Differential inhibition of platelet function by cilostazol in combination with clopidogrel

• Published in: European journal of clinical pharmacology Vol. 79; no. 12; pp. 1623 - 1630
• Main Authors: Yamazaki, Masako, Shirai, Yuka, Ohnishi, Tomoko, Hosokawa, Kazuya, Dahlen, Jeffrey R., Kitagawa, Kazuo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2023; Springer Nature B.V
• Subjects: Adenosine diphosphate; Artificial intelligence; Aspirin; Biomedical and Life Sciences; Biomedicine; Blood platelets; Clopidogrel; Collagen; Ischemia; Medicine; P-selectin; Pharmacology; Pharmacology/Toxicology; Platelets; Stroke; Vasodilator-stimulated phosphoprotein; Clopidogrel; Cilostazol; Platelet function tests; Ischemic stroke; Vasodilator-stimulated phosphoprotein
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-023-03553-w

Purpose
To assess the antiplatelet effect of cilostazol clinically, we compared the effects of cilostazol in combination with clopidogrel on various platelet function tests.
Methods
We recruited patients with ischemic stroke at high risk of recurrence who were treated with clopidogrel alone within 180 days after stroke onset. Subjects underwent baseline platelet function tests, and were then randomly assigned to receive dual antiplatelet therapy (DAPT) comprising clopidogrel and cilostazol or clopidogrel monotherapy (SAPT). After 6 months, platelet function was measured again and compared to that at baseline in each group, and the rate of change was compared between groups.
Results
Thirty-four patients were enrolled, but 4 patients were excluded for various reasons. In total, 30 subjects (13 in DAPT and 17 in SAPT group) were analyzed. Adenosine diphosphate- and collagen-induced aggregation, VerifyNow P2Y
12
reaction units, vasodilator-stimulated phosphoprotein (platelet reactivity index: PRI) and plasma p-selectin concentration were significantly lower (
P
 = 0.004, 0.042, 0.049, 0.003 and 0.006 respectively), while VerifyNow % inhibition was significantly higher at 6 months compared to baseline (
P
 = 0.003) in the DAPT group only. Comparison of the rate of change in each parameter from baseline to 6 months showed that while PRI decreased at a greater rate (
P
 = 0.012), VerifyNow % inhibition increased at a greater rate (
P
 = 0.003) in the DAPT group than the SAPT group.
Conclusions
The inhibitory effects of adjunctive cilostazol added to clopidogrel on platelet function differed by type of platelet function test. VerifyNow % inhibition and PRI were more inhibited than the other platelet function tests.
Trial registration
CSPS.com substudy in TWMU (UMIN000026672), registered on April 1, 2017. This study was performed as a substudy of CSPS.com (UMIN000012180, registered on October 31, 2013) and was retrospectively registered.