Genotype‐guided dual antiplatelet therapy in minor stroke or transient ischemic attack with metabolic syndrome: A post hoc analysis of CHANCE ‐2

AIMS: To evaluate the relationship between metabolic syndrome and the efficacy and safety of genotype-guided dual antiplatelet therapy (DAPT) in the CHANCE-2 trial. MATERIALS AND METHODS: This post hoc study used data from the CHANCE-2 trial. Patients with minor stroke or TIA who carried the CYP2C19 loss-of-function (LOF) allele were randomized to receive ticagrelor-aspirin (TIC-ASA) or clopidogrel-aspirin (CLO-ASA). The primary efficacy outcome was stroke recurrence within 90 days. The primary safety outcome was severe or moderate bleeding within 90 days. We classified patients into metabolic syndrome (MetS) and non-metabolic syndrome (non-MetS) groups. Differences in the outcome during 90-days follow-up period were assessed using the Cox proportional hazards model. RESULTS: Among 5652 patients, 3305 were non-MetS and 2347 were MetS. Compared with CLO-ASA, TIC-ASA significantly reduced the risk of stroke recurrence within 90 days among patients with MetS (6.44% vs. 9.90%; HR 0.64, 95% CI 0.48-0.85; p < 0.01); this benefit was not seen in non-MetS (6.03% vs. 5.96%; HR 1.01, 95% CI 0.77-1.34; p = 0.93), with a significant interaction effect (p for interaction = 0.03). Moreover, a linear trend was observed (p for trend = 0.04), indicating metabolic health status may modify the efficacy of genotype-guided DAPT in a dose-dependent manner. No significant difference was observed in severe or moderate bleeding events by metabolic syndrome (MetS: 0.42% vs. 0.35%, non-MetS: 0.25% vs. 0.36%; p for interaction = 0.55). CONCLUSIONS: Among CYP2C19 LOF carriers with minor stroke or TIA, patients with MetS received more clinical benefit from TIC-ASA versus CLO-ASA compared to those with non-MetS. Registry: ClinicalTrials.gov, TRN: NCT04078737.