Clopidogrel Dose Adjustment After Outpatient Screening for CYP2C19 Variant Alleles: A Pilot Study

Abstract

This pilot study examined the feasibility of outpatient screening and clopidogrel dose adjustment for patients with previous percutaneous coronary intervention and at least one CYP2C19 loss-of-function allele. After screening a total of 211 outpatients, 50 patients were enrolled in a crossover study comparing 30 days of standard dose (75 mg) to 30 days of high-dose clopidogrel (150 mg). Platelet function was assessed with the VerifyNow P2Y12 assay. In patients with CYP2C19*2, 150 mg daily of clopidogrel was associated with improved ADP-specific platelet inhibition (217 vs 258 P2Y12 reaction units, p = 0.01). Outpatient screening for CYP2C19 loss-of-function polymorphisms is feasible, and a strategy of clopidogrel dose escalation may improve platelet inhibition in appropriately selected patients.

Keywords::

• clopidogrel
• genetic testing
• platelet function
• polymorphism

Financial & competing interests disclosure

Funding was provided by a clinical trial agreement between Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership and the University of North Carolina (NC, USA). The investigators received no consulting fees or other research support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

Funding was provided by a clinical trial agreement between Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership and the University of North Carolina (NC, USA). The investigators received no consulting fees or other research support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.