There is dated and conflicting data about the optimal timing of initiation of P2Y12 inhibitors in elective percutaneous coronary intervention (PCI). Peri-PCI myocardial necrosis is frequent and associated with poor outcome.

We aimed to assess the impact of the P2Y12 inhibitor loading time (time from loading to PCI) on peri-procedural myocardial necrosis in the elective PCI population of the randomized ALPHEUS trial.

1809 patients of the ALPHEUS trial were divided into quartiles of loading time (0 to 0.2h, 0.2 to 1.7h, 1.7 to 4.1h and 4.1 to 24h). The ALPHEUS primary outcome was used (type 4 (a or b) myocardial infarction or major myocardial injury) as well as the main secondary outcome including minor myocardial injury. The risk of events was adjusted in a multivariate model.

Patients in the first quartile group (Q1) presented higher rates of the primary outcome (p=0.01). When compared to Q1, incidences of the primary outcome decreased in patients with longer loading times (adjOR 0.70 [0.52–0.95]; p=0.02 for Q2; adjOR 0.65 [0.48–0.88]; p<0.01 for Q3; adjOR 0.66 [0.49–0.89]; p<0.01 for Q4; Figure 1). Concordant results were found for the main secondary outcome (Figure 2). There was no interaction with the study drug allocated by randomization (clopidogrel or ticagrelor). Bleeding complications and clinical ischemic events were rare and did not differ between groups.

In elective PCI for chronic coronary syndrome, administration of the loading dose of oral P2Y12 inhibitor at the time of PCI is associated with more frequent peri-procedural myocardial necrosis than an earlier administration.