Long-term PT-INR levels and the clinical events in the patients with non-valvular atrial fibrillation: a special reference to low-intensity warfarin therapy

Abstract

Background: Anticoagulation therapy is essential in atrial fibrillation (AF), and in Japan, less intense control is popular.

Purpose: To assess the efficacy and safety with a special reference to low intensity warfarin therapy.

Subjects and methods: In 488 out of 508 patients with non-valvular AF, prothrombin time-international normalized ratio (PT-INR) was kept at 1.6-2.59, and they were followed for 49.5 months: 2098 person-years. The mean age was 73.7±9.9 years and 62% were male. The patients were divided by age: ≥70 years and <70 years, and by the intensity of warfarin therapy: PT-INR at 1.6-1.99 and at 2.0-2.59, respectively. The clinical data and event rates, ischemic stroke and major bleeding, were compared among the subgroups.

Results: Heart failure, previous stroke, and higher CHADS2 score were more often reported in patients ≥70 years while males were involved more often as younger patients. A total of 166 of 339 patients ≥70 years and 69 of 149 patients <70 years belonged to the low intensity group. Ischemic stroke and major bleeding occurred in 1.47%/year and 1.27%/year, respectively but there was no difference between the two age groups and between the two intensities of warfarin therapy. Time in therapeutic range was a predictor for ischemic stroke. A fall of PT-INR to <1.6 was found in 41.9% with ischemic stroke and a rise >2.61 in 40.0% with major bleeding at the time of the events. Blunt trauma and concomitant use of antiplatelets were risks for intracranial hemorrhage in the patients ≥70 years.

Conclusions: The event rates were similar between the low- (1.6-1.99) and high- (2.0-2.59) intensity warfarin therapy groups in aged patients: <70 years and ≥70 years. Time in therapeutic range and a transient fall or rise in PT-INR were risks for clinical events. Blunt head trauma and concomitant use of antiplatelets were risks for intracranial hemorrhage.

Keywords: Anticoagulants; Atrial fibrillation; Stroke; Warfarin.