Low-intensity warfarin (INR 1.5-2.1) was safer than conventional-intensity therapy for secondary stroke prevention in NVAF, with fewer major hemorrhages (0% vs 6.6% per year, P=0.01).
RCT (n=115)
Randomized
Yes
Does low-intensity warfarin therapy reduce major hemorrhagic complications and prevent recurrent ischemic stroke compared to conventional-intensity warfarin in patients with NVAF and prior stroke or TIA?
Low-intensity warfarin (INR 1.5-2.1) significantly reduces major bleeding risk without increasing recurrent ischemic stroke compared to conventional-intensity warfarin (INR 2.2-3.5) for secondary prevention in NVAF.
Absolute Event Rate: 0% vs 6.6%
p-value: p=0.01
BACKGROUND AND PURPOSE: The optimal intensity of warfarin therapy for secondary prevention of stroke in nonvalvular atrial fibrillation (NVAF) remains unclear. We studied the efficacy and safety of conventional- and low-intensity warfarin therapy in a prospective, randomized, multicenter trial. METHODS: The study population consisted of patients with NVAF (<80 years old) who had a stroke or transient ischemic attack. The patients were randomly allocated into a conventional-intensity group (international normalized ratio INR 2.2 to 3.5) and a low-intensity group (INR 1.5 to 2.1). They were carefully monitored, and the annual rate of recurrent ischemic stroke and major hemorrhagic complications were compared between the groups. RESULTS: We enrolled 115 patients (mean age 66.7+/-6.5 years) into the study. Fifty-five and 60 patients were allocated into the conventional- and low-intensity groups, respectively. The trial was stopped after a follow-up of 658+/-423 days, when major hemorrhagic complications occurred in 6 patients of the conventional-intensity group and the frequency (6.6% per year) was significantly higher than that in the low-intensity group (0% per year, P=0.01, Fisher's exact test). All of the 6 patients with major bleeding were elderly (mean age 74 years), and their mean INR before the major hemorrhage was 2.8. The annual rate of ischemic stroke was low in both groups (1.1% per year in the conventional-intensity group and 1.7% per year in the low-intensity groups) and did not differ significantly. CONCLUSIONS: For secondary prevention of stroke in persons with NVAF, especially in old patients, the low-intensity warfarin (INR 1.5 to 2. 1) treatment seems to be safer than the conventional-intensity (INR 2.2 to 3.5) treatment.
Takenori Yamaguchi (2000) conducted an RCT in Nonvalvular atrial fibrillation with prior stroke or TIA (n=115). Low-intensity warfarin vs. Conventional-intensity warfarin (INR 2.2 to 3.5) was evaluated on Annual rate of major hemorrhagic complications (p=0.01). Low-intensity warfarin (INR 1.5-2.1) was safer than conventional-intensity therapy for secondary stroke prevention in NVAF, with fewer major hemorrhages (0% vs 6.6% per year, P=0.01).