Dual Antithrombotic Therapy With Dabigatran and Ticagrelor in Patients With ACS and Non-valvular AF Undergoing PCI

Summary

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. 2230 patients with non-valvular AF that had undergone successful PCI due to an ACS within the previous 72 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.

Conditions

• Atrial Fibrillation
• Antithrombotic Therapy
• Acute Coronary Syndrome
• Percutaneous Coronary Interventions

Interventions

DRUG

Ticagrelor

Within 72 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.

DRUG

Dabigatran Etexilate

Within 72 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

DRUG

Aspirin

Within 72 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

DRUG

Clopidogrel

Within 72 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

Sponsors & Collaborators

• Medical University of Warsaw

  collaborator OTHER

• Nicolaus Copernicus University

  collaborator OTHER

• National Institute of Cardiology, Warsaw, Poland

  collaborator OTHER

• Military Institute od Medicine National Research Institute

  collaborator OTHER

• Bielanski Hospital

  collaborator OTHER

• Medical University of Silesia

  collaborator OTHER

• Poznan University of Medical Sciences

  collaborator OTHER

• University of Opole, Poland

  collaborator UNKNOWN

• Medical University of Łódź

  collaborator OTHER

• Voivodeship Hospital, Kielce, Poland

  collaborator UNKNOWN

• Voivode Specialist Hospital in Olsztyn, Poland

  collaborator UNKNOWN

• Medical University of Lublin

  collaborator OTHER

• Pomeranian Medical University Szczecin

  collaborator OTHER

• Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw, Poland

  collaborator OTHER

• Medical University of Gdansk

  lead OTHER

Principal Investigators

• Magdalena Leszczyńska-Wiloch, PhD · Department of Non-Commercial Clinical Research, Medical University of Gdansk

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-10-25

Primary Completion

2024-03-01

Completion

2026-03-31

Countries

• Poland

Study Locations