Evaluation of <i>CYP2C19</i> Clinical Decision Support Alerts to Guide P2Y₁₂ Inhibitor Prescribing

P2Y₁₂ inhibitor selection involves numerous factors, including CYP2C19 genetics, since evidence demonstrates reduced clopidogrel efficacy in patients with decreased or no function CYP2C19 variants. In 2020, Indiana University health embedded interruptive clinical decision support (CDS) alerts in the electronic health record (EHR) to recommend alternative P2Y₁₂ inhibitors for patients with decreased CYP2C19 function who had undergone percutaneous coronary intervention (PCI). The objective of this study was to evaluate prescriber response to these CDS alerts. Utilizing alert response data and P2Y₁₂ inhibitor prescriptions from October 2020 to December 2023, we evaluated prescriber response for 362 patients who had a mean of 2.2 (SD: 1.7) CYP2C19-clopidogrel alerts fire post-PCI. Alert recommendations were accepted 24.5% ± 36.8% (mean ± SD) of the time. Alternative (i.e., non-clopidogrel) P2Y₁₂ inhibitors were prescribed for 22.4% ± 36.8% of days during the year following PCI. Alerts were accepted more for CYP2C19 poor metabolizers than for intermediate metabolizers (P = 0.03). Each year after 2020 was associated with a 4.6% increase in the days prescribed alternative P2Y₁₂ inhibitors. In contrast, increasing age was associated with decreased alert acceptance and decreased percentage of days prescribed alternatives, and concomitant oral anticoagulant use was associated with decreased percentage of days prescribed alternatives. Provider clinical judgment was the most common alert override reason, accounting for 68% of clinician responses. Our findings demonstrate that CYP2C19-clopidogrel CDS alerts promoted genotype-guided P2Y₁₂ inhibitor prescribing in some cases (~22% of study days). Future research should better determine prescriber reasons for rejecting alert recommendations and establish best implementation practices to complement CDS alerts.