Prehospital Ticagrelor in ST-Segment Elevation Myocardial Infarction (ATLANTIC)

Selected in The New England Journal of Medicine by G. Harris

References

Authors

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

Reference

N Engl J Med 2014; 371:1016-1027

Published

September 2014

Link

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My Comment

Background

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.

Major Findings

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).

My comment

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.

3 comments

  • ALESSANDRO IADANZA 24 Oct 2014

    The Atlantic Trial does not show an improvement of Timi Flow in the context of ACS STEMI; I wonder how it is justified to assume in the hospital setting pre load oral Ticagrenol without knowing the magnitude of coronary artery disease (three-vessel, left main) or exclude threatening diseases (aortic dissection, pulmonary embolism, intracranial bleeding as a result of cardiogenic syncope in ACS) only for minimally reducing the percentage of acute stent thrombosis?

  • George Harris 21 Nov 2014

    Thank you for your questions. What you highlight is very important. To not make a diagnosis of STEMI without considering confounding variables. However, I would apply the same principles as when administrating thrombolytic therapy for STEMI. The benefit of ADP receptor blockade in patients with both unstable angina and myocardial infarction (non-STEMI), without having prior knowledge of the coronary anatomy, was demonstrated in the CURE trial (clopidogrel). Not only that, but the CABG mortality rate was lower in those patients taking clopidogrel, but a higher rate of blood transfusion was needed. Granted, Ticagrelor is a more potent drug than clopidogrel, but it is reversible, and had less CABG related bleeding in the PLATO trail. The PLATO trial included patients with both STEMI and non-STEMI. In PLATO, the Ticagrelor was also given upon admission.

  • mahesh honnalli 04 Nov 2014

    When we could give prehospital thrombolysis without knowing coronary anatomy or cardiac markers or without excluding other acute cardiac conditions, why not antiplatelets like Ticagrelor?