Tailored Adjunctive Cilostazol Therapy Based on CYP2C19 Genotyping in Patients With Acute Myocardial Infarction　― The CALDERA-GENE Study ―

Abstract

adverse cardiovascular events after PCI. 7-10 In this regard, patients with acute coronary syndrome undergoing PCI confirmed to be carriers of at least 1 reduced-function cytochrome P450 2C19 (CYP2C19) allele and treated with the DAPT of aspirin and clopidogrel have diminished platelet inhibition and a high rate of major adverse cardiovascular events. 11 CYP2C19 is one of the principal enzymes involved in the hepatic bioactivation of clopidogrel. Based on the clinical D ual antiplatelet therapy (DAPT) of aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) is essential for the regulation of activated platelets in disrupted coronary plaques in patients with acute myocardial infarction (AMI) and for reducing possible atherothrombotic complications in patients undergoing percutaneous coronary intervention (PCI).

Total Thrombus-Formation Analysis System (T-TAS): Clinical Application of Quantitative Analysis of Thrombus Formation in Cardiovascular Disease

“…VerifyNow can be used to assess efficacy and safety of different antiplatelet drugs by using different cartridges specific for P2Y 12 , aspirin, or glycoprotein IIb/IIIa inhibitor. Using this system, the platelet response to aspirin and P2Y 12 receptor inhibitors is expressed as aspirin reaction units (ARUs) and P2Y 12 reaction units (PRUs), respectively, with the PRU level being influenced by CYP2C19 genotype [50][51][52][53] and correlated with cardiovascular events. 54 There have been several reports in the analyses of antiplatelet therapies comparing the PL chip and agonist-dependent platelet function tests.…”

Differential Impact of Clinical and Genetic Factors on High Platelet Reactivity in Patients with Coronary Artery Disease Treated with Clopidogrel and Prasugrel

“…instance, patients with stage 3 CKD and non-insulindependent diabetes were at risk for HPR with prasugrel in only 17% (7 out of 41) in this study, whereas HPR with prasugrel accounted for 67% (8 of 12) of patients with hemodialysis and insulindependent diabetes. Given that the usefulness of genotype-guided antiplatelet strategies has been proposed in recent studies 35,36) , genetic factors may also play important roles in guiding antiplatelet therapy in clinical practice. Future studies investigating a risk scoring system with prasugrel and ticagrelor, including clinical and genetic factors, with significant subcategories are warranted.…”

Update on Cilostazol: A Critical Review of Its Antithrombotic and Cardiovascular Actions and Its Clinical Applications

“…In this context, in 128 patients with MI screened for CYP2C19 genotype immediately after PCI, adjunctive cilostazol therapy adjusted to CYP2C19 genotype appeared useful. 162 DAPT plus cilostazol reduced platelet reactivity unit levels in carriers of the CYP2C19 reduced-function allele (n = 46) to those encountered in the noncarrier/DAPT group (n = 40), and much lower levels than those found in the carrier/DAPT group (n = 42) at 2 weeks following PCI.…”

“…Thus, the better response to triple therapy may be explained by the weaker link between the antiplatelet action of triple therapy and the CYP2C19 loss‐of‐function allele carriage, which mainly affects clopidogrel and not cilostazol. In this context, in 128 patients with MI screened for CYP2C19 genotype immediately after PCI, adjunctive cilostazol therapy adjusted to CYP2C19 genotype appeared useful 162 . DAPT plus cilostazol reduced platelet reactivity unit levels in carriers of the CYP2C19 reduced‐function allele (n = 46) to those encountered in the noncarrier/DAPT group (n = 40), and much lower levels than those found in the carrier/DAPT group (n = 42) at 2 weeks following PCI.…”