The ATLANTIC (Administration of ticagrelor in the cath lab or in the ambulance for new ST-segment elevation myocardial infarction to open the coronary artery) study indicates that pre-hospital administration of ticagrelor (Brilique, AstraZeneca)—as has been seen with pre-hospital administration of prasugrel (Efient, Eli Lilly)—does not improve coronary reperfusion before percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, it may reduce the risk of stent thrombosis.
Presenting the study at the 2014 European Society of Cardiology meeting (ESC; 30 August–3 September, Barcelona, Spain) Gilles Montalescot (Institut de Cardiologie, Centre Hospitalier Universitaire Pité-Salpêtrière, Paris, France) reported that current European guidelines for myocardial reperfusion “strongly recommend” administration of P2Y12 receptor antagonists at first medical contact in STEMI patients but added that there was “little evidence” for this class I recommendation. He said: “That is why we conducted the ATLANTIC study.”
In the randomised double-blind study, 1,862 patients with ongoing STEMI of less than six hours’ duration were randomised to receive pre-hospital administration of ticagrelor (909) or to receive in-hospital administration of the drug (953). The two co-primary endpoints were the proportion of patients who did not have ≥70% resolution of ST-segment elevation before PCI and the proportion of patients who did not meet the criteria for thrombolysis in myocardial infarction (TIMI) grade 3 in the infarct-related artery at angiography before PCI. Secondary endpoints included a composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularisation at 30 days and definite stent thrombosis at 30 days. Safety endpoints included major bleeding, life-threatening bleeding, and minor bleeding within the first 48 hours and over the 30-day treatment period.
Montalescot reported that there were no significant differences for either of the co-primary endpoints. The proportion of patients with no ST-segment resolution of ≥70% before PCI was 86.8% in the pre-hospital group vs. 87.6% in the in-hospital group, and the proportion of patients with no TIMI 3 flow grade 3 in infarct-related artery before PCI was 82.6% in the pre-hospital group vs. 83.1% in the in-hospital group. He added that there were also no significant differences between groups in these endpoints after PCI. “The data were consistent for all of the subgroups except for patients who received morphine. In patients who received morphine, there was less of an effect of pre-hospital administration of ticagrelor. Actually, the primary endpoint of ST-segment resolution was significantly improved in patients without morphine when the ticagrelor was given before hospitalisation (p=0.005).” Montalescot commented that there were no significant differences in the safety endpoints between groups.
While the secondary composite endpoint of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularisation at 30 days did not differ between the two groups, there was a significant reduction of definite stent thrombosis at 24 hours between the pre-hospital and in-hospital group: 0% vs. 0.8%, respectively (p=0.008). Montalescot commented that these data were confirmed at 30 days (0.2 vs. 1.2%, respectively; p=0.02). He added that the rate of stent thrombosis seen in the in-hospital group was consistent with that observed with ticagrelor in the PLATO study (Platelet inhibition and patient outcomes), which showed the drug to significantly reduce the risk of stent thrombosis compared with clopidogrel (Plavix; Bristol-Myers Squibb and Sanofi Aventis).
Concluding, Montalescot said: “Pre-hospital administration of ticagrelor in patients with ongoing STEMI undergoing PCI is safe but does not improve pre-PCI reperfusion. It may however reduce the risk of post-PCI stent thrombosis.”
In his review of the ATLANTIC study, which he gave after Montalescot’s presentation, Paul Armstrong (Division of Cardiology at the University of Alberta, Edmonton, Canada), speculated that the finding that pre-hospital administration of ticagrelor may reduce stent thrombosis was “a play of chance”. He explained: “Indeed, there was an eight-patient excess of stent thrombosis in the in-hospital group. But, notice also that there were also 11 fewer stents, only three more myocardial infarctions, and two fewer strokes in this group. For me, the observation of less stent thrombosis [with pre-hospital administration of ticagrelor] needs to be looked at alongside the other clinical endpoints in this trial.”
Montalescot told Cardiovascular News: “Studies are never conducted to evaluate stent thrombosis as the primary endpoint; it is always a secondary endpoint. Therefore, a second study [examining the association between pre-hospital ticagrelor and reduce stent thrombosis] would be welcome.”