Comparison of Platelet Inhibition With Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel According to Hepatic Cytochrome 2C19 Allele (CYP2C19) Polymorphism

Phase 3

• Conditions: Coronary Artery Stenosis; Maximal Platelet Aggregation; Late Platelet Aggregation; High Post-Treatment Platelet Reactivity
• Interventions: Drug: cilostazol; Drug: clopidogrel; Drug: aspirin

• Registration Number: NCT00891670
• Lead Sponsor: Gyeongsang National University Hospital

Brief Summary

The purpose of this study was to determine the impact of adjunctive cilostazol on platelet inhibition in carriers and non-carriers of the loss-of-function CYP2C19 allele.

Detailed Description

The additional platelet inhibition with clopidogrel, a thienopyridine inhibitor of the platelet P2Y12 adenosine diphosphate (ADP) receptor, has reduced the risk of ischemic events after coronary stent implantation. Because of inter-individual variability in platelet response to clopidogrel, a significant proportion of suboptimal platelet inhibition has been reported. In addition, persistent residual platelet reactivity measured with platelet function testing has shown the association with the cardiovascular outcomes after percutaneous coronary intervention(PCI).

Various clinical factors and genetic polymorphisms have been studied to predict the degree of antiplatelet response to clopidogrel. Interestingly, recent studies found that carriers of the loss-of-function hepatic cytochrome (CYP) 2C19 allele had significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events than did non-carriers, in the setting of PCI and acute coronary syndrome(ACS). These findings raise the need of solutions to overcome enhanced post-clopidogrel platelet reactivity by the influence of the loss-of-function CYP2C19 allele. Increasing the dose of clopidogrel and new potent P2Y12 antagonists(such as prasugrel) may be alternative antiplatelet regimens in patients with the loss-of-function CYP variant.

Cilostazol reversibly induces platelet inhibition via its blockade of phosphodiesterase (PDE) type 3 and is catalysed mainly by CYP3A. A recent study demonstrated that adjunctive cilostazol to dual antiplatelet therapy (triple antiplatelet therapy) intensified platelet inhibition as compared with a high maintenance-dose (MD) of 150 mg/day. Therefore, triple antiplatelet therapy could also be an alternative antiplatelet therapy to improve platelet inhibition and clinical outcomes in carriers of CYP2C19 mutant allele.

Study Timeline

• Status Verified: 2009-04
• Study First Submitted: 2009-04-30
• Study First Submitted QC: 2009-04-30
• Last Update Submitted: 2009-04-30
• Study Start: 2009-05
• Study First Posted: 2009-05-01
• Last Update Posted: 2009-05-01
• Primary Completion: 2009-06
• Study Completion: 2009-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. The patient must be at least 18 years of age
2. Significant coronary artery stenosis (> 70% by visual estimate)
3. Elective coronary stent implantation

Exclusion Criteria

1. Acute myocardial infarction
2. Hemodynamic instability active bleeding and bleeding diatheses
3. Oral anticoagulation therapy with warfarin,use of peri-procedural glycoprotein IIb/IIIa inhibitors
4. Contraindication to antiplatelet therapy
5. Left ventricular ejection fraction < 30%
6. Leukocyte count < 3,000/mm3, platelet count < 100,000/mm3
7. AST or ALT ≥ 3 times upper normal
8. Serum creatinine level ≥ 2.5 mg/dL
9. stroke within 3 months
10. Noncardiac disease with a life expectancy < 1 year
11. Inability to follow the protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
triple group	aspirin	received cilostazol 100 mg twice daily in addition to aspirin 100mg and clopidogrel 75mg once daily
triple group	cilostazol	received cilostazol 100 mg twice daily in addition to aspirin 100mg and clopidogrel 75mg once daily
high maintenance dose group	clopidogrel	received clopidogrel 150 mg/day with aspirin 100mg once daily
high maintenance dose group	aspirin	received clopidogrel 150 mg/day with aspirin 100mg once daily

Primary Outcome Measures

Name	Time	Method
Reduction of maximal platelet aggregation	30 days

Secondary Outcome Measures

Name	Time	Method
Rate of high post-clopidogrel platelet reactivity	30 days

Trial Locations

Locations (1)

Gyeong-Sang National University Hospital; 🇰🇷 Jinju, Gyeong-Nam, Korea, Republic of