ATLANTIC: Prehospital Ticagrelor Safe in STEMI, But No Added Benefit Compared With In-Hospital Administration
BARCELONA, Spain—While prehospital administration of the antiplatelet ticagrelor is safe, it does not improve coronary reperfusion outcomes in patients with ST-segment elevation myocardial infarction (STEMI), according to results presented on September 1, 2014, at the European Society of Cardiology Congress and simultaneously published online in the New England Journal of Medicine.
| Methods |
| For the ATLANTIC trial, Gilles Montalescot, MD, PhD, of Centre Hospitalier Pitié-Salpêtrière (Paris, France), and colleagues randomized 1,862 patients (mean age 61 years; 20% women) with suspected STEMI and less than 6 hours of symptoms to receive in-ambulance (n = 909) or in-hospital (n = 953) ticagrelor (180 mg) from September 12, 2011, to October 3, 2012, from 102 ambulance services and 112 PCI centers in 13 countries. All patients subsequently received ticagrelor 90-mg twice daily for 30 days with a recommendation of treatment through 12 months. In-ambulance GPI use was discouraged but left to physician discretion. |
| Median time from symptom onset to STEMI diagnosis was 73 minutes. Two-thirds of patients had radial procedures and 87.5% had PCI, about half with DES. Approximately one-third of patients received GPIs before PCI. |
Both groups reported reduced platelet reactivity after
ticagrelor administration in a pharmacodynamic substudy of 37 patients.
Overall, there were no differences between the study arms in the proportion of
patients who did not have 70% or greater ST-segment resolution before or after
PCI and the proportion of patients who did not have TIMI flow of grade 3 in the
infarct-related artery at initial angiography or after PCI (table 1).
Table 1. Outcomes Before and After PCI
Results were confirmed across prespecified subgroups, except for patients who received morphine, where ST-segment resolution was significantly improved with prehospital administration (P = .005 for interaction).
The rate of the composite endpoint of death, MI, stroke, urgent coronary revascularization, or stent thrombosis was similar between the study groups. However, definite stent thrombosis was reduced in the in-ambulance group at both 24 hours (P = .008) and 30 days (P = .02). Anticoagulant type did not seem to affect the occurrence of stent thrombosis.
Mortality was 3.3% in the prehospital group and 2.0% in the in-hospital group (P = .08), and the most common causes of death were cardiogenic shock, cardiac arrest, mechanical complication, and heart failure.
Non-CABG-related bleeding rates were low through 30 days, and no differences were observed among patients treated with pre- or in-hospital ticagrelor, regardless of whether defined by PLATO, TIMI, or STEEPLE criteria. Additionally, no bleeding rate differences were found among the 11.1% of patients who did not undergo revascularization or the 8.6% of patients who were not ultimately diagnosed with STEMI.
Still an ‘Open Question’
Discussant Paul Wayne Armstrong, MD, of the University of Alberta (Alberta, Canada), commended the investigators for being “very quick,” both to treat patients and to publish.
Stent thrombosis events “need to be looked at in the presence of the other clinical endpoints of interest in this trial,” he said, given that all outcomes were relatively low.
Ultimately, “the ATLANTIC investigators were victims of their own success,” according to Dr. Armstrong. “They treated their patients exceedingly well … and provided us a substrate in which it was difficult to improve,” he said. “The short interval between the treatment groups and the dichotomous endpoints indeed structured a high bar …, and I think the play of chance with the small numbers needs to be considered.
“Whether early ticagrelor even at a higher dose with a broader window between the initial and the second [administration] in patients treated later will effect outcomes remains unproven and for me this remains an open question,” Dr. Armstrong concluded.
Source:
Montalescot G, van’t Hof AW,
Lapostolle F, et al. Prehospital ticagrelor in ST-segment elevation myocardial
infarction. N Engl J Med. 2014;Epub
ahead of print.
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Yael L. Maxwell is Senior Medical Journalist for TCTMD and Section Editor of TCTMD's Fellows Forum. She served as the inaugural…
Read Full BioDisclosures
- ATLANTIC was supported by AstraZeneca.
- Dr. Montalescot reports receiving consulting fees and grand support from numerous pharmaceutical and device manufacturers and foundations.
- Dr. Armstrong reports receiving research grants from Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck, Regado Biosciences, and Sanofi Aventis; consulting for AstraZeneca and Regado Biosciences; and serving on the data and safety monitoring boards of Bayer, Eli Lilly, Orexigen, and Roche.
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