The Effect and Safety of Different Intensity Anticoagulation Therapy in Elderly Patients With Non-valvular Atrial Fibrillation

Phase 4

Completed

• Conditions: Atrial Fibrillation
• Interventions: Drug: aspirin; Drug: Warfarin

• Registration Number: NCT01438580
• Lead Sponsor: Nanjing Medical University

Brief Summary

Current guidelines recommend standard warfarin anticoagulation international normalized ratio (INR) goal of 2.0-3.0 in adults with non valvular atrial fibrillation (NVAF). The investigators hypothesized that low-intensity warfarin (INR 1.5-2.0) has the same effectiveness and better security in elderly patients (\>75) with NVAF.

Detailed Description

Atrial fibrillation is the commonest chronic arrhythmia in clinical practice, especially in octogenarians. Nonvalvular atrial fibrillation increases the risk of ischemic stroke by approximately 5-fold and these strokes result in higher mortality and disability. Warfarin is recommended as first line anticoagulation treatment in patients with NVAF who are at moderate or high risk of stroke,while antiplatelet agents, such as aspirin, give a more convenient but less effective alternative in the prevention of ischemic stroke and are recommended in low risk patients.Current guideline about warfarin anticoagulation therapy recommend that target INR value must be maintained between 2.0 and 3.0,which not only reduces the frequency of ischaemic stroke but also its low incidence of major bleeding. However, the current status of anticoagulation therapy for elderly Chinese AF patients, particularly in aged over 80 years, is not clear. The purpose of the present study was to test the hypothesis that an INR target of 1.5-2.0 can provide the same efficacy and better safety as compare with a standard target of 2.0-3.0 in patients over 75 with NVAF.

Study Timeline

• Study Start: 2010-01
• Study First Submitted: 2011-09-14
• Study First Submitted QC: 2011-09-21
• Study First Posted: 2011-09-22
• Primary Completion: 2012-01
• Study Completion: 2012-04
• Status Verified: 2012-05
• Last Update Submitted: 2012-05-18
• Last Update Posted: 2012-05-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 260

Inclusion Criteria

1. Clinical diagnosis of atrial fibrillation
2. Echocardiography confirmed a non-valvular heart disease
3. Age≥75 years

Exclusion Criteria

1. Unable to cooperate with doctors
2. Life expectancy of less than 1 year
3. Rheumatic heart disease or dilated cardiomyopathy
4. History of artificial valve replacement surgery
5. Infectious endocarditis
6. Stroke or transient ischemic attack(TIA) within the last 6 months
7. Previous history of intracranial hemorrhage, gastrointestinal, respiratory or urogenital bleeding
8. Previous intolerance/allergy to warfarin or aspirin
9. Blood pressure greater than 180/110 mmHg
10. Chronic liver dysfunction, alanine aminotransferase above the normal reference value of the upper limit 3 times
11. Chronic renal failure, serum creatinine clearance rate (Ccr) less than 30 ml / min
12. Patient was receiving antiplatelet or anticoagulant therapy due to other reasons

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
aspirin group	aspirin	Eligible 81 patients(83.4±5.13,33.5%)with chronic NVAF were randomly assigned to this group and 100mg aspirin was administrated every day
standard intensity warfarin group	Warfarin	Eligible 80 patients(83.14±4.05,33.0%)with chronic NVAF were randomly assigned to this group and the target international normalised ratio(INR) was 2.1-3.0
low intensity warfarin group	Warfarin	Eligible 81 patients(84.0±4.71,33.5%)with chronic NVAF were randomly assigned to this group and the target international normalised ratio(INR) was 1.5-2.0

Primary Outcome Measures

Name	Time	Method
major haemorrhage	2 years	Major haemorrhage was defined as intracranial hemorrhage, gastrointestinal bleeding, bleeding requiring hospitalization and surgical intervention, a reduction of hemoglobin by≥2 g/dL, requiring red blood cells transfusion ≥2 units.; Follow-up study visits were scheduled for once a week in the first month and then every 3 months. The number and results of INR tests, liver and kidney function tests were recorded. In addition, the number of bleeding events was recorded.
ischaemic stroke	2 years	ischaemic stroke was defined as a blockage in an artery that supplies blood to the brain , resulting in a deficiency in blood flow and focal neurological deficit lasting \>24 hours.; Follow-up study visits were scheduled for once a week in the first month and then every 3 months. The number and results of INR tests, liver and kidney function tests were recorded. In addition, the number of ischaemic stroke was recorded.

Secondary Outcome Measures

Name	Time	Method
minor bleeding	2.5years	Minor bleeding was any other bleeding requiring modification of the antithrombotic regimen,such as hematuria, gingival, conjunctival bleeding and so on.; Follow-up study visits were scheduled for once a week in the first month and then every 3 months. The number and results of INR tests, liver and kidney function tests were recorded. In addition, the number of minor bleedinge was recorded.
myocardial infarction	2.5 years	Myocardial infarction was defined as occurrence of typical chest pain, ECG and cardiac enzyme abnormalities.; Follow-up study visits were scheduled for once a week in the first month and then every 3 months. The number and results of INR tests, liver and kidney function tests were recorded. The number of myocardial infarction was recorded.
deep vein thrombosis	2.5 years	Deep vein thrombosis (DVT) was defined as a blood clot in a major vein that usually develops in the legs and/or pelvis and blocks blood flow, which can be diagnosised by ultrasound.; Follow-up study visits were scheduled for once a week in the first month and then every 3 months. The number and results of INR tests, liver and kidney function tests were recorded. The number of deep vein thrombosis was recorded.
pulmonary embolism	2.5 years	Pulmonary embolism was defined as occurrence of typical shortness of breath, chest pain, D-dimer and CT pulmonary angiography abnormalities.; Follow-up study visits were scheduled for once a week in the first month and then every 3 months. The number and results of INR tests, liver and kidney function tests were recorded. The number of pulmonary embolism was recorded.
cardiovascular death	2.5 years	Cardiovascular causes of death included myocardial infarction, heart failure, cardiac arrhythmia.; Follow-up study visits were scheduled for once a week in the first month and then every 3 months. The number and results of INR tests, liver and kidney function tests were recorded. The number of cardiovascular death was recorded.

Trial Locations

Locations (1)

First Affiliated Hospital of Nanjing Medical University, Division of Geriatrics; 🇨🇳 Nanjing, Jiangsu, China