Influence of CYP2C19 Phenotype on the Effect of Clopidogrel in Patients Undergoing a Percutaneous Neurointervention Procedure

Abstract

This observational retrospective study assessed the antiplatelet response and clinical events after clopidogrel treatment in patients who underwent percutaneous neurointervention, related to CYP2C19 metabolizer status (normal (NM), intermediate/poor (IM-PM), and ultrarapid (UM); inferred from *2, *3, and *17 allele determination). From 123 patients, IM-PM had a higher aggregation value (201.1 vs. 137.6 NM, 149.4 UM, P < 0.05) and lower response rate (37.5% vs. 69.8% NM, 61.1% UM), along with higher treatment change rate (25% vs. 5.7% NM, 10.5% UM). The highest ischemic events incidence occurred in NM (11.3% vs. 6.3% IM, 10.5% UM) and hemorrhagic events in UM (13.2% vs. 0% IM and 3.8% NM). No differences were found regarding ischemic event onset time, while hemorrhagic event frequency in UM was higher with shorter onset time (P = 0.047). CYP2C19 no-function and increased function alleles defined the clopidogrel response. UM patients had increased bleeding risk. Therapeutic recommendations should include dose reduction or treatment change in UM.

<p>Clinical Utility of CYP2C19 Genotype-Guided Antiplatelet Therapy in Patients at Risk of Adverse Cardiovascular and Cerebrovascular Events: A Review of Emerging Evidence</p>

“…CYP2C19 metabolizer status was associated with clopidogrel’s antiplatelet effects in 123 patients undergoing a percutaneous neurointervention procedure. 67 Although no association between IM/PMs and ischemic outcomes was observed, UMs exhibited a higher risk of bleeding. A meta-analysis of 7 studies (n=442) found that CYP2C19 IM/PMs treated with clopidogrel had higher risk of thromboembolic complications post-neurointervention.…”

Impact of the CYP2C19*17 Allele on Outcomes in Patients Receiving Genotype‐Guided Antiplatelet Therapy After Percutaneous Coronary Intervention

“…During a median follow-up of 6.3 (1.0-11.0) months after PCI, 353 patients (10.6%) experienced a major atherothrombotic event. The risk of the primary outcome by CYP2C19 metabolizer status (29) 176 (19) 252 (31) 378 (34) 151 (32) < 0.001 0.466 Female 1,075 (32) 250 (27) 289 (36) 368 (33) 168 (35 (19) 247 (26) 129 (16) 192 1760 13Non-STEMI 939 (28) 275 (29) 230 (28) 297 (26) 137 29Unstable angina 723 (22) 167 (18) 182 (23) 253 23121 26Non-ACS 1,052 (31) 244 (26) 269 (33) 381 (34) 158 ( 83 (10) 118 (11) 67 (14) < 0.001…”

“…5,14 The CYP2C19*17 allele has been associated with increased active metabolite formation, enhanced inhibition of platelet aggregation, higher bleeding risk, and lower risk for ischemic events with clopidogrel. [15][16][17][18][19] However, other studies have reported no significant association between the *17 allele and clopidogrel pharmacokinetics, pharmacodynamics, and ischemic and bleeding outcomes after accounting for the *2 allele. 7,[20][21][22] It has been postulated that the observed relationship between the *17 allele and clopidogrel's antiplatelet effects may be due to absence of the no function *2 allele rather than presence of the increased function *17 allele.…”

“…The increased function CYP2C19*17 allele (rs12248560) is carried by approximately 30% of the US population, with individuals carrying one *17 allele and one normal function allele ( *1/*17 : rapid metabolizers, RM) or two *17 allele copies ( *17/*17 : ultrarapid metabolizers, UM) exhibiting increased CYP2C19 expression and metabolic function compared with normal metabolizers (NM) 5,14 . The CYP2C19*17 allele has been associated with increased active metabolite formation, enhanced inhibition of platelet aggregation, higher bleeding risk, and lower risk for ischemic events with clopidogrel 15–19 . However, other studies have reported no significant association between the *17 allele and clopidogrel pharmacokinetics, pharmacodynamics, and ischemic and bleeding outcomes after accounting for the *2 allele 7,20–22 .…”

Pharmacogenetics of Clopidogrel Therapy and Neurointerventional Procedures: We Need Precision Data for Precision Medicine

“…6 Similarly, Saiz-Rodr ıguez et al demonstrated that patients with the UM phenotype are at increased risk of bleeding after percutaneous neurointervention. 7 Lin et al provided a specific conclusion. They analyzed 108 patients undergoing neurointervention for intracranial aneurysms or stenosis and determined that the CY2C19*17 variant is related to the occurrence of ischemic events independently from the effect of clopidogrel.…”