UMIN-CTR Clinical Trial

Public title

Prospective Observational Study in Late-Stage Elderly Patients with Non-Valvular Atrial Fibrillation
All Nippon AF In Elderly Registry
-ANAFIE Registry-

Acronym

ANAFIE Registry

Scientific Title

Prospective Observational Study in Late-Stage Elderly Patients with Non-Valvular Atrial Fibrillation
All Nippon AF In Elderly Registry
-ANAFIE Registry-

Scientific Title:Acronym

ANAFIE Registry

Region

Japan

Condition

Non-Valvular Atrial Fibrillation

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The major objectives of this study are to elucidate the current status of, and prognosis under, anticoagulant therapy as well as to determine the risk factors for stroke/systemic embolism and intracranial hemorrhage in late-stage elderly patients (aged 75 years or more) with non-valvular atrial fibrillation (NVAF) to identify the best-suited patient population and the optimal dosing regimen for DOACs.

Basic objectives2

Others

Basic objectives -Others

The secondary objective of this study is to address various clinical questions related to NVAF.

Trial characteristics_1

Others

Trial characteristics_2

Others

Developmental phase

Not applicable

Primary outcomes

Development of stroke/systemic embolism during the observation period

Key secondary outcomes

Occurrence of the following events during the observation period:
(1)Hemorrhagic adverse events (major bleeding)
(2)Stroke
(3)Systemic embolism
(4)Ischemic stroke
(5)Hemorrhagic stroke
(6)Intracranial hemorrhage
(7)Cardiovascular events (stroke, myocardial infarction, cardiac intervention for cardiac events other than myocardial infarction, or heart failure requiring hospitalization)
(8)Death from cardiovascular disease (death for which possibility of causal relationship with any cardiovascular factor cannot be excluded)
(9)All-cause mortality

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

75

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

(1)Patients who have been given the definitive diagnosis of NVAF and who have the ability to attend the hospital at specified visits. If a new diagnosis of NVAF is to be given to a patient, ECG, Holter ECG, portable ECG, echocardiography, etc. should be performed to make a definitive diagnosis.
(2)Patients aged 75 years or more at the time of informed consent (male or female patients)
(3)Patients who have given informed consent in writing

Key exclusion criteria

(1)Patients who are currently participating/who are planning to participate in an interventional study
(2)Patients who have been given the definitive diagnosis of mitral stenosis
(3)Patients who have an artificial heart valve (mechanical valve or tissue valve prostheses) in their body
(4)Patients who have experienced any cardiovascular event (stroke, myocardial infarction, cardiac intervention for cardiac events other than myocardial infarction, or heart failure requiring hospitalization) or any bleeding leading to hospitalization within one month before enrollment
(5)Patients who have been diagnosed as having a life expectancy of less than one year for some kind of disease
(6)Patients for whom participation in this study is inappropriate for other reason than those mentioned in the exclusion criteria above

Target sample size

30000

Name of lead principal investigator

1st name	Takeshi
Middle name
Last name	Yamashita

Organization

The Cardiovascular Institute

Division name

Director

Zip code

106-0031

Address

3-2-19 Nishi-azabu, Minato-ku, Tokyo 106-0031

TEL

03-3408-2151

Email

ANAFIE_office@quintiles.com

Name of contact person

1st name	Yoshiro
Middle name
Last name	Hirano

Organization

IQVIA Services Japan K.K.

Division name

Real World & Late Phase Research

Zip code

5320003

Address

Nissay Shin-Osaka Bldg, 3-4-30 Miyahara, Yodogawa-ku, Osaka 532-0003

TEL

06-7668-9053

Homepage URL

http://www.anafie.net/

Email

ANAFIE_office@quintiles.com

Institute

Medical Science Department
Daiichi Sankyo Company, Limited.

Institute

Department

Personal name

Organization

Medical Science Department
Daiichi Sankyo Company, Limited.
3-5-1 Nihonbashi-honcho
Chuo-ku, Tokyo 103-8426

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

The Cardiovascular Institute Ethic committee

Address

3-2-19 Nishi-azabu, Minato-ku, Tokyo 106-0031

Tel

03-3408-2151

Email

matsuda@cvi.or.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2016

Year

09

Month

12

Day

URL releasing protocol

https://pubmed.ncbi.nlm.nih.gov/29625717/

Publication of results

Published

URL related to results and publications

https://academic.oup.com/ehjqcco/advance-article/doi/10.1093/ehjqcco/qcab025/6208893?searchresult=1

Number of participants that the trial has enrolled

33062

Results

Among 32275 patients included in the analysis, 2445 (7.6%) were not receiving oral anticoagulants (OACs) and 29830 (92.4%) were given OACs. Of these, 21585 (66.9%) were receiving direct OACs (DOACs) and 8233 (25.5%), warfarin. The 2-year incidence rates were 3.01% for stroke/systemic embolic events (SEE); 2.00%, major bleeding; and 6.95%, all-cause death. The hazard ratios of DOAC group vs warfarin group were lower for stroke/SEE, major bleeding, and all-cause death after adjusting for confounders.

Results date posted

2021

Year

12

Month

01

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2021

Year

04

Month

02

Day

Baseline Characteristics

Overall, 57.3% of patients were men, the mean body mass index (BMI) was 23.3？kg/m2, and the mean age was 81.5？years. Most patients were between 75 and 79？years of age (40.0%) or between 80 and 89？years of age (43.5%), and 6.5% were aged over 90？years. Paroxysmal AF was the most common type of AF, followed by persistent AF and long-standing persistent/permanent AF. The most common comorbidities were hypertension (75.3%) and heart failure (37.5%).
Of 32275 patients, 12 were using parenteral anticoagulants and were therefore excluded from further analyses according to types of anticoagulation. In total, 2445 (7.6%) patients were not receiving OACs (No OAC group), and 29830 (92.4%) were receiving OACs (OAC group). Of the latter, 8233 (25.5%) were using warfarin, and 21585 (66.9%) were using DOACs. In the warfarin group, the mean prothrombin time-international normalized ratio was 1.98 at enrolment, and the mean time in the therapeutic range (PT-INR 1.6-2.6) was 75.5% during the 6？months just before the enrolment. In the DOAC group, apixaban, rivaroxaban, edoxaban, and dabigatran was used in 8045 (24.9% of the total), 6403 (19.8%), 4790 (14.8%), and 2347 (7.3%) patients, respectively. The percentage of patients prescribed a reduced dose of each DOAC was 61.1%, and 27.5% of those were treated with doses below those recommended in the package insert.
The mean age of the No OAC group was the highest, followed in order by the warfarin and DOAC groups. Patients receiving DOACs tended to have a higher creatinine clearance and tended to be more frequently diagnosed with paroxysmal AF than warfarin groups. Patients using warfarin tended to have higher proportions of heart failure, diabetes mellitus, chronic kidney disease, and MI than those in the No OAC and DOAC groups. Non-pharmacological therapy for AF, including catheter ablation was more common in the No OAC group.

Participant flow

Of the 33062 patients enrolled, 787 were excluded, and a total of 32275 patients were included in the present analysis. There were 1109 (3.4%) patients lost to follow-up; the proportion did not differ among the No OAC, warfarin, and DOAC groups (P= 0.29). Meanwhile, 762 (2.4%) discontinued the study due to withdrawal of consent and other reasons; the proportion of patients who discontinued differed slightly but significantly among the three treatment groups (P= 0.005). The mean follow-up period was 1.88 years.

Adverse events

data not shown

Outcome measures

In total, the 2-year incidence rate was 3.01% for stroke/systemic embolic events (SEE); 2.00%, major bleeding; and 6.95%, all-cause death. When compared with the warfarin group, the DOAC group had a lower hazard ratio (HR) for stroke/SEE, major bleeding, and all-cause death after adjusting for confounders. The group without OACs had a higher HR for stroke/SEE and all-cause death, with a lower HR for major bleeding. History of falls within 1 year at enrolment and of catheter ablation were positive and negative independent risk factors, respectively, for stroke/SEE, major bleeding, and all-cause death.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Main results already published

Date of protocol fixation

2016

Year

06

Month

23

Day

Date of IRB

2016

Year

08

Month

02

Day

Anticipated trial start date

2016

Year

10

Month

01

Day

Last follow-up date

2020

Year

01

Month

31

Day

Date of closure to data entry

2020

Year

05

Month

18

Day

Date trial data considered complete

2020

Year

05

Month

31

Day

Date analysis concluded

Other related information

Multicenter Prospective Observational Study

Registered date

2016

Year

09

Month

12

Day

Last modified on

2021

Year

12

Month

01

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027432