Prehospital Ticagrelor in ST-Segment Elevation Myocardial Infarction (ATLANTIC)
Selected in The New England Journal of Medicine by G. Harris
G. Montalescot, A.W. van 't Hof, F. Lapostolle, J. Silvain, J. Flensted Lassen, L. Bolognese, W. J. Cantor, Á. Cequier, M. Chettibi, S. G. Goodman, C. J. Hammett, K. Huber, M. Janzon, B. Merkely, R.F. Storey, U. Zeymer, O. Stibbe, P. Ecollan, W.M.J.M. Heutz, E. Swahn, J-P. Collet, F. F. Willems, C. Baradat, M. Licour, A. Tsatsaris, E. Vicaut, C.W. Hamm, for the ATLANTIC Investigators
N Engl J Med 2014; 371:1016-1027
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Ticagrelor (cyclo-pentyl-triazole-pyrimidine) is an orally active absorbed reversible P2Y12 receptor blocker, with a maximum mean IPA effect between 2 and 4 hours lasting up to 8 hours.
It was used in the PLATO trial (compared to clopidogrel in in-hospital patients with acute coronary syndrome) where 91 patients needed to be treated to prevent 1 CV death.
Zijlstrta et al. (JACC, June 5, 2002) demonstrated the benefits of pre-hospital vs. in-hospital administration of aspirin and heparin in patients with acute myocardial infarction.
Despite this, there is a paucity of data concerning optimal treatment in the prehospital setting (provided the right diagnoses is made). The ATLANTIC trial sought to fill part of this void by assessing the efficacy of Ticagrelor in patients with ST segment elevation myocardial infarction given in the prehospital setting. NB the study was not powered for an assessment of mortality outcome.
There was no significant difference in the two co-primary endpoints between the pre-hospital and in-hospital groups.
The proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct related artery at initial angiography and a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention.
As a secondary endpoint between the pre-hospital and in hospital group of patients with a 70% or greater resolution of ST segment there was no difference (42.5% vs. 47.5%) .
There was also no significant difference in the rates of major cardiovascular events.
The rates of definite stent thrombosis were lower in the pre-hospital group (0% vs. 8% in the first 24hours and 0.2% vs. 1.2% at 30 days).
There was also no significant difference in major bleeding between the two groups.
However, 3.3% of the patients in the pre-hospital group died vs. 2.0% of patients in the in hospital group (P=0.08).
It is important to note the relatively short median time from symptom onset to angioplasty in this trial (159 min of “ischaemic” time). Would this time be longer, as is the case in many countries, greater benefit may have been derived.
In a subgroup analysis, the patients who received morphine and pre-hospital ticagrelor had slower ST segment resolution than those who did not. Morphine possibly influences the absorption rate of ticagrelor (As commented by Prof G Montalescot).
The rate of overall in-stent thrombosis in this trial was already low. All the events happened in the 1st 5 days. Despite this the pre-hospital group still had significantly fewer cases of in-stent thrombosis than the in hospital group. This may point to deriving benefit from earlier onset of action at the time of recanalization.
Should guidelines change to accommodate the pre hospital use of ticagrelor in patients with STEMI? Maybe a class IIB for patients presenting with STEMI where the diagnosis could confidently be made in the prehospital setting and where ticagrelor would have been the P2Y12 receptor blocker of choice in-hospital.