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December 15, 2009Pharmacogenetics and Genomics

Besides CYP2C19*2, the variant allele CYP2C9*3 is associated with higher on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective coronary stent implantation

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Key result

Besides CYP2C19*2, carriage of the CYP2C9*3 variant allele was associated with poor clopidogrel response in patients receiving a 300 mg loading dose (OR 11.1; 95% CI 1.6-78.8; P=0.016).

Why the study?

Do genetic variants CYP2C19*2 and CYP2C9*3 increase on-clopidogrel platelet reactivity in patients undergoing elective coronary stenting?

Population

428 consecutive patients undergoing elective coronary stenting on dual antiplatelet therapy.

Comparison

Carriage of genetic variants affecting… vs Non-carriers of the respective genetic variants.

Design

Cohort

Authors

AHAnkie M. HarmszeJWJochem W. van WerkumHBHeleen Bouman

Discussion

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Overview

CYP2C9*3 carriage may identify additional clopidogrel poor responders; extends pharmacogenetic data but remains hypothesis-generating.

Study Design

Type

Observational (n=428)

Structured PICO

Do genetic variants CYP2C19*2 and CYP2C9*3 increase on-clopidogrel platelet reactivity in patients undergoing elective coronary stenting?

P
Population
428 consecutive patients on dual antiplatelet therapy undergoing elective coronary stenting.
E
Exposure
Carriage of genetic variants affecting clopidogrel absorption, metabolism, and pharmacodynamics (specifically CYP2C19*2 and CYP2C9*3).
C
Comparator
Non-carriers of the respective genetic variants.
O
Outcome
Platelet reactivity assessed by light transmittance aggregometry and VerifyNow P2Y12 assay, and poor responder status.surrogate

Main Result

Odds Ratio: 11.1 (95% CI 1.6–78.8)

p-value: p=0.016

The CYP2C9*3 variant allele, alongside CYP2C19*2, is associated with higher on-clopidogrel platelet reactivity and poor responder status in patients undergoing elective coronary stenting.

Cite This Study

Harmsze et al. (2009) conducted an observational in Elective coronary stenting on dual antiplatelet therapy (n=428). CYP2C9*3 and CYP2C19*2 variant alleles vs. Non-carriers was evaluated on Poor responder status (high platelet reactivity) in the 300 mg clopidogrel loading dose group (OR 11.1, 95% CI 1.6-78.8, p=0.016). Besides CYP2C19*2, carriage of the CYP2C9*3 variant allele was associated with poor clopidogrel response in patients receiving a 300 mg loading dose (OR 11.1; 95% CI 1.6-78.8; P=0.016).

synapsesocial.com/papers/6a33035558530ca2eee1224dhttps://doi.org/10.1097/fpc.0b013e328333dafe
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Variability in on-treatment platelet reactivity explained by CYP2C19*2 genotype is modest in clopidogrel pretreated patients undergoing coronary stenting2011 · 95 citations
  2. 2Genetic variability in response to clopidogrel therapy: clinical implications2010 · 28 citations
  3. 3CYP2C19*2 and CYP2C9*3 alleles are associated with stent thrombosis: a case-control study2010 · 161 citations
  4. 4Cytochrome P450 2C19 681G>A Polymorphism and High On-Clopidogrel Platelet Reactivity Associated With Adverse 1-Year Clinical Outcome of Elective Percutaneous Coronary Intervention With Drug-Eluting or Bare-Metal Stents2008 · 543 citations
  5. 5The <i>CYP2C19*2</i> and <i>CYP2C19*17</i> Polymorphisms play a Vital Role in Clopidogrel Responsiveness after Percutaneous Coronary Intervention: A Pharmacogenomics Study2017 · 19 citations