Review of Prehospital Administration of Ticagrelor

Among patients with ST-segment elevation myocardial infarction (STEMI) about to undergo percutaneous coronary intervention (PCI), early, in-ambulance administration of the oral antiplatelet agent ticagrelor was safe but did not show evidence of improving pre-PCI coronary reperfusion, according to a recent trial [N Engl J Med. 2014; DOI:10.1056/NEJMoa1407024].

The ATLANTIC [Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery] study was a phase 4, international, randomized, double-blind trial in which patients were randomly assigned to either prehospital (ambulance) administration of ticagrelor or in-hospital (catheterization laboratory) treatment with ticagrelor. Patients also received aspirin in addition to standard care. The goal of the ATLANTIC study was to ascertain whether earlier treatment with ticagrelor would lead to improved coronary reperfusion. Patients with STEMI were eligible for study inclusion if they had been having symptoms for >30 minutes but <6 hours and their expected time from the qualifying electrocardiogram to the first balloon inflation was <2 hours.

Patients in the pre-hospital group received a 180 mg loading dose of ticagrelor before transfer and then a matching placebo in the catheterization laboratory. Those in the in-hospital group received a placebo before transfer followed by a 180 mg loading dose of ticagrelor in the catheterization laboratory. All patients later received ticagrelor at a dose of 90 mg twice daily for 30 days and were recommended to continue the regimen for a total of 12 months.

The coprimary end points 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 the TIMI [Thrombolysis In Myocardial Infarction] study flow grade 3 in the infarct-related artery at angiography before PCI. Some secondary end points included the composite of death, myocardial infarction, stent thrombosis, and stroke or urgent revascularization at 30 days. Safety end points included major, life-threatening, and minor bleeding. The researchers performed efficacy analyses in the modified intention-to-treat population and compared treatment groups using logistic regression.

Between September 2011 and October 2013, 1875 patients were enrolled in the study; 909 were randomized to receive prehospital ticagrelor and 953 were randomized to receive in-hospital ticagrelor. PCI was performed in 87.5% of the patients. The median time from symptom onset to STEMI diagnosis was 73 minutes; time from randomization to angiography was 48 minutes; and time between the 2 loading doses was 31 minutes.

The study’s results showed no significant difference between the 2 groups with regard to the coprimary end points. The primary end point of ST-segment resolution was significantly improved. The researchers also found no significant differences between the 2 groups with regard to the secondary end points, with the exception of definite stent thrombosis, which was reduced in the prehospital treatment group at both 24 hours and at 30 days. No significant difference with regard to the safety end points of bleeding existed between the 2 groups.

“There was no downside to early administration of ticagrelor in the ambulance, and a significant benefit was observed on early stent thrombosis,” said the study’s lead author, Gilles Montalescot, MD, PhD, in an interview with First Report Managed Care. “It would make sense that this strategy, combined with a longer transfer delay in real-life, would also be associated with a larger benefit.”

The researchers acknowledged limitations of the study, particularly the sample size and the short intervals between administration of the study drug and reperfusion.—Mary Mihalovic