Circadian Variation of Stent Thrombosis and the Effect of More Robust Platelet Inhibition: A Post Hoc Analysis of the TRITON-TIMI 38 Trial

Background: The well-described morning peak in the onset of acute coronary syndromes has been partly attributed to increased platelet activity upon arising. It has been suggested that stent thrombosis (ST) exhibits a similar pattern. We assessed whether a diurnal variation in ST occurs, and whether more robust antiplatelet therapy with prasugrel (vs clopidogrel) can attenuate a morning excess. Methods and Materials: Patients from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38 trial (N = 13608) with adjudicated ST classified per the Academic Research Consortium definitions of definite (N = 135) and probable (N = 27) were grouped into prespecified 8-hour intervals by time of onset: early (6 am-2 pm), late-day (2 pm-10 pm), and overnight (10 pm-6 am). We compared the rates per 1000 patients of ST across time intervals and stratified by treatment and stent type. Results: A diurnal variation in definite/probable ST was observed with rates of 6.5, 3.7, and 2.1 for early, late-day, and overnight intervals, respectively (P < .001), per 1000 patients treated. A sensitivity analysis excluding periprocedural acute-ST (<24 hours after index percutaneous coronary intervention [PCI]) resulted in similar findings (5.2, 2.5, and 1.8 per 1000, P < .001). The circadian variation in ST was observed in patients on clopidogrel (9.7, 4.8, and 3.1 per 1000, P < .001) with the highest rate of ST early in the day. Patients on prasugrel also demonstrated a circadian variation with particularly low rates of overnight ST (3.4, 3.0, and 1.1 per 1000, P = .020). Conclusions: In TRITON-TIMI 38 trial, the timing of ST exhibited a significant diurnal variation similar to that seen with onset of other acute coronary syndromes. ST occurred less frequently among patients randomized to prasugrel compared to clopidogrel with the greatest absolute reduction (6.2 per 1000 patients) in events earlier in the day when platelet activity is known to be highest.