Implementation of Rapid CYP2C19 Genotyping to Guide Antiplatelet Therapy for Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack

Clopidogrel is first‐line for secondary stroke prevention, but its effectiveness is affected by CYP2C19 genetic variation. An American Heart Association (AHA) scientific statement concluded that CYP2C19 ‐guided P2Y12 inhibitor (P2Y12i) therapy is evidence‐supported, though real‐world application depends on implementation factors (e.g., timely, understandable results). This prospective observational cohort quality improvement project used data from three comprehensive stroke centers within one health system, each offering rapid CYP2C19 testing. Eligible patients had CYP2C19 testing ordered, a P2Y12i prescribed (clopidogrel or ticagrelor), or a P2Y12i indication. Consensus recommendations were clopidogrel for CYP2C19 normal/rapid/ultrarapid metabolizers (NM/RM/UM) and ticagrelor for intermediate/poor metabolizers (IM/PM). The primary target population was patients with acute ischemic stroke or TIA (AIS/TIA) prescribed a P2Y12i. The primary outcome was the proportion of discharge ticagrelor prescriptions (among P2Y12i users) with AIS/TIA, compared between IM/PM and NM/RM/UM groups. Secondary endpoints included test turnaround time (TAT), result availability before discharge, and alignment of discharge P2Y12i with consensus recommendations (PGx‐aligned prescribing). The evaluation period was September 2024–August 2025. Results were available for 467 patients; 451 (97%) had results before discharge, with a median TAT of 5.2 hours (interquartile range 3.3–9.6). Of 337 patients prescribed a P2Y12i at discharge, 296 had AIS/TIA. Clinicians more often selected ticagrelor over clopidogrel for IM/PMs than NM/RM/UMs (89 of 102 [87%] vs. 11 of 194 [5.7%]; RR 15.4; 95% CI: 8.6–27.4; P < 0.0001). PGx‐aligned prescribing occurred in 272 (92%) of 296 patients. Rapid CYP2C19 testing efficiently translates into tailored P2Y12i prescribing in clinical practice.