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Objectives The aim of this observational study was to determine the benefits of the novel, orally delivered P2Y12‐inhibitors (Is) in terms of angiographic endpoints and in relation to the time of the loading dose (LD) administration. Background The goal of ST‐elevation myocardial infarction (STEMI) treatment is timely reperfusion. The P2Y12‐Is prasugrel and ticagrelor have improved the angiographic outcome of primary percutaneous coronary intervention (pPCI) and patients' prognosis. However, their onset of action is impaired in STEMI and delayed by their oral administration. Methods The 328 eligible patients with STEMI consecutively referred for pPCI were divided into three groups depending on the interval of “P2Y12‐I LD administration‐to‐balloon time”: Group 2 included patients that received P2Y12‐I LD at least 60 min prior to pPCI, Group 1 within 60 min prior to pPCI, and Group 0 at the moment of pPCI. Angiographic, clinical, and biochemical parameters were evaluated. Pre‐ and post‐pPCI TIMI flow grade (TFG) and ST resolution (STR) were used as outcome measures to determine efficacy and optimal timing of pretreatment. Results Pre‐pPCI TFG improved with increasing P2Y12‐I LD administration‐to‐balloon time; pre‐PCI TFG 0/1 was 74.5% in Group 0, 65.5% in Group 1 and 54.9% in Group 2 (P < 0.002). Post‐pPCI TFG 3 results also differed significantly between the three groups: 85.2% in Group 0, 88.1% in Group 1, 97.6% in Group 2 (P < 0.013). ST resolution rates were also positively associated with longer pretreatment intervals. Conclusions This observational study suggests that the angiographic benefit of P2Y12‐I administration is time‐dependent: longer pretreatment improves coronary reperfusion in terms of pre‐ and post‐pPCI TFG and STR.

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