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.

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