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

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Warfarin; Drug: aspirin

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 Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • First Affiliated Hospital of Nanjing Medical University, Division of Geriatrics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years to 94 years (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: standard intensity warfarin group; 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	Drug: Warfarin; Patients randomised to receive warfarin were initiated on treatment at the baseline dose of 1.25mg daily and then gradually increase the amount to the target INR range.
Experimental: low intensity warfarin group; 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	Drug: Warfarin; Patients randomised to receive warfarin were initiated on treatment at the baseline dose of 1.25mg daily and then gradually increase the amount to the target INR range.
Active Comparator: aspirin group; 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	Drug: aspirin; 100mg aspirin was administrated every day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major haemorrhage	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.	2 years
ischaemic stroke	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
minor bleeding	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.	2.5years
myocardial infarction	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.	2.5 years
deep vein thrombosis	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.	2.5 years
pulmonary embolism	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.	2.5 years
cardiovascular death	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.	2.5 years

Collaborators and Investigators

• Sponsor: Nanjing Medical University
• Investigators: Study Director: Guo Yan, doctor, The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

General Publications

• Wu J, Wang J, Jiang S, Xu J, Di Q, Zhou C, Min X, Pang S, Wang H, Xu D, Guo Y. The efficacy and safety of low intensity warfarin therapy in Chinese elderly atrial fibrillation patients with high CHADS2 risk score. Int J Cardiol. 2013 Sep 10;167(6):3067-8. doi: 10.1016/j.ijcard.2012.11.078. Epub 2012 Nov 28. No abstract available.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: September 14, 2011
• First Submitted That Met QC Criteria: September 21, 2011
• First Posted (Estimate): September 22, 2011

Study Record Updates

• Last Update Posted (Estimate): May 21, 2012
• Last Update Submitted That Met QC Criteria: May 18, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: stroke; warfarin; aspirin; atrial fibrillation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Anticoagulants; Aspirin; Warfarin
• Other Study ID Numbers: 30900602