Association of CYP2C19*17 Allele and Choice of P2Y12 Inhibitor on Cardiovascular Outcomes Following Percutaneous Coronary Intervention
Tuesday, May 21, 2019
Belmont Ballroom 2-3 (The Cosmopolitan of Las Vegas)
Yash Varma
,
Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA
Craig R Lee, PhD, PharmD
,
University of North Carolina at Chapel Hill, Chapel Hill, NC
Joseph Rossi, M.D., FSCAI
,
University of North Carolina Hospitals, Chapel Hill, NC
Rick Stouffer, M.D.
,
UNC McAllister Heart Institute , Chapel Hill, NC
Background:
The CYP2C19*17 allele variant is a gain-of-function polymorphism leading to increased levels of the active metabolite of clopidogrel. The *17 allele is associated with an increased risk of bleeding during clopidogrel therapy but it is unclear whether the use of alternative P2Y12 inhibitors such as prasugrel or ticagrelor would lead to better clinical outcomes in patients undergoing percutaneous coronary intervention (PCI).
Methods
:
A single-center observational study was conducted in 928 patients who underwent PCI, had
CYP2C19 testing and received dual anti-platelet therapy (DAPT). Choice of DAPT was at the discretion of the treating physician. Risk of major adverse cardiovascular or cerebrovascular events (MACCE) and clinically significant bleeding over 12 months were compared across genotype and DAPT groups by proportional hazards regression.
Results:
584 patients were treated with clopidogrel and 344 patients were treated with alternative therapy. In the group treated with clopidogrel, 173 patients were hetero- or homo-zygote for the *17 allele and 91 patients were hetero- or homo-zygote for a loss of function allele (LOF; *2 or *3). Patients treated with clopidogrel were older, more likely to be female, and more likely to have hypertension, diabetes and an acute coronary syndrome (ACS) than patients treated with alternative therapy. There was no difference in MACCE or clinically significant bleeding event in patients with a *17 allele treated with clopidogrel compared to patients treated with alternative therapy in either the total population (p=0.54) or in patients with ACS (p=0.98). In contrast, patients with one or more LOF alleles were 3.4 times more likely in the total population (p <0.0001) and 6.7 times more likely in patients with ACS (p <0.0001) to have MACCE if prescribed clopidogrel compared with alternative therapy.
Conclusions:
Patients with *17 allele had equivalent clinical outcomes when treated with clopidogrel or alternative P2Y12 inhibitor therapy.
