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Genotype-guided antiplatelet decisions after PCI may improve outcomes
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In patients prescribed antiplatelet therapy after PCI, clopidogrel was less effective in those who had a CYP2C19 loss-of-function allele, according to the results of a single-center observational study.
While it is known that CYP2C19 loss-of-function alleles can impair the effectiveness of clopidogrel as part of a dual antiplatelet therapy strategy after PCI, the clinical impact, feasibility and sustainability of a genotype-guided DAPT selection process was not known, the researchers wrote in the study background.
Craig R. Lee, PharmD, PhD, from the division of pharmacology and experimental therapeutics, UNC Eshelman School of Pharmacy, and colleagues analyzed 1,193 patients who underwent PCI and received DAPT according to an algorithm recommending prasugrel (Effient, Daiichi Sankyo/Eli Lilly) or ticagrelor (Brilinta, AstraZeneca) instead of clopidogrel in patients who had a CYP2C19 loss-of-function allele.
The primary endpoints were frequency of genotype testing and alternative DAPT selection. The researchers also compared risk for MACCE and clinically significant bleeding events at 12 months among patients stratified by genotype and by DAPT selection.
Genotyping and prescriptions
Lee and colleagues identified genotype for CYP2C19 in 72.8% of patients, they wrote. Of those genotyped, 30.4% had one or two CYP2C19 loss-of-function alleles.
In patients with one or two CYP2C19 loss-of-function alleles, 70.7% received a prescription for prasugrel or ticagrelor instead of clopidogrel, while those genotyped and found not to have a loss-of-function allele received a prescription for prasugrel or ticagrelor 23.6% of the time., Further, those not genotyped received a prescription for prasugrel or ticagrelor 11.1% of the time, according to the researchers.
Loss-of-function allele was a significant predictor of prasugrel or ticagrelor selection (OR = 13.1; 95% CI, 8.84-19.7).
Genotyping was more likely to occur in patients with ACS (OR = 2.56; 95% CI, 1.94-3.38), a stent in the left anterior descending artery (OR = 1.6; 95% CI, 1.21-2.13) and a stent in the left main artery (OR = 4.72; 95% CI, 1.57-20.5), and was less likely to occur in patients taking a P2Y12 inhibitor before PCI, the investigators wrote.
Feasible implementation
“The feasible implementation and sustainable use of a genotype-guided algorithm at our institution was possible because of several key factors that alleviated logistical barriers,” the researchers wrote. “Notably, in-house genotype testing with prompt turnaround of results in the [electronic health record], and interdisciplinary collaboration among physicians, clinical pharmacists and nurses have proven critical.”
Risk for MACCE was higher in patients with at least one loss-of-function allele who received clopidogrel instead of prasugrel or ticagrelor (adjusted HR = 4.65; 95% CI, 2.22-10), but this was not the case in patients with no loss-of-function alleles (adjusted HR = 1.37; 95% CI, 0.72-2.85), according to the researchers.
Risk for clinically significant bleeding did not vary by genotype or DAPT selection (log-rank P = .816), they wrote.
“The adverse cardiovascular outcomes associated with clopidogrel use in patients with a CYP2C19 [loss-of-function] allele suggest that the use of genotype-guided antiplatelet therapy in practice may significantly improve clinical outcomes,” Lee and colleagues wrote. “Given the increasing number of institutions that seek to clinically implement genotype-guided antiplatelet therapy, our results offer insight into the feasibility, sustainability and clinical impact of using a CYP2C19 genotyping strategy to optimize P2Y12 inhibitor selection in PCI patients.” – by Erik Swain
Disclosure: The authors report no relevant financial disclosures.
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