Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery - ATLANTIC

Description:

The goal of the trial was to evaluate administration of ticagrelor in the ambulance compared with administration in the catheterization laboratory among participants with ST-segment elevation myocardial infarction (STEMI).

Contribution to the Literature: The ATLANTIC trial failed to show that prehospital ticagrelor improved ST resolution or TIMI flow pre-PCI; however, early stent thrombosis was reduced by this approach.

 

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Participants with STEMI being transferred for primary PCI 

    Number of enrollees: 1,862
    Duration of follow-up: 1-12 months
    Mean patient age: 61 years
    Percentage female: 19%

Primary Endpoints:

  • Proportion of participants who did not have ≥70% resolution of ST-segment elevation before PCI
  • Proportion of participants who did not have TIMI flow 3 before PCI

Secondary Endpoints:

  • Major adverse cardiovascular events
  • Stent thrombosis
  • Major bleeding

Drug/Procedures Used:

Participants with STEMI were randomized to ticagrelor 180 mg in the ambulance plus placebo in the catheterization laboratory (n = 909) versus placebo in the ambulance plus ticagrelor 180 mg in the catheterization laboratory (n = 953). All patients then received ticagrelor 90 mg twice daily for 1-12 months.

Concomitant Medications:

Aspirin: 99%

Principal Findings:

Overall, 1,862 patients were randomized. The mean age was 61 years, 19% were women, 19.5% had a body mass index ≥30 kg/m2, and 12.7% had diabetes. Radial access was obtained in 68%, aspiration thrombectomy was performed in 52%, stenting was performed in 84% (of which 51% was a drug-eluting stent), unfractionated heparin was used in 67%, and glycoprotein IIb/IIIa inhibitor was used before PCI in 30%.

The first co-primary endpoint, proportion of participants who did not have ≥70% resolution of ST-segment elevation before PCI, occurred in 86.8% of the ambulance group vs. 87.6% of the catheterization laboratory group (p = 0.63). ST-segment resolution appeared to be improved by ticagrelor administration in the ambulance among those who did not receive morphine (p for interaction = 0.005).

The second co-primary endpoint, proportion of participants who did not have TIMI flow 3 before PCI, occurred in 82.6% of the ambulance group vs. 83.1% of the catheterization laboratory group (p = 0.82).

- Death, MI, or urgent revascularization: 4.3% vs. 3.6% (p = 0.42), respectively

- Death, MI, urgent revascularization, stent thrombosis, or bailout glycoprotein IIb/IIIa inhibitor use at 24 hours: 10.4% vs. 13.7% (p = 0.039), respectively

- Death at 24 hours: 1.1% vs. 0.2% (p = 0.048), respectively
- Definite stent thrombosis at 30 days: 0.2% vs. 1.2% (p = 0.02), respectively

- Non–coronary artery bypass grafting (CABG) major bleeding (PLATO criteria): 1.8% vs. 1.6% (p = 0.76), respectively
- Non-CABG major bleeding (TIMI criteria): 1.3% vs. 1.3% (p = 0.91), respectively
- Non-CABG major bleeding (STEEPLE criteria): 2.9% vs. 2.5% (p = 0.65), respectively

In the subset of subjects that actually underwent primary PCI, the composite outcome of death, MI, stent thrombosis, stroke, or urgent revascularization occurred in 10.4% of the prehospital ticagrelor group versus 13.7% of the ticagrelor in the catheterization laboratory group (p = 0.039). Prehospital ticagrelor was also associated with a reduction in definite stent thrombosis (p = 0.0078) and MI (p = 0.031).

Interpretation:

Among participants with STEMI, ambulance administration of ticagrelor did not improve myocardial perfusion pre-PCI compared with administration in the catheterization laboratory. Although ambulance administration of ticagrelor did not improve the study co-primary outcomes, there was a reduction in early stent thrombosis, with no bleeding hazard. Among those who actually underwent primary PCI, there was a reduction in adverse ischemic events from prehospital ticagrelor. It remains possible that morphine delayed the onset of action of ticagrelor. The association of increased mortality with ambulance administration of ticagrelor is somewhat concerning; however, this needs to be interpreted with caution since this was a secondary outcome and is not explained by increased major bleeding.

References:

Montalescot G, van't Hof AW, Bolognese L, et al. Effect of Pre-Hospital Ticagrelor in the First 24 Hours After Primary PCI in Patients With ST-Segment Elevation Myocardial Infarction: The ATLANTIC-H24 Analysis. JACC Cardiovasc Interv 2016;Mar 9:[Epub ahead of print].

Montalescot G, Van’t Hof AW, Lapostolle F, et al., on behalf of the ATLANTIC Investigators. Prehospital Ticagrelor in ST-Segment Elevation Myocardial Infarction. N Engl J Med 2014;371:1016-27.

Presented by Dr. Gilles Montalescot at the European Society of Cardiology Congress, Barcelona, Spain, September 1, 2014.

Presented by Dr. Gilles Montalescot at the European Society of Cardiology Congress, London, August 31, 2015.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery

Keywords: Myocardial Infarction, Drug-Eluting Stents, Heparin, Morphine, Percutaneous Coronary Intervention, Body Mass Index, Thrombectomy, Thrombosis, Pharmaceutical Preparations, Catheterization, Organoplatinum Compounds, Coronary Artery Bypass, Diabetes Mellitus, Platelet Glycoprotein GPIIb-IIIa Complex, ESC Congress, ESC Congress


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