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May 28, 2015Journal of the American Heart AssociationOpen Access

CYP2C19 Metabolizer Status and Clopidogrel Efficacy in the Secondary Prevention of Small Subcortical Strokes (SPS3) Study

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Key result

CYP2C19 metabolizer status was not significantly associated with recurrent stroke in the overall cohort of subcortical stroke patients on dual antiplatelet therapy (OR 1.81; 95% CI 0.76-4.30).

Why the study?

Does CYP2C19 intermediate or poor metabolizer status increase the risk of recurrent stroke or major bleeding in subcortical stroke patients taking dual antiplatelet therapy compared to extensive or ultrarapid metabolizers?

Population

522 patients with subcortical stroke treated with dual antiplatelet therapy from the Secondary Prevention of…

Comparison

CYP2C19 intermediate or poor metabolizer status vs CYP2C19 extensive or ultrarapid metabolizer status

Design

Cohort

Authors

CMCaitrin W. McDonoughLMLeslie A. McClureBMBraxton D. Mitchell

Discussion

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Overview

No overall association observed; hypothesis-generating for white patients and should not yet change practice.

Study Design

Type

Cohort (n=522)

Structured PICO

Does CYP2C19 intermediate or poor metabolizer status increase the risk of recurrent stroke or major bleeding in subcortical stroke patients taking dual antiplatelet therapy compared to extensive or ultrarapid metabolizers?

P
Population
522 subcortical stroke patients treated with dual antiplatelet therapy with aspirin and clopidogrel from the SPS3 study.
E
Exposure
CYP2C19 intermediate or poor metabolizer status (inferred from CYP2C19*2 and CYP2C19*17 genotypes)
C
Comparator
CYP2C19 extensive or ultrarapid metabolizer status
O
Outcome
Recurrent strokehard clinical

Main Result

Odds Ratio: 1.81 (95% CI 0.76–4.3)

CYP2C19 loss-of-function variants may increase the risk of recurrent stroke in white patients with subcortical stroke receiving dual antiplatelet therapy, extending pharmacogenetic findings from coronary disease to stroke.

Limitations

  • This study was relatively underpowered
  • relatively underpowered

Cite This Study

McDonough et al. (2015) conducted a cohort in Subcortical stroke (n=522). CYP2C19 intermediate or poor metabolizer status vs. Extensive or ultrarapid metabolizer status was evaluated on Recurrent stroke (OR 1.81, 95% CI 0.76 to 4.30). CYP2C19 metabolizer status was not significantly associated with recurrent stroke in the overall cohort of subcortical stroke patients on dual antiplatelet therapy (OR 1.81; 95% CI 0.76-4.30).

synapsesocial.com/papers/6a7c430fd249c0c91c3be1dbhttps://doi.org/10.1161/jaha.114.001652
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Also Consider

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

  1. 1Variant recurrent risk among stroke patients with different<i>CYP2C19</i>phenotypes and treated with clopidogrel2014 · 49 citations
  2. 2Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI2010 · 1,140 citations
  3. 3Cytochrome P-450 Polymorphisms and Response to Clopidogrel2008 · 2,502 citations
  4. 4Operational Implementation of Prospective Genotyping for Personalized Medicine: The Design of the Vanderbilt PREDICT Project2012 · 417 citations
  5. 5The natural history of lacunar infarction: the Oxfordshire Community Stroke Project.1987 · 430 citations