INTENSITY OF ANTICOAGULATION IN OCTOGENARIANS WITH NONVALVULAR ATRIAL FIBRILLATION

Abstract

To the Editor: The intensity of anticoagulation currently used for octogenarians1, 2 and for patients aged 76 and older (mean age 81.5)3 with nonvalvular atrial fibrillation (NVAF) might be a strategy of high risk and low benefit. This intensity of anticoagulation, characterized by an international normalized ratio (INR) of 2 to 3, is the optimum one for patients aged 18 and older with NVAF.4 Evidence that this may be inappropriate for octogenarians comes from a study that enrolled 427 subjects aged 65 and older (including 153 aged≥80) with NVAF who were anticoagulated to a target INR of 2 to 3. In that study, patients aged 80 and older experienced significantly more (P=.01) episodes of severe hemorrhage than their younger counterparts.2 Given the fact that hemorrhagic risk is positively correlated with intensity of anticoagulation,5 fewer hemorrhagic episodes might have occurred had lower intensities of anticoagulation been used, as in the earlier studies that documented the efficacy of warfarin in preventing NVAF-related stroke.6, 7 One such study was the Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF), in which 32 of 404 participants were aged 80 and older, and the target INR was 1.5 to 2.7. In that study, warfarin was found to confer a 2.3% per year absolute reduction in the risk of NVAF-related stroke. This was associated with only two major hemorrhagic events (one of them intracranial) in 212 warfarin-treated patients and one major extracranial hemorrhagic event in 208 patients assigned to placebo.6 Comparable prophylactic benefit was documented in the Stroke Prevention in Nonrheumatic Atrial Fibrillation (SPINAF) study, in which a target INR of 1.4 to 2.8 was found to confer a 3.3% per year absolute reduction in the risk of NVAF-related stroke. Unlike the BAATAF, in which patients taking regular aspirin medication contributed 46% of all the patient-years in the control group, none of the SPINAF participants were taking aspirin.7 These results6, 7 compared favorably with those obtained in the Copenhagen Atrial Fibrillation, Aspirin and Anticoagulant Therapy Study, in which the much higher target INR of 2.8 to 4.2 was found to confer an absolute reduction of 2.6% per year in the risk of stroke.8 Only in the Stroke Prevention in Atrial Fibrillation 1 Study was a comparable intensity of anticoagulation, namely an INR 2 to 4.5, found to confer a greater reduction in the risk of stroke. In that trial, of the 421 participants in the warfarin or placebo group, eight of those allocated to warfarin were aged 76 and older, and eight of those allocated to placebo were aged 76 and older. The absolute reduction in stroke risk was 4.7% per year.9 Three “relevant” hemorrhagic episodes (2 of them intracranial) occurred in 210 patients on warfarin, and only one intracranial hemorrhagic episode occurred in the 211 patients assigned to placebo.9 In the absence of a prospective study of low-intensity anticoagulation (INR 1.4–2.8) in subjects aged 80 and older, a comparison of beneficial outcomes of low-intensity anticoagulation (target INR 1.5–2.7) in trials such as BAATAF,6 in which some of the participants were aged 80 and older, and the adverse outcomes when subjects in that age group were anticoagulated to the higher target INR of 2 to 3,2 should therefore guide the choice of anticoagulation intensity. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the author and has determined that the author has no financial or any other kind of personal conflicts with this article. Auhtor Contribution: OMJ is the sole author of this paper. Sponsor's Role: None.