Can lower-intensity warfarin reduce major bleeding after a stroke in people with nonvalvular atrial fibrillation?

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The optimal intensity of warfarin for preventing another stroke in people with nonvalvular atrial fibrillation (NVAF) remains unclear. Researchers compared the efficacy and safety of conventional- and low-intensity warfarin in a prospective, randomized, multicenter trial.

Participants were patients under 80 years old with NVAF who had experienced a stroke or transient ischemic attack. They were randomly assigned to conventional-intensity warfarin, targeting an international normalized ratio (INR) of 2.2 to 3.5, or low-intensity warfarin, targeting an INR of 1.5 to 2.1. Patients were carefully monitored, and the groups were compared for annual rates of recurrent ischemic stroke and major hemorrhagic complications.

The trial enrolled 115 patients, with a mean age of 66.7 ± 6.5 years. Of these, 55 were assigned to conventional-intensity treatment and 60 to low-intensity treatment.

The trial was stopped after a follow-up of 658 ± 423 days, when major hemorrhagic complications had occurred in 6 patients in the conventional-intensity group. The annual frequency was significantly higher with conventional-intensity treatment: 6.6% per year versus 0% per year with low-intensity treatment (P=0.01, Fisher's exact test). All 6 patients with major bleeding were elderly, with a mean age of 74 years; their mean INR before the major hemorrhage was 2.8.

Annual ischemic stroke rates were low in both groups: 1.1% per year with conventional-intensity treatment and 1.7% per year with low-intensity treatment. This difference was not statistically significant.

The researchers concluded that, for secondary stroke prevention in people with NVAF, especially older patients, low-intensity warfarin (INR 1.5 to 2.1) seems safer than conventional-intensity warfarin (INR 2.2 to 3.5).