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Hyper-Response to Clopidogrel in Japanese Patients Undergoing Transcatheter Aortic Valve Implantation
Yusuke Watanabe1, Ken Kozuma, Shuichi Ishikawa
1Department of Medicine, Teikyo University School of Medicine.
Insights
Dual antiplatelet therapy after transcatheter aortic valve implantation (TAVI) showed a high rate of clopidogrel hyper-response, linked to increased bleeding events. Genetic factors, specifically CYP2C19 loss-of-function alleles, were common but did not fully explain this hyper-response.
Area of Science:
- Cardiology
- Pharmacogenomics
- Interventional Cardiology
Background:
- Dual antiplatelet therapy is standard post-transcatheter aortic valve implantation (TAVI).
- Clopidogrel response varies, influenced by genetic factors like CYP2C19 loss-of-function alleles.
- Understanding clopidogrel's impact on platelet function and bleeding risk after TAVI is crucial.
Purpose of the Study:
- To evaluate clopidogrel's effect on platelet function in patients undergoing TAVI.
- To determine the role of CYP2C19 loss-of-function genotypes in clopidogrel response.
- To correlate platelet reactivity with clinical outcomes, including bleeding events.
Main Methods:
- Thirty-two patients receiving clopidogrel post-TAVI were studied.
- Platelet reactivity was assessed using the VerifyNow P2Y12 assay (cutoff 95 PRU).
- CYP2C19 genotypes were identified using the Spartan RX system.
Main Results:
- A hyper-response to clopidogrel (≥95 PRU) was observed in 34.3% of patients.
- 80% of patients carried at least one CYP2C19 reduced-function allele.
- Hyper-response was significantly associated with increased rates of life-threatening bleeding, minor bleeding, and transfusion.
Conclusions:
- One-third of TAVI patients exhibit clopidogrel hyper-response, increasing bleeding risk.
- CYP2C19 genotype alone does not fully explain clopidogrel hyper-response in this cohort.
- Further investigation into managing antiplatelet therapy after TAVI is warranted.
Abstract:
Dual antiplatelet therapy is empirically recommended following transcatheter aortic valve implantation (TAVI). The aims of the present study were to analyze the effect of clopidogrel on platelet function and to determine the relative contribution of each CYP2C19 loss-of-function genotype undergoing TAVI.Thirty-two patients undergoing TAVI and with clopidogrel treatment were studied. All patients were treated with an Edwards SapienXT valve. Platelet reactivity was measured by the VerifyNow P2Y12 point-of-care assay at 7 days and 30 days after the procedure and a cutoff value of 95 PRU was used to identify a hyper-response of platelet reactivity. The Spartan RX(TM) sample-to-result point-of-care DNA testing system was used to identify CYP2C19 loss-of-function genotypes. Hyper-response of platelet reactivity was identified in 11 (34.3%) patients, although 24 (80%) were carriers of at least one CYP2C19 reduced-function allele. The PRU values did not change significantly from 7 days to 30 days after TAVI (136.7 ± 73.4 versus 150.4 ± 83.2, P = 0.13). The incidences of life-threatening bleeding, minor bleeding, and transfusion were significantly higher among the hyper-response of platelet reactivity group (27.3% versus 0%, P = 0.03, 36.4% versus 4.8%, P = 0.04, 81.8% versus 42.9%, P = 0.04, respectively).A hyper-response to clopidogrel was observed in one-third of patients undergoing TAVI and was related to bleeding events, even though 80% of the patients were carriers of the CYP2C19 reduced-function allele.
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