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

Registration Number
NCT02642419
Lead Sponsor
Japan Cardiovascular Research Foundation
Brief Summary

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).

Detailed Description

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

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
2200
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Rivaroxaban and single antiplatelet drugRivaroxaban and single antiplatelet drug (aspirin, clopidogrel or prasugrel)-
RivaroxabanRivaroxaban-
Primary Outcome Measures
NameTimeMethod
Composite endpoint of cardiovascular eventsmean duration: 2 years, maximum duration: 3 years

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

Major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteriamean duration: 2 years, maximum duration: 3 years
Secondary Outcome Measures
NameTimeMethod
Ischemic cardiovascular events and deathmean duration: 2 years, maximum duration: 3 years

* All-cause mortality

* Cardiovascular death

* non-cardiovascular death

* Myocardial infarction

* Unstable angina pectoris requiring revascularization

* Ischemic stroke

* Transient ischemic attack

* non-CNS embolism (systemic embolism pulmonary embolism, deep vein thrombosis)

* PCI/CABG

* Stent thrombosis

* Ischemic stroke and systemic embolism

Adverse events excluding hemorrhagic eventsmean duration: 2 years, maximum duration: 3 years
Comparison of the primary endpoints, ischemic cardiovascular events and mortality between patients treated with aspirin and patients treated with thienopyridine derivativesmean duration: 2 years, maximum duration: 3 years
Subgroup analysis of primary endpoints, ischemic cardiovascular events and mortality according to the CHADS2 score and CHA2DS2-VASc scoremean duration: 2 years, maximum duration: 3 years
Subgroup analysis of primary endpoints, ischemic cardiovascular events and mortality according to subject characteristicsmean duration: 2 years, maximum duration: 3 years
Comparison of the incidence of bleeding events according to whether or not proton pump inhibitors (PPIs) are usedmean duration: 2 years, maximum duration: 3 years
Comparison of the incidence of the primary endpoints according to whether rivaroxaban is administered in the morning or eveningmean duration: 2 years, maximum duration: 3 years

Primary endpoints include the composite endpoint of cardiovascular events (stroke, non-CNS embolism, myocardial infarction, unstable angina pectoris requiring revascularization or cardiovascular death) and major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria.

Correlation of discontinuation of antithrombotic agents with ischemic cardiovascular events, bleeding events and adverse eventsmean duration: 2 years, maximum duration: 3 years
Correlation of prothrombin time at trough with bleeding events and evaluation of the cutoff values in patients with and without co-administration of antiplatelet drugmean duration: 2 years, maximum duration: 3 years
The incidence of the primary endpoints according to different rates of adherencemean duration: 2 years, maximum duration: 3 years

Primary endpoints include the composite endpoint of cardiovascular events (stroke, non-CNS embolism, myocardial infarction, unstable angina pectoris requiring revascularization or cardiovascular death) and major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria.

The rate of adherence will be calculated by dividing the number of prescribed tablets by the period of treatment: e.g., if 240 tablets are prescribed for 300 days, the rate of adherence will be 80.0% (240/300).

Net adverse clinical and cerebral events (NACCE)mean duration: 2 years, maximum duration: 3 years

composite of all-cause death, myocardial infarction, stroke and major bleeding.

All bleeding eventsmean duration: 2 years, maximum duration: 3 years
Subgroup analysis of major bleeding and all bleeding events according to the HAS-BLED score in patients with and without co-administration of antiplatelet drug and analysis of specificity and sensitivitymean duration: 2 years, maximum duration: 3 years

Trial Locations

Locations (1)

Japan Cardiovascular Research Foundation

🇯🇵

Suita, Osaka, Japan

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