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

Kazuyuki Nagatsuka, Shigeki Miyata, Akiko Kada, Atsushi Kawamura, Jyoji Nakagawara, Eisuke Furui, Shin Takiuchi, Katsushi Taomoto, Kazuomi Kario, Shinichiro Uchiyama, Kozue Saito, Takehiko Nagao, Kazuo Kitagawa, Naohisa Hosomi, Keiji Tanaka, Koichi Kaikita, Yasuo Katayama, Takeo Abumiya, Hiroshi Nakane, Hideo WadaAkira Hattori, Kazumi Kimura, Takaaki Isshiki, Masakatsu Nishikawa, Takemori Yamawaki, Naohiro Yonemoto, Hiromi Okada, Hisao Ogawa, Kazuo Minematsu, Toshiyuki Miyata

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)356-368
Number of pages13
JournalThrombosis and Haemostasis
Issue number2
Publication statusPublished - 08-2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology


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