Cardiovascular events occur independently of high on-aspirin platelet reactivity and residual COX-1 activity in stable cardiovascular patients.
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.
Kazuyuki
K
Nagatsuka
Dr. Shigeki Miyata, Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan, Tel.: +81 6 6833 5012 ext. 2294, Fax: +81 6 6872 8175, E-mail: smiyata@ncvc.go.jp.
Shigeki
S
Miyata
Akiko
A
Kada
Atsushi
A
Kawamura
Jyoji
J
Nakagawara
Eisuke
E
Furui
Shin
S
Takiuchi
Katsushi
K
Taomoto
Kazuomi
K
Kario
Shinichiro
S
Uchiyama
Kozue
K
Saito
Takehiko
T
Nagao
Kazuo
K
Kitagawa
Naohisa
N
Hosomi
Keiji
K
Tanaka
Koichi
K
Kaikita
Yasuo
Y
Katayama
Takeo
T
Abumiya
Hiroshi
H
Nakane
Hideo
H
Wada
Akira
A
Hattori
Kazumi
K
Kimura
Takaaki
T
Isshiki
Masakatsu
M
Nishikawa
Takemori
T
Yamawaki
Naohiro
N
Yonemoto
Hiromi
H
Okada
Hisao
H
Ogawa
Kazuo
K
Minematsu
Toshiyuki
T
Miyata
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology* / Q000517:prevention & control; D015331:Cohort Studies; D051545:Cyclooxygenase 1 / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D055502:Secondary Prevention; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine
D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin
Aspirin; cardiovascular diseases; platelets; secondary prevention