Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG (PACES)

Mount Sinai Health System

Status and phase: Enrolling; Phase 3

Conditions: Atrial Fibrillation; Stroke; Bleeding

Treatments: Drug: Antiplatelet-only strategy; Drug: Oral Anticoagulant plus background antiplatelet therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04045665

2U01HL088942-12 (U.S. NIH Grant/Contract)

GCO 08-1078

Details and patient eligibility

About

The primary objective of this study is to evaluate the effectiveness (prevention of thromboembolic events) and safety (major bleeding) of adding oral anticoagulation (OAC) to background antiplatelet therapy in patients who develop new-onset post-operative atrial fibrillation (POAF) after isolated coronary artery bypass graft (CABG) surgery.

All patients with a qualifying POAF event, who decline randomization, will be offered the option of enrollment in a parallel registry that captures their baseline risk profile and their treatment strategy in terms of anticoagulants or antiplatelets received. These patients will also be asked to fill out a brief decliner survey.

Full description

This is a prospective, multicenter, open-label, randomized trial comparing OAC with no OAC (1:1 ratio) in patients who develop new-onset POAF after CABG. The primary effectiveness endpoint is the composite of death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction (MI), systemic arterial thromboembolism or venous thromboembolism (VTE) at 90 days after randomization. The primary safety endpoint is BARC (Bleeding Academic Research Consortium) grade 3 or 5 bleeding at 90 days after randomization. The overall intent is to evaluate the trade-off in prevention of thromboembolic events versus an increase in bleeding.

Patients will be randomly assigned to the following treatment strategies:

• OAC-based strategy (experimental arm): OAC with vitamin K antagonist (VKA) with international normalized ratio (INR) target 2-3 or any approved direct oral anticoagulant (apixaban, rivaroxaban, edoxaban or dabigatran) in addition to background antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)
• Antiplatelet-only strategy (control arm): single antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)

The protocol-specified duration of anticoagulation is 90 days. Patients, who are randomized to the control arm and develop recurrent AF after 30 days, may be crossed-over to an OAC. Accrual is expected to take 60 months. Study follow-up visits will be performed at 90 days and phone follow-up at days 30, 60, and 180 days.

Data for patients enrolled in the registry will be ascertained from the local clinical site via a review of medical records. The baseline risk profile of registry patients (i.e., patients eligible but unwilling to be randomized) will be analyzed and compared to that of patients randomized in the trial. The usage of anticoagulant and antiplatelet therapies in the registry population overall and baseline CHA2DS2-VASC ischemic stroke risk score will also be determined.

Up to 500 patients will also be offered the option to participate in a digital health substudy which includes a wearable heart rhythm monitor device for 30 days post discharge.

Enrollment: 3,200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients of age ≥18 years who undergo isolated CABG for coronary artery disease
• POAF that persists for >60 minutes or is recurrent (more than one episode) within 7 days after the index CABG surgery

Exclusion criteria

• Clinical history of either permanent, persistent or paroxysmal atrial fibrillation

• Any pre-existing clinical indication for long-term OAC

• Any absolute contraindication to OAC

• Planned use of post-operative dual antiplatelet therapy (DAPT)

  a. This includes, but is not limited to, patients with recent PCI with drug-eluting or bare-metal stent.

• Cardiogenic shock

• Major perioperative complication* occurring between CABG and randomization

  a. including, but not limited to, stroke, TIA, MI, major bleeding (BARC type 4 bleeding), severe sepsis, renal failure requiring dialysis, or need for reoperation due to bleeding (e.g. pericardial tamponade).

• Concomitant left atrial appendage closure during CABG

• Concomitant valve surgery during CABG or prior valve surgery (including aortic, mitral, tricuspid or pulmonary)

• Concomitant mitral valve annuloplasty during CABG

• Concomitant carotid artery endarterectomy during CABG

• Concomitant aortic root replacement during CABG

• Concomitant surgery for AF during CABG

• Liver cirrhosis or Child-Pugh Class C chronic liver disease

• Pharmacologic therapy with an investigational drug or device within 30-days prior to randomization or plan to enroll patient in an investigational drug or device trial during participation in this trial

• Pregnancy at the time of randomization

• Unable or unwilling to provide inform consent

• Unable or unwilling to comply with the study treatment and follow-up

• Existence of underlying disease that limits life expectancy to less than one year

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,200 participants in 2 patient groups

Antiplatelet Therapy

Active Comparator group

Description:

Antiplatelet-only strategy

Treatment:

Drug: Antiplatelet-only strategy

Oral Anticoagulant

Active Comparator group

Description:

OAC-based strategy

Treatment:

Drug: Oral Anticoagulant plus background antiplatelet therapy