Physicians' Academy for Cardiovascular Education

The effects of pre-hospital ticagrelor in STEMI are apparent after PCI

Literature - Montalescot G, et al. J Am Coll Cardiol Intv 2016


Effect of Pre-Hospital Ticagrelor During the First 24 Hours After Primary PCI in Patients With ST-Segment Elevation Myocardial Infarction
The ATLANTIC-H24 Analysis

Montalescot G, van t Hof AW, Bolognese L, et al.
J Am Coll Cardiol Intv 2016;9(7):646
 

Background

The objective of the ATLANTIC study was to evaluate whether the pre-hospital administration of the P2Y12 receptor antagonist ticagrelor can improve coronary reperfusion and clinical outcomes in STEMI patients [1]. The pre-hospital administration of ticagrelor in these patients was safe but did not improve pre-PCI coronary reperfusion compared with the in-hospital administration of the same agent, based on TIMI flow and ECG measures [2]. The ATLANTIC study results have been attributed to the short median times from randomisation to angiography that resulted in a median time difference of only about 30 minutes between the two treatment strategies [3]. On the other hand, the pre-hospital administration of ticagrelor was associated with a reduction in the risk of stent thrombosis at 30 days [2]. These observations led to the hypothesis that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer times.
In the present exploratory analysis, all data available from the ATLANTIC study during the first 24 hours after primary PCI were examined. The available data included platelet function reactivity, coronary reperfusion, ischemic endpoints, and safety outcomes. The ATLANTIC-H24 analysis included 1,629 patients who underwent PCI.
Main results
The platelet function substudy in a small subset of the population (n = 37) showed that the biological effect of ticagrelor did not become apparent until 1 h after PCI. The largest (but non-significant) difference in mean PRU levels between the two treatment strategies (pre-hospital vs. in-hospital) was observed 1 - 6 hours after PCI.
 
The bailout use of glycoprotein IIb/IIIa inhibitors was numerically lower with pre-hospital versus in-hospital administration of ticagrelor (9.4% vs. 12.0%; OR: 0.76; 95% CI: 0.55 - 1.04), which corresponds to an absolute (non-significant) difference of 2.6%.
 
There were no significant differences between the pre- and in-hospital ticagrelor groups in terms of either post-PCI TIMI flow grade 3 or ≥70% ST-segment elevation resolution at 1 h. However, both endpoints showed numerical differences in favor of the pre-hospital group:  
  • ST-segment elevation resolution ≥70% measured 1 h after PCI occurred in 57.5% of patients in the pre-hospital group and in 52.5% of patients in the in-hospital group (P = 0.055)
  • The degree of ST-segment elevation resolution after PCI was significantly different between the 2 groups (median of 75.0% in the pre-hospital group vs. 71.4% in the in-hospital group, P = 0.049)
Similar results were observed in the global population for pre- versus in-hospital ticagrelor for:
  • post-PCI/angiography TIMI flow grade 3 (82.1% vs.80.4%; P = 0.389)
  • ST-segment elevation resolution ≥70% (54.5% vs. 50.1%; P = 0.080)
  • degree of ST-segment elevation resolution (median, 73.3% vs. 70.0%; P = 0.045)
 
Clinical outcomes at 24 h:
  • The composite endpoint of death, MI, urgent revascularization, definite stent thrombosis, or bail-out glycoprotein IIb/IIIa inhibitor use was significantly lower proportionally by 27% with pre- versus in-hospital administration of ticagrelor (10.4% vs. 13.7%; P = 0.039)
  • On exclusion of bail-out glycoprotein IIb/IIIa inhibitor use from the composite endpoint, the difference remained in favor of pre-hospital ticagrelor but was no longer significant (1.3% vs. 2.0%; P = 0.212)
  • The 2 individual endpoints of definite stent thrombosis and new MI were significantly lower in the pre-hospital group (P = 0.0078 and P = 0.031, respectively)
  • All endpoints except death (1.1% vs. 0.2%, P = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events. Of note, this study was underpowered to compare the patient groups in terms of mortality.
 

Conclusion

In STEMI patients included in the ATLANTIC study, the effects of the pre-hospital versus the in-hospital administration of ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion. The clinical outcomes within the first 24 hours were in favour of the pre-hospital use of ticagrelor, with the exception of a small excess of mortality.
 
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References

1. Montalescot G, Lassen JF, Hamm CW, et al. Ambulance or in-catheterization laboratory administration of ticagrelor for primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: rationale and design of the randomized, double-blind Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) study. Am Heart J 2013;165:51522
2 Montalescot G, van ’t Hof AW, Lapostolle F, et al. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med 2014;371:101627
3. Montalescot G, van ’t Hof AW. Prehospital ticagrelor in ST-segment elevation myocardial infarction (letter). N Engl J Med 2014;371:2339
J Am Coll Cardiol Intv. 2016;9(7):657-659

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