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

NCT02642419 | Unknown Phase 4 DMC

• 1 other identifier: AFIRE Study
• Study Type: interventional
• Target: 2,200
• Locations: 1 country
• Sites: 1

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).

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (2)

• Composite endpoint of cardiovascular events

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

  mean duration: 2 years, maximum duration: 3 years

• Major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria

  mean duration: 2 years, maximum duration: 3 years

Secondary Outcomes (13)

• Net adverse clinical and cerebral events (NACCE)

  mean duration: 2 years, maximum duration: 3 years

• Ischemic cardiovascular events and death

  mean duration: 2 years, maximum duration: 3 years

• All bleeding events

  mean duration: 2 years, maximum duration: 3 years

• Adverse events excluding hemorrhagic events

  mean 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 derivatives

  mean duration: 2 years, maximum duration: 3 years

Study Arms (2)

Rivaroxaban

EXPERIMENTAL

Drug: Rivaroxaban

Rivaroxaban and single antiplatelet drug

EXPERIMENTAL

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

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.

Rivaroxaban and single antiplatelet drug

Rivaroxaban DRUG

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.

Rivaroxaban

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients who underwent percutaneous coronary intervention(PCI), including plain old balloon angioplasty(POBA), at least one year ago
• Patients who have coronary stenosis requiring no percutaneous coronary intervention (50% or more stenosis) as indicated by coronary CT or coronary angiography(CAG)
• Patients who underwent coronary artery bypass graft (CABG) at least one year ago

You may not qualify if:

• 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

Sponsors & Collaborators

• Japan Cardiovascular Research Foundation: lead

Study Sites (1)

Japan Cardiovascular Research Foundation

Suita, Osaka, 565-8565, Japan

RECRUITING

Related Publications (13)

• Yamaguchi J, Arashi H, Hagiwara N, Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Nakamura M, Miyauchi K, Matsui K, Ogawa H; AFIRE Investigators. Age-Stratified Effect of Rivaroxaban Monotherapy for Atrial Fibrillation in Stable Coronary Artery Disease: A Post Hoc Analysis of the AFIRE Randomized Clinical Trial. JAMA Cardiol. 2025 Aug 13;10(10):990-9. doi: 10.1001/jamacardio.2025.2611. Online ahead of print.

  PMID: 40802193 DERIVED

• Iijima R, Tokue M, Nakamura M, Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H; AFIRE Investigators. Thrombocytopenia as a Bleeding Risk Factor in Atrial Fibrillation and Coronary Artery Disease: Insights From the AFIRE Study. J Am Heart Assoc. 2023 Oct 17;12(20):e031096. doi: 10.1161/JAHA.123.031096. Epub 2023 Oct 10.

  PMID: 37815031 DERIVED

• Ishii M, Kaikita K, Yasuda S, Akao M, Ako J, Matoba T, Nakamura M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Nishihara E, Nakamura S, Matsui K, Ogawa H, Tsujita K; AFIRE Investigators. Risk prediction score for clinical outcome in atrial fibrillation and stable coronary artery disease. Open Heart. 2023 May;10(1):e002292. doi: 10.1136/openhrt-2023-002292.

  PMID: 37173099 DERIVED

• Ishii M, Kaikita K, Yasuda S, Akao M, Ako J, Matoba T, Nakamura M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H, Tsujita K; AFIRE Investigators. Rivaroxaban Monotherapy in Atrial Fibrillation and Stable Coronary Artery Disease Across Body Mass Index Categories. JACC Asia. 2022 Aug 27;2(7):882-893. doi: 10.1016/j.jacasi.2022.08.004. eCollection 2022 Dec.

  PMID: 36713761 DERIVED

• Naito R, Miyauchi K, Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Nakamura M, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H; AFIRE Investigators. Rivaroxaban Monotherapy vs Combination Therapy With Antiplatelets on Total Thrombotic and Bleeding Events in Atrial Fibrillation With Stable Coronary Artery Disease: A Post Hoc Secondary Analysis of the AFIRE Trial. JAMA Cardiol. 2022 Aug 1;7(8):787-794. doi: 10.1001/jamacardio.2022.1561.

  PMID: 35704345 DERIVED

• Arashi H, Yamaguchi J, Hagiwara N, Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Nakamura M, Miyauchi K, Kimura K, Hirayama A, Matsui K, Ogawa H; AFIRE investigators. Rivaroxaban Underdose for Atrial Fibrillation with Stable Coronary Disease: The AFIRE Trial Findings. Thromb Haemost. 2022 Sep;122(9):1584-1593. doi: 10.1055/s-0042-1744543. Epub 2022 Jun 13.

  PMID: 35697255 DERIVED

• Matsui K, Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Nakamura M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Ogawa H. The impact of kidney function in patients on antithrombotic therapy: a post hoc subgroup analysis focusing on recurrent bleeding events from the AFIRE trial. BMC Med. 2022 Feb 25;20(1):69. doi: 10.1186/s12916-022-02268-6.

  PMID: 35209924 DERIVED

• Matoba T, Yasuda S, Kaikita K, Akao M, Ako J, Nakamura M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H; AFIRE Investigators. Rivaroxaban Monotherapy in Patients With Atrial Fibrillation After Coronary Stenting: Insights From the AFIRE Trial. JACC Cardiovasc Interv. 2021 Nov 8;14(21):2330-2340. doi: 10.1016/j.jcin.2021.07.045.

  PMID: 34736731 DERIVED

• Matsuzawa Y, Kimura K, Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Nakamura M, Miyauchi K, Hagiwara N, Hirayama A, Matsui K, Ogawa H; AFIRE Investigators. Antithrombotic Therapy for Atrial Fibrillation and Coronary Artery Disease in Patients With Prior Atherothrombotic Disease: A Post Hoc Analysis of the AFIRE Trial. J Am Heart Assoc. 2021 Nov 2;10(21):e020907. doi: 10.1161/JAHA.121.020907. Epub 2021 Oct 18.

  PMID: 34658247 DERIVED

• Kaikita K, Yasuda S, Akao M, Ako J, Matoba T, Nakamura M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H. Bleeding and Subsequent Cardiovascular Events and Death in Atrial Fibrillation With Stable Coronary Artery Disease: Insights From the AFIRE Trial. Circ Cardiovasc Interv. 2021 Nov;14(11):e010476. doi: 10.1161/CIRCINTERVENTIONS.120.010476. Epub 2021 Sep 3.

  PMID: 34474583 DERIVED

• Fukaya H, Ako J, Yasuda S, Kaikita K, Akao M, Matoba T, Nakamra M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H. Aspirin versus P2Y12 inhibitors with anticoagulation therapy for atrial fibrillation. Heart. 2021 Nov;107(21):1731-1738. doi: 10.1136/heartjnl-2021-319321. Epub 2021 Jul 14.

  PMID: 34261738 DERIVED

• Akao M, Yasuda S, Kaikita K, Ako J, Matoba T, Nakamura M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H. Rivaroxaban monotherapy versus combination therapy according to patient risk of stroke and bleeding in atrial fibrillation and stable coronary disease: AFIRE trial subanalysis. Am Heart J. 2021 Jun;236:59-68. doi: 10.1016/j.ahj.2021.02.021. Epub 2021 Feb 28.

  PMID: 33657403 DERIVED

• Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Nakamura M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H; AFIRE Investigators. Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease. N Engl J Med. 2019 Sep 19;381(12):1103-1113. doi: 10.1056/NEJMoa1904143. Epub 2019 Sep 2.

  PMID: 31475793 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Rivaroxaban; Platelet Aggregation Inhibitors; Aspirin; Clopidogrel; Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hematologic Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines

Study Officials

• Hisao Ogawa

  Japan Cardiovascular Research Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Saburo Saito

CONTACT

+81-6-6872-0010; afire@jcvrf.jp

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: December 30, 2015
• Study Start: January 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: December 30, 2015

Record last verified: 2015-12

Locations

JP (1)