Rivaroxaban vs. Warfarin for Post Cardiac Surgery Atrial Fibrillation (NEW-AF)

Mass General Brigham

Status and phase: Completed; Phase 3

Conditions: Atrial Fibrillation; Stroke; Bleeding

Treatments: Drug: Warfarin; Drug: Rivaroxaban

Study type: Interventional

Funder types: Other

Identifiers

NCT03702582

2018P002307

Details and patient eligibility

About

This prospective, randomized, active-controlled, parallel arm study compares the safety and financial benefits of arterial thromboembolism prophylaxis with Warfarin vs. Rivaroxaban (A novel oral anticoagulant) in patients with new onset atrial fibrillation after sternotomy for cardiac operations.

Full description

New onset atrial fibrillation (NOAF) is a common occurrence following cardiac surgery, occurring in 20-30% of patients post-operatively. Historically, Vitamin K antagonist therapy with Warfarin has been the treatment of choice for prophylaxis against stroke and systemic arterial thromboembolism in NOAF. Warfarin inhibits the Vitamin K dependent factors involved in both the intrinsic and extrinsic coagulation cascades, thus decreasing systemic clotting. However, Warfarin therapy comes with many challenges including prolonged titration, tedious monitoring requirements and in some cases, increased bleeding risk.

The limitations associated with Warfarin may be mitigated by using new oral anticoagulants (NOACs) like Rivaroxaban which have no routine monitoring requirements. Rivaroxaban is a direct inhibitor of Factor Xa, a central reactant in both the intrinsic and extrinsic coagulation cascades. Studies in non-operative patients with atrial fibrillation have shown that Rivaroxaban is non-inferior to Warfarin for stroke prophylaxis with similar risk profiles. This study aims to compare the efficacy, safety and financial cost of these two drugs when used for the management of new onset atrial fibrillation that occurs after cardiac operations.

Enrollment: 100 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or Female ≥ 18 years
• At least one of the following procedures: coronary artery bypass grafting, aortic valve repair, mitral valve repair, non-mechanical aortic valve replacement, any combination of these procedures
• Two or more episodes of New Onset Atrial Fibrillation (each lasting > 20 minutes) or persistent atrial fibrillation lasting > 24 hours (Or for >18 hours over a 24-hour interval)
• If female of child-bearing age, use of adequate contraception

Exclusion criteria

• Pre-existing paroxysmal atrial fibrillation before cardiac surgery
• Pre-existing indications for therapeutic anticoagulation (Including but not limited to PE, DVT, mechanical valve)
• Moderate-to-severe mitral valve stenosis not surgically corrected
• Pre-existing allergy to study medications
• Recent (< 1 year) or ongoing pregnancy (Urine pregnancy test will be obtained for women of child bearing age at the time of enrollment into the study)
• Stroke within 1 month prior to surgery or postoperatively prior to initiation of study drugs
• Postoperative bleeding episode prior to initiation of study drug
• Severe dysfunction of another organ system including GFR < 30 ml/min, baseline INR > 1.7, ileus or other gastrointestinal pathology hindering ability to absorb oral medications, and known coagulation pathway deficiencies
• Postoperative need for non-aspirin anti-platelet therapy that cannot be discontinued when therapeutic anticoagulation is initiated
• Patient taking medications with known major interactions with study drugs with no therapeutic alternatives)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

100 participants in 2 patient groups

Rivaroxaban

Experimental group

Description:

Rivaroxaban: Direct inhibitor of Factor Xa, an enzyme that stimulates the formation of thrombin from prothrombin (A critical step in both the intrinsic and extrinsic aspects of the coagulation cascade) Dosage form: Per Os (Oral) Dosage and Frequency: 20 mg every evening with the evening meal (No titration requirements). For patients with decreased glomerular filtration rate (GFR between 15 ml/min and 50 ml/min), dosing will be decreased to 15 mg every evening with the evening meal. Duration: 30 days (Possibility of continuation after post-operative cardiology clinic visit)

Treatment:

Drug: Rivaroxaban

Warfarin

Active Comparator group

Description:

Warfarin: Competitive inhibitor of vitamin K epoxide reductase complex 1, an important enzyme in the activation pathway for vitamin K dependent coagulation factors Dosage form: Per Os (Oral) Dosage and Frequency: Initial dose of 2 - 5 mg nightly after the evening meal (QHS) with appropriate titration to goal INR 2.0 - 3.0 (Initial dose based on weight, age, gender, co-morbidities and concurrent medications). INR will be checked daily to weekly depending on stability of dosing and medication regimen. Duration: 30 days (Possibility of continuation after post-operative Cardiology clinic visit)

Treatment:

Drug: Warfarin