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Introduction In patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI), ticagrelor and prasugrel are established potent P2Y12 inhibitors. Selection between these agents represents a recurrent clinical decision and, despite similar positioning in guidance, real-world use varies across centres and pathways. Although registry evidence demonstrates evolving potent P2Y12 inhibitor use and centre-level variation after PCI for ACS, the national direction and magnitude of substitution between ticagrelor and prasugrel have not been quantified. Characterising pathway-specific substitution patterns is essential to contextualise contemporary practice and inform evaluation of clinical and system-level implications. We examined temporal trends, directional substitution, and heterogeneity of ticagrelor and prasugrel use across PCI-treated ACS pathways over seven years.Methods National Audit of Percutaneous Coronary Interventions (NAPCI) data from National Institute for Cardiovascular Outcomes Research (NICOR) was analysed from 2018/19 to 2024/20. Three cohorts were examined: all ACS undergoing PCI, NSTEMI undergoing PCI, and STEMI treated with primary PCI (PPCI). Annual utilisation proportions were calculated for ticagrelor, prasugrel, and either potent P2Y12 inhibitor. Directional substitution was quantified using a substitution index (prasugrel minus ticagrelor proportion, percentage points) and prescribing heterogeneity using entropy measures. Linear regression estimated absolute percentage-point change per year (pp/yr).Results Directional substitution from ticagrelor toward prasugrel was observed across all cohorts, with largest magnitude in PPCI-treated STEMI. In STEMI, prasugrel use increased 3.64 pp/yr (p<0.001) while ticagrelor declined 2.04 pp/yr (p=0.001); overall potent agent use increased 1.71 pp/yr (p=0.020). The substitution index moved from −36.0 in 2018/19 to −4.0 in 2024/20 ( figure 1), with entropy increasing from 0.377 to 0.696. In NSTEMI, prasugrel increased 0.39 pp/yr (p<0.001) with concomitant ticagrelor decline (−0.60 pp/yr, p=0.010), while overall potent agent use remained stable (p=0.20). In all ACS, prasugrel increased 1.20 pp/yr (p<0.001) and ticagrelor declined 0.74 pp/yr (p=0.023), without significant change in overall potent agent use (p=0.11). Annual changes in agent use are summarised in figure 2. Prescribing entropy increased, indicating greater heterogeneity of agent selection.Conclusions National PCI data demonstrate a consistent, pathway-dependent directional shift from ticagrelor toward prasugrel across PCI-treated ACS over seven years, most pronounced in PPCI-treated STEMI, alongside increasing heterogeneity. This evolution occurred despite unchanged guideline recommendations since NICE NG185, potentially reflecting evolving practice preferences or local pathway factors. Findings suggest national reassessment of P2Y12 inhibitor selection in STEMI may be warranted; linkage to outcome data is required to evaluate clinical implications of this prescribing shift.Abstract 491 Figure 1Directional substitution between P2Y12 inhibitors over time. Temporal trends in the substitution index (prasugrel proportion minus ticagrelor proportion, percentage points) across three PCI-treated ACS cohorts from 2018/19 to 2024/20. Positive values indicate net shift toward prasugrel; negative values indicate net shift toward ticagrelor. Progressive convergence toward parity is observed in STEMI treated with primary PCI (PPCI), with the substitution index moving from -36.0 to -4.0 percentage points. More modest but consistent directional shifts are observed in NSTEMI undergoing PCI and all ACS cohorts. Data source: National Audit of Percutaneous Coronary Interventions (NAPCI)Abstract 491 Figure 2Annual change in P2Y12 inhibitor use by cohort and agent. Heatmap displaying linear regression slopes (percentage points per year, pp/yr) for use of either potent P2Y12 inhibitor, ticagrelor, and prasugrel across three PCI-treated ACS cohorts. Color intensity represents magnitude and direction of change. STEMI treated with PPCI demonstrates the largest increase in prasugrel uptake (+3.64 pp/yr, p<0.001) alongside concurrent ticagrelor decline (-2.04 pp/yr, p=0.001). NSTEMI and all ACS cohorts show smaller directional shifts in agent selection. Data from financial years 2018/19 to 2024/20. Data source: National Audit of Percutaneous Coronary Interventions (NAPCI)