuka Pharmaceutical. K Kimura has received honoraria from AstraZeneca and Daiichi Sankyo, clinical research funding from Daiichi Sankyo, and a scholarship grant from Daiichi Sankyo. T Takayama has received clinical research funding from Daiichi Sankyo and Tanabe Mitsubishi. A Hirayama has received honoraria from TOA EIYO, Boehringer Ingelheim Japan, Sanofi, Astellas Pharma, Sumitomo Dainippon Pharma, Bristol-Myers Squibb, Amgen Astellas Biopharma, AstraZeneca, Daiichi Sankyo and Bayer Yakuhin, and teaches courses endowed by Boston Scientific Japan, Otsuka Pharmaceutical, Fukuda Denshi, St. Jude Medical Japan, Medtronic Japan, and Japan Lifeline. T Isshiki has received patent royalties from Nipro, honoraria from Sanofi and Daiichi Sankyo, and clinical research funding from Daiichi Sankyo. H Yokoi has received honoraria from Daiichi Sankyo, Sanofi, Bayer Yakuhin, Terumo, and a scholarship grant from Daiichi Sankyo. The other authors have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
Study flow diagram of the j-CHIPS registry
Fig. 2.
Fig. 2.
Platelet reactivity before and after PCI A: Platelet reactivity in patients with ACS (●) or with stable CAD (○). B: Platelet reactivity in patients treated with loading (■) or non-loading (▴) doses of clopidogrel.
Fig. 3.
Fig. 3.
Kaplan-Meier analysis of 1-year MACCE (A) and all-cause death (B) in patients with and without HTPR HTPR formula image, No-HTPR formula image
See this image and copyright information in PMC

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