Dabigatran Versus Conventional Treatment for Prevention of Silent Cerebral Infarct in Atrial Fibrillation Associated With Valvular Disease "DECISIVE"

Not yet recruiting

Phase 4 Results N/A

Trial Description

The prevalence of AF, which is tachyarrhythmia, is approximately 2% of the entire population and 5% of the population at the age of 60 or older. AF is the cause of approximately 20% of all events of ischemic stroke, and patients with AF are known to be at 6 to 10% risk of ischemic stroke per year. Patients with valvular AF are known to have a higher incidence of stroke than patients with nonvalvular AF. However, the relevant data are insufficient as large randomized studies comparing NOAC treatment with warfarin, a conventional treatment, did not include many patients with moderate and severe valvular AF.
Ischemic stroke is divided into symptomatic stroke with brain lesions on brain magnetic resonance imaging (MRI) and silent cerebral infarct with lesions on brain MRI but without stroke symptoms. According to a brain MRI follow-up study, the incidence of silent cerebral infarct was 17.7% (254 subjects) over a period of 5 years, with 11.4% of 254 subjects reporting to have experienced symptoms. This means that the incidence of silent cerebral infarct is approximately 9 times that of symptomatic stroke. In addition, patients with a history of silent cerebral infarct are known to be approximately twice more likely to experience stroke in the future than those without a history of silent. Brain microbleed is easily detected by brain MRI and is a well-known independent predictor of intraparenchymal hemorrhage and silent cerebral infarct. The prevention of stroke by the study drug can be indirectly assessed based on the incidence of silent cerebral infarct and brain microbleed on brain MRI. Investigators tried to compare effect of dabigatran with conventional treatment in terms of prevention of stroke by comparing incidences of silent cerebral infarct and brain microbleed and symptomatic stroke using brain MRI.

Detailed Description

Amongst different types of cardiac arrhythmia, tachyarrhythmia shows the highest prevalence. The prevalence of AF, which is tachyarrhythmia, is approximately 2% of the entire population and 5% of the population at the age of 60 or older. AF is the cause of approximately 20% of all events of ischemic stroke, and patients with AF are known to be at 6 to 10% risk of ischemic stroke per year. In addition, AF results in heart failure and doubles mortalities. With an increase in the elderly population, there is a worldwide trend of increased hospitalization rate and medical cost caused by cardiac arrhythmia. In addition, whereas AF has been known to occur mainly in the elderly, the incidence of AF is also increasing in younger population, which is thought to be associated with the increased prevalence of heart diseases, dietary changes, and increased environmental pollution.
A. Previous studies related to atrial fibrillation and stroke i. While AF is characterized by a single electrophysiological abnormality, depending on cases, the risk of stroke varies from below 1%/year to 20%/year or above.
ii. New oral anticoagulant (NOAC), left atrial appendage occlusion, etc. have been studied as treatments to replace warfarin and aspirin and their effects have been also demonstrated.
B. Relevant study trends and limitations i. Patients with valvular AF are known to have a higher incidence of stroke than patients with nonvalvular AF. However, the relevant data are insufficient as large randomized studies comparing NOAC treatment with warfarin, a conventional treatment, did not include many patients with moderate and severe valvular AF.
ii. The exclusion of valvular AF from the study is based on the assumption that the pathogenesis of thromboembolism would vary according to the type of AF. However, the difference in pathogenesis of thromboembolism between valvular AF and nonvalvular AF remains unknown.
C. Study features i. Ischemic stroke is divided into symptomatic stroke with brain lesions on brain magnetic resonance imaging (MRI) and silent cerebral infarct with lesions on brain MRI but without stroke symptoms.
ii. According to a brain MRI follow-up study, the incidence of silent cerebral infarct was 17.7% (254 subjects) over a period of 5 years, with 11.4% of 254 subjects reporting to have experienced symptoms. This means that the incidence of silent cerebral infarct is approximately 9 times that of symptomatic stroke.
iii. In addition, patients with a history of silent cerebral infarct are known to be approximately twice more likely to experience stroke in the future than those without a history of silent.
iv. Brain microbleed is easily detected by brain MRI and is a well-known independent predictor of intraparenchymal hemorrhage and silent cerebral infarct.
v. The prevention of stroke by the study drug can be indirectly assessed based on the incidence of silent cerebral infarct and brain microbleed on brain MRI at the start of study and at 1 year follow-up.
D. Significance of the study i. The incidence of stroke is higher in valvular AF than in nonvalvular AF. ii. There is lack of data on dabigatran treatment, an NOAC, in valvular AF. iii. To compare dabigatran with conventional treatment in terms of prevention of stroke by comparing incidences of silent cerebral infarct and brain microbleed and symptomatic stroke at the start of study and at 1 year follow-up using brain MRI.
This is a single center, prospective, randomized study to evaluate the effectiveness and safety of dabigatran versus conventional treatment in patients with valvular AF by comparing the incidence of silent cerebral infarct and brain microbleed using brain MRI. Aspirin or warfarin treatment will be continued in patients randomly allocated to conventional treatment group, and changed to dabigatran treatment in those randomly allocated to dabigatran group.

Conditions

Interventions

  • Warfarin (Coumadin┬«)Drug
    ARM 1: Kind: Experimental
    Label: Conventional Treatment
    Description: Acetylsalicylic acid or warfarin treatment will be continued in patients allocated to conventional treatment group.
  • Dabigatran (Pradaxa)Drug
    Other Names: Pradaxa
    ARM 1: Kind: Experimental
    Label: Dabigatran
    Description: Previous treatment of aspirin or warfarin will be changed to dabigatran treatment in patients allocated to dabigatran group.
  • Acetylsalicylic acid Drug
    Other Names: Aspirin 81 mg
    ARM 1: Kind: Experimental
    Label: Conventional Treatment
    Description: Acetylsalicylic acid or warfarin treatment will be continued in patients allocated to conventional treatment group.

Outcomes

Type Measure Time Frame Safety Issue
Primary Composite of clinical cerebral infarct or new cerebral MRI lesions 12 months
Secondary Silent cerebral infarct 12 months
Secondary Clinical cerebral infarct 12 months
Secondary New cerebral microbleed 12 months
Secondary Major bleeding 12 months

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