Duration of ischemia and treatment effects of pre- versus in-hospital ticagrelor in patients with ST-segment elevation myocardial infarction: Insights from the ATLANTIC study

Am Heart J. 2018 Feb;196:56-64. doi: 10.1016/j.ahj.2017.10.021. Epub 2017 Nov 4.

Abstract

Background: Among patients with STEMI in the ATLANTIC study, pre-hospital administration of ticagrelor improved post-PCI ST-segment resolution and 30-day stent thrombosis. We investigated whether this clinical benefit with pre-hospital ticagrelor differs by ischemic duration.

Methods: In a post hoc analysis we compared absence of ST-segment resolution post-PCI and stent thrombosis at 30 days between randomized treatment groups (pre- versus in-hospital ticagrelor) stratified by symptom onset to first medical contact (FMC) duration [≤1 hour (n = 773), >1 to ≤3 hours (n = 772), and >3 hours (n = 311)], examining the interaction between randomized treatment strategy and duration of symptom onset to FMC for each outcome.

Results: Patients presenting later after symptom onset were older, more likely to be female, and have higher baseline risk. Patients with symptom onset to FMC >3 hours had the greatest improvement in post-PCI ST-segment elevation resolution with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 2.9% vs. >1 to ≤3 hours, 3.6% vs. >3 hours, 12.2%; adjusted p for interaction = 0.13), while patients with shorter duration of ischemia had greater improvement in stent thrombosis at 30 days with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 1.3% vs. >1 hour to ≤3 hours, 0.7% vs. >3 hours, 0.4%; adjusted p for interaction = 0.55). Symptom onset to active ticagrelor administration was independently associated with stent thrombosis at 30 days (adjusted OR 1.89 per 100 minute delay, 95%CI 1.20-2.97, P < .01), but not post-PCI ST-segment resolution (P = .41).

Conclusions: The effect of pre-hospital ticagrelor to reduce stent thrombosis was most evident when given early within 3 hours after symptom onset, with delay in ticagrelor administration after symptom onset associated with higher rate of stent thrombosis. These findings re-emphasize the need for early ticagrelor administration in primary PCI treated STEMI patients.

Trial registration: ClinicalTrials.gov NCT01347580.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Coronary Angiography / methods
  • Disease Progression
  • Double-Blind Method
  • Electrocardiography / methods
  • Emergency Medical Services / methods*
  • Female
  • Humans
  • Internationality
  • Male
  • Middle Aged
  • Myocardial Ischemia / diagnostic imaging
  • Myocardial Ischemia / drug therapy*
  • Myocardial Ischemia / physiopathology
  • Percutaneous Coronary Intervention / methods*
  • Percutaneous Coronary Intervention / mortality
  • Prognosis
  • Risk Assessment
  • ST Elevation Myocardial Infarction / diagnostic imaging
  • ST Elevation Myocardial Infarction / drug therapy*
  • ST Elevation Myocardial Infarction / mortality
  • ST Elevation Myocardial Infarction / therapy
  • Stents
  • Survival Analysis
  • Ticagrelor / administration & dosage*
  • Time-to-Treatment
  • Treatment Outcome

Substances

  • Ticagrelor

Associated data

  • ClinicalTrials.gov/NCT01347580