Genotype-Guided P2Y12 Inhibitor Selection Reduces Risk for All Age Groups

Both younger and older patients benefit from CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI), according to study results presented at the American College of Cardiology Annual Meeting, held online from May 15 to May 17, 2021.

In patients taking clopidogrel following PCI, CYP2C19 loss-of-function (LOF) alleles are associated with increased risk for major adverse cardiovascular or cerebrovascular events (MACCE). Investigators of this single-center, retrospective study sought to evaluate if CYP2C19 genotype-guided selection of P2Y12 inhibitor therapy after PCI improved clinical outcomes in older patient populations.

The study cohort included 1469 patients who underwent CYP2C19 genotyping from 2012 to 2016 following PCI. Patients with CYP2C19 LOF alleles were recommended treatment with alternative P2Y12 inhibitors (prasugrel or ticagrelor); the remaining cohort was treated with the CYP2C19-activated antiplatelet drug clopidogrel. Study outcomes were MACCE (stent thrombosis, ischemic stroke, transient ischemic attack, nonfatal acute coronary syndrome, or cardiovascular death) and compared during a 12-month period by age group, intervention, and LOF allele carrier status.

The cohort was divided into a younger group of patients less than 70 years of age (n=1066) and a group 70 years of age or older (n=403). Among participants without LOF alleles, younger patients used alternative P2Y12 inhibitors more often than older patients (35% vs 10%; P <.001); younger patients with a LOF allele were also more likely to use alternative inhibitors (67% vs 55%; P =.02).

In younger patients treated with clopidogrel, risk for MACCE was significantly higher among LOF allele carriers vs patients without LOF alleles (17.4% vs 10.4%; adjusted HR 2.01; 95% CI, 1.17-3.46; P =.012). Similarly, older patients treated with clopidogrel were more likely to experience MACCE with a LOF allele vs without LOF alleles (19.2% vs 12.7%; HR 2.32; 95% CI, 1.07-5.05; P =.034).

In younger LOF allele carriers, risk for MACCE was significantly higher when treated with clopidogrel vs alternative P2Y12 inhibitors (17.1% vs 8.1%; HR 2.25; 95% CI, 1.26-4.04; P =.006), but not in the older group of LOF allele carriers (19.2% vs 9.8%; HR 2.30; 95% CI, 0.86-6.14; P =.098). In patients without LOF alleles, risk for MACCE was similar for clopidogrel compared with alternate therapies in both younger (10.4% vs 8.1%; HR 1.12; 95% CI, 0.72-1.74; P =.614) and older cohorts (12.7% vs 9.8%; HR 0.99; 95% CI, 0.44-2.21; P =.98).

Clopidogrel was associated with an increased risk for MACCE outcomes in LOF allele carriers of any age. Study researchers concluded that CYP2C19 genotype-guided antiplatelet therapy after PCI improved risk for MACCE in both older and younger patient populations. Researchers suggested that future studies should validate these findings in a larger, multicenter study.

Reference

Wood B, Mulrenin IR, Gower MN, et al. Examining the effects of aging on clinical outcomes in patients receiving genotype-guided P2Y12 inhibitor selection after percutaneous coronary intervention. Presented at: ACC 2021; May 15-17, 2021. Abstract 2221.