These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Background CYP2C19 loss-of-function (LOF) alleles impair clopidogrel effectiveness after percutaneous coronary intervention (PCI). The feasibility, sustainability and clinical impact of using CYP2C19 genotype-guided dual antiplatelet therapy (DAPT) selection in practice remains unclear. Methods and Results A single-center observational study was conducted in 1193 patients who underwent PCI and received DAPT following implementation of an algorithm that recommends CYP2C19 testing in high-risk patients and alternative DAPT (prasugrel or ticagrelor) in LOF allele carriers. The frequency of genotype testing and alternative DAPT selection were the primary implementation endpoints. Risk of major adverse cardiovascular or cerebrovascular (MACCE) and clinically significant bleeding events over 12 months were compared across genotype and DAPT groups by proportional hazards regression. CYP2C19 genotype was obtained in 868 (72.8%) patients. Alternative DAPT was prescribed in 186 (70.7%) LOF allele carriers. CYP2C19 testing (P<0.001) and alternative DAPT use in LOF allele carriers (P=0.001) varied over time. Risk for MACCE was significantly higher in LOF carriers prescribed clopidogrel versus alternative DAPT (adjusted hazard ratio [HR] 4.65, 95% confidence interval [CI] 2.22–10.0, P<0.001), whereas no significant difference was observed in those without a LOF allele (adjusted HR 1.37, 95% CI 0.72–2.85, P=0.347). Bleeding event rates were similar across groups (log-rank P=0.816). Conclusions Implementing CYP2C19 genotype-guided DAPT is feasible and sustainable in a real-world setting, but challenging to maintain at a consistently high level of fidelity. The higher risk of MACCE associated with clopidogrel use in CYP2C19 LOF allele carriers suggests that use of genotype-guided DAPT in practice may improve clinical outcomes.

Purpose-To evaluate the frequency and clinical impact of switches in antiplatelet therapy following implementation of CYP2C19 genotyping after percutaneous coronary intervention (PCI). Methods-The frequency of escalation (clopidogrel switched to prasugrel/ticagrelor) and deescalation (prasugrel/ticagrelor switched to clopidogrel) was evaluated in 1063 PCI patients who underwent CYP2C19 genotyping. Risk of major adverse cardiovascular or cerebrovascular (MACCE) and bleeding events over one-year was evaluated. Results-Antiplatelet therapy switches were common (19%), with escalation (101/115: 88%) and de-escalation (77/84: 92%) occurring predominantly in patients with and without a CYP2C19 nonfunctional allele, respectively. Nonfunctional allele carriers initiated and continued on clopidogrel had a significantly higher risk of experiencing either a MACCE or bleeding event Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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