The Effect of Cognitive Impairment in the Elderly on the Initial and Long-Term Stability of Warfarin Therapy

Abstract

Despite guidelines that clearly outline the benefits of warfarin, it remains underutilized. Various reasons are associated with the underuse of warfarin; however, cognitive impairment (CI) has been identified as one of the most common causes for not electing to anticoagulate elderly patients with atrial fibrillation. Nevertheless, there are limited data on warfarin use in such patients; therefore, we investigated anticoagulation stability in patients with and without CI. Our objectives were to (i) examine if mild to moderate CI delayed the time required to achieve initial therapeutic anticoagulation; (ii) determine if mild to moderate CI was associated with long-term anticoagulation instability; and (iii) assess if initial anticoagulation problems predicted long-term anticoagulation instability. A retrospective study in a pharmacist-managed anticoagulation clinic was conducted in community-dwelling patients ≥60 years of age on warfarin therapy with a target international normalized ratio (INR) of 2.0-3.0. Our study included 57 patients; 20 were initiated on warfarin and 54 were analysed for long-term anticoagulation stability. Age, ethnicity, gender, warfarin indication, co-morbidities and caregiver involvement were recorded. We defined CI as having a Mini-Mental State Examination (MMSE) score of ≤26. To evaluate initial anticoagulation stability between groups, we analysed (i) number of clinic visits and days to achieve therapeutic INR; and (ii) minor and major adverse events upon initiation of warfarin. To evaluate long-term anticoagulation stability, we analysed (i) time in therapeutic range (TTR); (ii) the percentage of clinic visits with a reported dose mishap and the frequency of out-of-range INRs resulting from dose mishaps; and (iii) parameters associated with the intensity of clinic management: weekly warfarin dose changes, transient dose adjustments, any dose manipulation and the length of time between clinic visits. We found no difference in the number (mean ± SD) of visits (control = 5.8 ± 4.3, CI = 4.6 ± 2.4; p = 0.44) or days (control = 51.6 ± 45.7, CI = 35.8 ± 30.5; p = 0.36) required to achieve initial therapeutic anticoagulation. No adverse effects were reported in either group. In terms of long-term stability, TTR (mean ± SD) was similar for both groups (control = 65 ± 20% vs CI = 61 ± 16%; p = 0.36). Although the proportion of dose mishaps did not differ (control = 74 in 705 visits, CI = 86 in 691 visits; p = 0.18), dose mishaps resulted in a greater frequency of out-of-range INRs for patients with CI (p = 0.01). There were no differences in clinic management measures between groups (p = not statistically significant [NS] for all). Finally, we found no correlation between the time to reach initial anticoagulation stability and long-term stability for either group (p = NS for all). We found mild to moderate CI neither delayed the time required to achieve therapeutic anticoagulation, nor decreased anticoagulation stability versus patients with normal cognitive function. Additionally, CI did not require more intensive clinic management. CI should not necessarily be a barrier to the use of warfarin anticoagulation in elderly patients attending an anticoagulation clinic.