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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Wu Jun, Nanjing Medical University
ClinicalTrials.gov Identifier:
NCT01438580
First received: September 14, 2011
Last updated: May 18, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Drug: Warfarin
Drug: aspirin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Nanjing Medical University:

Primary Outcome Measures:
  • major haemorrhage [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

    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:
  • minor bleeding [ Time Frame: 2.5years ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]

    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 [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]

    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 [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]

    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 [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]

    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.



Enrollment: 260
Study Start Date: January 2010
Study Completion Date: April 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   75 Years to 94 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01438580

Locations
China, Jiangsu
First Affiliated Hospital of Nanjing Medical University, Division of Geriatrics
Nanjing, Jiangsu, China, 210029
Sponsors and Collaborators
Nanjing Medical University
Investigators
Study Director: Guo Yan, doctor The First Hospital of Nanjing Medical University
  More Information

No publications provided by Nanjing Medical University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Wu Jun, First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University
ClinicalTrials.gov Identifier: NCT01438580     History of Changes
Other Study ID Numbers: 30900602
Study First Received: September 14, 2011
Last Updated: May 18, 2012
Health Authority: China: Ethics Committee

Keywords provided by Nanjing Medical University:
atrial fibrillation
stroke
warfarin
aspirin

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Aspirin
Warfarin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Anticoagulants

ClinicalTrials.gov processed this record on April 15, 2014