MIRTOS trial: Ticagrelor versus Clopidogrel in patients with STEMI treated with thrombolysis

Selected in EuroIntervention by A. N. Calik , C. Karabay

The MIRTOS trial, which included STEMI patients receiving DAPT and thrombolysis ‘together’, aimed to evaluate whether ticagrelor could improve microvascular perfusion and reduce MACE compared to clopidogrel

Reviewers

Ali Nazmi Calik

@ANazmiCalik

Interventional cardiologist / Cardiologist

Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Center - Istanbul, Türkiye

Can Yücel Karabay

@canyucelkarabay

Interventional cardiologist / Cardiologist

Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research hospital - ISTANBUL, Türkiye

Our Comment

Why this study? – the rationale/objective

Current guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in ST-elevation myocardial infarction (STEMI) patients treated with fibrinolysis. Nonetheless, despite ticagrelor therapy provides many benefits when compared to clopidogrel in terms of reducing major cardiovascular events (MACE) in patients undergoing primary percutaneous coronary intervention (PCI), there is a shortage of data with regards to demonstrating same benefits in fibrinolytic-treated STEMI patients. The results of the TREAT trial, which was conducted to fill this gap, showed similar efficacy and safety of ticagrelor and clopidogrel when administered ‘11 hours’ later than fibrinolytic therapy.

The MIRTOS trial, which included STEMI patients receiving DAPT and thrombolysis ‘together’, aimed to evaluate whether ticagrelor could improve microvascular perfusion and reduce MACE compared to clopidogrel.

How was it executed? – the methodology

MIRTOS is a multicenter, prospective and randomized trial that comprises a total of 335 STEMI patients who are under 75 years old and eligible for thrombolytic therapy. In all patients, thrombolysis was the preferred reperfusion modality as primary PCI was not applicable within two hours of the first medical contact. The key method of the study was initiating P2Y12 inhibitor together with fibrinolytic agent and randomizing patients to receive clopidogrel (n=167) or ticagrelor (n=168). Following angiograms (pre- and post PCI) were evaluated to measure the determinants of vessel patency. Of note, patients who did not undergo PCI after angiogram were excluded from the study (n=76).

The primary angiographic endpoint of the study was corrected TIMI frame count (CTFC). Other angiographic parameters including pre- and post-PCI TIMI myocardial perfusion grade (MPG), thrombus grade, TIMI flow and myocardial blush grade were defined as the secondary endpoints, as well as MACE (death, stroke, myocardial infarction, revascularization) during the three month follow-up period.

What is the main result?

Primary endpoint analysis included 259 patients (129 clopidogrel and 130 ticagrelor) that underwent PCI, and 154 angiograms were found to be adequate for analysis. No significant difference was found between the clopidogrel (n=85) and ticagrelor (n=69) groups for post-PCI CTFC (24.33±17.35 vs 28.33±17.59, p=0.10), and also for secondary angiographic endpoints of the study. With regards to MACE and major bleeding events, there were no significant differences between randomization groups (OR 2.0, 95% CI 0.18-22.2, p=0.99).

Critical reading and the relevance for clinical practice:

The use of potent antiplatelet agents such as ticagrelor is not recommended within 24 hours of thrombolysis, mainly due to safety concerns and lack of evidence showing superiority compared to clopidogrel.

Despite its small sample size and lack of power for testing differences in bleeding events, the MIRTOS trial revealed the safety of ticagrelor when administered together with thrombolysis in STEMI patients younger than 75 years old. However, angiographic and clinical outcomes did not demonstrate the superiority of ticagrelor compared to clopidogrel in terms of microvascular integrity and MACE.

Taken the results of the study together ticagrelor might be a reliable option in STEMI patients treated with thrombolysis. Nonetheless, its potential to decrease MACE compared to clopidogrel needs further confirmation in larger trials.