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Thromb Haemost 2016; 116(02): 356-368
DOI: 10.1160/TH15-11-0864
Atherosclerosis and Ischaemic Disease
Schattauer GmbH

Cardiovascular events occur independently of high on-aspirin platelet reactivity and residual COX-1 activity in stable cardiovascular patients

Kazuyuki Nagatsuka
1   National Cerebral and Cardiovascular Center, Suita, Japan
,
Shigeki Miyata
1   National Cerebral and Cardiovascular Center, Suita, Japan
,
Akiko Kada
1   National Cerebral and Cardiovascular Center, Suita, Japan
2   NHO Nagoya Medical Center, Nagoya, Japan
,
Atsushi Kawamura
1   National Cerebral and Cardiovascular Center, Suita, Japan
,
Jyoji Nakagawara
1   National Cerebral and Cardiovascular Center, Suita, Japan
3   Nakamura Memorial Hospital, Sapporo, Japan
,
Eisuke Furui
4   Kohnan Hospital, Sendai, Japan
,
Shin Takiuchi
5   Higashi Takarazuka Satoh Hospital, Takarazuka, Japan
,
Katsushi Taomoto
6   Ohnishi Neurological Center, Akashi, Japan
,
Kazuomi Kario
7   Jichi Medical University School of Medicine, Shimotsuke, Japan
,
Shinichiro Uchiyama
8   Tokyo Women’s Medical University, Tokyo, Japan
9   International University of Health and Welfare, Sanno Hospital and Sanno Medical Center, Tokyo, Japan
,
Kozue Saito
1   National Cerebral and Cardiovascular Center, Suita, Japan
10   Nara Medical University, Kashihara, Japan
,
Takehiko Nagao
8   Tokyo Women’s Medical University, Tokyo, Japan
11   Tokyo Metropolitan HMTC Ebara Hospital, Tokyo, Japan
12   Nippon Medical School, Tokyo, Japan
,
Kazuo Kitagawa
8   Tokyo Women’s Medical University, Tokyo, Japan
13   Osaka University Graduate School of Medicine, Suita, Japan
,
Naohisa Hosomi
14   Kagawa University School of Medicine, Kagawa, Japan
15   Hiroshima University Graduate School of Biomedical Sciences, Higashihiroshima, Japan
,
Keiji Tanaka
12   Nippon Medical School, Tokyo, Japan
,
Koichi Kaikita
16   Kumamoto University, Kumamoto, Japan
,
Yasuo Katayama
12   Nippon Medical School, Tokyo, Japan
,
Takeo Abumiya
17   Hokkaido Neurosurgical Memorial Hospital, Sapporo, Japan
,
Hiroshi Nakane
18   NHO Fukuoka-Higashi Medical Center, Fukuoka, Japan
,
Hideo Wada
19   Mie University Graduate School of Medicine, Tsu, Japan
,
Akira Hattori
20   Sado General Hospital, Sado, Japan
,
Kazumi Kimura
12   Nippon Medical School, Tokyo, Japan
21   Kawasaki Medical School, Kurashiki, Japan
,
Takaaki Isshiki
22   Teikyo University, Tokyo, Japan
,
Masakatsu Nishikawa
19   Mie University Graduate School of Medicine, Tsu, Japan
,
Takemori Yamawaki
15   Hiroshima University Graduate School of Biomedical Sciences, Higashihiroshima, Japan
,
Naohiro Yonemoto
23   National Center of Neurology and Psychiatry, Kodaira, Japan
,
Hiromi Okada
1   National Cerebral and Cardiovascular Center, Suita, Japan
,
Hisao Ogawa
1   National Cerebral and Cardiovascular Center, Suita, Japan
16   Kumamoto University, Kumamoto, Japan
,
Kazuo Minematsu
1   National Cerebral and Cardiovascular Center, Suita, Japan
,
Toshiyuki Miyata
1   National Cerebral and Cardiovascular Center, Suita, Japan
› Author Affiliations Financial support: This study was supported by a Grant-in-Aid from the Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation of Japan (06–51) and a Health and Labour Sciences Research Grant from the Ministry of Health, Labour and Welfare of Japan.
Further Information

Publication History

Received: 11 November 2015

Accepted after major revision: 05 April 2016

Publication Date:
09 November 2017 (online)

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Summary

Several studies have indicated that approximately 25% of patients treated with aspirin exhibit high on-treatment platelet reactivity (HTPR), which is potentially associated with cardiovascular events (CVEs). However, this association is still controversial, since the mechanisms by which HTPR contributes to CVEs remain unclear and a no standardised definition of HTPR has been established. To determine whether HTPR is associated with CVE recurrence and what type of assay would best predict CVE recurrence, we conducted a multicentre prospective cohort study of 592 stable cardiovascular outpatients treated with aspirin monotherapy for secondary prevention. Their HTPR was determined by arachidonic acid- or collagen-induced aggregation assays using two different agonist concentrations. Residual cyclooxygenase (COX)-1 activity was assessed by measuring serum thromboxane (TX)B2 or urinary 11-dehydro TXB2. Shear-induced platelet thrombus formation was also examined. We followed all patients for two years to evaluate how these seven indexes were related to the recurrence of CVEs (cerebral infarction, transient ischaemic attack, myocardial infarction, unstable angina, revascularisation, other arterial thrombosis, or cardiovascular death). Of 583 patients eligible for the analysis, CVEs occurred in 69 (11.8%). A Cox regression model identified several classical risk factors associated with CVEs. However, neither HTPR nor high residual COX-1 activity was significantly associated with CVEs, even by applying cut-off values suggested in previous reports or a receiver-operating characteristic analysis. In conclusion, recurrence of CVEs occurred independently of HTPR and residual COX-1 activity. Thus, our findings do not support the use of platelet or COX-1 functional testing for predicting clinical outcomes in stable cardiovascular patients.

Supplementary Material to this article is available at www.thrombosis-online.com.

Keywords

Aspirin - cardiovascular diseases - platelets - secondary prevention

 

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