Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study

Japan Cardiovascular Research Foundation2,200 enrolled

Overview

In patients with atrial fibrillation (AF) complicated with coronary artery disease (CAD), antiplatelet drugs are commonly used for the prevention of recurrence of stent thrombosis and cardiovascular events in combination with anticoagulant drugs. Based on the observations that the incidence of hemorrhagic complications increased when an antiplatelet drug was administered in combination with vitamin K antagonist (VKA), the guidelines for antithrombotic therapy after PCI in the US and EU recommend that DAPT (dual anti-platelets therapy) should be used in AF-complicated CAD patients for as short a time as possible following single anti-platelet and VKA, and that monotherapy with VKA should be started from one year after PCI. In 2013 the European Heart Rhythm Association (EHRA) published the guidelines for the use of NOACs in NVAF patients, which state that NOACs may have advantage to VKAs in terms of anti-thrombotic effects in NVAF patients undergoing PCI. However, no clinical evidence has ever been generated to reveal the efficacy and safety of mono-drug therapy with a NOACs in stable CAD patients one year or more after PCI. AFIRE study is planned to evaluate the efficacy and safety of mono-drug therapy with a rivaroxaban in stable CAD patients. Among NOACs, rivaroxaban was chosen because of the evidence in Japanese patients and the results of a sub-analysis of ROCKET AF suggesting that rivaroxaban is more effective than VKA in reducing the incidence of myocardial infarction (MI).

Study Design:prospective, randomized, open-label trial Allocation:ratio to rivaroxaban monotherapy and rivaroxaban in co-administration with a single anti-platelet therapy is 1: 1 using WEB system

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

2,200

Interventions

Rivaroxaban and single antiplatelet drug (aspirin, clopidogrel or prasugrel)DRUG

* Rivaroxaban will be orally administered after a meal at a dose of 15 mg if the creatinine clearance (CLcr) is 50 mL/min or more and at a dose of 10 mg if the CLcr is 15-49 mL/min (regardless of time) * Antiplatelet will be selected from aspirin or thienopyridine derivatives (clopidogrel or prasugrel) * Aspirin will be orally administered once a day at a dose of 81 mg or 100 mg * Clopidogrel will be orally administered once a day after a meal at a dose of 75 mg. The dose will be reduced to 50mg once a day depending on age, body weight or clinical findings. * Prasugrel will be orally administered once a day at a dose of 3.75 mg. If the body weight is 50kg or less a reduced dose(2.5 mg once a day) will be considered depending on the age, renal function or other bleeding and thrombotic risk.

RivaroxabanDRUG

Rivaroxaban will be orally administered at a dose of 15 mg if the creatinine clearance (CLcr) is 50 mL/min or more and at a dose of 10 mg if the CLcr is 15-49 mL/min.

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: Patients with non-valvular atrial fibrillation complicated with stable coronary artery disease who are 20 years or older, with CHADS2 score are ≧1 , and that fulfill one of the following criteria and can provide written consent for participation in the present study will be eligible. 1. Patients who underwent percutaneous coronary intervention(PCI), including plain old balloon angioplasty(POBA), at least one year ago 2. Patients who have coronary stenosis requiring no percutaneous coronary intervention (50% or more stenosis) as indicated by coronary CT or coronary angiography(CAG) 3. Patients who underwent coronary artery bypass graft (CABG) at least one year ago Exclusion Criteria: * Patients for whom rivaroxaban is contraindicated * Patients for whom aspirin, thienopyridine derivatives (clopidogrel or prasugrel) are contraindicated * Patients who underwent PCI, including POBA, in the past one year * Patients who are going to undergo revascularization * Patients who have a past history of stent thrombosis * Those who are going to undergo invasive surgery (excluding digestive endoscopy and biopsy) * Patients who have active tumors * Patients who have poorly-controlled hypertension (systolic blood pressure at hospital admission: 160 mmHg or more) * Patients who cannot discontinue treatment with antiplatelet drugs (the physician in charge will make a decision on the basis of the lesion shape, lesion site and type of stents.) * Patients judged as inappropriate for this study by investigators

Outcomes

Primary Outcomes

Composite endpoint of cardiovascular events

stroke, non-CNS embolism, myocardial infarction, unstable angina pectoris requiring revascularizations or all-cause mortality