<Original article> Assessment of cilostazol inhibition using whole blood samples : comparison of three platelet function tests

Q: What are the key findings of this study?

Cilostazol significantly inhibited platelet aggregation by 69% compared to pre-therapy baseline in patients with cerebral infarction when assessed using the VerifyNow IIb/IIIa test with 10 nM PGE1.

Q: What is the clinical evidence from this study?

Population: Cerebral infarction (n=35). Intervention: Cilostazol vs. Pre-therapy baseline. Primary outcome: Platelet aggregation assessed by VerifyNow IIb/IIIa test in the presence of 10 nM PGE1 (69% inhibition, p=<0.05).

Q: What does this research mean for the field?

The VerifyNow IIb/IIIa test, when used in the presence of 10 nM prostaglandin E1, is the most suitable whole blood assay for monitoring the platelet-inhibitory efficacy of cilostazol. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To establish an effective whole-blood platelet aggregation assay for monitoring cilostazol inhibition by comparing three diagnostic platforms in the presence of prostaglandin E1.

Masato Ohta; Kaneo Satoh; Isao Fukasawa; Kazuya Hosokawa; Tomoko Oonishi; Junko Nakagomi; Yukio\r Ozaki

doi:10.34429/00002678

January 1, 2017Open Access

<Original article> Assessment of cilostazol inhibition using whole blood samples : comparison of three platelet function tests

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Key result

Cilostazol reduces platelet aggregation by ~69% versus baseline in cerebral infarction patients.

69% inhibition
P<0.05
n=35

Why the study?

This study aimed to establish a cilostazol monitoring assay using whole blood samples.

Which whole blood platelet function test is most suitable for monitoring the antiplatelet efficacy of cilostazol?

Key Points

To establish an effective whole-blood platelet aggregation assay for monitoring cilostazol inhibition by comparing three diagnostic platforms in the presence of prostaglandin E1.
Evaluated platelet aggregation in vitro with 3 µM cilostazol and ex vivo following a single 100 mg oral dose in healthy volunteers using VerifyNow, Multiplate, and T-TAS with varying concentrations of prostaglandin E1 (PGE1).
Monitored cilostazol efficacy in cerebral infarction patients before and after drug uptake using VerifyNow IIb/IIIa assays with 3 nM and 10 nM PGE1.
In vitro, VerifyNow detected cilostazol inhibition in the presence of PGE1 with the aspirin test (19%, 608 ± 45 to 495 ± 40 ARU) and the IIb/IIIa test (44%, 213 ± 45 to 119 ± 54 ARU), whereas Multiplate and T-TAS failed to detect efficacy.
Following oral uptake in healthy volunteers, VerifyNow decreased platelet aggregation by 46% (125 ± 53.2 to 67 ± 44 PAU) on the IIb/IIIa test and 24% (233 ± 34 to 178 ± 46 PRU) on the P2Y12 test.
In cerebral infarction patients, post-therapy VerifyNow IIb/IIIa tests showed significant platelet inhibition of 37% with 3 nM PGE1 and 69% with 10 nM PGE1 compared with pre-therapy samples.

Structured PICO

Which whole blood platelet function test is most suitable for monitoring the antiplatelet efficacy of cilostazol?

P

Population

In vitro blood samples, healthy volunteers, and patients with cerebral infarction

I

Intervention

Cilostazol (in vitro addition, single oral dose, or clinical therapy) assessed with VerifyNow, Multiplate, and Total Thrombus-formation Analysis System (T-TAS) in the presence of prostaglandin E1 (PGE1)

C

Comparator

Pre-therapy blood samples or absence of cilostazol

O

Outcome

Platelet aggregationsurrogate

Main Result

Effect estimate: 69% inhibition

p-value: p=<0.05

The VerifyNow IIb/IIIa test with added PGE1 is a suitable and effective tool for monitoring the antiplatelet efficacy of cilostazol in clinical settings.

Limitations

Discrepancies between in vitro and ex vivo studies with the aspirin and P2Y12 tests without a reasonable explanation.
Lack of a method to measure the intracellular concentration of cilostazol.
Small sample size.

Implication

Supports VerifyNow IIb/IIIa with PGE1 for cilostazol monitoring in cerebral infarction; extends whole-blood assay validation to post-stroke patients.

Abstract

Introduction: Cilostazol inhibits phosphodiesterase, with resultant increase in intracellular cyclic AMP, leading to platelet inhibition, particularly in the presence of prostaglandin E1 (PGE1). This study aimed to establish a cilostazol monitoring assay, using whole blood samples. Methods: Platelet aggregation in the presence or absence of indicated concentrations of PGE1 were assessed using VerifyNowR, MultiplateR and Total Thrombus-formation Analysis System (T-TASR). Results: In the presence of added PGE1, cilostazol inhibited in vitro platelet aggregation of VerifyNow, with the aspirin test by 19% and the IIb/IIIa test by 44%, respectively. After a single oral uptake of cilostazol in healthy volunteers, cilostazol decreased platelet aggregation, with the IIb/IIIa test by 46% and with the P2Y12 test by 24%, respectively. Multiplate or T-TAS failed to detect cilostazol effi cacy both in vitro and ex vivo. VerifyNow IIb/IIIa tests were used to monitor cilostazol effi cacy on cerebral infarction patients. Compared with pre-therapy blood samples, those after cilostazol uptake showed signifi cant inhibition of platelet aggregation in the presence of 3 nM (37%) and 10 nM PGE1 (69%). Conclusion: The IIb/IIIa tests of VerifyNow in the presence of 10 nM PGE1 is the most suitable tool for monitoring assessing cilostazol.

Discussion

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Cite This Study

Ohta et al. (2017) studied Cerebral infarction (n=35). Cilostazol vs. Pre-therapy baseline was evaluated on Platelet aggregation assessed by VerifyNow IIb/IIIa test in the presence of 10 nM PGE1 (69% inhibition, p=<0.05). Cilostazol significantly inhibited platelet aggregation by 69% compared to pre-therapy baseline in patients with cerebral infarction when assessed using the VerifyNow IIb/IIIa test with 10 nM PGE1.

synapsesocial.com/papers/6a1e732830b38c64201b661f https://doi.org/10.34429/00002678

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<Original article> Assessment of cilostazol inhibition using whole blood samples : comparison of three platelet function tests

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

<Original article> Assessment of cilostazol inhibition using whole blood samples : comparison of three platelet function tests

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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