More than 25% of patients referred for diagnostic coronary angiography and percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS) suffer from non-valvular atrial fibrillation (AF). In this particular setting, balancing between the prevention of thrombosis and the risk of bleeding remains challenging. Oral anticoagulation (OAC) prevents stroke and systemic embolism, but has not been shown to prevent stent thrombosis (ST). Dual antiplatelet therapy (DAPT) reduces the incidence of recurrent ischemic events and ST, but is less effective in reducing the incidence of cardioembolic stroke associated with AF. A common guideline-supported practice is to combine three drugs (OAC, aspirin and clopidogrel) in a triple therapy, which is associated with high annual risk (up to 25%) of major bleeding. Thus, new therapeutic strategies are urgently needed to maintain the efficacy while improving the safety of treatment in patients with AF and ACS undergoing PCI.
This is a prospective, randomized, open-label, blinded-endpoint, non-inferiority trial. 1194 patients with non-valvular AF that had undergone successful PCI due to an ACS within the previous 120 hours will be randomized in 1:1 ratio to receive one of the two treatments: dual therapy with dabigatran (150 mg twice daily or 110 mg twice daily) and ticagrelor (90 mg twice daily for 1 month, followed by 60 mg twice daily up to 12 months), or standard therapy according to current guidelines triple therapy with dabigatran (150 mg b.i.d. or 110 mg b.i.d.) plus clopidogrel (75 mg o.d.) plus aspirin (75 mg o.d.) followed by double therapy depending on the bleeding and ischaemic risk. Study treatment will be continued for 12 months. The primary study end-point is the first major or clinically relevant non-major bleeding event (per ISTH), in a time-to-event analysis. The main secondary end-point is a composite efficacy end-point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization (PCI or coronary artery bypass grafting) at 12 months.
We expect that dual antithrombotic therapy including reduced dose ticagrelor and dabigatran is at least non-inferior regarding bleeding risk and ischaemic protection, compared to the standard triple therapy in patients with AF and after ACS, treated with PCI.
Male and female patients aged ≥18 years'
Patients with new-onset or pre-existing non-valvular AF that have been receiving oral anticoagulant treatment with dabigatran for at least 48 hours or were treatment naïve prior to PCI. AF may be paroxysmal, persistent or permanent, but must not be secondary to a reversible disorder such as MI, pulmonary embolism, recent surgery, pericarditis or thyrotoxicosis unless long-term treatment with an OAC is anticipated.
Patients presenting with ACS that had undergone a successful PCI with drug-eluting stent (DES) implantation or plain old balloon angioplasty within the previous 120 hours. ACS may be ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina (UA). Successful treatment with PCI is defined as achievement of <30% residual diameter stenosis of the target lesion assessed by visual inspection or quantitative coronary angiography and no in-hospital major adverse cardiac events (AMI or repeat coronary revascularisation of the target lesion). For ACS patients with ST-segment elevation, persistent ST-segment elevation of at least 0.1 mV in at least two contiguous leads or a new left bundle-branch block should be present. For ACS patients without ST-segment elevation, at least two of the following three criteria should be met: (i) ST-segment changes on electrocardiography, indicating ischemia; (ii) a positive test of a biomarker, indicating myocardial necrosis; or (iii) one of several risk factors (age ≥60 years; previous myocardial infarction or coronary artery bypass grafting; coronary artery disease with stenosis of ≥50% in at least two vessels; previous ischemic stroke, transient ischemic attack, carotid stenosis of at least 50%, or cerebral revascularization; diabetes mellitus; peripheral arterial disease; chronic renal dysfunction, defined as a creatinine clearance of <60 ml per minute per 1.73 m2 of body surface area).
The patient must be able to give informed consent in accordance with ICH GCP guidelines and local legislation and/or regulations.
Mechanical or biological heart valve prosthesis;
PCI with bare-metal stent insertion;
Unsuccessful PCI (>30% residual stenosis of the target lesion);
Cardiogenic shock during current hospitalization;
Parallel
Ticagrelor
DrugWithin 120 hours post PCI, patients will be randomized in a 1:1 ratio to receive one of the two treatments: dual therapy with ticagrelor (90 mg twice daily for one month, followed by 60 mg twice daily up to 12 months) plus dabigatran (150 mg twice daily or 110 mg twice daily; standard of care) or triple therapy with clopidogrel (75 mg once daily) plus aspirin (75 mg once daily) plus dabigatran (150 mg twice daily or 110 mg twice daily), according to current guidelines. Study treatment will be continued for 12 months.
Dabigatran Etexilate
DrugWithin 120 hours post PCI, patients will be randomized in a 1:1 ratio to receive one of the two treatments: dual therapy with ticagrelor (90 mg twice daily for one month, followed by 60 mg twice daily up to 12 months) plus dabigatran (150 mg twice daily or 110 mg twice daily; standard of care) or triple therapy with clopidogrel (75 mg once daily) plus aspirin (75 mg once daily) plus dabigatran (150 mg twice daily or 110 mg twice daily), according to current guidelines. Study treatment will be continued for 12 months
Aspirin
DrugWithin 120 hours post PCI, patients will be randomized in a 1:1 ratio to receive one of the two treatments: dual therapy with ticagrelor (90 mg twice daily for one month, followed by 60 mg twice daily up to 12 months) plus dabigatran (150 mg twice daily or 110 mg twice daily; standard of care) or triple therapy with clopidogrel (75 mg once daily) plus aspirin (75 mg once daily) plus dabigatran (150 mg twice daily or 110 mg twice daily), according to current guidelines. Study treatment will be continued for 12 months
Clopidogrel
DrugWithin 120 hours post PCI, patients will be randomized in a 1:1 ratio to receive one of the two treatments: dual therapy with ticagrelor (90 mg twice daily for one month, followed by 60 mg twice daily up to 12 months) plus dabigatran (150 mg twice daily or 110 mg twice daily; standard of care) or triple therapy with clopidogrel (75 mg once daily) plus aspirin (75 mg once daily) plus dabigatran (150 mg twice daily or 110 mg twice daily), according to current guidelines. Study treatment will be continued for 12 months
Primary safety endpoint - first major or clinically relevant non-major bleeding event, as defined by the ISTH
First major or clinically relevant non-major bleeding event, as defined by the International Society on Thrombosis and Haemostasis (ISTH)
Secondary efficacy endpoint - thromboembolic events or death or unplanned revascularization; individual thromboembolic events; definite stent thrombosis
Composite efficacy endpoint of thromboembolic events (myocardial infarction, stroke, or systemic embolism) or death or unplanned revascularization (PCI or coronary artery bypass grafting); individual thromboembolic events (death, myocardial infarction, stroke, systemic embolism); definite stent thrombosis
Secondary safety endpoint - major bleeding events; clinically relevant non-major bleeding events; clinically relevant bleeding; minor and total bleeding; intracranial hemorrhage
major bleeding events (per ISTH); clinically relevant non-major bleeding events; clinically relevant bleeding (BARC ≥3 or TIMI major and minor); minor and total bleeding (ISTH, BARC, TIMI; total bleeding is the sum of all major and minor bleeds); intracranial hemorrhage
Click on the lead sponsor to view all of their trials.
Medical University of Gdansk
Lead sponsor
Medical University of Warsaw
Collaborator
Nicolaus Copernicus University
Collaborator
National Institute of Cardiology, Warsaw, Poland
Collaborator
Military Institute od Medicine National Research Institute
Collaborator
Bielanski Hospital
Collaborator
Medical University of Silesia
Collaborator
Poznan University of Medical Sciences
Collaborator
University of Opole, Poland
Collaborator
Medical University of Łódź
Collaborator
Voivodeship Hospital, Kielce, Poland
Collaborator
Voivode Specialist Hospital in Olsztyn, Poland
Collaborator
Medical University of Lublin
Collaborator
Pomeranian Medical University Szczecin
Collaborator
Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw, Poland
Collaborator
American Heart of Poland
Collaborator
University of Warmia and Mazury in Olsztyn
Collaborator
