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Report for Clinical Trial NCT00915733

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Comparison of Platelet Inhibitory Effect With Adjunctive Cilostazol Versus High Maintenance-dose ClopidogrEL in Acute Myocardial Infarction Patients According to CYP2C19 Polymorphism

Percutaneous coronary intervention (PCI) with stent implantation is the preferred reperfusion strategy for treatment of acute myocardial infarction (AMI). Despite advances in both devices and pharmacological support for AMI patients undergoing PCI, the risk of recurrent ischemic events has been higher than that of elective PCI. Among therapeutic options for surmounting clopidogrel hyporesponsiveness, higher loading doses and maintenance doses of clopidogrel achieved significant enhancements in the speed of onset and intensity of inhibition and these approaches have been widely adapted in clinical practice. 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, new potent P2Y12 antagonists (such as prasugrel), or other antiplatelet drugs such as cilostazol may be alternative antiplatelet regimens in patients with the loss-of-function CYP variant. 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. 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. The investigators compared the enhanced inhibition of platelet aggregation by adjunctive cilostazol 100 mg twice daily versus high-MD clopidogrel 150 mg/day in AMI patients treated with emergent coronary stenting, according to the CYP2C19 polymorphism.

NCT00915733 Myocardial Infarction
MeSH: Myocardial Infarction Infarction
HPO: Myocardial infarction

4 Interventions

Name: cilostazol

Description: 100 mg twice daily for at least 1 month

Type: Drug

triple group

Name: clopidogrel (Plavix)

Description: 150 mg once daily (high maintenance dose group arm), 75 mg once daily (triple group arm)

Type: Drug

high maintenance dose group triple group

Name: CYP2C19

Description: CYP2C19 polymorphism study: Two CYP2C19 polymorphisms, CYP2C19*2 (rs4244285, c. 681G>A, p.P227P), and CYP2C19*3 (rs4986893, c. 636G>A, p. W212X), are investigated using the ABI SNaPshot reaction and the ABI 3100 automated genetic analyzer.

Type: Genetic

high maintenance dose group triple group

Name: aspirin (Acetylsalicylic acid)

Description: aspirin 100 mg qd

Type: Drug

high maintenance dose group triple group


Primary Outcomes

Measure: Absolute reduction of maximal platelet aggregation (Aggmax) by 5 & 20 μM ADP induced LTA

Time: 30 days

Secondary Outcomes

Measure: Absolute reduction of late platelet aggregation (Agglate) by 5 & 20 μM ADP induced LTA

Time: 30 days

Measure: Absolute reduction of P2Y12 reaction unit (PRU)

Time: 30 days

Measure: The rate of high post-treatment platelet reactivity

Time: 30 days

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 rs4244285

2. Two CYP2C19 polymorphisms, CYP2C19*2 (rs4244285, c. 681G>A, p.P227P), and CYP2C19*3 (rs4986893, c. 636G>A, p. W212X), are investigated using the ABI SNaPshot reaction and the ABI 3100 automated genetic analyzer (Applied Biosystems, Foster City, CA, USA).


2 rs4986893

2. Two CYP2C19 polymorphisms, CYP2C19*2 (rs4244285, c. 681G>A, p.P227P), and CYP2C19*3 (rs4986893, c. 636G>A, p. W212X), are investigated using the ABI SNaPshot reaction and the ABI 3100 automated genetic analyzer (Applied Biosystems, Foster City, CA, USA).



HPO Nodes


HPO:
Myocardial infarction
Genes 79
IL12B TLR4 LDLRAP1 LDLR GTF2I GLA APOB STAT4 CCR1 BAZ1B IKZF1 TP53 SH2B3 CLIP2 ABCG8 CYP27A1 MYH9 CTNNB1 HLA-B AGPAT2 ELN FOS RFC2 ENPP1 CAVIN1 ERAP1 MEF2A MYH9 BCHE CAV1 MEFV LRP6 LMNA HLA-B LPL THOC2 CYP27A1 KLRC4 TET2 IL10 SCNN1B UBAC2 CEP19 HLA-B PIGA TBL2 CFTR RAF1 MPL BRAF C4A GTF2IRD1 IL12A-AS1 CALR IL12A IL23R JAK2 SCNN1A ABCA1 WRN JAK2 SCNN1G HGD PTPN11 MEFV BSCL2 CBS LIMK1 ABCA1 DYRK1B BRAF SLC2A10 SH2B3 PPARG PCSK9 FAS ABCG5 MLX ABCC6